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Sample records for spondyloarthropathy disease complex

  1. Seronegative spondyloarthropathies and allergic diseases in patients with ulcerative colitis

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    F. Ayala

    2011-09-01

    Full Text Available Seronegative spondyloarthropathy (SpA and allergic diseases are frequently observed in Ulcerative Colitis (UC. The aim of this study was to evaluate possible relationships between SpA, allergic contact dermatitis (ACD and IgE-mediated allergic disease (AD in patients with UC. Fifty consecutive UC patients were graded with clinical, endoscopic and histologic activity scores and classified on the basis of Rachmilewitz and Truelove & Richard criteria. The rheumatologic evaluation included history and physical examination. Axial and peripheral joint involvement was confirmed by radiographic and scintiscan examination. SpA was diagnosed according to the ESSG criteria. The allergologic evaluation included personal history of allergy, prick and patch exposition to airborne, food and contact allergens. AD was confirmed by specific provocation tests, while ACD was determined by using the European Standard Series. Fifty healthy subjects served as controls. Fourteen patients (28% and 1 control subject (2% showed SpA (p<0.001. Diagnosis of rhinitis, conjunctivitis or asthma was made in 19 patients (38% and 6 controls (12% (p=0.01, while ACD was found in 10 (20% and 3 (6% (p=0.03, respectively. Only 2 patients had a concurrence of SpA and AD (p=0.03, while SpA and ACD coexisted in 5 (p=n.s.. No patients contemporarily showed AD and ACD (p=0.008. Notwithstanding the high frequency of AD, SpA and ACD found in UC, the concurrence of AD with SpA or ACD is an unusual finding, while SpA and ACD may coexist. These data seem to indicate that AD and SpA, as well as AD and ACD, are strongly polarized conditions tending to mutual exclusion.

  2. Early diagnosis of the Spondyloarthropathies

    International Nuclear Information System (INIS)

    Gonzalez Naranjo, Luis Alonso; Londono, John D; Valle, Rafael Raul

    2005-01-01

    Spondyloarthropathies are a cluster of chronic inflammatory diseases that primarily include ankylosing spondylitis, reactive arthritis, psoriatic arthritis; arthritis associated with inflammatory bowel diseases and undifferentiated spondyloarthropathies. The most common subgroups of spondyloarthropathies are ankylosing spondylitis and undifferentiated spondyloarthropathy. The diagnosis of ankylosing spondylitis is mainly based on unequivocal radiographic sacroiliitis of at least grade 2 bilaterally or grade 3 unilaterally. How ever, in the early phase of disease, conventional radiographs are often too insensitive to show sacroiliitis and it usually takes several years for definite radiographic sacroiliitis to evolve. Thus, the diagnosis of ankylosing spondylitis is a commonly delayed by 8 to 11 years after the onset of symptoms. As a result, diagnosing axial spondyloarthropathy in the absence of radiographic sacroiliitis is very difficult to rheumatologists. In the early phase of disease, HLA B27 test and magnetic resonance imaging of sacroiliac joints may be helpful to the early diagnosis. In the presence of chronic low back pain the probability of axial spondyloarthropathy is about 5% and is about 14% if the back pain is inflammatory. The presence of = 3 features of spondyloarthropathy (heel pain, uveitis, dactylitis, positive family history, alternating buttock pain, psoriasis, inflammatory bowel disease, asymmetrical arthritis, positive response to anti-inflammatory drugs) increase the probability of axial spondyloarthropathy to 90%. Both, the positive HLA B27 and magnetic resonance imaging with signs of sacroiliitis increase the probability of spondyloarthropathy, particularly in patients without spondyloarthropathies features or with only 1 or 2 features. Since ankylosing spondylitis in association with psoriasis and inflammatory bowel disease is often HLA B27 negative, this test is of limited value under theses circumstances. Is important to consider that

  3. Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthropathy, Following Lyme Disease

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    Arvikar, Sheila L.; Crowley, Jameson T.; Sulka, Katherine B.; Steere, Allen C.

    2016-01-01

    Objective To describe systemic autoimmune joint diseases following Lyme disease and to compare their clinical features with Lyme arthritis. Methods Records of all adult patients referred to our Lyme arthritis clinic over a 13-year period in whom we diagnosed a systemic autoimmune joint disease following Lyme disease were reviewed. For comparison, records of patients enrolled in our Lyme arthritis (LA) cohort over the most recent 2-year period were analyzed. IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured. Results We identified 30 patients who developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease, usually erythema migrans (EM). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthropathy (SpA). The 30 patients typically had polyarthritis; and those with PsA/SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 LA patients, monoarticular knee arthritis, without prior EM, was the usual clinical picture. Most systemic autoimmune patients had positive tests for B. burgdorferi IgG antibodies by ELISA, but they had significantly lower titers and lower frequencies of Lyme-associated autoantibodies than LA patients. Prior to our evaluation, the patients often received additional antibiotics for presumed Lyme arthritis without benefit. We prescribed anti-inflammatory therapies, most commonly disease modifying anti-rheumatic drugs (DMARDs), resulting in improvement. Conclusion Systemic autoimmune joint diseases, RA, PsA/SpA, may follow Lyme disease. Development of polyarthritis after antibiotic-treated erythema migrans, previous psoriasis, or low-titer B. burgdorferi antibodies are clues to the correct diagnosis. PMID:27636905

  4. Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy.

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    Baeten, Dominique; Kruithof, Elli; De Rycke, Leen; Boots, Anemieke M; Mielants, Herman; Veys, Eric M; De Keyser, Filip

    2005-01-01

    Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes and/or global disease activity in SpA. Synovial biopsies obtained from 99 SpA and 86 RA patients with active knee synovitis were analyzed for 15 histological and immunohistochemical markers. Correlations with swollen joint count, serum C-reactive protein concentrations, and erythrocyte sedimentation rate were analyzed using classical and multiparameter statistics. SpA synovitis was characterized by higher vascularity and infiltration with CD163+ macrophages and polymorphonuclear leukocytes (PMNs) and by lower values for lining-layer hyperplasia, lymphoid aggregates, CD1a+ cells, intracellular citrullinated proteins, and MHC-HC gp39 complexes than RA synovitis. Unsupervised clustering of the SpA samples based on synovial features identified two separate clusters that both contained different SpA subtypes but were significantly differentiated by concentration of C-reactive protein and erythrocyte sedimentation rate. Global disease activity in SpA correlated significantly with lining-layer hyperplasia as well as with inflammatory infiltration with macrophages, especially the CD163+ subset, and with PMNs. Accordingly, supervised clustering using these synovial parameters identified a cluster of 20 SpA patients with significantly higher disease activity, and this finding was confirmed in an independent SpA cohort. However, multiparameter models based on synovial histopathology were relatively poor predictors of disease activity in individual patients. In conclusion, these data indicate that inflammatory infiltration of the synovium with CD163+ macrophages and PMNs as well as lining-layer hyperplasia reflect global disease activity in SpA, independently of the SpA subtype

  5. and inflammatory spondyloarthropathies

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    Katarzyna Białowąs

    2014-09-01

    Full Text Available The most recent studies confirm the link between rheumatoid arthritis (RA and periodontal disease. RA patients have higher prevalence of chronic periodontitis and periodontal disease is often more severe in these patients. Both RA and PD show similar pathophysiological mechanisms and risk factors. Autoimmunity to citrullinated peptides is the primary element in the pathogenesis of RA, not found in other diseases. Porphyromonas gingivalis, the major periodontal pathogen associated with the etiology of chronic periodontitis, is the only bacterium currently known to produce the enzyme peptidylarginine deiminase (PAD allowing protein citrullination. This bacterium likely fulfils a significant role in the pathogenesis of RA due to its capacity for citrullination of its own protein and host peptides, which may result in a loss of immune tolerance. A few epidemiological studies also indicate the potential link between spondyloarthropathies and periodontal disease.

  6. Prognosis and adjacent segment disease after lumbar spinal fusion surgery for destructive spondyloarthropathy in long-term hemodialysis patients.

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    Maruo, Keishi; Moriyama, Tokuhide; Tachibana, Toshiya; Inoue, Shinichi; Arizumi, Fumihiro; Kusuyama, Kazuki; Yoshiya, Shinichi

    2017-03-01

    Lumbar destructive spondyloarthropathy (DSA) is a serious complication in long-term hemodialysis patients. There have not been many reports regarding the surgical management for lumbar DSA. In addition, the adjacent segment pathology after lumbar fusion surgery for DSA is unclear. The objective of this study was to assess the clinical outcome and occurrence of adjacent segmental disease (ASD) after lumbar instrumented fusion surgery for DSA in long-term hemodialysis patients. A consecutive series of 36 long-term hemodialysis patients who underwent lumbar instrumented fusion surgery for DSA were included in this study. The mean age at surgery was 65 years. The mean follow-up period was 4 years. Symptomatic ASD was defined as symptomatic spinal stenosis or back pain with radiographic ASD. The Japanese Orthopedic Association score (JOA score), recovery rate (Hirabayashi method), complications, and reoperation were reviewed. The mean JOA score significantly increased from 13.5 before surgery to 21.3 at the final follow-up. The mean recovery rate was 51.4%. Six of the 36 patients died within 1 year after index surgery. One patient died due to perioperative complication. Symptomatic ASD occurred in 43% (13 of 30) of the cases. Of these 13 cases, 5 had adjacent segment disc degeneration and 8 had adjacent segment spinal stenosis. Three cases (10%) required reoperation due to proximal ASD. Multi-level fusion surgery increased the risk of ASD compared with single-level fusion surgery (59% vs. 23%). The recovery rate was significantly lower in the ASD group than the non-ASD group (38% vs. 61%). This study demonstrated that symptomatic ASD occurred in 43% of patients after surgery for lumbar DSA. A high mortality rate and complication rate were observed in long-term hemodialysis patients. Therefore, care should be taken for preoperative planning for surgical management of DSA. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights

  7. Hepatitis C virus seroprevalence and genotypes in patients with diffuse connective tissue diseases and spondyloarthropathies

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    Barbosa V.S.

    2005-01-01

    Full Text Available Many extrahepatic manifestations, including rheumatic diseases, have been reported to be associated with hepatitis C virus (HCV infection. In order to investigate the prevalence of HCV infection among patients with rheumatic diseases, in the present study we interviewed 367 patients and tested their blood samples for HCV antibodies (anti-HCV by an enzyme-linked immunosorbent assay. Anti-HCV-reactive samples were retested for confirmation by a line immunoassay and also for HCV RNA detection by the polymerase chain reaction. HCV RNA-positive samples were genotyped by INNO-LIPA. An overall HCV infection prevalence of 1.9% (7/367 was found. Of the 7 HCV-infected patients, 4 had systemic lupus erythematosus and 3 rheumatoid arthritis, resulting in positivity rates of 2.3 and 3.4%, respectively. HCV RNA genotyping revealed the presence of subtypes 1a (57.1%, 1b (28.6% and 3a (14.3%. The clinical course was favorable for all HCV-infected patients, except one, who died due to renal insufficiency related to lupus nephritis. These results demonstrate a low HCV infection prevalence among the population studied. In the few positive cases, we observed no adverse influence of this infection on the clinical evolution of the rheumatic disease.

  8. Detection of Crohn Disease in Patients with Spondyloarthropathy: The SpACE Capsule Study.

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    Kopylov, Uri; Starr, Michael; Watts, Craig; Dionne, Serge; Girardin, Marc; Seidman, Ernest G

    2018-02-15

    Inflammatory bowel disease (IBD) is generally reported to be associated with spondylarthropathies (SpA) in 5%-15% of cases. Systematic colonoscopic assessment by protocol demonstrated mucosal inflammation characteristic of Crohn disease (CD) in up to one-third of patients with SpA. Video capsule endoscopy (CE) is a superior diagnostic tool to detect small bowel mucosal disease. Our study compared the accuracy of CE to standard colonoscopy for detection of inflammatory bowel lesions in patients with SpA, and to describe predictors of small bowel inflammation (SBI) in this cohort. Prospective cross-sectional study of adult patients followed for SpA. Patients were evaluated by CE and standard colonoscopy with biopsies. SBI was quantified using the Lewis Score. Additional screening tests included fecal calprotectin (FCP), C-reactive protein (CRP), and a diagnostic panel of serologic, inflammatory and genetic tests (SGI). There were 64 patients recruited (53% female, mean age 42 ± 13 yrs). Chronic gastrointestinal (GI) symptoms were present in 57%. CE revealed significant SBI in 27/64 (42.2%), compared to 7/64 (10.9%) by standard colonoscopy (p = 0.035). Elevated FCP was associated with small bowel CD (OR 4.5, 95% CI 1.01-19.9; p = 0.042). No correlation was observed with presence of GI symptoms, CRP, or SGI results. Finding CD led to a change in management in 65.2% of cases. CE uncovered SBI consistent with CD in 42.2% of patients with SpA, with a significant incremental yield over colonoscopy of 31%. FCP levels were significantly correlated with CE results, while GI symptoms and SGI results were poor predictors of SBI.

  9. Stability of fatigue, pain, patient global assessment and the Bath Ankylosing Spondylitis Functional Index (BASFI) in spondyloarthropathy patients with stable disease according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

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    Madsen, Ole Rintek

    2018-01-01

    The study objective was to examine natural variation of the patient-reported outcome measures fatigue, pain, patient global assessment (PaGl) and the Bath Ankylosing Spondylitis Functional Index (BASFI) in patients with stable axial spondyloarthropathy (ax-SpA) defined on the basis of the Bath...... Spondylitis Ankylosing Disease Activity Index (BASDAI). 107 TNF-inhibitor treated stable ax-SpA patients were identified in the Danish rheumatology registry (DANBIO). According to the Assessment of SpondyloArthritis international Society (ASAS) response criteria, stable disease was defined as a change...

  10. Reproducibility of the Bath Ankylosing Spondylitis Indices of disease activity (BASDAI), functional status (BASFI) and overall well-being (BAS-G) in anti-tumour necrosis factor-treated spondyloarthropathy patients

    DEFF Research Database (Denmark)

    Madsen, Ole R; Rytter, Anne; Hansen, Lonnie B

    2010-01-01

    The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Function Index (BASFI) and the Bath Ankylosing Spondylitis Global Score (BAS-G) (ranges 0-10) have gained widespread in use as self-reported measures of disease activity, functional impairment...... and overall well-being in patients with ankylosing spondylitis and other spondyloarthropathies (SpA). In Denmark, BASDAI, BASFI and BAS-G are systematically used to monitor treatment response in patients treated with tumour necrosis factor (TNF) inhibitors. The purpose of the present study was to examine...

  11. Diagnostic imaging of sacroiliac joints and the spine in the course of spondyloarthropathies

    International Nuclear Information System (INIS)

    Sudoł-Szopinska, Iwona; Urbanik, Andrzej

    2013-01-01

    Spondyloarthropathies belong to a group of rheumatic diseases, in which inflammatory changes affect mainly the sacroiliac joints, spine, peripheral joints, tendon, ligaments and capsule attachments (entheses). This group includes 6 entities: ankylosing spondylitis, arthritis associated with inflammatory bowel disease, reactive arthritis, undifferentiated spondyloarthropathy, psoriatic arthritis and juvenile spondyloarthropathy. In 2009, ASAS (Assessment in SpondyloArthritis international Society) association, published classification criteria for spondyloarthropathies, which propose standardization of clinical-diagnostic approach in the case of sacroiliitis, spondylitis and arthritis. Radiological diagnosis of inflammatory changes of sacroiliac joints is based on a 4 step radiographic grading method from 1966. According to modified New York criteria, the diagnosis of ankylosing spondylitis is made based on the presence of advanced lesions, sacroiliitis of at least 2 grade bilaterally or 3–4 unilaterally. In case of other types of spondyloarthropathies diagnosis is made based on presence of at least grade 1 changes. In MRI, active inflammation of sacroiliac joints is indicated by the presence of subchondral bone marrow edema, synovitis, bursitis, or enthesitis. ASAS discusses only the classic form of axial spondyloarthropathies, which is ankylosing spondylitis. To quantify radiological inflammatory changes in the course of the disease, Stoke Ankylosing spondylitis classification Spinal Score (SASSS) is recommended. The signs of inflammation and scarrying of the spinal cord in the course of ankylosing spondylitis, present in MRI include: bone marrow edema, sclerosis, fat metaplasia, formation of syndesmophytes, and ankylosis

  12. [Dialysis-associated spondyloarthropathy. Case report and literature review].

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    Khalfallah, M; Faure, A; Hamel, O; Cantarovich, D; Doe, K; Raoul, S; Bord, E; Robert, R

    2005-09-01

    Hemodialysis has considerably prolonged the life of patients suffering from terminal renal failure. However, long-term hemodialysis leads to new bone complications and spinal disorders such as destructive spondyloarthropathy (DSA). At the present time DSA is reported in 8% to 18% of the dialysed patients. Diagnosis is based on severe narrowing of the intervertebral disk, erosions and geodes of the adjacent vertebral plates simulating infectious spondylitis. Lesions progressively involve posterior joints and may lead to severe destruction of the spine. The pathogenesis of this syndrome is still unknown. Several factors have been implicated, including microcrystal deposition, amyloidosis, inflammatory and foreign body reactions and suggest that the pathogenesis of erosive spondyloarthropathies of hemodialysed patients is multifactorial. Spinal instability inducing myelopathy and radiculopathy were observed in 8% of the cases. Treatment must be accorded to the natural disease course and to the quality of the bone. We report the case of a chronic dialysed patient with destructive spondyloarthropathy involving the cervical and thoracic spine. Pathogenesis, radiological datas and therapeutic approach are discussed.

  13. [Cross-cultural adaptation and validation of Lithuanian questionnaires for the spondyloarthropathies].

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    Venceviciene, Lina; Rugiene, Rita; Venalis, Algirdas; Butrimiene, Irena

    2009-01-01

    Original English questionnaires--Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Patient Global Score, and Bath Ankylosing Spondylitis Disease Activity Index--are designed to evaluate health, physical and psychical state of patients with spondyloarthropathies and to assess efficiency of the treatment. The objective of the study was to adapt Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Patient Global Score, Bath Ankylosing Spondylitis Disease Activity Index questionnaires to the Lithuanian context and examine their psychometric aspects: reliability and validity. Validation and linguistic and cultural adaptation of Lithuanian questionnaires were performed according to the requirements for adaptation of the international questionnaires. Psychometric features of Lithuanian questionnaires were examined in 139 patients with spondyloarthropathies. The validity of questionnaires was tested by comparing these questionnaires with Health Assessment Questionnaire Modified for Spondyloarthropathies, metrology indices (tragus-to-wall distance, lateral flexion, modified Schober's distance, intermalleolar distance), pain intensity, patient's well-being, physician's assessment of the disease activity, and total enthesis count. The reliability of questionnaires was assessed by determining internal consistency of scales and scale stability and by calculating the intraclass correlation coefficient. The linguistic and cultural adaptation of these questionnaires was made during the study. Internal consistency was high for functional and disease activity index (Cronbach alpha>/=0.80) and moderate for the Bath Ankylosing Spondylitis Patient Global Score (Cronbach alpha=0.58). High stability in regard to time was characteristic of all three questionnaires (intraclass correlation coefficient >0.95). A significant association between the separate questions of examined instruments, their joint results and other factors reflecting patient

  14. A simplified staging system based on the radiological findings in different stages of ochronotic spondyloarthropathy

    International Nuclear Information System (INIS)

    Jebaraj, Isaac; Chacko, Binita Riya; Chiramel, George Koshy; Matthai, Thomas; Parameswaran, Apurve

    2013-01-01

    This study describes a group of 26 patients with ochronotic spondyloarthropathy who were on regular treatment and follow-up at a tertiary level hospital and proposes a simplified staging system for ochronotic spondyloarthropathy based on radiographic findings seen in the thoracolumbar spine. This proposed classification makes it easy to identify the stage of the disease and start the appropriate management at an early stage. Four progressive stages are described: an inflammatory stage (stage 1), the stage of early discal calcification (stage 2), the stage of fibrous ankylosis (stage 3), and the stage of bony ankylosis (stage 4). To our knowledge, this is the largest reported series of radiological description of spinal ochronosis, and emphasizes the contribution of the spine radiograph in the diagnosis and staging of the disease

  15. The interaction between host genetics and the microbiome in the pathogenesis of spondyloarthropathies.

    Science.gov (United States)

    Asquith, Mark; Rosenbaum, James T

    2016-07-01

    The intestinal microbiome is increasingly implicated in the pathogenesis of ankylosing spondylitis, reactive arthritis, and other diseases collectively known as the spondyloarthropathies (SpAs). In common with other complex inflammatory diseases, SpAs have both a strong genetic and environmental component. Recent genetic studies have highlighted host pathways that may intersect the host-microbiota interaction and offer novel paradigms to understand the pathophysiology of these diseases. Genetic association studies have identified genes such as RUNX3, PTPEN2, and IL-33 as susceptibility loci for SpAs. Functional studies in humans have extended knowledge of established genetic risk factors for ankylosing spondylitis that include ERAP1, ERAP2, and interleukin-23R. Recent basic research has identified new mechanisms that regulate host immune responses to the microbiota that conceivably may be dysregulated in SpA. Intestinal barrier function, deletional tolerance, Th17 signature response, and endoplasmic reticulum stress pathways have been recently linked to SpA. Dysregulated immune responses to the gut microbiota and an altered microbial community structure are shared features of SpA. Although the cause-effect dynamic of this relationship remains equivocal, it nonetheless has major implications for both intestinal and extra-intestinal pathology observed in SpA.

  16. Genetics of complex diseases

    DEFF Research Database (Denmark)

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...

  17. Spondylo-arthropathies or ossifying polyenthesites. Scintigraphic and scannographic results

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    Gaucher, A.; Pere, P.; Regent, D.; Grandhaye, P.; Aussedat, R.; Vivard, T.

    1987-03-01

    Ossifying enthesites present an undeniable diagnostic value in every chronic inflammatory rheumatism at an early stage, not only in adults but also in children. Bony scintigraphy discovers them in most localizations at a preradiological stage, as soon as they cause pain. The scanner examination enables to follow the anatomical evolution of the ossifications. It is perfectly suitable for the study of sacro-iliac and interapophyseal joints. Ossifying enthesites, the evolution of which spreads over several years, often depend on mechanical, professional or athletic constraints. Ossifying enthesitis is a common characteristics of ''classic'' spondylo-arthropathies which are all ossifying polyenthesites: ankylosing spondylarthritis, psoriasic rheumatism, rheumatism of enteropathies, Fiessinger-Leroy-Reiter syndrome and juvenile spondylo-arthropathies.

  18. Spondylo-arthropathies or ossifying polyenthesites. Scintigraphic and scannographic results

    International Nuclear Information System (INIS)

    Gaucher, A.; Pere, P.; Regent, D.; Grandhaye, P.; Aussedat, R.; Vivard, T.

    1987-01-01

    Ossifying enthesites present an undeniable diagnostic value in every chronic inflammatory rheumatism at an early stage, not only in adults but also in children. Bony scintigraphy discovers them in most localizations at a preradiological stage, as soon as they cause pain. The scanner examination enables to follow the anatomical evolution of the ossifications. It is perfectly suitable for the study of sacro-iliac and interapophyseal joints. Ossifying enthesites, the evolution of which spreads over several years, often depend on mechanical, professional or athletic constraints. Ossifying enthesitis is a common characteristics of ''classic'' spondylo-arthropathies which are all ossifying polyenthesites: ankylosing spondylarthritis, psoriasic rheumatism, rheumatism of enteropathies, Fiessinger-Leroy-Reiter syndrome and juvenile spondylo-arthropathies [fr

  19. Musculoskeletal Findings in Behcet's Disease

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    Ali Bicer

    2012-01-01

    Full Text Available Behcet's disease is a multisystem disease characterized by recurrent oral and genital ulcers, relapsing uveitis, mucocutaneous, articular, gastrointestinal, neurologic, and vascular manifestations. Rheumatologic manifestations may also occur in Behcet's disease, and arthritis and arthralgia are the most common musculoskeletal findings followed by enthesopathy, avascular necrosis, myalgia, and myositis. Although the main pathology of Behcet's disease has been known to be the underlying vasculitis, the etiology and exact pathogenesis of the disease are still unclear. Musculoskeletal findings of Behcet's disease, the relationship between Behcet's disease and spondyloarthropathy disease complex, and the status of bone metabolism in patients with Behcet's disease were discussed in this paper.

  20. Medical biostatistics for complex diseases

    National Research Council Canada - National Science Library

    Emmert-Streib, Frank; Dehmer, Matthias

    2010-01-01

    ... and factors that may all act together to lead to a frank disorder in the individual patient. Based on this assumption, the evaluation of such complex diseases with respect to the affected cells and cell systems by appropriate biostatistical analysis, including high capacity assays and highly developed multi-parameter evaluation-assays, is a clear me...

  1. Reproducibility of the Bath Ankylosing Spondylitis Indices of disease activity (BASDAI), functional status (BASFI) and overall well-being (BAS-G) in anti-tumour necrosis factor-treated spondyloarthropathy patients

    DEFF Research Database (Denmark)

    Madsen, Ole R; Rytter, Anne; Hansen, Lonnie B

    2010-01-01

    The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Function Index (BASFI) and the Bath Ankylosing Spondylitis Global Score (BAS-G) (ranges 0-10) have gained widespread in use as self-reported measures of disease activity, functional impairment...

  2. Destructive spondyloarthropathy of the cervical spine in long-term hemodialyzed patients: a five-year clinical radiological prospective study

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    Leone, A.; Marano, P. [Dept. of Radiology, Univ. Cattolica, Rome (Italy); Sundaram, M. [Dept. of Radiology, Mayo Clinic, Rochester, MN (United States); Cerase, A. [Unit of Neuroradiology, Policlinico ' ' Le Scotte' ' , Siena (Italy); Magnavita, N. [Dept. of Occupational Medicine, Univ. Cattolica, Rome (Italy); Tazza, L. [Dept. of Surgery, Univ. Cattolica, Rome (Italy)

    2001-08-01

    To describe the radiographic features and progression of cervical spine destructive spondyloarthropathy (DSA) in hemodialyzed patients, and to evaluate the relationship between this disease and patient characteristics, biochemical values, and hemodialysis duration. Design and patients: Standard radiographs, and lateral flexion and extension views of the cervical spine, were performed annually for 5 years in 31 hemodialyzed patients who were divided into three groups at the commencement of the study: those showing (I) DSA, (II) vertebral rim erosions (VRE) without DSA, and (III) absence of DSA and VRE. Magnetic resonance (MR) imaging and computed tomography (CT) were performed in seven and two patients respectively. The imaging features were evaluated for the presence and progression of spondyloarthropathy and correlated with clinical and biochemical variables. Statistical analysis was performed using one-way analysis of variance. The duration of hemodialysis appeared to be the main predictive factor (P=0.0003) for DSA, which was found in six patients (19%). DSA was found to correlate with higher levels of beta2-microglobulin (P<0.00001), parathyroid hormone (P<0.05), and alkaline phosphatase (P<0.05). Clinical symptoms were minimal. In two patients, MR imaging revealed changes mimicking spondylodiscitis. In another patient, CT of the craniocervical junction showed bone resorption due to a pseudotumor, and basilar invagination. DSA of the cervical spine is often clinically silent. Pathogenesis of DSA may be multifactorial but its progression is most influenced by the duration of hemodialysis. On MR imaging, DSA may mimic spondylodiscitis. (orig.)

  3. Selective IgA deficiency and spondyloarthropathy: a distinct disease?

    OpenAIRE

    Herrero-Beaumont, G; Armas, J B; Elswood, J; Will, R K; Calin, A

    1990-01-01

    A woman with selective IgA deficiency and severe ankylosing spondylitis (AS), complicated by intractable peripheral arthritis, is described. Three previous cases of selective IgA deficiency and AS have been reported, all of whom had severe AS. It is suggested that selective IgA deficiency is a poor prognostic factor in AS and therefore warrants further investigation to determine the clinical course of such patients.

  4. Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls

    NARCIS (Netherlands)

    Haynes, D. R.; Barg, E.; Crotti, T. N.; Holding, C.; Weedon, H.; Atkins, G. J.; Zannetino, A.; Ahern, M. J.; Coleman, M.; Roberts-Thomson, P. J.; Kraan, M.; Tak, P. P.; Smith, M. D.

    2003-01-01

    OBJECTIVES: To demonstrate the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in synovial tissue from rheumatoid arthritis (RA) patients, establish the cell lineage expressing OPG and compare the expression of OPG in RA, spondyloarthropathies,

  5. Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles

    NARCIS (Netherlands)

    Gu, Jieruo; Rihl, Markus; Märker-Hermann, Elisabeth; Baeten, Dominique; Kuipers, Jens G.; Song, Yeong Wook; Maksymowych, Walter P.; Burgos-Vargas, Ruben; Veys, Eric M.; de Keyser, Filip; Deister, Helmuth; Xiong, Momiao; Huang, Feng; Tsai, Wen Chan; Yu, David Tak Yan

    2002-01-01

    OBJECTIVE: To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, and to identify which cytokines/chemokines are being expressed and which cell fractions

  6. A 588-gene microarray analysis of the peripheral blood mononuclear cells of spondyloarthropathy patients

    NARCIS (Netherlands)

    Gu, J.; Märker-Hermann, E.; Baeten, D.; Tsai, W. C.; Gladman, D.; Xiong, M.; Deister, H.; Kuipers, J. G.; Huang, F.; Song, Y. W.; Maksymowych, W.; Kalsi, J.; Bannai, M.; Seta, N.; Rihl, M.; Crofford, L. J.; Veys, E.; de Keyser, F.; Yu, D. T. Y.

    2002-01-01

    OBJECTIVES: To identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects. METHODS: A 588-gene microarray was used as a screening

  7. Network-based analysis of complex diseases.

    Science.gov (United States)

    Liu, Z-P; Wang, Y; Zhang, X-S; Chen, L

    2012-02-01

    Complex diseases are commonly believed to be caused by the breakdown of several correlated genes rather than individual genes. The availability of genome-wide data of high-throughput experiments provides us with new opportunity to explore this hypothesis by analysing the disease-related biomolecular networks, which are expected to bridge genotypes and disease phenotypes and further reveal the biological mechanisms of complex diseases. In this study, the authors review the existing network biology efforts to study complex diseases, such as breast cancer, diabetes and Alzheimer's disease, using high-throughput data and computational tools. Specifically, the authors categorise these existing methods into several classes based on the research topics, that is, disease genes, dysfunctional pathways, network signatures and drug-target networks. The authors also summarise the pros and cons of those methods from both computation and application perspectives, and further discuss research trends and future topics of this promising field.

  8. Bioenergetic Origins of Complexity and Disease

    Science.gov (United States)

    Wallace, D.C.

    2015-01-01

    The organizing power of energy flow is hypothesized to be the origin of biological complexity and its decline the basis of “complex” diseases and aging. Energy flow through organic systems creates nucleic acids, which store information, and the annual accumulation of information generates today's complexity. Energy flow through our bodies is mediated by the mitochondria, symbiotic bacteria whose genomes encompass the mitochondrial DNA (mtDNA) and more than 1000 nuclear genes. Inherited and/or epigenomic variation of the mitochondrial genome determines our initial energetic capacity, but the age-related accumulation of somatic cell mtDNA mutations further erodes energy flow, leading to disease. This bioenergetic perspective on disease provides a unifying pathophysiological and genetic mechanism for neuropsychiatric diseases such as Alzheimer and Parkinson Disease, metabolic diseases such as diabetes and obesity, autoimmune diseases, aging, and cancer. PMID:22194359

  9. Epigenetic Epidemiology of Complex Diseases Using Twins

    DEFF Research Database (Denmark)

    Tan, Qihua

    2013-01-01

    through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting...... a more efficient use of twins in epigenetic studies of complex human diseases....

  10. Complexity, fractals, disease time, and cancer.

    Science.gov (United States)

    Spillman, W B; Robertson, J L; Huckle, W R; Govindan, B S; Meissner, K E

    2004-12-01

    Despite many years of research, a method to precisely and quantitatively determine cancer disease state remains elusive. Current practice for characterizing solid tumors involves the use of varying systems of tumor grading and staging and thus leaves diagnosis and clinical staging dependent on the experience and skill of the physicians involved. Although numerous disease markers have been identified, no combination of them has yet been found that produces a quantifiable and reliable measure of disease state. Newly developed genomic markers and other measures based on the developing sciences of complexity offer promise that this situation may soon be changed for the better. In this paper, we examine the potential of two measures of complexity, fractal dimension and percolation, for use as components of a yet to be determined "disease time" vector that more accurately quantifies disease state. The measures are applied to a set of micrographs of progressive rat hepatoma and analyzed in terms of their correlation with cell differentiation, ratio of tumor weight to rat body weight and tumor growth time. The results provide some support for the idea that measures of complexity could be important elements of any future cancer "disease time" vector.

  11. Nephronophthisis and medullary cystic kidney disease complex

    Directory of Open Access Journals (Sweden)

    Stanišić Marijana

    2005-01-01

    Full Text Available Background. Nephronophthisis and medullary cystic kidney disease complex refers to the genetic heterogeneous group of inherited tubulointerstital nephritis. Nephronophthisis comprises at last 3 clinical manifestations, has the autosomal recessive pattern of inheritance, appears early in life and is the most frequent inherited kidney disease that causes terminal renal failure in childhood, while medullary cystic kidney disease has the autosomal dominant pattern of inheritance, is less frequent, and terminal renal failure appears later in life. These two forms have similar clinical and morphological findings but extrarenal manifestations, the median ages of occurrence of terminal renal failure, and siblings presence help us distinguish these diseases. Case report. In this article we illustrated the case of a 20- years old patient with the suspicion of having complex nephornophthisis and medullary cystic kidney disease based upon mild renal failure, seen in routinely taken laboratory findings and bilateral cysts in corticomedullary region of the kidneys verified on abdominal ultrasound examination. Conclusion. This disease should rise suspicion in children or adolescents with progressive renal failure, a typical clinical manifestation, blood and urine samples results, bilateral cysts in the corticomedullary region of the kidneys seen during ultrasound examination of the kidneys and family inheritance.

  12. Endocrine autoimmune disease: genetics become complex.

    Science.gov (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Major histocompatibility complex: its role in the pathogenesis of autoimmune rheumatic diseases - doi:10.5020/18061230.2006.p155

    Directory of Open Access Journals (Sweden)

    Crésio Alves

    2012-01-01

    Full Text Available In order to allow early diagnosis and more efficient treatments, many studies have been trying to define genetic markers of rheumatic diseases. Amongst them, antigens and alleles of the HLA (Human Leukocyte Antigens system are distinguished. Located in the short arm of chromosome 6, the HLA system exerts genetic influence on the susceptibility and severity of these diseases. The discovery of new molecular methods to typify HLA alleles and the recent nomenclature updates have been contributing to a better understanding of this system. Unfortunately, this information has not been adequately published in the clinical literature. The present work aimed at presenting the function, nomenclature and methods of detection of the HLA polymorphism; and to review its associations with rheumatic fever, systemic erythematosus lupus, rheumatoid arthritis, juvenile idiopathic arthritis and spondyloarthropathies. Articles that were published between 1980 and 2005 were searched in the MEDLINE and LILACS data basis. This review demonstrated that although the HLA association is well established for some rheumatic diseases (e.g., HLA-B27 and spondyloarthropathies, HLA DR-3 and HLA-DR4 with rheumatoid arthritis, HLA-DR4 and lupus others vary in different ethnic-racial group and illnesses, due to its polymorphism. It is necessary to study populations from different ethnic backgrounds to identify new associations or to strengthen associations with the ones already identified. This knowledge will contribute to future prophylactic or therapeutic interventions in patients with rheumatic disorders or at risk to develop them.

  14. Clinical significance of abdominal scintigraphy using {sup 99m}Tc-HMPAO-labelled leucocytes in patients with seronegative spondyloarthropathies

    Energy Technology Data Exchange (ETDEWEB)

    Alonso Farto, J.C.; Almoguera Arias, I.; Ortega Valle, A.; Perez Vazquez, J.M. [Department of Nuclear Medicine, Univ. Complutense, Madrid (Spain); Lopez Longo, F.J.; Gonzalez Fernandez, C.M.; Monteagudo Saez, I.; Bascones, M.; Carreno Perez, L. [Department of Rheumatology, ' ' Hospital Universitario Gregorio Maranon' ' , Universidad Complutense, Madrid (Spain)

    2000-12-01

    Abdominal scintigraphy shows silent gut inflammation in patients with spondyloarthropathies (Sp) without clinical evidence of gut inflammation. Abdominal scintigraphy images are different than those obtained in patients with ulcerative colitis or Crohn's disease and are not related to the anti-inflammatory drugs administered. The aim of this study was to examine the clinical associations of findings on abdominal scintigraphy in patients with Sp. A total of 204 Sp patients (European Spondylarthropathy Study Group 1991 criteria) and 54 non-Sp controls receiving non-steroidal anti-inflammatory drugs were studied. Abdominal scintigraphy images were obtained at 30 and 120 min after injection of technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO)-labelled leucocytes. {sup 99m}Tc-HMPAO-labelled leucocyte scans were positive in 104 Sp patients (50.9%) and in six non-Sp controls (2.9%) (P<0.001; OR=8.32; 95% CI=3.23-22.67). Silent gut inflammation was not associated with any of the following: age of onset, duration of evolution, sex, family history of Sp or psoriasis, articular manifestations, extra-articular manifestations, radiological findings or HLA-B27 positivity. Positive abdominal scintigraphy was associated with active disease (P<0.0001; OR=52.7; 95% CI=19-145.6) and an increase in the C-reactive protein (P<0.005; OR=3.4; 95% CI=1.5-7.4). It is concluded that (a) abdominal scintigraphy using {sup 99m}Tc-HMPAO-labelled leucocytes is of value in detecting the silent gut inflammation in Sp patients, and (b) silent gut inflammation is related to the clinical activity, but is not associated with any particular type of illness or with HLA-B27. (orig.)

  15. Major histocompatibility complex genomics and human disease.

    Science.gov (United States)

    Trowsdale, John; Knight, Julian C

    2013-01-01

    Over several decades, various forms of genomic analysis of the human major histocompatibility complex (MHC) have been extremely successful in picking up many disease associations. This is to be expected, as the MHC region is one of the most gene-dense and polymorphic stretches of human DNA. It also encodes proteins critical to immunity, including several controlling antigen processing and presentation. Single-nucleotide polymorphism genotyping and human leukocyte antigen (HLA) imputation now permit the screening of large sample sets, a technique further facilitated by high-throughput sequencing. These methods promise to yield more precise contributions of MHC variants to disease. However, interpretation of MHC-disease associations in terms of the functions of variants has been problematic. Most studies confirm the paramount importance of class I and class II molecules, which are key to resistance to infection. Infection is likely driving the extreme variation of these genes across the human population, but this has been difficult to demonstrate. In contrast, many associations with autoimmune conditions have been shown to be specific to certain class I and class II alleles. Interestingly, conditions other than infections and autoimmunity are also associated with the MHC, including some cancers and neuropathies. These associations could be indirect, owing, for example, to the infectious history of a particular individual and selective pressures operating at the population level.

  16. 9 CFR 381.82 - Diseases of the leukosis complex.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Diseases of the leukosis complex. 381.82 Section 381.82 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Carcasses and Parts § 381.82 Diseases of the leukosis complex. Carcasses of poultry affected with any one or...

  17. Molecular diagnostics for the Sigatoka disease complex of banana

    NARCIS (Netherlands)

    Arzanlou, M.; Abeln, E.C.A.; Kema, G.H.J.; Waalwijk, C.; Carlier, J.; Crous, P.W.

    2007-01-01

    The Sigatoka disease complex of banana involves three related ascomycetous fungi, Mycosphaerella fijiensis, M. musicola, and M. eumusae. The exact distribution of these three species and their disease epidemiology remain unclear, because their symptoms and life cycles are rather similar. Disease

  18. Complex liver cysts in Autosomal Dominant Polycystic Kidney Disease.

    Science.gov (United States)

    Farooq, Zerwa; Behzadi, Ashkan Heshmatzadeh; Blumenfeld, Jon D; Zhao, Yize; Prince, Martin R

    To determine prevalence of complex liver cysts in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Abdominal MRI in 186 ADPKD subjects were evaluated by two independent observers to determine prevalence of complex liver cysts. 23 (12%) of subjects, had at least 1 complex cyst. Only 8 (4%) were reported to have a complex cyst prospectively, representing an under-reporting rate of 65%. Median total cyst volume was 66-times greater for subjects with complex cysts compared to subjects without (p<0.0001). Complex hepatic cysts were observed in 12% of ADPKD cases, occurring more frequently in livers with extensive cystic involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Role of Interleukin- (IL- 17 in the Pathogenesis and Targeted Therapies in Spondyloarthropathies

    Directory of Open Access Journals (Sweden)

    I-Tsu Chyuan

    2018-01-01

    Full Text Available Spondyloarthropathy (SpA is a unique type of joint inflammation characterized by coexisting erosive bone damage and pathological new bone formation. Previous genetic association studies have demonstrated that several cytokine pathways play a critical role in the pathogenesis of ankylosing spondylitis (AS, psoriatic arthritis (PsA, and other types of SpA. In addition to several well-known proinflammatory cytokines, recent studies suggest that IL-17 plays a pivotal role in the pathogenesis of SpA. Further evidence from human and animal studies have defined that IL-17 and IL-17-producing cells contribute to tissue inflammation, autoimmunity, and host defense, leading to the following pathologic events associated with SpA. Recently, several clinical trials targeting IL-17 pathways demonstrated the positive response of IL-17 blockade in treating AS, indicating a great potential of IL-17-targeting therapy in SpA. In this review article, we have discussed the contributing role of IL-17 and different IL-17-producing cells in the pathogenesis of SpA and provided an outline of therapeutic application of the IL-17 blockade in the treatment of SpA. Other targeted cytokines associated with IL-17 axis in SpA will also be included.

  20. [Destructive cervical amyloidotic spondyloarthropathy in patients undergoing periodic dialysis. Personal experience].

    Science.gov (United States)

    Madia, G; Mughetti, M; Muratore, F; Mignani, R; Leurini, R; Boccadoro, R; Denicolò, M

    1990-12-01

    The accumulation of amyloid (beta 2-microglobulin) in several organs and tissues of patients in chronic dialysis is a recent pathologic condition. A wide range of cases, supported by specific tests for amyloid on bioptic and autoptic samples, showed a radiographic semiology of osteostructural alterations in various areas which allows amyloidotic condition of bone to be diagnosed with high reliability. In 11 of 62 patients (17.74%) we observed destructive cervical amyloidotic spondyloarthropathy (DCAS). The radiological patterns common to all patients were subchondral sclerosis, erosions of vertebral body plates, widening/narrowing of intervertebral spaces, no/poor osteophytosis. Over-hanging was present in 54.5% of cases, and deformation of vertebral bodies in 45.4%. CT was useful in improving the definition of the various alterations, and in locating others, such as cavitations in vertebral bodies and involvement of apophyseal joints. Constant factors were the association with extravertebral osseous amyloidosis, dyalitic age over 60 months, and the use of Cuprophan membranes for dialysis. The frequent (72.72%) association with alterations involving the lumbar rachis (subchondral sclerosis, erosions and geodes) was suggestive of amyloidotic condition.

  1. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

    Hu, Jessica Xin; Thomas, Cecilia Engel; Brunak, Søren

    2016-01-01

    The co-occurrence of diseases can inform the underlying network biology of shared and multifunctional genes and pathways. In addition, comorbidities help to elucidate the effects of external exposures, such as diet, lifestyle and patient care. With worldwide health transaction data now often being...

  2. Complexity theory in the management of communicable diseases.

    Science.gov (United States)

    Simmons, Mike

    2003-06-01

    In nature, apparently complex behavioural patterns are the result of repetitive simple rules. Complexity science studies the application of these rules and looks for applications in society. Complexity management opportunities have developed from this science and are providing a revolutionary approach in the constantly changing workplace. This article discusses how complexity management techniques have already been applied to communicable disease management in Wales and suggests further developments. A similar approach is recommended to others in the field, while complexity management probably has wider applications in the NHS, not least in relation to the developing managed clinical networks.

  3. Results of complex treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Kolygin, B.A.; Lebedev, S.V.; Borodina, A.F.; Kochurova, N.V.; Malinin, A.P.; Safonova, S.A.; Punanov, Yu.A.

    2000-01-01

    The evaluation of remote results of the complex treatment (polychemotherapy plus radiotherapy) for identification of the forecasting factor which may be applied, by stratification into the risk groups, is carried out. The group of 334 children up to 15 years with lymphogranulomatosis, subjected to not less than 2 cycles of inductive polychemotherapy and consolidating radiotherapy, is analyzed. The irradiation was conducted at the radiotherapeutic devices ROCUS LUE-25 and LUEV-15 M1. The complete remission after the treatment program was fixed by 95.1% of the patients the partial remission-by 6.3%; no effect was noted by 0.6% of the patients. Actuarial 10-year survival constituted 85.9%, the frequency of nonrelapsing flow - 74.3% [ru

  4. Comprehension of Complex Discourse in Different Stages of Huntington's Disease

    Science.gov (United States)

    Saldert, Charlotta; Fors, Angelika; Stroberg, Sofia; Hartelius, Lena

    2010-01-01

    Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group…

  5. Detecção do DNA de Chlamydia trachomatis em espondiloartropatias e artrite reumatóide Detection of Chlamydia trachomatis DNA in spondyloarthropathies and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Rafael Navarrete Fernandez

    2005-10-01

    em atividade, a C. trachomatis não pode ser excluída como agente desencadeador.Chlamydia trachomatis is the bacteria responsible for the most prevalent sexually transmitted disease worldwide. Most of the infections in men and women is asymptomatic and when undiagnosed and untreated may reach the joints causing not only arthritis, but also other acknowledged complications related to the female reproductive system. OBJECTIVE: To investigate C. trachomatis DNA in the urine and synovial fluid from patients with spondyloarthropathies (SpA and rheumatoid arthritis (RA and evaluate serum anti-C. trachomatis IgG and IgM antibodies. METHODS: The population consisted of 15 patients with spondyloarthropathies, being 9 with undifferentiated spondyloarthropathy (US and 6 with reactive arthritis (ReA (group I, and 15 patients with rheumatoid arthritis (RA (group II. The chlamydial DNA was assessed in synovial fluid and urine samples of all patients by Amplicor (Roche, Swiss PCR. The anti-chlamydial IgG and IgM antibodies were quantified through indirect imunofluorescence (IIF, while 15 patients of group I were typed for HLA-B27 by the use of flow citometry. Sociodemographical data and all information on sexual behaviour and presence of symptoms were collected through a (questionnaire in the form of an interview. RESULTS: C. trachomatis DNA was found in only one synovial fluid sample from patient with ReA (6,7%. In two patients with RA, chlamydial DNA was identified in the urine sample (13,3%. The anti-chlamydial IgG antibodies were present in eight patients of the population studied; being three patients from group I (20%, and five from group II (33,3%. The greatest titer of this antibody 1/256 was associated with the presence of chlamydial DNA in a patient from group II. The IgM antibody was not detected in any of the samples from both groups. Four individuals from group II (26,7% were HLA-B27 positive and its presence was related to sacroiliitis. CONCLUSIONS: The results in

  6. Understanding Parkinson Disease: A Complex and Multifaceted Illness.

    Science.gov (United States)

    Gopalakrishna, Apoorva; Alexander, Sheila A

    2015-12-01

    Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care.

  7. Immune evasion by pathogens of bovine respiratory disease complex.

    Science.gov (United States)

    Srikumaran, Subramaniam; Kelling, Clayton L; Ambagala, Aruna

    2007-12-01

    Bovine respiratory tract disease is a multi-factorial disease complex involving several viruses and bacteria. Viruses that play prominent roles in causing the bovine respiratory disease complex include bovine herpesvirus-1, bovine respiratory syncytial virus, bovine viral diarrhea virus and parinfluenza-3 virus. Bacteria that play prominent roles in this disease complex are Mannheimia haemolytica and Mycoplasma bovis. Other bacteria that infect the bovine respiratory tract of cattle are Histophilus (Haemophilus) somni and Pasteurella multocida. Frequently, severe respiratory tract disease in cattle is associated with concurrent infections of these pathogens. Like other pathogens, the viral and bacterial pathogens of this disease complex have co-evolved with their hosts over millions of years. As much as the hosts have diversified and fine-tuned the components of their immune system, the pathogens have also evolved diverse and sophisticated strategies to evade the host immune responses. These pathogens have developed intricate mechanisms to thwart both the innate and adaptive arms of the immune responses of their hosts. This review presents an overview of the strategies by which the pathogens suppress host immune responses, as well as the strategies by which the pathogens modify themselves or their locations in the host to evade host immune responses. These immune evasion strategies likely contribute to the failure of currently-available vaccines to provide complete protection to cattle against these pathogens.

  8. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

    Science.gov (United States)

    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A; Sanz, Ferran; Furlong, Laura I

    2011-01-01

    Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The

  9. Coupled disease-behavior dynamics on complex networks: A review

    Science.gov (United States)

    Wang, Zhen; Andrews, Michael A.; Wu, Zhi-Xi; Wang, Lin; Bauch, Chris T.

    2015-12-01

    It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease-behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease-behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.

  10. Coupled disease-behavior dynamics on complex networks: A review.

    Science.gov (United States)

    Wang, Zhen; Andrews, Michael A; Wu, Zhi-Xi; Wang, Lin; Bauch, Chris T

    2015-12-01

    It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease-behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease-behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Can data repositories help find effective treatments for complex diseases?

    Science.gov (United States)

    Farber, Gregory K

    2017-05-01

    There are many challenges to developing treatments for complex diseases. This review explores the question of whether it is possible to imagine a data repository that would increase the pace of understanding complex diseases sufficiently well to facilitate the development of effective treatments. First, consideration is given to the amount of data that might be needed for such a data repository and whether the existing data storage infrastructure is enough. Several successful data repositories are then examined to see if they have common characteristics. An area of science where unsuccessful attempts to develop a data infrastructure is then described to see what lessons could be learned for a data repository devoted to complex disease. Then, a variety of issues related to sharing data are discussed. In some of these areas, it is reasonably clear how to move forward. In other areas, there are significant open questions that need to be addressed by all data repositories. Using that baseline information, the question of whether data archives can be effective in understanding a complex disease is explored. The major goal of such a data archive is likely to be identifying biomarkers that define sub-populations of the disease. Published by Elsevier Ltd.

  12. Complex social contagion makes networks more vulnerable to disease outbreaks

    Science.gov (United States)

    Campbell, Ellsworth; Salathé, Marcel

    2013-01-01

    Social network analysis is now widely used to investigate the dynamics of infectious disease spread. Vaccination dramatically disrupts disease transmission on a contact network, and indeed, high vaccination rates can potentially halt disease transmission altogether. Here, we build on mounting evidence that health behaviors - such as vaccination, and refusal thereof - can spread across social networks through a process of complex contagion that requires social reinforcement. Using network simulations that model health behavior and infectious disease spread, we find that under otherwise identical conditions, the process by which the health behavior spreads has a very strong effect on disease outbreak dynamics. This dynamic variability results from differences in the topology within susceptible communities that arise during the health behavior spreading process, which in turn depends on the topology of the overall social network. Our findings point to the importance of health behavior spread in predicting and controlling disease outbreaks. PMID:23712758

  13. The impact of the human genome project on complex disease.

    Science.gov (United States)

    Bailey, Jessica N Cooke; Pericak-Vance, Margaret A; Haines, Jonathan L

    2014-07-16

    In the decade that has passed since the initial release of the Human Genome, numerous advancements in science and technology within and beyond genetics and genomics have been encouraged and enhanced by the availability of this vast and remarkable data resource. Progress in understanding three common, complex diseases: age-related macular degeneration (AMD), Alzheimer's disease (AD), and multiple sclerosis (MS), are three exemplars of the incredible impact on the elucidation of the genetic architecture of disease. The approaches used in these diseases have been successfully applied to numerous other complex diseases. For example, the heritability of AMD was confirmed upon the release of the first genome-wide association study (GWAS) along with confirmatory reports that supported the findings of that state-of-the art method, thus setting the foundation for future GWAS in other heritable diseases. Following this seminal discovery and applying it to other diseases including AD and MS, the genetic knowledge of AD expanded far beyond the well-known APOE locus and now includes more than 20 loci. MS genetics saw a similar increase beyond the HLA loci and now has more than 100 known risk loci. Ongoing and future efforts will seek to define the remaining heritability of these diseases; the next decade could very well hold the key to attaining this goal.

  14. genetic variability for tuber yield, quality, and virus disease complex ...

    African Journals Online (AJOL)

    Administrator

    GENETIC VARIABILITY FOR TUBER YIELD, QUALITY, AND VIRUS DISEASE. COMPLEX TRAITS IN UGANDA SWEETPOTATO GERMPLASM. E. GASURA, A.B. MASHINGAIDZE1 and S.B. MUKASA. Department of Crop Science, Makerere University, P. O. Box 7062 Kampala, Uganda. 1Department of Crop Science, ...

  15. Pathway-based analysis tools for complex diseases: a review.

    Science.gov (United States)

    Jin, Lv; Zuo, Xiao-Yu; Su, Wei-Yang; Zhao, Xiao-Lei; Yuan, Man-Qiong; Han, Li-Zhen; Zhao, Xiang; Chen, Ye-Da; Rao, Shao-Qi

    2014-10-01

    Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases. Copyright © 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  16. Forward-time simulations of human populations with complex diseases.

    Directory of Open Access Journals (Sweden)

    Bo Peng

    2007-03-01

    Full Text Available Due to the increasing power of personal computers, as well as the availability of flexible forward-time simulation programs like simuPOP, it is now possible to simulate the evolution of complex human diseases using a forward-time approach. This approach is potentially more powerful than the coalescent approach since it allows simulations of more than one disease susceptibility locus using almost arbitrary genetic and demographic models. However, the application of such simulations has been deterred by the lack of a suitable simulation framework. For example, it is not clear when and how to introduce disease mutants-especially those under purifying selection-to an evolving population, and how to control the disease allele frequencies at the last generation. In this paper, we introduce a forward-time simulation framework that allows us to generate large multi-generation populations with complex diseases caused by unlinked disease susceptibility loci, according to specified demographic and evolutionary properties. Unrelated individuals, small or large pedigrees can be drawn from the resulting population and provide samples for a wide range of study designs and ascertainment methods. We demonstrate our simulation framework using three examples that map genes associated with affection status, a quantitative trait, and the age of onset of a hypothetical cancer, respectively. Nonadditive fitness models, population structure, and gene-gene interactions are simulated. Case-control, sibpair, and large pedigree samples are drawn from the simulated populations and are examined by a variety of gene-mapping methods.

  17. The dichotomy between disease phenotype databases and the implications for understanding complex diseases involving the major histocompatibility complex.

    Science.gov (United States)

    Clark, P M; Kunkel, M; Monos, D S

    2015-12-01

    Many genes related to innate and adaptive immunity reside within the major histocompatibility complex (MHC) and have been associated with a multitude of complex, immune-related disorders. Despite years of genetic study, this region has seen few causative determinants discovered for immune-mediated diseases. Reported associations have been curated in various databases including the Genetic Association Database, NCBI database of clinically relevant variants (ClinVar) and the Human Gene Mutation Database and together capture genetic associations and annotated pathogenic loci within the MHC and across the genome for a variety of complex, immune-mediated diseases. A review of these three distinct databases reveals disparate annotations between associated genes and pathogenic loci, alluding to the polygenic, multifactorial nature of immune-mediated diseases and the pleiotropic character of genes within the MHC. The technical limitations and inherent biases imposed by current approaches and technologies in studying the MHC create a strong case for the need to perform targeted deep sequencing of the MHC and other immunologically relevant loci in order to fully elucidate and study the causative elements of complex immune-mediated diseases. © 2015 The Authors. International Journal of Immunogenetics Published by John Wiley & Sons Ltd.

  18. Increasing mortality burden among adults with complex congenital heart disease.

    Science.gov (United States)

    Greutmann, Matthias; Tobler, Daniel; Kovacs, Adrienne H; Greutmann-Yantiri, Mehtap; Haile, Sarah R; Held, Leonhard; Ivanov, Joan; Williams, William G; Oechslin, Erwin N; Silversides, Candice K; Colman, Jack M

    2015-01-01

    Progress in management of congenital heart disease has shifted mortality largely to adulthood. However, adult survivors with complex congenital heart disease are not cured and remain at risk of premature death as young adults. Thus, our aim was to describe the evolution and mortality risk of adult patient cohorts with complex congenital heart disease. Among 12,644 adults with congenital heart disease followed at a single center from 1980 to 2009, 176 had Eisenmenger syndrome, 76 had unrepaired cyanotic defects, 221 had atrial switch operations for transposition of the great arteries, 158 had congenitally corrected transposition of the great arteries, 227 had Fontan palliation, and 789 had repaired tetralogy of Fallot. We depict the 30-year evolution of these 6 patient cohorts, analyze survival probabilities in adulthood, and predict future number of deaths through 2029. Since 1980, there has been a steady increase in numbers of patients followed, except in cohorts with Eisenmenger syndrome and unrepaired cyanotic defects. Between 1980 and 2009, 308 patients in the study cohorts (19%) died. At the end of 2009, 85% of survivors were younger than 50 years. Survival estimates for all cohorts were markedly lower than for the general population, with important differences between cohorts. Over the upcoming two decades, we predict a substantial increase in numbers of deaths among young adults with subaortic right ventricles, Fontan palliation, and repaired tetralogy of Fallot. Anticipatory action is needed to prepare clinical services for increasing numbers of young adults at risk of dying from complex congenital heart disease. © 2014 The Authors. Congenital Heart Disease Published by Wiley Periodicals, Inc.

  19. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    non-coding RNAs (ncRNAs). The integration of transcriptomics data with genomic data in a systems genetics context represents a valuable possibility to go deep into the causal and regulatory mechanisms that generate complex traits and diseases. However RNA-Seq data have to be treated carefully......Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand...... the biological mechanisms behind complex diseases or traits. In the recent past, transcriptomic studies with microarrays have been replaced with the new powerful RNA-seq technologies. This has led to detection of novel gene transcripts, novel regulatory mechanisms, allele specific gene expression and numerous...

  20. Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

    Science.gov (United States)

    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A.; Sanz, Ferran; Furlong, Laura I.

    2011-01-01

    Background Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. Principal Findings We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. Conclusions For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors

  1. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

    Directory of Open Access Journals (Sweden)

    Anna Bauer-Mehren

    Full Text Available BACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and

  2. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Timothy G Lesnick

    2007-06-01

    Full Text Available While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics. The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance predisposed to a complex disease (Parkinson disease [PD]. We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38, survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48, and PD age at onset (R(2 = 0.68, p = 1.68 x 10(-51. By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

  3. Molecular diagnostics for the sigatoka disease complex of banana.

    Science.gov (United States)

    Arzanlou, Mahdi; Abeln, Edwin C A; Kema, Gert H J; Waalwijk, Cees; Carlier, Jean; Vries, Ineke de; Guzmán, Mauricio; Crous, Pedro W

    2007-09-01

    ABSTRACT The Sigatoka disease complex of banana involves three related ascomycetous fungi, Mycosphaerella fijiensis, M. musicola, and M. eumusae. The exact distribution of these three species and their disease epidemiology remain unclear, because their symptoms and life cycles are rather similar. Disease diagnosis in the Mycosphaerella complex of banana is based on the presence of host symptoms and fungal fruiting structures, which hamper preventive management strategies. In the present study, we have developed rapid and robust species-specific molecular-based diagnostic tools for detection and quantification of M. fijiensis, M. musicola, and M. eumusae. Conventional species-specific polymerase chain reaction (PCR) primers were developed based on the actin gene that detected DNA at as little as 100, 1, and 10 pg/mul from M. fijiensis, M. musicola, and M. eumusae, respectively. Furthermore, TaqMan real-time quantitative PCR assays were developed based on the beta-tubulin gene and detected quantities of DNA as low as 1 pg/mul for each Mycosphaerella sp. from pure cultures and DNA at 1.6 pg/mul per milligram of dry leaf tissue for M. fijiensis that was validated using naturally infected banana leaves.

  4. Pacing and Defibrillators in Complex Congenital Heart Disease

    Science.gov (United States)

    Chubb, Henry; O’Neill, Mark; Rosenthal, Eric

    2016-01-01

    Device therapy in the complex congenital heart disease (CHD) population is a challenging field. There is a myriad of devices available, but none designed specifically for the CHD patient group, and a scarcity of prospective studies to guide best practice. Baseline cardiac anatomy, prior surgical and interventional procedures, existing tachyarrhythmias and the requirement for future intervention all play a substantial role in decision making. For both pacing systems and implantable cardioverter defibrillators, numerous factors impact on the merits of system location (endovascular versus non-endovascular), lead positioning, device selection and device programming. For those with Fontan circulation and following the atrial switch procedure there are also very specific considerations regarding access and potential complications. This review discusses the published guidelines, device indications and the best available evidence for guidance of device implantation in the complex CHD population. PMID:27403295

  5. [Magnetic therapy for complex treatment of chronic periodontal disease].

    Science.gov (United States)

    P'yanzina, A V

    The aim of the study was to elaborate the methodology of magnetic therapy for complex treatment of chronic periodontal disease (CPD). The study included 60 patients aged 35 to 65 years with moderate CPD divided in 2 groups. Patients in group 1 (controls) received impulse carbonate irrigation for 12 min №10, group 2 additionally received magnetic therapy for 5 min №10 in maxillary and mandibular areas. periodontal and rheological indices proved magnetic therapy to be useful tool for eradication of inflammation, periodontal tissue functional recovery and stabilization.

  6. Understanding complexity in neurodegenerative diseases: in silico reconstruction of emergence

    Directory of Open Access Journals (Sweden)

    Alexey eKolodkin

    2012-07-01

    Full Text Available Healthy functioning is an emergent property of the network of interacting biomolecules that comprise an organism. It follows that disease (a network shift that causes malfunction is also an emergent property, emerging from a perturbation of the network. On one hand, the biomolecular network of every individual is unique and this is evident when similar disease-producing agents cause different individual pathologies. Consequently, a personalized model and approach for every patient may be required for therapies to become effective across mankind. On the other hand, diverse combinations of internal and external perturbation factors may cause a similar shift in network functioning. We offer this as an explanation for the multi-factorial nature of most diseases: they are ‘systems biology diseases’, or ‘network diseases’. Here we focus on neurodegenerative diseases, like Parkinson’s disease, as an example. Because of the inherent complexity of these networks, it is difficult to understand multi-factorial diseases using simply our ‘naked brain’. When describing interactions between biomolecules through mathematical equations and integrating those equations into a mathematical model, we try to reconstruct the emergent properties of the system in silico. The reconstruction of emergence from interactions between huge numbers of macromolecules is one of the aims of systems biology. Systems biology approaches enable us to break through the limitation of the human brain to perceive the extraordinarily large number of interactions, but this also means that we delegate the understanding of reality to the computer. We no longer recognize all those essences in the system’s design crucial for important physiological behavior (the so-called ‘design principles’ of the system. In this paper we review evidence that by using more abstract approaches and by experimenting in silico, one may still be able to discover and understand the design

  7. Poverty, Disease, and the Ecology of Complex Systems

    Science.gov (United States)

    Pluciński, Mateusz M.; Murray, Megan B.; Farmer, Paul E.; Barrett, Christopher B.; Keenan, Donald C.

    2014-01-01

    Understanding why some human populations remain persistently poor remains a significant challenge for both the social and natural sciences. The extremely poor are generally reliant on their immediate natural resource base for subsistence and suffer high rates of mortality due to parasitic and infectious diseases. Economists have developed a range of models to explain persistent poverty, often characterized as poverty traps, but these rarely account for complex biophysical processes. In this Essay, we argue that by coupling insights from ecology and economics, we can begin to model and understand the complex dynamics that underlie the generation and maintenance of poverty traps, which can then be used to inform analyses and possible intervention policies. To illustrate the utility of this approach, we present a simple coupled model of infectious diseases and economic growth, where poverty traps emerge from nonlinear relationships determined by the number of pathogens in the system. These nonlinearities are comparable to those often incorporated into poverty trap models in the economics literature, but, importantly, here the mechanism is anchored in core ecological principles. Coupled models of this sort could be usefully developed in many economically important biophysical systems—such as agriculture, fisheries, nutrition, and land use change—to serve as foundations for deeper explorations of how fundamental ecological processes influence structural poverty and economic development. PMID:24690902

  8. OEIS complex with glomerulocystic kidney disease: a case report.

    Science.gov (United States)

    Hong, Ran; Lim, Sung-Chul; Jang, Jung-Whan; Suh, Chae-Hong; Jeon, Ho-Jong; Lee, Mi-Ja; Kim, Youn-Shin

    2007-01-01

    We present a case of OEIS complex (omphalocele, exstrophy of bladder, imperforated anus, spinal defect) combined with colonic agenesis and glomerulocystic kidney disease (GCKD). The baby was born at 35.2 weeks of gestational age, weighing 2.51 kg. A prenatal ultrasound examination showed spina bifida, hydroureter, and a unilateral polycystic kidney. The postdelivery examination, which included a physical examination, simple X-ray, and pelvic MRI, showed a lower abdominal wall defect through which a small pouch with a segment of bowel protruded, imperforated anus, ambiguous external genitalia, spina bifida with meningomyelocele at the lumbosacral junction, and nonunion of pubic symphysis. The baby underwent surgery, including nephrectomy, colostomy, and repair of the abdominal wall defect. In addition to the abnormalities mentioned, a tailgut as a result of colonic agenesis and 2 appendices were identified in the course of surgery. The result of histopathological examination confirmed the polycystic kidney identified as GCKD. These radiological, surgical, and histopathologic findings are consistent with the OEIS complex. The postoperative course was uneventful during a period of 4 months of follow up. We herein report a case of the very rare OEIS complex in a newborn male baby and review the available literature.

  9. Employment characteristics of a complex adult congenital heart disease cohort.

    Science.gov (United States)

    Pickup, L; Gaffey, T; Clift, P; Bowater, S; Thorne, S; Hudsmith, L

    2017-08-01

    Due to advances in surgical techniques and subsequent management, there have been remarkable improvements in the survival of patients with congenital heart disease. In particular, larger numbers of patients with complex disease are now living into adulthood and are entering the workforce. To establish the types of employment complex adult congenital heart disease (ACHD) patients are engaged in, based on the largest cohort of patients with a single-ventricle circulation in the UK. Records of all patients with a univentricular (Fontan) circulation at the Queen Elizabeth Hospital were reviewed. Employment status was categorized according to the Standard Occupational Classification criteria (2010). A total of 210 patient records were reviewed. There was the same proportion of professionals in our cohort compared to the rest of the UK (20% versus 20%). There were greater proportions working in the caring, leisure and other service occupations (15% versus 9%), the elementary occupations (17% versus 11%), sales and customer service occupations (14% versus 8%) and administrative and secretarial occupations (12% versus 11%). The reverse trend was observed for associate professions and technical occupations (7% versus 14%), skilled trades (10% versus 11%), process, plant and machine operatives (3% versus 6%) and managers, directors and senior officials (2% versus 10%). The data show that ACHD patients with a single ventricle are engaged in a diverse range of occupations. It is essential that early education and employment advice are given to this cohort to maximize future employment potential. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Polypharmacy and enteral nutrition in patients with complex chronic diseases

    Science.gov (United States)

    Romero Jiménez, Rosa Mª; Ortega Navarro, Cristina; Cuerda Compés, Cristina

    2017-05-08

    Oral medications are often administered through enteral feeding tubes in patients with complex chronic diseases. It is important to consider possible interactions between drugs and enteral nutrition that might lead to unsuccessful treatment or tube occlusion. These patients become subjects for higher risk of problems and errors such as drug incompatibility with enteral nutrition and inappropriate dosage form selection. It is possible to minimize the risk of tube occlusion and incompatibilities problems by recognizing potential medication errors, selecting the most appropriate drug and dosage form and using appropriate administration techniques. In this context, high-alert medications for patients with chronic diseases deserve special attention. Furthermore, risk exposure should be considered among healthcare professionals and patient caregivers handling hazardous drugs. Therefore, main incompatibility problems between drugs and enteral nutrition have been reviewed, including general recommendations for administration of oral medications through enteral feeding tubes and safe handling of hazardous drugs. Specific recommendations for administration of high-alert medications for patients with chronic diseases are also included.

  11. Unintended consequences of conservation actions: managing disease in complex ecosystems.

    Directory of Open Access Journals (Sweden)

    Aliénor L M Chauvenet

    Full Text Available Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV targeted at conserving the African lion (Panthera leo, could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus. Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions.

  12. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    Science.gov (United States)

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease. © 2016 John Wiley & Sons Ltd.

  13. Patient access to complex chronic disease records on the Internet.

    Science.gov (United States)

    Bartlett, Cherry; Simpson, Keith; Turner, A Neil

    2012-08-06

    Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine) available to patients over the Internet in a project involving more than half of renal units in the UK. Content and presentation of the Renal PatientView (RPV) system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrollment and usage were extracted from the webserver. By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs) but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enroll each patient. Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular, providing an increased sense of empowerment and understanding, with no

  14. Patient access to complex chronic disease records on the Internet

    Directory of Open Access Journals (Sweden)

    Bartlett Cherry

    2012-08-01

    Full Text Available Abstract Background Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine available to patients over the Internet in a project involving more than half of renal units in the UK. Methods Content and presentation of the Renal PatientView (RPV system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrolments and usage were extracted from the webserver. Results By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enrol each patient. Conclusions Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular

  15. Tuberous sclerosis complex and polycystic kidney disease contiguous gene syndrome with Moyamoya disease.

    Science.gov (United States)

    Lai, Jonathan; Modi, Lopa; Ramai, Daryl; Tortora, Matthew

    2017-04-01

    Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two diseases sharing close genetic loci on chromosome 16. Due to contiguous gene syndrome, also known as contiguous gene deletion syndrome, the proximity of TSC2 and PKD1 genes increases the risk of co-deletion resulting in a shared clinical presentation. Furthermore, Moyamoya disease (MMD) is a rare vaso-occlusive disease in the circle of Willis. We present the first case of TSC2/PKD1 contiguous gene syndrome in a patient with MMD along with detailed histopathologic, radiologic, and cytogenetic analyses. We also highlight the clinical presentation and surgical complications in this case. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Visualizing the indefinable: three-dimensional complexity of 'infectious diseases'.

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    Gabriel Leitner

    Full Text Available The words 'infection' and 'inflammation' lack specific definitions. Here, such words are not defined. Instead, the ability to visualize host-microbial interactions was explored.Leukocyte differential counts and four bacterial species (Staphylococcus aureus, Streptococcus dysgalactiae, Staphylococcus chromogenes, and Escherichia coli were determined or isolated in a cross-sectional and randomized study conducted with 611 bovine milk samples. Two paradigms were evaluated: (i the classic one, which measures non-structured (count or percent data; and (ii a method that, using complex data structures, detects and differentiates three-dimensional (3D interactions among lymphocytes (L, macrophages (M, and neutrophils (N.Classic analyses failed to differentiate bacterial-positive (B+ from -negative (B- observations: B- and B+ data overlapped, even when statistical significance was achieved. In contrast, the alternative approach showed distinct patterns, such as perpendicular data inflections, which discriminated microbial-negative/mononuclear cell-predominating (MCP from microbial-positive/phagocyte-predominating (PP subsets. Two PP subcategories were distinguished, as well as PP/culture-negative (false-negative and MCP/culture-positive (false-positive observations. In 3D space, MCP and PP subsets were perpendicular to one another, displaying ≥ 91% specificity or sensitivity. Findings supported five inferences: (i disease is not always ruled out by negative bacterial tests; (ii low total cell counts can coexist with high phagocyte percents; (iii neither positive bacterial isolation nor high cell counts always coincide with PP profiles; (iv statistical significance is not synonymous with discrimination; and (v hidden relationships cannot be detected when simple (non-structured data formats are used and statistical analyses are performed before data subsets are identified, but can be uncovered when complexity is investigated.Pattern recognition

  17. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    Science.gov (United States)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.; White, Kevin P.; Rzhetsky, Andrey

    2013-01-01

    Summary Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute non-additively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. PMID:24074861

  19. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    OpenAIRE

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.

    2013-01-01

    Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection...

  20. Micro RNA, A Review: Pharmacogenomic drug targets for complex diseases

    Directory of Open Access Journals (Sweden)

    Sandhya Bawa

    2010-01-01

    differentially expressed in malignant cells compared to normal cells altering the regulation of expression of many important genes. MiRNA expression has been used for prognosis and early diagnosis of these complex diseases.  The present paper focuses on the role of miRNAs in various complex diseases, which will help in improving the drug discovery process and personalized medicines.

     

  1. Identification of susceptible genes for complex chronic diseases based on disease risk functional SNPs and interaction networks.

    Science.gov (United States)

    Li, Wan; Zhu, Lina; Huang, Hao; He, Yuehan; Lv, Junjie; Li, Weimin; Chen, Lina; He, Weiming

    2017-10-01

    Complex chronic diseases are caused by the effects of genetic and environmental factors. Single nucleotide polymorphisms (SNPs), one common type of genetic variations, played vital roles in diseases. We hypothesized that disease risk functional SNPs in coding regions and protein interaction network modules were more likely to contribute to the identification of disease susceptible genes for complex chronic diseases. This could help to further reveal the pathogenesis of complex chronic diseases. Disease risk SNPs were first recognized from public SNP data for coronary heart disease (CHD), hypertension (HT) and type 2 diabetes (T2D). SNPs in coding regions that were classified into nonsense and missense by integrating several SNP functional annotation databases were treated as functional SNPs. Then, regions significantly associated with each disease were screened using random permutations for disease risk functional SNPs. Corresponding to these regions, 155, 169 and 173 potential disease susceptible genes were identified for CHD, HT and T2D, respectively. A disease-related gene product interaction network in environmental context was constructed for interacting gene products of both disease genes and potential disease susceptible genes for these diseases. After functional enrichment analysis for disease associated modules, 5 CHD susceptible genes, 7 HT susceptible genes and 3 T2D susceptible genes were finally identified, some of which had pleiotropic effects. Most of these genes were verified to be related to these diseases in literature. This was similar for disease genes identified from another method proposed by Lee et al. from a different aspect. This research could provide novel perspectives for diagnosis and treatment of complex chronic diseases and susceptible genes identification for other diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis. A prospective, randomized 9-month comparison.

    Science.gov (United States)

    Carter, John D; Valeriano, Joanne; Vasey, Frank B

    2004-10-01

    Chlamydia is a known trigger of reactive arthritis (ReA). It may also be common cause of undifferentiated spondyloarthropathy (uSpA). Persistent, metabolically active, Chlamydiae have been observed in the synovial tissue of these patients years after their initial exposure. Trials with lymecycline and rifampin have shown benefit in early/acute Chlamydia-induced arthritis. In vitro data suggest that persistent Chlamydia become resistant to chronic monotherapy of tetracyclines or rifampin, whereas no such resistance is noted when rifampin is added to antimicrobials that are active against Chlamydia. Rifampin and doxycycline also show synergistic effect against Chlamydia. In addition, rifampin inhibits chlamydial production of heat shock proteins (HSP). HSP60 plays a key role in the chronic persistent state of Chlamydia. We conducted a prospective, randomized 9-month trial to evaluate the efficacy of doxycycline versus a combination of doxycycline and rifampin in the treatment of uSpA. The study enrolled 30 patients with chronic inflammatory arthritis (average disease duration 10 yrs) who fulfilled the European Spondylarthropathy Study Group criteria, with no evidence of inflammatory bowel disease, psoriasis, ankylosing spondylitis, or preceding dysentery. Patients received doxycycline 100 mg po twice daily or a combination of doxycycline 100 mg po twice daily and rifampin 600 mg po daily. They received a 4-question self-questionnaire and a blinded joint examination at each visit. The questions include a visual analog scale (VAS) for their current amount of back pain, duration of morning stiffness, back pain at night, and peripheral joint pain. The blinded joint examination consisted of a swollen joint count (SJC) and a tender joint count (TJC). These 6 variables were assessed at baseline and at 1, 3, 6, and 9 months. Responders were defined as those who improved > or = 20% in at least 4 of the 6 variables at 9 months of therapy. Comparing the doxycycline + rifampin

  3. Galectin-9: From cell biology to complex disease dynamics

    Indian Academy of Sciences (India)

    Author Affiliations. SEBASTIAN JOHN1 RASHMI MISHRA1. Department of Neurobiology and Genetics, Division of Disease Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695014, India ...

  4. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

    OpenAIRE

    Spataro, Nino, 1984-; Rodríguez, Juan Antonio; Navarro i Cuartiellas, Arcadi, 1969-; Bosch Fusté, Elena

    2017-01-01

    Abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevan...

  5. Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy

    Directory of Open Access Journals (Sweden)

    Gravenor Michael B

    2008-01-01

    Full Text Available Abstract Background The clinical effectiveness of complementary and alternative medicines (CAMs is widely debated because of a lack of clinical trials. The internet may provide an effective and economical approach for undertaking randomised controlled trials (RCTs of low-risk interventions. We investigated whether the internet could be used to perform an internet-based RCT of a CAM fulfilling the revised CONSORT (Consolidated Standards of Reporting Trials statement quality checklist for reporting of RCTs. A secondary aim was to examine the effect of probiotics compared to placebo in terms of well-being over 12 weeks. Methods People aged ≥18 years with confirmed spondyloarthropathy living in the United Kingdom with internet access were invited to participate in an internet-based RCT of probiotic compared to placebo for improving well-being and bowel symptoms. The intervention was a probiotic containing 4 strains of live bacteria or identical placebo taken by mouth daily for 3 months. The primary outcome measure was the performance of the trial according to the revised CONSORT statement. Results 147 people were randomised into the trial. The internet-based trial of the CAM fulfilled the revised CONSORT statement such as efficient blinding, allocation concealment, intention to treat analysis and flow of participants through the trial. Recruitment of the required number of participants was completed in 19 months. Sixty-five percent (96/147 completed the entire 3 months of the trial. The trial was low cost and demonstrated that in an intention to treat analysis, probiotics did not improve well-being or bowel symptoms. Conclusion The internet-based RCT proved to be a successful and economical method for examining this CAM intervention. Recruitment, adherence and completion rate were all similar to those reported with conventional RCTs but at a fraction of the cost. Internet-based RCTs can fulfil all the criteria of the revised CONSORT statement and

  6. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology.

    Science.gov (United States)

    Spataro, Nino; Rodríguez, Juan Antonio; Navarro, Arcadi; Bosch, Elena

    2017-02-01

    Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease. © The Author 2017. Published by Oxford University Press.

  7. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

    Directory of Open Access Journals (Sweden)

    Amr T. M. Saeb

    2016-01-01

    Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

  8. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    with complex diseases are enriched in the genes indicated by this ‘‘Mendelian code.’’ Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset......Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes...... to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated...

  9. genetic variability for tuber yield, quality, and virus disease complex

    African Journals Online (AJOL)

    Administrator

    improvement of yield and quality attributes. Cultivar Munyeera displayed the highest level of SPVD resistance followed by New Kawogo and Polyster as exhibited by relative area under disease progress curves following natural field infection and graft inoculation with SPVD causing viruses, Sweet potato chlorotic stunt virus ...

  10. Galectin-9: From cell biology to complex disease dynamics

    Indian Academy of Sciences (India)

    Galectins is a family of non-classically secreted, β-galactoside-binding proteins that has recently received considerableattention in the spatio-temporal regulation of surface 'signal lattice' organization, membrane dynamics, cell-adhesionand disease therapeutics. Galectin-9 is a unique member of this family, with two ...

  11. Complex lipid trafficking in Niemann-Pick disease type C.

    Science.gov (United States)

    Vanier, Marie T

    2015-01-01

    Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".

  12. Understanding complexity in neurodegenerative diseases: in silico reconstruction of emergence.

    NARCIS (Netherlands)

    Kolodkin, A.; Simeonidis, E.; Balling, R.; Westerhoff, H.V.

    2012-01-01

    Healthy functioning is an emergent property of the network of interacting biomolecules that comprise an organism. It follows that disease (a network shift that causes malfunction) is also an emergent property, emerging from a perturbation of the network. On the one hand, the biomolecular network of

  13. Hyperparathyroidism in chronic kidney disease: complexities within the commonplace.

    Science.gov (United States)

    Cai, Michael M; McMahon, Lawrence P; Smith, Edward R; Williams, David S; Holt, Stephen G

    2012-08-01

    Secondary hyperparathyroidism in patients with chronic kidney disease (CKD) is common and usually caused by associated metabolic abnormalities, in particular, hypocalcaemia and hyperphosphataemia. Nevertheless, other causes of hyperparathyroidism can exist concurrently with CKD, challenging diagnostic interpretation and therapeutic intervention. We present four cases of hyperparathyroidism in patients with CKD that highlight some of these dilemmas.

  14. An integer programming framework for inferring disease complexes from network data.

    Science.gov (United States)

    Mazza, Arnon; Klockmeier, Konrad; Wanker, Erich; Sharan, Roded

    2016-06-15

    Unraveling the molecular mechanisms that underlie disease calls for methods that go beyond the identification of single causal genes to inferring larger protein assemblies that take part in the disease process. Here, we develop an exact, integer-programming-based method for associating protein complexes with disease. Our approach scores proteins based on their proximity in a protein-protein interaction network to a prior set that is known to be relevant for the studied disease. These scores are combined with interaction information to infer densely interacting protein complexes that are potentially disease-associated. We show that our method outperforms previous ones and leads to predictions that are well supported by current experimental data and literature knowledge. The datasets we used, the executables and the results are available at www.cs.tau.ac.il/roded/disease_complexes.zip roded@post.tau.ac.il. © The Author 2016. Published by Oxford University Press.

  15. A new conceptual framework for investigating complex genetic disease

    Directory of Open Access Journals (Sweden)

    Shobbir eHussain

    2015-11-01

    Full Text Available Some common diseases are known to have an inherited component, however their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. Studies that have attempted to identify the causative genetic factors have been designed on this polygenic framework, but so far the yield has been largely unsatisfactory. Based on accumulating recent observations concerning the roles of somatic mosaicism in disease, in this article a second framework which posits a single gene-two hit model which can be modulated by a mutator/anti-mutator genetic background is suggested. I discuss whether such a model can be considered a viable alternative based on current knowledge, its advantages over the current polygenic framework, and describe practical routes via which the new framework can be investigated.

  16. Chronic obstructive pulmonary disease: a complex comorbidity of lung cancer

    OpenAIRE

    Grose, Derek; Milroy, Robert

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a significantly increased incidence of lung cancer and may influence treatment options and outcome. Impaired lung function confirming COPD is an independent risk factor for lung cancer. Oxidative stress and inflammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer development. COPD negat...

  17. Analysis of altered complexity of gait dynamics with aging and Parkinson’s disease using ternary Lempel–Ziv complexity

    Directory of Open Access Journals (Sweden)

    Chandrakar Kamath

    2016-12-01

    Full Text Available Fluctuations in stride interval series show complex dynamical behavior in healthy young adults. Hypothesizing that these stride interval complexity changes would be altered by changes in neurological function associated with aging and certain disease states, we aimed to develop a tool to facilitate clinical judgments to assess the complex dynamical behavior in the stride series in discerning young, elderly, and Parkinson’s disease (PD classes. This novel approach, which employs a new variant of coarse-graining in conjunction with Lempel–Ziv complexity measure, yields useful, reliable, and predictive results. We also show the presence of nonlinear deterministic structures in the stride time series and appropriateness of the application of our nonlinear approach through surrogate data analysis. The findings show that the fluctuations are more complex/random in elderly and PD classes than those in young class. These findings may add to the growing body of literature supporting the clinical utility of this new approach to stride time series.

  18. Infectious disease outbreaks and increased complexity of care.

    Science.gov (United States)

    Musau, J; Baumann, A; Kolotylo, C; O'Shea, T; Bialachowski, A

    2015-09-01

    This study examined the effects of healthcare-associated infectious disease outbreaks on nurses' work in a large acute care hospital in Ontario, Canada. The incidence of healthcare-associated infections has increased. Previous research focuses on epidemiology, healthcare systems, and the economic burden of outbreaks. Few published studies focus on the impact of outbreaks on nurses' work in acute care facilities. Since the severe acute respiratory syndrome epidemic in 2003, combating infectious diseases has become a key issue. Hospitals have implemented measures related to healthcare-associated infections. However, nurses experience challenges in preventing, controlling, and contending with outbreaks. A retrospective exploratory case study approach was used. Data were collected over a 4-month period in 2012. The incidence rates of site-specific HAIs were analysed, and individual interviews were held with 23 bedside nurses and five nurse managers. Five themes emerged from the interviews: comparison of healthcare-associated infections outbreaks; the nature of nurses' work; impact of outbreaks on patient care; innovation and quality control in clinical practice; and increased and expanded IPAC measures. The incidence rates of methicillin-resistant Staphylococcus aureus, Clostridium difficile and vancomycin-resistant enterococci at the study site decreased, but remained above provincial benchmarks. Nurses experienced workload challenges, time pressures and psychological effects stemming from outbreaks and developed various innovations in response. Patient care was also affected. Nurses' work has been impacted by healthcare-associated infectious disease outbreaks. Nursing workloads should be quantified to facilitate the development of guidelines for optimum nurse-patient ratio during outbreaks. A strong evidence-based policy framework is required to address healthcare-associated infectious disease outbreaks. Infection prevention and control guidelines and procedures

  19. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients

    Directory of Open Access Journals (Sweden)

    Adler Charles

    2009-07-01

    Full Text Available Abstract Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23.

  20. The role of protein complexes in a complex disease: molecular mechanisms of ALS

    NARCIS (Netherlands)

    Blokhuis, A.M.

    2016-01-01

    Amyotrophic Lateral Sclerosis is a devastating neurodegenerative diease caused by the selective loss of motor neurons. The pathogenic mechanism underlying the disease is largely unknown but a number of genes, proteins and cellular processes have been implicated. In this thesis we aimed to identify

  1. An Ocular Protein Triad Can Classify Four Complex Retinal Diseases

    Science.gov (United States)

    Kuiper, J. J. W.; Beretta, L.; Nierkens, S.; van Leeuwen, R.; Ten Dam-van Loon, N. H.; Ossewaarde-van Norel, J.; Bartels, M. C.; de Groot-Mijnes, J. D. F.; Schellekens, P.; de Boer, J. H.; Radstake, T. R. D. J.

    2017-01-01

    Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.

  2. Bioresorbable vascular scaffold in patients with complex coronary artery disease.

    Science.gov (United States)

    Tamburino, Claudia I; Capranzano, Piera; Longo, Giovanni; Immè, Sebastiano; Tamburino, Giacomo; Scalia, Matteo; Condorelli, Antonio; Francaviglia, Bruno; LA Manna, Alessio; Sgroi, Carmelo; Grasso, Carmelo; DI Salvo, Maria E; Capodanno, Davide; Tamburino, Corrado

    2016-08-01

    The advent of fully bioresorbable stent technology is heralded as breakthrough technology in the current era of percutaneous coronary interventions (PCI). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, representing an anatomical and functional "vascular restoration" therapy instead of an artificial stiff tube encased by persistent metallic foreign body. Among BRS, the everolimus-eluting scaffold (ABSORB, Abbott Vascular, Santa Clara, CA, USA) has been the most extensively investigated in clinical studies. The use of ABSORB in the treatment of relatively simple lesions appears to provide a similar degree of safety and efficacy compared with metallic drug-eluting stent (DES) treated under randomized trials conditions, but patients treated in real-world practice are far more complex than those included in randomized trials. Therefore, several ABSORB all-comers registries dealing with real world conditions are being performed. Their currently available results are summarized in the present overview.

  3. Postoperative management in patients with complex congenital heart disease.

    Science.gov (United States)

    Tweddell, James S; Hoffman, George M

    2002-01-01

    Life-threatening problems occur in the neonate and infant after cardiac surgery because of the interplay of diminished cardiac output (CO), increased metabolic demand, inflammatory responses to cardiopulmonary bypass, and maladaptive responses to stress. Therefore, the postoperative management of patients with complex congenital heart defects is directed at optimization of oxygen delivery to maintain end-organ function and promote wound healing. Traditionally, assessment of circulation in the postoperative congenital heart patient has depended on indirect assessment of CO using parameters such as blood pressure, pulses, capillary refill, and urine output. Because of the limitations of indirect and observer-dependent assessment of CO, we rely on objective measures of tissue oxygen levels for the complex postoperative patient. We have found that continuous monitoring of the mixed venous saturation (SvO2) allows for identification of acute changes in systemic oxygen delivery and frequently precedes other indicators of decreased CO. The postoperative patient can be expected to have a period of decreasing CO, and the need for intervention should be anticipated because critical low output syndrome will develop in a subset of patients. Strategies for postoperative care are developed based on the diagnosis and procedure, but optimizing SvO2 is a consistent goal. A uniform approach to airway maintenance, vascular access, and drug infusions, all universal concerns during the perioperative period, minimizes the potential for these predictable and necessary interventions to result in morbidity or mortality. Management of the postoperative single ventricle patient targets stabilization of the systemic vascular resistance through the use of vasodilators to improve systemic perfusion and simplify ventilator management. Management of any individual patient should be driven by objective analysis of available data and must include efforts to re-evaluate the treatment plan as well as

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

    Directory of Open Access Journals (Sweden)

    David Goldman

    2007-01-01

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

  5. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.; Snoek, L.B.; Bono, de M.; Kammenga, J.E.

    2013-01-01

    Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human

  6. Paget's disease of bone: evidence for complex pathogenetic interactions.

    Science.gov (United States)

    Chung, Pui Yan Jenny; Van Hul, Wim

    2012-04-01

    Paget's disease of bone (PDB), with a prevalence of 2 to 5% in Caucasians >55 years, is the second most frequent metabolic bone disease, after osteoporosis. PDB characteristics are bone lesions with an imbalanced bone remodeling, resulting in disorganized and nonfully fledged new bone. PDB etiology is not completely understood. In this review, current views on the etiology, clinical aspects, and PDB treatment are summarized and discussed. The PubMed database was searched using the keywords PDB, sequestosome1 (SQSTM1), valosin-containing protein (VCP), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), RANK ligand (RANKL), mutation, genetic variants, virus, osteosarcoma, bisphosphonates, and denosumab. Environmental evidence (e.g. viruses) and also genetic risk factors have been found for PDB. Until now, SQSTM1 was the only PDB-causing gene identified. However, PDB patients without SQSTM1 mutations seem to have susceptibility genetic polymorphisms in regions containing the CaSR, ESR1, TNFRSF11B (OPG), TNFRSF11A (RANK), CSF1 (M-CSF), OPTN, TM7SF4 (DC-STAMP), VCP, NUP205, RIN3, PML, and GOLGA6A genes, resulting in an increased risk of developing PDB. The nature of these genes indicates that the regulation of osteoclastogenesis is a key process in PDB pathogenesis. Furthermore, with the involvement of SQSTM1 and VCP in autophagy and in forming protein aggregates, this might also indicate that a disturbance of these processes might be a risk factor. Unraveling the PDB genetic background is instrumental to understanding the PDB pathogenesis and the role of slow viruses. Furthermore, it might make early detection and subsequently treatment of risk individuals possible. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM.

    Science.gov (United States)

    Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

    2015-01-01

    Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

  8. Researchers and stakeholders shape advances in management of tree and vine trunk-disease complexes

    Science.gov (United States)

    The grapevine trunk-disease complex limits grape production and vineyard longevity worldwide. Every vineyard in California eventually is infected by one or more trunk diseases. The causal fungi, which are taxonomically unrelated Ascomycetes, infect and then degrade the permanent woody structure of t...

  9. Bacterial pathogens of the bovine respiratory disease complex.

    Science.gov (United States)

    Griffin, Dee; Chengappa, M M; Kuszak, Jennifer; McVey, D Scott

    2010-07-01

    Pneumonia caused by the bacterial pathogens discussed in this article is the most significant cause of morbidity and mortality of the BRDC. Most of these infectious bacteria are not capable of inducing significant disease without the presence of other predisposing environmental factors, physiologic stressors, or concurrent infections. Mannheimia haemolytica is the most common and serious of these bacterial agents and is therefore also the most highly characterized. There are other important bacterial pathogens of BRD, such as Pasteurella multocida, Histophulus somni, and Mycoplasma bovis. Mixed infections with these organisms do occur. These pathogens have unique and common virulence factors but the resulting pneumonic lesions may be similar. Although the amount and quality of research associated with BRD has increased, vaccination and therapeutic practices are not fully successful. A greater understanding of the virulence mechanisms of the infecting bacteria and pathogenesis of pneumonia, as well as the characteristics of the organisms that allow tissue persistence, may lead to improved management, therapeutics, and vaccines. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Contrasting regional architectures of schizophrenia and other complex diseases using fast variance components analysis

    DEFF Research Database (Denmark)

    Loh, Po-Ru; Bhatia, Gaurav; Gusev, Alexander

    2015-01-01

    Heritability analyses of genome-wide association study (GWAS) cohorts have yielded important insights into complex disease architecture, and increasing sample sizes hold the promise of further discoveries. Here we analyze the genetic architectures of schizophrenia in 49,806 samples from the PGC...... and nine complex diseases in 54,734 samples from the GERA cohort. For schizophrenia, we infer an overwhelmingly polygenic disease architecture in which ≥71% of 1-Mb genomic regions harbor ≥1 variant influencing schizophrenia risk. We also observe significant enrichment of heritability in GC-rich regions...... and in higher-frequency SNPs for both schizophrenia and GERA diseases. In bivariate analyses, we observe significant genetic correlations (ranging from 0.18 to 0.85) for several pairs of GERA diseases; genetic correlations were on average 1.3 tunes stronger than the correlations of overall disease liabilities...

  11. Still's Disease and Recurrent Complex Regional Pain Syndrome Type-I: The First Description

    Science.gov (United States)

    Faillace, César; de Carvalho, Jozélio Freire

    2012-01-01

    Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder characterized by neuropathic pain associated with local edema and changes suggestive of autonomic involvement such as altered sweating, skin color, and skin temperature of the affected region. CRPS was described associated with several diseases, such as trauma, psychiatric conditions, and cancer. However, no case associated with Still's disease has been previously described. In this paper, the authors describe the first case of CRPS associated with Still's disease. PMID:22162802

  12. [Role of environment in complex diseases: air pollution and food contaminants].

    Science.gov (United States)

    Scheen, A J; Giet, D

    2012-01-01

    Our polluted environment exposes human beings, along their life, to various toxic compounds that could trigger and aggravate different complex diseases. Such a phenomenon is well recognized for cardiovascular diseases, respiratory diseases and cancers, but other chronic inflammatory disorders may also been implicated. The most common factors, but also the most toxic, and thereby the most extensively investigated, are air pollutants (both indoor and outdoor pollution) and various contaminants present in drinking water and food (organic compounds, chemical products, heavy metals, ...). The complex interrelationships between food and pollutants, on the one hand, and between gene and environmental pollutants, including the influence of epigenetics, on the other hand, deserve further careful studies.

  13. Heterogeneity of mitochondrial diseases caused by defects in mitochondrial respiratory chain complex I

    Directory of Open Access Journals (Sweden)

    E. A. Nikolaeva

    2015-01-01

    Full Text Available The common cause of mitochondrial diseases is hereditary defects in mitochondrial respiratory chain complex I, which account for about 30% of the cases of mitochondrial diseases in children. Complex I is the largest and most complicated enzyme complex of the respiratory electron chain. The function of Complex I is controlled by both nuclear and mitochondrial genomes and it seems to be determined by at least 300 genes. Complex I is comprised of 45 subunits: 7 of them are encoded by mitochondrial DNA, the others are by nuclear DNA. Besides, there are additional factors that are located outside Complex I, but determine its stability and activity. The paper analyzes the clinical forms of Complex I deficiency-induced diseases; the most common of them is Leigh syndrome. The diseases are generally characterized by an early onset, severe involvement of the nervous, muscular, and cardiovascular systems. If the treatment is ineffective, it is particularly important to identify a gene mutation to verify the diagnosis, as well as antenatal diagnosis. 

  14. Is Behçet's disease a 'class 1-opathy'? The role of HLA-B*51 in the pathogenesis of Behçet's disease.

    Science.gov (United States)

    Giza, M; Koftori, D; Chen, L; Bowness, P

    2018-01-01

    The association between carriage of the human leucocyte antigen (HLA)-B*51 allele and development of Behçet's disease (BD) has been known since the early 1970s, but the exact mechanisms responsible for its role in pathogenesis remain much-debated. In an effort to explain the disease process, it has been suggested that BD constitutes one of a newly termed group of diseases, the 'MHC-I-opathies'. Other MHC-I-opathies include ankylosing spondylitis and HLA-B*27-associated spondyloarthropathies and HLA-C*0602-associated skin psoriasis. Recent work analysing the peptidome of HLA-B*51 suggests that altered peptide presentation by HLA-B*51 is vital to the disease process. In this review, we argue that immune receptor interactions with HLA-B*51 or the HLA-B*51-peptide complex could lead to development of inflammation in BD. The evidence for CD8 + T cell involvement is weak, and based on emerging studies it seems more likely that natural killer (NK) or other cell interactions, perhaps mediated by leucocyte immunoglobulin-like receptor (LILR) or killer immunoglobulin-like receptor (KIR) receptors, are culpable in pathogenesis. HLA misfolding leading directly to inflammation is another hypothesis for BD pathogenesis that deserves greater investigation. Ultimately, greater understanding of HLA-B*51's unique role in BD will probably lead to improved development of therapeutic strategies. © 2017 British Society for Immunology.

  15. Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

    Science.gov (United States)

    Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

    2016-09-21

    Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.

  16. Inflammatory spine disease as a cause of back pain

    International Nuclear Information System (INIS)

    Schlossbauer, T.; Panteleon, A.; Becker-Gaab, C.

    2006-01-01

    The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-α antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-α antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the effectiveness of anti-inflammatory therapy. (orig.) [de

  17. Several Indicators of Critical Transitions for Complex Diseases Based on Stochastic Analysis.

    Science.gov (United States)

    Wang, Gang; Li, Yuanyuan; Zou, Xiufen

    2017-01-01

    Many complex diseases (chronic disease onset, development and differentiation, self-assembly, etc.) are reminiscent of phase transitions in a dynamical system: quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. Understanding such nonlinear behaviors is critical to dissect the multiple genetic/environmental factors that together shape the genetic and physiological landscape underlying basic biological functions and to identify the key driving molecules. Based on stochastic differential equation (SDE) model, we theoretically derive three statistical indicators, that is, coefficient of variation (CV), transformed Pearson's correlation coefficient (TPC), and transformed probability distribution (TPD), to identify critical transitions and detect the early-warning signals of the phase transition in complex diseases. To verify the effectiveness of these early-warning indexes, we use high-throughput data for three complex diseases, including influenza caused by either H3N2 or H1N1 and acute lung injury, to extract the dynamical network biomarkers (DNBs) responsible for catastrophic transition into the disease state from predisease state. The numerical results indicate that the derived indicators provide a data-based quantitative analysis for early-warning signals for critical transitions in complex diseases or other dynamical systems.

  18. Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice.

    Science.gov (United States)

    Lee, Youngjoo; Kim, Jiyeon; An, Jinho; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2017-03-01

    We developed spontaneous diet-induced metabolic disease in mice by feeding them a high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to examine its restorative effect on immune disorders and metabolic syndrome. A series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte proliferation and antigen-specific immunity as determined by the restored functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum TNF-α level was also regulated by Aloe QDM complex treatment, which suggested its complex therapeutic potential. As for metabolic phenotypes, oral administration of Aloe QDM complex significantly improved diabetic symptoms, including high fasting glucose levels and glucose tolerance, and distinctly alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous restoration of Aloe QDM complex on metabolic syndrome and host immune dysfunction, especially on the specific CTL killing was first elucidated in our study.

  19. Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel.

    Science.gov (United States)

    Wojtovich, Andrew P; Smith, C Owen; Haynes, Cole M; Nehrke, Keith W; Brookes, Paul S

    2013-05-01

    In recent years, it has become apparent that there exist several roles for respiratory complex II beyond metabolism. These include: (i) succinate signaling, (ii) reactive oxygen species (ROS) generation, (iii) ischemic preconditioning, (iv) various disease states and aging, and (v) a role in the function of the mitochondrial ATP-sensitive K(+) (mKATP) channel. This review will address the involvement of complex II in each of these areas, with a focus on how complex II regulates or may be involved in the assembly of the mKATP. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. Copyright © 2012. Published by Elsevier B.V.

  20. Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Liesbeth Borgermans

    2014-01-01

    Full Text Available Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.

  1. Understanding complex clinical reasoning in infectious diseases for improving clinical decision support design.

    Science.gov (United States)

    Islam, Roosan; Weir, Charlene R; Jones, Makoto; Del Fiol, Guilherme; Samore, Matthew H

    2015-11-30

    Clinical experts' cognitive mechanisms for managing complexity have implications for the design of future innovative healthcare systems. The purpose of the study is to examine the constituents of decision complexity and explore the cognitive strategies clinicians use to control and adapt to their information environment. We used Cognitive Task Analysis (CTA) methods to interview 10 Infectious Disease (ID) experts at the University of Utah and Salt Lake City Veterans Administration Medical Center. Participants were asked to recall a complex, critical and vivid antibiotic-prescribing incident using the Critical Decision Method (CDM), a type of Cognitive Task Analysis (CTA). Using the four iterations of the Critical Decision Method, questions were posed to fully explore the incident, focusing in depth on the clinical components underlying the complexity. Probes were included to assess cognitive and decision strategies used by participants. The following three themes emerged as the constituents of decision complexity experienced by the Infectious Diseases experts: 1) the overall clinical picture does not match the pattern, 2) a lack of comprehension of the situation and 3) dealing with social and emotional pressures such as fear and anxiety. All these factors contribute to decision complexity. These factors almost always occurred together, creating unexpected events and uncertainty in clinical reasoning. Five themes emerged in the analyses of how experts deal with the complexity. Expert clinicians frequently used 1) watchful waiting instead of over- prescribing antibiotics, engaged in 2) theory of mind to project and simulate other practitioners' perspectives, reduced very complex cases into simple 3) heuristics, employed 4) anticipatory thinking to plan and re-plan events and consulted with peers to share knowledge, solicit opinions and 5) seek help on patient cases. The cognitive strategies to deal with decision complexity found in this study have important

  2. [Autosomal recessive polycystic kidney disease and complex nephronophtisis medullary cystic disease].

    Science.gov (United States)

    2008-12-01

    Reseach during the past decade has led to the discovery that defects in some proteins that localize to primary cilia or the basal body are the main contributors to renal cyst development. Autosomal recessive polycystic disease and nephronophthisis- medullary cystic kidney disease are named ciliopathies. The cilium is a microtubule-based organelle that is found on most mammalian cells. Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might sense stimuli in the cell enviroment and control cell polarity and mitosis. A new set of pathogenic mechanisms in renal cystic disease defined new therapeutic targets, control of intracellular calcium, inhibition of cAMP and down regulation cannonical Wnt signaling.

  3. Leadless pacemaker implantation in a patient with complex congenital heart disease and limited vascular access

    Directory of Open Access Journals (Sweden)

    Paolo Ferrero

    2016-11-01

    Full Text Available Management of rhythm related issues might be particularly challenging in patients with congenital heart disease due to complex anatomy and restricted vascular access. The leadless technology appears a suitable and attractive alternative for this population. We describe a patient with single ventricle physiology who successfully underwent implantation of a leadless pacemaker.

  4. Intervention Fidelity for a Complex Behaviour Change Intervention in Community Pharmacy Addressing Cardiovascular Disease Risk

    Science.gov (United States)

    McNamara, K. P.; O'Reilly, S. L.; George, J.; Peterson, G. M.; Jackson, S. L.; Duncan, G.; Howarth, H.; Dunbar, J. A.

    2015-01-01

    Background: Delivery of cardiovascular disease (CVD) prevention programs by community pharmacists appears effective and enhances health service access. However, their capacity to implement complex behavioural change processes during patient counselling remains largely unexplored. This study aims to determine intervention fidelity by pharmacists…

  5. Mycobacterium avium complex pulmonary disease: characteristics and treatment in an Irish patient cohort.

    LENUS (Irish Health Repository)

    Judge, EP

    2016-04-01

    The prevalence of Mycobacterium avium complex (MAC) pulmonary disease is increasing globally. However, reliable national and international data relating to its epidemiology and management is lacking. During the period 2003-2014, MAC was isolated from the pulmonary samples of 75 patients at the Irish Mycobacteria Reference Laboratory (IMRL). Most patients (42, 56%) had underlying pulmonary disease, and 37 (49%) had clinical\\/radiographic characteristics consistent with MAC pulmonary disease. However, only 18 patients (24%) fulfilled internationally accepted criteria for diagnosis\\/treatment of this disease. Treatment was started in 13 (72%) of these cases, which is similar to internationally published treatment rates. The diagnosis of significant MAC pulmonary disease can be difficult, and treatment is not always warranted even when diagnostic criteria are met.

  6. Genomic risk prediction of complex human disease and its clinical application.

    Science.gov (United States)

    Abraham, Gad; Inouye, Michael

    2015-08-01

    Recent advances in genome-wide association studies have stimulated interest in the genomic prediction of disease risk, potentially enabling individual-level risk estimates for early intervention and improved diagnostic procedures. Here, we review recent findings and approaches to genomic prediction model construction and performance, then contrast the potential benefits of such models in two complex human diseases, aiding diagnosis in celiac disease and prospective risk prediction for cardiovascular disease. Early indications are that optimal application of genomic risk scores will differ substantially for each disease depending on underlying genetic architecture as well as current clinical and public health practice. As costs decline, genomic profiles become common, and popular understanding of risk and its communication improves, genomic risk will become increasingly useful for the individual and the clinician. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Lessons from model organisms: phenotypic robustness and missing heritability in complex disease.

    Directory of Open Access Journals (Sweden)

    Christine Queitsch

    Full Text Available Genetically tractable model organisms from phages to mice have taught us invaluable lessons about fundamental biological processes and disease-causing mutations. Owing to technological and computational advances, human biology and the causes of human diseases have become accessible as never before. Progress in identifying genetic determinants for human diseases has been most remarkable for Mendelian traits. In contrast, identifying genetic determinants for complex diseases such as diabetes, cancer, and cardiovascular and neurological diseases has remained challenging, despite the fact that these diseases cluster in families. Hundreds of variants associated with complex diseases have been found in genome-wide association studies (GWAS, yet most of these variants explain only a modest amount of the observed heritability, a phenomenon known as "missing heritability." The missing heritability has been attributed to many factors, mainly inadequacies in genotyping and phenotyping. We argue that lessons learned about complex traits in model organisms offer an alternative explanation for missing heritability in humans. In diverse model organisms, phenotypic robustness differs among individuals, and those with decreased robustness show increased penetrance of mutations and express previously cryptic genetic variation. We propose that phenotypic robustness also differs among humans and that individuals with lower robustness will be more responsive to genetic and environmental perturbations and hence susceptible to disease. Phenotypic robustness is a quantitative trait that can be accurately measured in model organisms, but not as yet in humans. We propose feasible approaches to measure robustness in large human populations, proof-of-principle experiments for robustness markers in model organisms, and a new GWAS design that takes differences in robustness into account.

  8. Complex Fibroadenoma and Breast Cancer Risk: A Mayo Clinic Benign Breast Disease Cohort Studya

    Science.gov (United States)

    Nassar, Aziza; Visscher, Daniel W.; Degnim, Amy C.; Frank, Ryan D.; Vierkant, Robert A.; Frost, Marlene; Radisky, Derek C.; Vachon, Celine M.; Kraft, Ruth A.; Hartmann, Lynn C.; Ghosh, Karthik

    2015-01-01

    Purpose To examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. Methods The study included women aged 18 to 85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed vs expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression (nonproliferative disease, proliferative disease without atypia [PDWA], or atypical hyperplasia). Results Fibroadenoma was identified in 2,136 women (noncomplex, 1,835 [85.9%]; complex, 301 [14.1%]). SIR for noncomplex fibroadenoma was 1.49 (95% CI, 1.26–1.74); for complex fibroadenoma, it was 2.27 (95% CI, 1.63–3.10) (test for heterogeneity in SIR, P=.02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (eg, incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Conclusions Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics. PMID:26264469

  9. Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study.

    Science.gov (United States)

    Nassar, Aziza; Visscher, Daniel W; Degnim, Amy C; Frank, Ryan D; Vierkant, Robert A; Frost, Marlene; Radisky, Derek C; Vachon, Celine M; Kraft, Ruth A; Hartmann, Lynn C; Ghosh, Karthik

    2015-09-01

    The purpose of this study is to examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. The study included women aged 18-85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed versus expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression [nonproliferative disease, proliferative disease without atypia (PDWA), or atypical hyperplasia]. Fibroadenoma was identified in 2136 women [noncomplex, 1835 (85.9%); complex, 301 (14.1%)]. SIR for noncomplex fibroadenoma was 1.49 (95% CI 1.26-1.74); for complex fibroadenoma, it was 2.27 (95% CI 1.63-3.10) (test for heterogeneity in SIR, P = .02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (e.g., incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics.

  10. Characteristics of Lipoprotein(a)-Containing Circulating Immune Complexes as Markers of Coronary Heart Disease.

    Science.gov (United States)

    Klesareva, E A; Afanas'eva, O I; Donskikh, V V; Adamova, I Yu; Pokrovskii, S N

    2016-12-01

    We studied the composition of circulating immune complexes precipitated in the presence of various concentrations of polyethylene glycol in patients with coronary heart disease (CHD) and high concentration of lipoprotein(a) - Lp(a). Precipitation of highly purified Lp(a) preparation with polyethylene glycol was evaluated. The contents of Lp(a), autoantibodies to Lp(a), IgG, and IgM in circulating immune complexes isolated from the sera of donors and CHD patients with normal and high levels of Lp(a) were measured. Circulating immune complexes containing Lp(a) were detected in the plasma of CHD patients with high Lp(a) concentrations. The presence of high concentrations of Lp(a), autoantibodies to Lp(a), and circulating immune complexes in CHD patients suggests that immunological factor contributes to high atherothrombogenicity of Lp(a).

  11. Identifying driving gene clusters in complex diseases through critical transition theory

    Science.gov (United States)

    Wolanyk, Nathaniel; Wang, Xujing; Hessner, Martin; Gao, Shouguo; Chen, Ye; Jia, Shuang

    A novel approach of looking at the human body using critical transition theory has yielded positive results: clusters of genes that act in tandem to drive complex disease progression. This cluster of genes can be thought of as the first part of a large genetic force that pushes the body from a curable, but sick, point to an incurable diseased point through a catastrophic bifurcation. The data analyzed is time course microarray blood assay data of 7 high risk individuals for Type 1 Diabetes who progressed into a clinical onset, with an additional larger study requested to be presented at the conference. The normalized data is 25,000 genes strong, which were narrowed down based on statistical metrics, and finally a machine learning algorithm using critical transition metrics found the driving network. This approach was created to be repeatable across multiple complex diseases with only progression time course data needed so that it would be applicable to identifying when an individual is at risk of developing a complex disease. Thusly, preventative measures can be enacted, and in the longer term, offers a possible solution to prevent all Type 1 Diabetes.

  12. Gene-Environment Interactions in the Development of Complex Disease Phenotypes

    Directory of Open Access Journals (Sweden)

    Kenneth Olden

    2008-03-01

    Full Text Available The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called “environmental response machinery” (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in geneenvironment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding

  13. On rational complex of investigation methods in prophylactic examination of patients with chronic kidney diseases

    International Nuclear Information System (INIS)

    Yazykov, A.S.; Telichko, F.F.

    1989-01-01

    A retrospective evaluation of the total quantity of X-ray procedures and the radiation degree in 310 patients with chronic kidney diseases is given. It is ascertained that only account of integral absorbed dose in the organ tissues, comprising the doses of X-ray examinations of other organs during the patient lifetime, can serve as the main condition for developing well-grounded recommendations concerning rational complex of examination methods during prophylactic examination of patients with chronic kidney disease. 9 refs.; 4 figs

  14. Framework for Smart Electronic Health Record- Linked Predictive Models to Optimize Care for Complex Digestive Diseases

    Science.gov (United States)

    2015-03-01

    INTRODUCTION: Complex disorders result from the interaction of genetic, metabolic and environmental factors that may not produce disease themselves but...constructed using demographic (age>55yrs, Race, Gender, BMI, Tobacco use, Alcohol Use), lab values (BUN, Creatinine , Lipids, WBC, Hemaglobin, AST, Calcium...lead to us to look more closely at those CD patients with concomitant mood disorders and irritable bowel syndrome (IBS). We found that patients with

  15. Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.

    Science.gov (United States)

    Kumagai, N; Kaneko, F; Tsunematsu, S; Tsuchimoto, K; Tada, S; Saito, H; Hibi, T

    2007-07-01

    Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

  16. Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease.

    Science.gov (United States)

    Moreno-Moral, Aida; Pesce, Francesco; Behmoaras, Jacques; Petretto, Enrico

    2017-01-01

    Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

  17. The treatment of complex airway diseases with inverted Y-shaped self-expandable metal stent

    International Nuclear Information System (INIS)

    Li Jianming; Jia Guangzhi

    2011-01-01

    Objective: To investigate the application and therapeutic effects of inverted Y-shaped self-expandable metal airway stent in treating complex airway diseases (stenosis or fistula). Methods: According to the distinctive anatomic structure and the pathological changes of complex airway stenosis or fistula, the inverted y-shaped self-expandable metal airway stent was designed. Under fluoroscopic monitoring, a total of 12 inverted Y-shaped self-expandable metal stents were implanted in 12 patients with complex airway diseases. Results: Stent placement in the trachea-bronchial tree was technically successful in all patients. After the operation, the symptom of dyspnea was immediately relieved and the bucking following food intake disappeared. The general physical condition and living quality were much improved in all patients. Conclusion: The use of inverted Y-shaped self-expandable metal airway stent for the management of complex airway stenosis involving the tracheal carina was a simple and safe procedure and it has satisfactory short-term clinical results. (authors)

  18. Comparison of family history and SNPs for predicting risk of complex disease.

    Directory of Open Access Journals (Sweden)

    Chuong B Do

    Full Text Available The clinical utility of family history and genetic tests is generally well understood for simple Mendelian disorders and rare subforms of complex diseases that are directly attributable to highly penetrant genetic variants. However, little is presently known regarding the performance of these methods in situations where disease susceptibility depends on the cumulative contribution of multiple genetic factors of moderate or low penetrance. Using quantitative genetic theory, we develop a model for studying the predictive ability of family history and single nucleotide polymorphism (SNP-based methods for assessing risk of polygenic disorders. We show that family history is most useful for highly common, heritable conditions (e.g., coronary artery disease, where it explains roughly 20%-30% of disease heritability, on par with the most successful SNP models based on associations discovered to date. In contrast, we find that for diseases of moderate or low frequency (e.g., Crohn disease family history accounts for less than 4% of disease heritability, substantially lagging behind SNPs in almost all cases. These results indicate that, for a broad range of diseases, already identified SNP associations may be better predictors of risk than their family history-based counterparts, despite the large fraction of missing heritability that remains to be explained. Our model illustrates the difficulty of using either family history or SNPs for standalone disease prediction. On the other hand, we show that, unlike family history, SNP-based tests can reveal extreme likelihood ratios for a relatively large percentage of individuals, thus providing potentially valuable adjunctive evidence in a differential diagnosis.

  19. Phenome-wide association study maps new diseases to the human major histocompatibility complex region.

    Science.gov (United States)

    Liu, Jixia; Ye, Zhan; Mayer, John G; Hoch, Brian A; Green, Clayton; Rolak, Loren; Cold, Christopher; Khor, Seik-Soon; Zheng, Xiuwen; Miyagawa, Taku; Tokunaga, Katsushi; Brilliant, Murray H; Hebbring, Scott J

    2016-10-01

    Over 160 disease phenotypes have been mapped to the major histocompatibility complex (MHC) region on chromosome 6 by genome-wide association study (GWAS), suggesting that the MHC region as a whole may be involved in the aetiology of many phenotypes, including unstudied diseases. The phenome-wide association study (PheWAS), a powerful and complementary approach to GWAS, has demonstrated its ability to discover and rediscover genetic associations. The objective of this study is to comprehensively investigate the MHC region by PheWAS to identify new phenotypes mapped to this genetically important region. In the current study, we systematically explored the MHC region using PheWAS to associate 2692 MHC-linked variants (minor allele frequency ≥0.01) with 6221 phenotypes in a cohort of 7481 subjects from the Marshfield Clinic Personalized Medicine Research Project. Findings showed that expected associations previously identified by GWAS could be identified by PheWAS (eg, psoriasis, ankylosing spondylitis, type I diabetes and coeliac disease) with some having strong cross-phenotype associations potentially driven by pleiotropic effects. Importantly, novel associations with eight diseases not previously assessed by GWAS (eg, lichen planus) were also identified and replicated in an independent population. Many of these associated diseases appear to be immune-related disorders. Further assessment of these diseases in 16 484 Marshfield Clinic twins suggests that some of these diseases, including lichen planus, may have genetic aetiologies. These results demonstrate that the PheWAS approach is a powerful and novel method to discover SNP-disease associations, and is ideal when characterising cross-phenotype associations, and further emphasise the importance of the MHC region in human health and disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Impact of asymptomatic infection on coupled disease-behavior dynamics in complex networks

    Science.gov (United States)

    Zhang, Hai-Feng; Xie, Jia-Rong; Chen, Han-Shuang; Liu, Can; Small, Michael

    2016-05-01

    Studies on how to model the interplay between diseases and behavioral responses (so-called coupled disease-behavior interaction) have attracted increasing attention. Owing to the lack of obvious clinical evidence of diseases, or the incomplete information related to the disease, the risks of infection cannot be perceived and may lead to inappropriate behavioral responses. Therefore, how to quantitatively analyze the impacts of asymptomatic infection on the interplay between diseases and behavioral responses is of particular importance. In this letter, under the complex network framework, we study the coupled disease-behavior interaction model by dividing infectious individuals into two states: U-state (without evident clinical symptoms, labelled as U) and I-state (with evident clinical symptoms, labelled as I). A susceptible individual can be infected by U- or I-nodes, however, since the U-nodes cannot be easily observed, susceptible individuals take behavioral responses only when they contact I-nodes. The mechanism is considered in the improved Susceptible-Infected-Susceptible (SIS) model and the improved Susceptible-Infected-Recovered (SIR) model, respectively. Then, one of the most concerned problems in spreading dynamics: the epidemic thresholds for the two models are given by two methods. The analytic results quantitatively describe the influence of different factors, such as asymptomatic infection, the awareness rate, the network structure, and so forth, on the epidemic thresholds. Moreover, because of the irreversible process of the SIR model, the suppression effect of the improved SIR model is weaker than the improved SIS model.

  1. Ocean warming and acidification have complex interactive effects on the dynamics of a marine fungal disease

    Science.gov (United States)

    Williams, Gareth J.; Price, Nichole N.; Ushijima, Blake; Aeby, Greta S.; Callahan, Sean M.; Davy, Simon K.; Gove, Jamison M.; Johnson, Maggie D.; Knapp, Ingrid S.; Shore-Maggio, Amanda; Smith, Jennifer E.; Videau, Patrick; Work, Thierry M.

    2014-01-01

    Diseases threaten the structure and function of marine ecosystems and are contributing to the global decline of coral reefs. We currently lack an understanding of how climate change stressors, such as ocean acidification (OA) and warming, may simultaneously affect coral reef disease dynamics, particularly diseases threatening key reef-building organisms, for example crustose coralline algae (CCA). Here, we use coralline fungal disease (CFD), a previously described CCA disease from the Pacific, to examine these simultaneous effects using both field observations and experimental manipulations. We identify the associated fungus as belonging to the subphylum Ustilaginomycetes and show linear lesion expansion rates on individual hosts can reach 6.5 mm per day. Further, we demonstrate for the first time, to our knowledge, that ocean-warming events could increase the frequency of CFD outbreaks on coral reefs, but that OA-induced lowering of pH may ameliorate outbreaks by slowing lesion expansion rates on individual hosts. Lowered pH may still reduce overall host survivorship, however, by reducing calcification and facilitating fungal bio-erosion. Such complex, interactive effects between simultaneous extrinsic environmental stressors on disease dynamics are important to consider if we are to accurately predict the response of coral reef communities to future climate change.

  2. Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

    Directory of Open Access Journals (Sweden)

    Min Kyung Sung

    2014-12-01

    Full Text Available Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE data: type 2 diabetes mellitus (DM, hypertension (HT, and coronary artery disease (CAD. We showed that epistatic single-nucleotide polymorphisms (SNPs were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012, which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE. Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

  3. Entropy-based complexity measures for gait data of patients with Parkinson's disease

    Science.gov (United States)

    Afsar, Ozgur; Tirnakli, Ugur; Kurths, Juergen

    2016-02-01

    Shannon, Kullback-Leibler, and Klimontovich's renormalized entropies are applied as three different complexity measures on gait data of patients with Parkinson's disease (PD) and healthy control group. We show that the renormalized entropy of variability of total reaction force of gait is a very efficient tool to compare patients with respect to disease severity. Moreover, it is a good risk predictor such that the sensitivity, i.e., the percentage of patients with PD who are correctly identified as having PD, increases from 25% to 67% while the Hoehn-Yahr stage increases from 2.5 to 3.0 (this stage goes from 0 to 5 as the disease severity increases). The renormalized entropy method for stride time variability of gait is found to correctly identify patients with a sensitivity of 80%, while the Shannon entropy and the Kullback-Leibler relative entropy can do this with a sensitivity of only 26.7% and 13.3%, respectively.

  4. Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease

    DEFF Research Database (Denmark)

    Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars

    2016-01-01

    OBJECTIVE: To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. DESIGN: Randomized clinical trial. SETTING: Denmark. PATIENTS: A total of 158 adolescents aged 13-16years with no physical activity...... restrictions after repaired complex congenital heart disease. INTERVENTIONS: PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. OUTCOMES......·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. CONCLUSIONS: Adding a tailored eHealth intervention to health education and individual...

  5. Ring chromosome in myeloid neoplasms is associated with complex karyotype and disease progression.

    Science.gov (United States)

    Rosenbaum, Matthew W; Pozdnyakova, Olga; Geyer, Julia T; Dal Cin, Paola; Hasserjian, Robert P

    2017-10-01

    Ring chromosome (RC) is a poorly understood genetic anomaly seen in myeloid neoplasms. This study aims to shed light on the clinical significance of this finding. We identified 96 cases of myeloid neoplasms with RC from 3 academic hospitals. Clinicopathologic features and overall (OS) and leukemia-free survival were reviewed and compared to cases of myeloid neoplasms lacking RC. We identified 59 acute myeloid leukemias (AML-RC) and 37 myelodysplastic syndromes (MDS-RC) with RC identified on routine karyotyping. Seventy-five percent of AML-RC and 97% of MDS-RC had complex (>3 independent cytogenetic abnormalities) karyotypes. The median OS of AML-RC with complex karyotype was significantly shorter than AML-RC patients with a non-complex (≤3 independent cytogenetic abnormalities) karyotype (P=.001), but similar to AML patients with complex karyotype lacking RC (P=not significant). Compared to complex-karyotype MDS lacking RC, MDS-RC patients had shorter leukemia-free survival (P=.016) and a trend for shorter OS (P=.10). RCs were sometimes lost after therapy or appeared during disease relapse, suggesting that they may be associated with genetic instability. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Multidisciplinary management of pregnancy in complex congenital heart disease: a model for coordination of care.

    Science.gov (United States)

    Harris, Rachel C; Fries, Melissa H; Boyle, Annelee; Adeniji-Adele, Hassan; Cherian, Zacharia; Klein, Nancy; John, Anitha S

    2014-01-01

    With advancements in medical care, many women with complex congenital heart disease (CHD) are now living into adulthood and childbearing years. The strains of pregnancy and parturition can be dangerous in such patients, and careful interdisciplinary plans must be made to optimize maternal and fetal health through this process. Several large studies have been published regarding risk prediction and medical management of pregnancy in complex CHD, though few case studies detailing clinical care plans have been published. The objective of this report is to describe the process of developing a detailed pregnancy and delivery care plan for three women with complex CHD, including perspectives from the multidisciplinary specialists involved in the process. This article demonstrates that collaboration between specialists in the fields of cardiology, anesthesiology, high-risk obstetrics, maternal fetal medicine, and neonatology results in clinically successful individualized treatment plans for the management of pregnancy in complex CHD. Multidisciplinary collaboration is a crucial element in the management of pregnancy in complex CHD. We provide a template used in three cases which can serve as a model for the design of future care plans. © 2014 Wiley Periodicals, Inc.

  7. The complexity, relative value, and financial worth of curbside consultations in an academic infectious diseases unit.

    Science.gov (United States)

    Grace, Christopher; Alston, W Kemper; Ramundo, Mary; Polish, Louis; Kirkpatrick, Beth; Huston, Christopher

    2010-09-15

    Curbside consultations are common in clinical practice. The complexity, relative value, and revenue loss associated with curbside consultations are not well defined. Curbside consultations performed during a 1-year period were studied. Each curbside consultation was assigned a Current Procedural Terminology (CPT) code on the basis of the inpatient versus outpatient status of the patient, initial versus subsequent care, and clinical complexity. On the basis of the CPT code, the physician work component of the relative value unit (wRVU) was assigned for each curbside consultation. The 2005 Centers for Medicaid and Medicare Services conversion factor of $37.89 per wRVU was used for cost estimates. Comparisons were made with formal consultations performed during the same time period. A total of 1001 curbside consultations were fielded: 66% involved outpatients, and 97% were coded as initial consultations. A total of 78% of curbside consultations were considered complex in nature, being assigned a CPT code of level 4-5, including 84% of the inpatient and 75% of the outpatient curbside consultations. These curbside consultations would have generated 2480 wRVUs. During the same period, formal consultations generated 12,121 wRVUs. Thus, curbside consultations represented 17% (2480/14,601) of the clinical work value of the infectious diseases unit. If the infectious diseases unit had performed these curbside consultations as formal consultations, an additional $93,979 in revenue would have been generated. Curbside consultations are common and complex. The curbside consultation should be incorporated into measures of infectious diseases providers' productivity and compensation.

  8. Antennal phenotype of Mexican haplogroups of the Triatoma dimidiata complex, vectors of Chagas disease.

    Science.gov (United States)

    May-Concha, Irving; Guerenstein, Pablo G; Ramsey, Janine M; Rojas, Julio C; Catalá, Silvia

    2016-06-01

    Triatoma dimidiata (Latreille) is a species complex that spans North, Central, and South America and which is a key vector of all known discrete typing units (DTU) of Trypanosoma cruzi, the etiologic agent of Chagas disease. Morphological and genetic studies indicate that T. dimidiata is a species complex with three principal haplogroups (hg) in Mexico. Different markers and traits are still inconclusive regarding if other morphological differentiation may indicate probable behavioral and vectorial divergences within this complex. In this paper we compared the antennae of three Mexican haplogroups (previously verified by molecular markers ND4 and ITS-2) and discussed possible relationships with their capacity to disperse and colonized new habitats. The abundance of each type of sensillum (bristles, basiconics, thick- and thin-walled trichoids) on the antennae of the three haplogroups, were measured under light microscopy and compared using Kruskal-Wallis non-parametric and multivariate non-parametric analyses. Discriminant analyses indicate significant differences among the antennal phenotype of haplogroups either for adults and some nymphal stages, indicating consistency of the character to analyze intraspecific variability within the complex. The present study shows that the adult antennal pedicel of the T. dimidiata complex have abundant chemosensory sensilla, according with good capacity for dispersal and invasion of different habitats also related to their high capacity to adapt to conserved as well as modified habitats. However, the numerical differences among the haplogroups are suggesting variations in that capacity. The results here presented support the evidence of T. dimidiata as a species complex but show females and males in a different way. Given the close link between the bug's sensory system and its habitat and host-seeking behavior, AP characterization could be useful to complement genetic, neurological and ethological studies of the closely

  9. Assessing the impact of vaccination programmes on burden of disease: Underlying complexities and statistical methods.

    Science.gov (United States)

    Mealing, Nicole; Hayen, Andrew; Newall, Anthony T

    2016-06-08

    It is important to assess the impact a vaccination programme has on the burden of disease after it is implemented. For example, this may reveal herd immunity effects or vaccine-induced shifts in the incidence of disease or in circulating strains or serotypes of the pathogen. In this article we summarise the key features of infectious diseases that need to be considered when trying to detect any changes in the burden of diseases at a population level as a result of vaccination efforts. We outline the challenges of using routine surveillance databases to monitor infectious diseases, such as the identification of diseased cases and the availability of vaccination status for cases. We highlight the complexities in modelling the underlying patterns in infectious disease rates (e.g. presence of autocorrelation) and discuss the main statistical methods that can be used to control for periodicity (e.g. seasonality) and autocorrelation when assessing the impact of vaccination programmes on burden of disease (e.g. cosinor terms, generalised additive models, autoregressive processes and moving averages). For some analyses, there may be multiple methods that can be used, but it is important for authors to justify the method chosen and discuss any limitations. We present a case study review of the statistical methods used in the literature to assess the rotavirus vaccination programme impact in Australia. The methods used varied and included generalised linear models and descriptive statistics. Not all studies accounted for autocorrelation and seasonality, which can have a major influence on results. We recommend that future analyses consider the strength and weakness of alternative statistical methods and justify their choice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

    Science.gov (United States)

    van der Crabben, Saskia N.; Hennus, Marije P.; McGregor, Grant A.; Ritter, Deborah I.; Nagamani, Sandesh C.S.; Wells, Owen S.; Harakalova, Magdalena; Chinn, Ivan K.; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M.; Terheggen-Lagro, Suzanne W.; van Lieshout, Stef; van Roosmalen, Markus J.; Renkens, Ivo; Duran, Karen; Nijman, Isaac J.; Kloosterman, Wigard P.; Hennekam, Eric; van Hasselt, Peter M.; Wheeler, David A.; Palecek, Jan J.; Lehmann, Alan R.; Oliver, Antony W.; Pearl, Laurence H.; Plon, Sharon E.; Murray, Johanne M.

    2016-01-01

    The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

  11. The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Landreth Gary E

    2006-11-01

    Full Text Available Abstract Alzheimer's disease is the most common cause of dementia in the elderly, and manifests as progressive cognitive decline and profound neuronal loss. The principal neuropathological hallmarks of Alzheimer's disease are the senile plaques and the neurofibrillary tangles. The senile plaques are surrounded by activated microglia, which are largely responsible for the proinflammatory environment within the diseased brain. Microglia are the resident innate immune cells in the brain. In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules. Evidence suggests that oxidative stress emanating from activated microglia contribute to the neuronal loss characteristic of this disease. The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH oxidase. The NADPH oxidase is a multicomponent enzyme complex that, upon activation, produces the highly reactive free radical superoxide. The cascade of intracellular signaling events leading to NADPH oxidase assembly and the subsequent release of superoxide in fibrillar beta-amyloid stimulated microglia has recently been elucidated. The induction of reactive oxygen species, as well as nitric oxide, from activated microglia can enhance the production of more potent free radicals such as peroxynitrite. The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death. The elimination of beta-amyloid-induced oxidative damage through the inhibition of the NADPH oxidase represents an attractive therapeutic target for the treatment of Alzheimer's disease.

  12. Three viruses of the bovine respiratory disease complex apply different strategies to initiate infection.

    Science.gov (United States)

    Kirchhoff, Jana; Uhlenbruck, Sabine; Goris, Katherina; Keil, Günther M; Herrler, Georg

    2014-02-18

    Bovine respiratory disease complex (BRDC) is the major cause of serious respiratory tract infections in calves. The disease is multifactorial, with either stress or reduced immunity allowing several pathogens to emerge. We investigated the susceptibility of bovine airway epithelial cells (BAEC) to infection by the three major viruses associated with the BRDC: bovine respiratory syncytial virus (BRSV), bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza virus type 3 (BPIV3). For this purpose, two culture systems for well-differentiated BAEC were used: the air-liquid interface (ALI) system, where filter-grown BAEC differentiate into a pseudostratified respiratory epithelium and precision-cut lung slices (PCLS) where BAEC are maintained in the original tissue organisation. Comparative infection studies demonstrated that entry and release of BPIV3 occurred specifically via the apical membrane with ciliated cells being the major target cells. By contrast, airway epithelial cells were largely resistant to infection by BHV-1. When the epithelial barrier was abolished by opening tight junctions or by injuring the cell monolayer, BHV-1 infected mainly basal cells. Respiratory epithelial cells were also refractory to infection by BRSV. However, this virus infected neither differentiated epithelial cells nor basal cells when the integrity of the epithelial barrier was destroyed. In contrast to cells of the airway epithelium, subepithelial cells were susceptible to infection by BRSV. Altogether, these results indicate that the three viruses of the same disease complex follow different strategies to interact with the airway epithelium. Possible entry mechanisms are discussed.

  13. Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

    Directory of Open Access Journals (Sweden)

    Jay S. Coggan

    2015-09-01

    Full Text Available Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.

  14. AN INTEGRATED NETWORK APPROACH TO IDENTIFYING BIOLOGICAL PATHWAYS AND ENVIRONMENTAL EXPOSURE INTERACTIONS IN COMPLEX DISEASES.

    Science.gov (United States)

    Darabos, Christian; Qiu, Jingya; Moore, Jason H

    2016-01-01

    Complex diseases are the result of intricate interactions between genetic, epigenetic and environmental factors. In previous studies, we used epidemiological and genetic data linking environmental exposure or genetic variants to phenotypic disease to construct Human Phenotype Networks and separately analyze the effects of both environment and genetic factors on disease interactions. To better capture the intricacies of the interactions between environmental exposure and the biological pathways in complex disorders, we integrate both aspects into a single "tripartite" network. Despite extensive research, the mechanisms by which chemical agents disrupt biological pathways are still poorly understood. In this study, we use our integrated network model to identify specific biological pathway candidates possibly disrupted by environmental agents. We conjecture that a higher number of co-occurrences between an environmental substance and biological pathway pair can be associated with a higher likelihood that the substance is involved in disrupting that pathway. We validate our model by demonstrating its ability to detect known arsenic and signal transduction pathway interactions and speculate on candidate cell-cell junction organization pathways disrupted by cadmium. The validation was supported by distinct publications of cell biology and genetic studies that associated environmental exposure to pathway disruption. The integrated network approach is a novel method for detecting the biological effects of environmental exposures. A better understanding of the molecular processes associated with specific environmental exposures will help in developing targeted molecular therapies for patients who have been exposed to the toxicity of environmental chemicals.

  15. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

    Science.gov (United States)

    Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

    2016-11-17

    Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. A novel approach to simulate gene-environment interactions in complex diseases

    Directory of Open Access Journals (Sweden)

    Nicodemi Mario

    2010-01-01

    Full Text Available Abstract Background Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.. Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS, a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte

  17. Role of angiocardiography in the diagnosis and management of complex/complicated congenital heart disease

    International Nuclear Information System (INIS)

    Ling Jian; Liu Yuqing

    2006-01-01

    Objective: To evaluate the role of angiocadiography (ACG) in the diagnosis and management of complex/complicated congenital heart disease (CHD). Methods: A retrospective study of ACG findings in 360 cases with complex/complicated CHD was performed with a comparision to that of echocardiography (Echo) and related clinical examination. Results: The present series of CHD cases included pulmonary atresia with ventricular septal defect in 75 cases, double outlet of right ventricle in 62 cases, Fallot's tetralogy in 60 cases, single ventricle in 52 cases, transposition of the great arteries in 42 cases, tricuspid valve atresia in 15 cases, coronary abnormality in 6 eases, total abnormal pulmonary venous connection in 5 cases, total endocardial cushion defect in 5 cases, persistent truncus arteriosus in 4 cases, pulmonary atresia with normal ventricular septum in 3 cases, other disorders in 7 eases, and postsurgical operation in 24 cases. ACG was superior to that of Echo in demonstrating the abnormalities of systemic, pulmonary, and coronary arteries and their branches of complex/complicated CHD as well as measuring the pressure of pulmonary artery, vein, and systemic-pulmonary collateral vessels. Conclusion: In the diagnosis and differential diagnosis of knotty cases with complex and complicated CHD, particularly in the demonstration of full view of systemic, pulmonary, and coronary arterial branches and accurate measurement of' pulmonary arterial pressure/resistance, and atrial, ventricular, and systemic arterial pressure, ACG (including DSA) still plays an important and irreplaceable role. (authors)

  18. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence......A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

  19. Relation of ABO blood groups to coronary lesion complexity in patients with stable coronary artery disease.

    Science.gov (United States)

    Kaya, Ahmet; Tanboğa, İbrahim Halil; Kurt, Mustafa; Işık, Turgay; Kaya, Yasemin; Günaydın, Zeki Yüksel; Aksakal, Enbiya

    2014-02-01

    We aimed to investigate the relationship between ABO blood groups and complexity of coronary lesions assessed by SYNTAX score (SS) in stable coronary artery disease (CAD) patients. Our cross-sectional and observational study population consisted of 559 stable CAD patients. From all patients, ABO blood group was determined and the SS was calculated as low SYNTAX score (0-22), intermediate SYNTAX (23-32) score and high SYNTAX score (>32). Statistical analysis was performed using Student's t-test or Mann-Whitney U test, ANOVA, or Kruskal-Wallis test and chi-square test. Multiple logistic regression analysis was used to identify the independent predictors of high SS. The analysis between the SS tertiles revealed that the frequency of non-O blood group was significantly higher in the upper SS tertiles (56.2% vs. 75.9 vs. 80.2%, pABO blood groups and complexity of angiographic CAD.

  20. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  1. Design considerations for massively parallel sequencing studies of complex human disease.

    Directory of Open Access Journals (Sweden)

    Bing-Jian Feng

    Full Text Available Massively Parallel Sequencing (MPS allows sequencing of entire exomes and genomes to now be done at reasonable cost, and its utility for identifying genes responsible for rare Mendelian disorders has been demonstrated. However, for a complex disease, study designs need to accommodate substantial degrees of locus, allelic, and phenotypic heterogeneity, as well as complex relationships between genotype and phenotype. Such considerations include careful selection of samples for sequencing and a well-developed strategy for identifying the few "true" disease susceptibility genes from among the many irrelevant genes that will be found to harbor rare variants. To examine these issues we have performed simulation-based analyses in order to compare several strategies for MPS sequencing in complex disease. Factors examined include genetic architecture, sample size, number and relationship of individuals selected for sequencing, and a variety of filters based on variant type, multiple observations of genes and concordance of genetic variants within pedigrees. A two-stage design was assumed where genes from the MPS analysis of high-risk families are evaluated in a secondary screening phase of a larger set of probands with more modest family histories. Designs were evaluated using a cost function that assumes the cost of sequencing the whole exome is 400 times that of sequencing a single candidate gene. Results indicate that while requiring variants to be identified in multiple pedigrees and/or in multiple individuals in the same pedigree are effective strategies for reducing false positives, there is a danger of over-filtering so that most true susceptibility genes are missed. In most cases, sequencing more than two individuals per pedigree results in reduced power without any benefit in terms of reduced overall cost. Further, our results suggest that although no single strategy is optimal, simulations can provide important guidelines for study design.

  2. Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ruse, Charlotte E; Hill, Maureen C; Tobin, Martin; Neale, Natalie; Connolly, Martin J; Parker, Stuart G; Wardlaw, Andrew J

    2007-02-01

    We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

  3. A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation Patterns for Complex Disease.

    Science.gov (United States)

    Xu, Chao; Zhang, Ji-Gang; Lin, Dongdong; Zhang, Lan; Shen, Hui; Deng, Hong-Wen

    2017-07-05

    Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi)genomic factors from diverse omics data; and (iii) Until present, the combination of more than two omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model, and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for glioblastoma multiforme (GBM) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules, with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but more importantly, it can incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases. Copyright © 2017 Xu et al.

  4. Understanding the Role of GPCR Heteroreceptor Complexes in Modulating the Brain Networks in Health and Disease.

    Science.gov (United States)

    Borroto-Escuela, Dasiel O; Carlsson, Jens; Ambrogini, Patricia; Narváez, Manuel; Wydra, Karolina; Tarakanov, Alexander O; Li, Xiang; Millón, Carmelo; Ferraro, Luca; Cuppini, Riccardo; Tanganelli, Sergio; Liu, Fang; Filip, Malgorzata; Diaz-Cabiale, Zaida; Fuxe, Kjell

    2017-01-01

    The introduction of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes of the central nervous system (CNS) gave a new dimension to brain integration and neuropsychopharmacology. The molecular basis of learning and memory was proposed to be based on the reorganization of the homo- and heteroreceptor complexes in the postjunctional membrane of synapses. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins. The observation of the GPCR heterodimer network (GPCR-HetNet) indicated that the allosteric receptor-receptor interactions dramatically increase GPCR diversity and biased recognition and signaling leading to enhanced specificity in signaling. Dysfunction of the GPCR heteroreceptor complexes can lead to brain disease. The findings of serotonin (5-HT) hetero and isoreceptor complexes in the brain over the last decade give new targets for drug development in major depression. Neuromodulation of neuronal networks in depression via 5-HT, galanin peptides and zinc involve a number of GPCR heteroreceptor complexes in the raphe-hippocampal system: GalR1-5-HT1A, GalR1-5-HT1A-GPR39, GalR1-GalR2, and putative GalR1-GalR2-5-HT1A heteroreceptor complexes. The 5-HT1A receptor protomer remains a receptor enhancing antidepressant actions through its participation in hetero- and homoreceptor complexes listed above in balance with each other. In depression, neuromodulation of neuronal networks in the raphe-hippocampal system and the cortical regions via 5-HT and fibroblast growth factor 2 involves either FGFR1-5-HT1A heteroreceptor complexes or the 5-HT isoreceptor complexes such as 5-HT1A-5-HT7 and 5-HT1A-5-HT2A. Neuromodulation of neuronal networks in cocaine use disorder via dopamine (DA) and adenosine signals involve A2AR-D2R and A2AR-D2R-Sigma1R heteroreceptor complexes in the dorsal and

  5. The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque.

    Science.gov (United States)

    Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

    2013-01-01

    Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.

  6. PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

    Science.gov (United States)

    Kiefer, Florian W; Winhofer, Yvonne; Iacovazzo, Donato; Korbonits, Márta; Wolfsberger, Stefan; Knosp, Engelbert; Trautinger, Franz; Höftberger, Romana; Krebs, Michael; Luger, Anton; Gessl, Alois

    2017-08-01

    Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development. PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients. © 2017 European Society of Endocrinology.

  7. Importance of reciprocal balance of T cell immunity in Mycobacterium abscessus complex lung disease.

    Directory of Open Access Journals (Sweden)

    Su-Young Kim

    Full Text Available Little is known about the nature of the host immune response to Mycobacterium abscessus complex (MABC infection. The aim of the present study was to investigate whether alterations in serum immunomolecule levels after treating MABC lung disease patients with antibiotics can reflect the disease-associated characteristics.A total of 22 immunomolecules in 24 MABC lung disease patients before and after antibiotic therapy were quantitatively analyzed using a multiplex bead-based system.In general, the pre-treatment levels of T helper type 1 (Th1-related cytokines, i.e., interferon (IFN-γ and interleukin (IL-12, and Th2-related cytokines, i.e., IL-4 and IL-13, were significantly decreased in patients compared with control subjects. In contrast, the pre-treatment levels of Th17-related cytokines, i.e., IL-17 and IL-23, were significantly increased in MABC patients. Interestingly, significantly higher levels of IFN-γ-induced protein (IP-10 and monokine induced by IFN-γ protein (MIG were detected in patients with failure of sputum conversion at post-treatment compared to patients with successful sputum conversion.Reduced Th1 and Th2 responses and enhanced Th17 responses in patients may perpetuate MABC lung disease, and the immunomolecules IP-10 and MIG, induced through IFN-γ, may serve as key markers for indicating the treatment outcome.

  8. Infectious Bursal disease virus: ribonucleoprotein complexes of a double-stranded RNA virus.

    Science.gov (United States)

    Luque, Daniel; Saugar, Irene; Rejas, María Teresa; Carrascosa, José L; Rodríguez, José F; Castón, José R

    2009-02-27

    Genome-binding proteins with scaffolding and/or regulatory functions are common in living organisms and include histones in eukaryotic cells, histone-like proteins in some double-stranded DNA (dsDNA) viruses, and the nucleocapsid proteins of single-stranded RNA viruses. dsRNA viruses nevertheless lack these ribonucleoprotein (RNP) complexes and are characterized by sharing an icosahedral T=2 core involved in the metabolism and insulation of the dsRNA genome. The birnaviruses, with a bipartite dsRNA genome, constitute a well-established exception and have a single-shelled T=13 capsid only. Moreover, as in many negative single-stranded RNA viruses, the genomic dsRNA is bound to a nucleocapsid protein (VP3) and the RNA-dependent RNA polymerase (VPg). We used electron microscopy and functional analysis to characterize these RNP complexes of infectious bursal disease virus, the best characterized member of the Birnaviridae family. Mild disruption of viral particles revealed that VP3, the most abundant core protein, present at approximately 450 copies per virion, is found in filamentous material tightly associated with the dsRNA. We developed a method to purify RNP and VPg-dsRNA complexes. Analysis of these complexes showed that they are linear molecules containing a constant amount of protein. Sensitivity assays to nucleases indicated that VP3 renders the genomic dsRNA less accessible for RNase III without introducing genome compaction. Additionally, we found that these RNP complexes are functionally competent for RNA synthesis in a capsid-independent manner, in contrast to most dsRNA viruses.

  9. Balloon Angioplasty as a Modality to Treat Children with Pulmonary Stenosis Secondary to Complex Congenital Heart Diseases

    Directory of Open Access Journals (Sweden)

    Yan Gu

    2017-01-01

    Conclusions: Balloon angioplasty was proven to be a safe and useful modality in children with complex congenital heart diseases and postoperative pulmonary stenosis, which should be the initial therapeutic modality in selected patients.

  10. Modelling fast spreading patterns of airborne infectious diseases using complex networks

    Science.gov (United States)

    Brenner, Frank; Marwan, Norbert; Hoffmann, Peter

    2017-04-01

    The pandemics of SARS (2002/2003) and H1N1 (2009) have impressively shown the potential of epidemic outbreaks of infectious diseases in a world that is strongly connected. Global air travelling established an easy and fast opportunity for pathogens to migrate globally in only a few days. This made epidemiological prediction harder. By understanding this complex development and its link to climate change we can suggest actions to control a part of global human health affairs. In this study we combine the following data components to simulate the outbreak of an airborne infectious disease that is directly transmitted from human to human: em{Global Air Traffic Network (from openflights.org) with information on airports, airport location, direct flight connection, airplane type} em{Global population dataset (from SEDAC, NASA)} em{Susceptible-Infected-Recovered (SIR) compartmental model to simulate disease spreading in the vicinity of airports. A modified Susceptible-Exposed-Infected-Recovered (SEIR) model to analyze the impact of the incubation period.} em{WATCH-Forcing-Data-ERA-Interim (WFDEI) climate data: temperature, specific humidity, surface air pressure, and water vapor pressure} These elements are implemented into a complex network. Nodes inside the network represent airports. Each single node is equipped with its own SIR/SEIR compartmental model with node specific attributes. Edges between those nodes represent direct flight connections that allow infected individuals to move between linked nodes. Therefore the interaction of the set of unique SIR models creates the model dynamics we will analyze. To better figure out the influence on climate change on disease spreading patterns, we focus on Influenza-like-Illnesses (ILI). The transmission rate of ILI has a dependency on climate parameters like humidity and temperature. Even small changes of environmental variables can trigger significant differences in the global outbreak behavior. Apart from the direct

  11. Magnetic resonance imaging of complex congenital heart disease in aduits; Magnetresonanztomographie komplexer kongenitaler Herzerkrankungen beim Erwachsenen

    Energy Technology Data Exchange (ETDEWEB)

    Bremerich, J. [San Francisco Univ, CA (United States). Dept. of Radiology]|[Universitaetsklinik Basel (Switzerland). Abt. fuer Medizinische Radiologie; Wyttenbach, R.; Higgins, C.B. [San Francisco Univ, CA (United States). Dept. of Radiology; Buser, P. [Universitaetsklinik Basel (Switzerland). Abt. fuer Kardiologie; Steinbrich, W. [Universitaetsklinik Basel (Switzerland). Abt. fuer Medizinische Radiologie

    1999-04-01

    An increasing number of patients with complex congenital heart disease reaches adulthood, because treatment and patient outcome have improved considerably in recent years. Monitoring of these patients requires both definition of cardiac anatomy and assessment of function with good reproducibility. Complications after surgical repair such as restenoses of pulmonary arteries after surgical repair of Tetralogy of Fallot, ventricular hypertrophy, stenoses or leakage of baffles, or stenosis and aneurysms of anastomoses have to be detected at an early stage. Magnetic Resonance Imaging (MRI) is an excellent tool to monitor these patients because of its noninvasive nature, its good interstudy and interobserver reproducibility, and because it allows assessment of both cardiac anatomy and function. This paper reviews the current applications of MRI in complex congenital heart disease in adults. (orig.) [Deutsch] Durch Verbesserungen in der Diagnose und Therapie komplexer kongenitaler Herzerkrankungen kann eine zunehmende Anzahl von betroffenen Patienten das Erwachsenenalter erreichen. Diese Patienten benoetigen regelmaessige postoperative Verlaufskontrollen, um Komplikationen wie z.B. Restenosen der grossen Arterien, Stenosen, Lecks und Aneurysmata von Anastomosen, Ventrikelhypertrophie und -dilatation oder Klappendysfunktionen fruehzeitig zu erkennen und zu behandeln. Fuer nichtinvasive regelmaessige Verlaufskontrollen bietet sich die Magnetresonanztomographie (MRT) des Herzens an, da sie eine umfassende Untersuchung sowohl der Morphologie als auch der Funktion des Herzens mit guter Reproduzierbarkeit erlaubt. Die gegenwaertigen klinischen Anwendungen der MRT bei komplexen kongenitalen Herzerkrankungen beim Erwachsenen werden in dieser Uebersicht beschrieben. (orig.)

  12. Transmission of sexually transmitted disease in complex network of the Penna model

    Science.gov (United States)

    Chen, Feng; Li, Chunguang

    2007-04-01

    The Penna model is a computational model which can encompass the inheritance, mutation, evolution and ageing phenomena of population successfully. Some researchers considered social interactions in an asexual Penna model, got a complex network and found some interesting properties. We consider a sexual Penna model to study the transmission of sexually transmitted diseases (STD). Our model can also generate a complex network and we observed some properties in real networks, such as small-world and assortative mixing. In the real world, the fatality of STD is changing with the advancing of medicine and it can affect our life. In this paper, we uncover the effect induced by the fatality of STD. We found that fatality plays an important role in the transmission of STD because whether the STD will disappear or continue to exist depends on the fatality of STD. Also, the fatality of STD can affect the evolution of inherited diseases and average life span. Some properties found in the model should be useful for the prevention and control of STD.

  13. Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease.

    Science.gov (United States)

    Zhou, Fusheng; Cao, Hongzhi; Zuo, Xianbo; Zhang, Tao; Zhang, Xiaoguang; Liu, Xiaomin; Xu, Ricong; Chen, Gang; Zhang, Yuanwei; Zheng, Xiaodong; Jin, Xin; Gao, Jinping; Mei, Junpu; Sheng, Yujun; Li, Qibin; Liang, Bo; Shen, Juan; Shen, Changbing; Jiang, Hui; Zhu, Caihong; Fan, Xing; Xu, Fengping; Yue, Min; Yin, Xianyong; Ye, Chen; Zhang, Cuicui; Liu, Xiao; Yu, Liang; Wu, Jinghua; Chen, Mengyun; Zhuang, Xuehan; Tang, Lili; Shao, Haojing; Wu, Longmao; Li, Jian; Xu, Yu; Zhang, Yijie; Zhao, Suli; Wang, Yu; Li, Ge; Xu, Hanshi; Zeng, Lei; Wang, Jianan; Bai, Mingzhou; Chen, Yanling; Chen, Wei; Kang, Tian; Wu, Yanyan; Xu, Xun; Zhu, Zhengwei; Cui, Yong; Wang, Zaixing; Yang, Chunjun; Wang, Peiguang; Xiang, Leihong; Chen, Xiang; Zhang, Anping; Gao, Xinghua; Zhang, Furen; Xu, Jinhua; Zheng, Min; Zheng, Jie; Zhang, Jianzhong; Yu, Xueqing; Li, Yingrui; Yang, Sen; Yang, Huanming; Wang, Jian; Liu, Jianjun; Hammarström, Lennart; Sun, Liangdan; Wang, Jun; Zhang, Xuejun

    2016-07-01

    The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

  14. Bromodomain Inhibitors Correct Bioenergetic Deficiency Caused by Mitochondrial Disease Complex I Mutations.

    Science.gov (United States)

    Barrow, Joeva J; Balsa, Eduardo; Verdeguer, Francisco; Tavares, Clint D J; Soustek, Meghan S; Hollingsworth, Louis R; Jedrychowski, Mark; Vogel, Rutger; Paulo, Joao A; Smeitink, Jan; Gygi, Steve P; Doench, John; Root, David E; Puigserver, Pere

    2016-10-06

    Mitochondrial diseases comprise a heterogeneous group of genetically inherited disorders that cause failures in energetic and metabolic function. Boosting residual oxidative phosphorylation (OXPHOS) activity can partially correct these failures. Herein, using a high-throughput chemical screen, we identified the bromodomain inhibitor I-BET 525762A as one of the top hits that increases COX5a protein levels in complex I (CI) mutant cybrid cells. In parallel, bromodomain-containing protein 4 (BRD4), a target of I-BET 525762A, was identified using a genome-wide CRISPR screen to search for genes whose loss of function rescues death of CI-impaired cybrids grown under conditions requiring OXPHOS activity for survival. We show that I-BET525762A or loss of BRD4 remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by mutations or chemical inhibition of CI. These studies show that BRD4 inhibition may have therapeutic implications for the treatment of mitochondrial diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Characterization of complexity in the electroencephalograph activity of Alzheimer's disease based on fuzzy entropy.

    Science.gov (United States)

    Cao, Yuzhen; Cai, Lihui; Wang, Jiang; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

    2015-08-01

    In this paper, experimental neurophysiologic recording and statistical analysis are combined to investigate the nonlinear characteristic and the cognitive function of the brain. Fuzzy approximate entropy and fuzzy sample entropy are applied to characterize the model-based simulated series and electroencephalograph (EEG) series of Alzheimer's disease (AD). The effectiveness and advantages of these two kinds of fuzzy entropy are first verified through the simulated EEG series generated by the alpha rhythm model, including stronger relative consistency and robustness. Furthermore, in order to detect the abnormality of irregularity and chaotic behavior in the AD brain, the complexity features based on these two fuzzy entropies are extracted in the delta, theta, alpha, and beta bands. It is demonstrated that, due to the introduction of fuzzy set theory, the fuzzy entropies could better distinguish EEG signals of AD from that of the normal than the approximate entropy and sample entropy. Moreover, the entropy values of AD are significantly decreased in the alpha band, particularly in the temporal brain region, such as electrode T3 and T4. In addition, fuzzy sample entropy could achieve higher group differences in different brain regions and higher average classification accuracy of 88.1% by support vector machine classifier. The obtained results prove that fuzzy sample entropy may be a powerful tool to characterize the complexity abnormalities of AD, which could be helpful in further understanding of the disease.

  16. Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases.

    Science.gov (United States)

    da Silva-Boghossian, Carina Maciel; do Souto, Renata Martins; Luiz, Ronir R; Colombo, Ana Paula Vieira

    2011-09-01

    Pathogens related to systemic infections have been detected in the periodontal microbiota. The relationship amongst these pathogens, periodontal bacteria and periodontal clinical status is poorly understood. This study evaluated the association amongst red complex, A. actinomycetemcomitans (A.a) and non-oral pathogenic bacteria in subjects with good periodontal health (PH), gingivitis (G), chronic (CP) and aggressive (AP) periodontitis. Subgingival biofilm samples were obtained from 51 PH, 42 G, 219 CP and 90 AP subjects. The presence and levels of A.a, red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola), Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by DNA probes and DNA-DNA hybridization technique. CP and AP subjects presented significantly higher prevalence and levels of A.a, red complex and A. baumannii than G and PH individuals (pperiodontal disease (pperiodontal pathogens and non-oral bacteria alone or in association were strongly associated with periodontitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. [The X+ chronic granulomatous disease as a fabulous model to study the NADPH oxidase complex activation].

    Science.gov (United States)

    Stasia, Marie-José

    2007-05-01

    Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack NADPH oxidase activity. Patients with CGD suffer from recurrent bacterial and fungal infections because of the absence of superoxide anions (O2- degrees ) generatingsystem. The NADPH oxidase complex is composed of a membranous cytochrome b558, cytosolic proteins p67phox, p47phox, p40phox and two small GTPases Rac2 and Rap1A. Cytochrome b558 consists of two sub-units gp91phox and p22phox. The most common form of CGD is due to mutations in CYBB gene encoding gp91phox. In some rare cases, the mutated gp91phox is normally expressed but is devoided of oxidase activity. These variants called X+ CGD, have provided interesting informations about oxidase activation mechanisms. However modelization of such variants is necessary to obtain enough biological material for studies at the molecular level. A cellular model (knock-out PLB-985 cells) has been developed for expressing recombinant mutated gp91phox for functional analysis of the oxidase complex. Recent works demonstrated that this cell line genetically deficient in gp91phox is a powerful tool for functional analysis of the NADPH oxidase complex activation.

  18. Health-related fitness profiles in adolescents with complex congenital heart disease.

    Science.gov (United States)

    Klausen, Susanne Hwiid; Wetterslev, Jørn; Søndergaard, Lars; Andersen, Lars L; Mikkelsen, Ulla Ramer; Dideriksen, Kasper; Zoffmann, Vibeke; Moons, Philip

    2015-04-01

    This study investigates whether subgroups of different health-related fitness (HrF) profiles exist among girls and boys with complex congenital heart disease (ConHD) and how these are associated with lifestyle behaviors. We measured the cardiorespiratory fitness, muscle strength, and body composition of 158 adolescents aged 13-16 years with previous surgery for a complex ConHD. Data on lifestyle behaviors were collected concomitantly between October 2010 and April 2013. A cluster analysis was conducted to identify profiles with similar HrF. For comparisons between clusters, multivariate analyses of covariance were used to test the differences in lifestyle behaviors. Three distinct profiles were formed: (1) Robust (43, 27%; 20 girls and 23 boys); (2) Moderately Robust (85, 54%; 37 girls and 48 boys); and (3) Less robust (30, 19%; 9 girls and 21 boys). The participants in the Robust clusters reported leading a physically active lifestyle and participants in the Less robust cluster reported leading a sedentary lifestyle. Diagnoses were evenly distributed between clusters. The cluster analysis attributed some of the variability in cardiorespiratory fitness among adolescents with complex ConHD to lifestyle behaviors and physical activity. Profiling of HrF offers a valuable new option in the management of person-centered health promotion. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  19. Decreased Complexity in Alzheimer's Disease: Resting-State fMRI Evidence of Brain Entropy Mapping

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2017-11-01

    Full Text Available Alzheimer's disease (AD is a frequently observed, irreversible brain function disorder among elderly individuals. Resting-state functional magnetic resonance imaging (rs-fMRI has been introduced as an alternative approach to assessing brain functional abnormalities in AD patients. However, alterations in the brain rs-fMRI signal complexities in mild cognitive impairment (MCI and AD patients remain unclear. Here, we described the novel application of permutation entropy (PE to investigate the abnormal complexity of rs-fMRI signals in MCI and AD patients. The rs-fMRI signals of 30 normal controls (NCs, 33 early MCI (EMCI, 32 late MCI (LMCI, and 29 AD patients were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI database. After preprocessing, whole-brain entropy maps of the four groups were extracted and subjected to Gaussian smoothing. We performed a one-way analysis of variance (ANOVA on the brain entropy maps of the four groups. The results after adjusting for age and sex differences together revealed that the patients with AD exhibited lower complexity than did the MCI and NC controls. We found five clusters that exhibited significant differences and were distributed primarily in the occipital, frontal, and temporal lobes. The average PE of the five clusters exhibited a decreasing trend from MCI to AD. The AD group exhibited the least complexity. Additionally, the average PE of the five clusters was significantly positively correlated with the Mini-Mental State Examination (MMSE scores and significantly negatively correlated with Functional Assessment Questionnaire (FAQ scores and global Clinical Dementia Rating (CDR scores in the patient groups. Significant correlations were also found between the PE and regional homogeneity (ReHo in the patient groups. These results indicated that declines in PE might be related to changes in regional functional homogeneity in AD. These findings suggested that complexity analyses using PE

  20. Congenital heart disease: interrelation between German diagnosis-related groups system and Aristotle complexity score.

    Science.gov (United States)

    Sinzobahamvya, Nicodème; Photiadis, Joachim; Arenz, Claudia; Kopp, Thorsten; Hraska, Viktor; Asfour, Boulos

    2010-06-01

    The Disease-Related Groups (DRGs) system postulates that inpatient stays with similar levels of clinical complexity are expected to consume similar amounts of resources. This, applied to surgery of congenital heart disease, suggests that the higher the complexity of procedures as estimated by the Aristotle complexity score, the higher hospital reimbursement should be. This study analyses how much case-mix index (CMI) generated by German DRG 2009 version correlates with Aristotle score. A total of 456 DRG cases of year 2008 were regrouped according to German DRG 2009 and related cost-weight values and overall CMI evaluated. Corresponding Aristotle basic and comprehensive complexity scores (ABC and ACC) and levels were determined. Associated surgical performance (Aristotle score times hospital survival) was estimated. Spearman 'r' correlation coefficients were calculated between Aristotle scores and cost-weights. Goodness of fit 'r(2)' from derived regression was determined. Correlation was estimated to be optimal if Spearman 'r' and derived goodness of fit 'r(2)' approached 1 value. CMI was 8.787 while mean ABC and ACC scores were 7.64 and 9.27, respectively. Hospital survival was 98.5%: therefore, surgical performance attained 7.53 (ABC score) and 9.13 (ACC score). ABC and ACC scores and levels positively correlated with cost-weights. With Spearman 'r' of 1 and goodness of fit 'r(2)' of 0.9790, scores of the six ACC levels correlated at best. The equation was y = 0.5591 + 0.939x, in which y stands for cost-weight (CMI) and x for score of ACC level. ACC score correlates almost perfectly with corresponding cost-weights (CMI) generated by the German DRG 2009. It could therefore be used as the basis for hospital reimbursement to compensate in conformity with procedures' complexity. Extrapolated CMI in this series would be 9.264. Modulation of reimbursement according to surgical performance could be established and thus 'reward' quality in congenital heart surgery

  1. Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1994-09-01

    Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

  2. [Children's medically complex diseases unit. A model required in all our hospitals].

    Science.gov (United States)

    Climent Alcalá, Francisco José; García Fernández de Villalta, Marta; Escosa García, Luis; Rodríguez Alonso, Aroa; Albajara Velasco, Luis Adolfo

    2018-01-01

    The increase in survival of children with severe diseases has led to the rise of children with chronic diseases, sometimes with lifelong disabilities. In 2008, a unit for the specific care of medically complex children (MCC) was created in Hospital La Paz. To describe the work and care activities of this Unit. Patients and methods An analysis was performed on all discharge reports of the Unit between January 2014 and July 2016. The MCC Unit has 6 beds and daily outpatient clinic. A total of 1,027 patients have been treated since the creation of the unit, with 243 from 2014. The median age was 24.2 months (IQ: 10.21-84.25). The large majority (92.59%) have multiple diseases, the most frequent chronic conditions observed were neurological (76.95%), gastrointestinal (63.78%), and respiratory diseases (61.72%). More than two-thirds (69.54%) of MCC are dependent on technology, 53.49% on respiratory support, and 35.80% on nutritional support. Hospital admission rates have increased annually. There have been 403 admissions since 2014, of which 8.93% were re-admissions within 30 days of hospital discharge. The median stay during 2014-2016 was 6 days (IQ: 3-14). The occupancy rate has been above 100% for this period. Currently, 210 patients remain on follow-up (86.42%), and 11 children (4.53%) were discharged to their referral hospitals. The mortality rate is 9.05% (22 deaths). The main condition of these 22 patients was neurological (9 patients). Infectious diseases were the leading cause of death. MCC should be treated in specialized units in tertiary or high-level hospitals. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Complex genetic architecture of cardiac disease in a wild type inbred strain of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Zhi Zhang

    Full Text Available Natural populations of the fruit fly, Drosophila melanogaster, segregate genetic variation that leads to cardiac disease phenotypes. One nearly isogenic line from a North Carolina peach orchard, WE70, is shown to harbor two genetically distinct heart phenotypes: elevated incidence of arrhythmias, and a dramatically constricted heart diameter in both diastole and systole, with resemblance to restrictive cardiomyopathy in humans. Assuming the source to be rare variants of large effect, we performed Bulked Segregant Analysis using genomic DNA hybridization to Affymetrix chips to detect single feature polymorphisms, but found that the mutant phenotypes are more likely to have a polygenic basis. Further mapping efforts revealed a complex architecture wherein the constricted cardiomyopathy phenotype was observed in individual whole chromosome substitution lines, implying that variants on both major autosomes are sufficient to produce the phenotype. A panel of 170 Recombinant Inbred Lines (RIL was generated, and a small subset of mutant lines selected, but these each complemented both whole chromosome substitutions, implying a non-additive (epistatic contribution to the "disease" phenotype. Low coverage whole genome sequencing was also used to attempt to map chromosomal regions contributing to both the cardiomyopathy and arrhythmia, but a polygenic architecture had to be again inferred to be most likely. These results show that an apparently simple rare phenotype can have a complex genetic basis that would be refractory to mapping by deep sequencing in pedigrees. We present this as a cautionary tale regarding assumptions related to attempts to map new disease mutations on the assumption that probands carry a single causal mutation.

  4. Susceptibility genes for lung diseases in the major histocompatibility complex revealed by lung expression quantitative trait loci analysis

    NARCIS (Netherlands)

    Lamontagne, Maxime; Joubert, Philippe; Timens, Wim; Postma, Dirkje S.; Hao, Ke; Nickle, David; Sin, Don D.; Pare, Peter D.; Laviolette, Michel; Bosse, Yohan

    The major histocompatibility complex (MHC) has been linked with hundreds of diseases [1]. The MHC is one of the most complex regions of the human genome, because of the high gene density, extended linkage disequilibrium (LD) and sequence diversity [2]. Recent genome-wide association studies (GWAS)

  5. Diagnosis of early sacroiliitis in seronegative spondyloarthropathies by DWI and correlation of clinical and laboratory findings with ADC values

    International Nuclear Information System (INIS)

    Gezmis, Esin; Donmez, Fuldem Y.; Agildere, Muhtesem

    2013-01-01

    Purpose: Sacroiliitis is one of the diagnostic criteria of seronegative SpA. The purpose of our study is to show the signal characteristics of the sacral and iliac surfaces by DWI which may contribute in early diagnosis of sacroiliitis and investigate the correlation between ADC values and clinical and laboratory parameters. Materials and methods: 62 patients with inflammatory low back pain, with a history or suspect of seronegative SpA are enrolled into the study. 40 age and sex-matched subjects without SpA constituted the control group. After obtaining routine T1 and T2 weighted sequences, echo planar imaging at b values of 0, 400 and 800 was performed. ADC values on both surfaces of the both sacroiliac joints were measured in all subjects. The CRP and sedimentation results and the presence of arthritis and enthesitis were also correlated with the ADC values. Results: ADC values on both surfaces of the both sacroiliac joints were found 0.23 × 10 −3 mm 2 /sn in the control group. In the patient group, mean ADC value of 0.48 × 10 −3 mm 2 /sn was obtained (p < 0.001), which was statistically significant, compatible with the increased diffusion due to medullary edema in early sacroiliitis. There was a slight correlation between CRP and ADC values; presumed to be showing the relation between the activity of the disease and the active inflammation on DWI. There was no correlation between arthritis and enthesitis and the ADC values (p > 0.001). Conclusion: DWI, by measuring ADC values, adds significant information in the early diagnosis of sacroiliitis and may help to evaluate the efficiency of the treatment

  6. Diagnosis of early sacroiliitis in seronegative spondyloarthropathies by DWI and correlation of clinical and laboratory findings with ADC values

    Energy Technology Data Exchange (ETDEWEB)

    Gezmis, Esin; Donmez, Fuldem Y., E-mail: fuldemyildirim@yahoo.com; Agildere, Muhtesem

    2013-12-01

    Purpose: Sacroiliitis is one of the diagnostic criteria of seronegative SpA. The purpose of our study is to show the signal characteristics of the sacral and iliac surfaces by DWI which may contribute in early diagnosis of sacroiliitis and investigate the correlation between ADC values and clinical and laboratory parameters. Materials and methods: 62 patients with inflammatory low back pain, with a history or suspect of seronegative SpA are enrolled into the study. 40 age and sex-matched subjects without SpA constituted the control group. After obtaining routine T1 and T2 weighted sequences, echo planar imaging at b values of 0, 400 and 800 was performed. ADC values on both surfaces of the both sacroiliac joints were measured in all subjects. The CRP and sedimentation results and the presence of arthritis and enthesitis were also correlated with the ADC values. Results: ADC values on both surfaces of the both sacroiliac joints were found 0.23 × 10{sup −3} mm{sup 2}/sn in the control group. In the patient group, mean ADC value of 0.48 × 10{sup −3} mm{sup 2}/sn was obtained (p < 0.001), which was statistically significant, compatible with the increased diffusion due to medullary edema in early sacroiliitis. There was a slight correlation between CRP and ADC values; presumed to be showing the relation between the activity of the disease and the active inflammation on DWI. There was no correlation between arthritis and enthesitis and the ADC values (p > 0.001). Conclusion: DWI, by measuring ADC values, adds significant information in the early diagnosis of sacroiliitis and may help to evaluate the efficiency of the treatment.

  7. Home-based interval training increases endurance capacity in adults with complex congenital heart disease.

    Science.gov (United States)

    Sandberg, Camilla; Hedström, Magnus; Wadell, Karin; Dellborg, Mikael; Ahnfelt, Anders; Zetterström, Anna-Klara; Öhrn, Amanda; Johansson, Bengt

    2017-12-04

    The beneficial effects of exercise training in acquired heart failure and coronary artery disease are well known and have been implemented in current treatment guidelines. Knowledge on appropriate exercise training regimes for adults with congenital heart disease is limited, thus further studies are needed. The aim of this study was to examine the effect of home-based interval exercise training on maximal endurance capacity and peak exercise capacity. Randomized controlled trial. Twenty-six adults with complex congenital heart disease were recruited from specialized units for adult congenital heart disease. Patients were randomized to either an intervention group-12 weeks of home-based interval exercise training on a cycle ergometer (n = 16), or a control group (n = 10). The latter was instructed to maintain their habitual physical activities. An incremental cardiopulmonary exercise test and a constant work rate cardiopulmonary exercise test at 75% of peak workload were performed preintervention and postintervention. Twenty-three patients completed the protocol and were followed (intervention n = 13, control n = 10). Postintervention exercise time at constant work rate cardiopulmonary exercise test increased in the intervention group compared to controls (median[range] 12[-4 to 52]min vs 0[-4 to 5]min, P = .001). At incremental cardiopulmonary exercise test, peak VO 2 increased 15% within the intervention group (P = .019) compared to 2% within the control group (P = .8). However, in comparison between the groups no difference was found (285[-200 to 535] ml/min vs 17[-380 to 306] ml/min, P = .10). In addition, peak workload at incremental cardiopulmonary exercise test increased in the intervention group compared to controls (20[-10 to 70]W vs 0[-20 to 15]W, P = .003). Home-based interval exercise training increased endurance capacity and peak exercise capacity in adults with complex congenital heart disease. Aerobic endurance

  8. Cellular immune responses to ESAT-6 discriminate between patients with pulmonary disease due to Mycobacterium avium complex and those with pulmonary disease due to Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Lein, A D; von Reyn, C F; Ravn, P

    1999-01-01

    ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of the Mycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-gamma) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary...... disease due to either Mycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-gamma responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0...

  9. Consequence of Mycobacterium avium complex pulmonary disease judging from the change of the chest CT image

    International Nuclear Information System (INIS)

    Fujiwara, Kiyohiro

    2008-01-01

    The long term consequence of the disease in Mycobacterium avium complex pulmonary disease (MACPD) is scarcely reported. This paper describes consequences of CT images and clinical symptoms in MACPD patients with rather poorer prognosis than usual during chemotherapy for one or more years in authors' hospital until May 2007. Subjects are 17 patients (average age 65.3 y, M 6/F 11) diagnosed as MACPD by the criteria by Jap. Soc. Tuberculosis (2003), whose follow up period is 14-105 (av. 58.1) months, and are classified in tuberculoid type (tt, 2 cases), bronchiectasis post surgery (2) and bronchia type (bt, 13, mostly primary MACPD). Chemotherapy is done with clarithromycin (CAM)+ethambutol (EB)+rifampicin (RHP) (+streptomycin (SM) for progression). Consequences of typical chest CT images are presented for each classification in this paper. Cavitation is seen even in bt as well as in tt and, if observed, the disease tends to deteriorate. In the secondary MACPD post surgery, the exacerbation of clinical symptom is often more severe despite slow changes in CT finding than in bt. Thus, careful follow up is necessary for the two cases above. (R.T.)

  10. Tissue Tropism in Host Transcriptional Response to Members of the Bovine Respiratory Disease Complex.

    Science.gov (United States)

    Behura, Susanta K; Tizioto, Polyana C; Kim, JaeWoo; Grupioni, Natalia V; Seabury, Christopher M; Schnabel, Robert D; Gershwin, Laurel J; Van Eenennaam, Alison L; Toaff-Rosenstein, Rachel; Neibergs, Holly L; Regitano, Luciana C A; Taylor, Jeremy F

    2017-12-20

    Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host's immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as 'key players' within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD.

  11. Neuronal complex I deficiency occurs throughout the Parkinson's disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage.

    Science.gov (United States)

    Flønes, Irene H; Fernandez-Vizarra, Erika; Lykouri, Maria; Brakedal, Brage; Skeie, Geir Olve; Miletic, Hrvoje; Lilleng, Peer K; Alves, Guido; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Dölle, Christian; Zeviani, Massimo; Tzoulis, Charalampos

    2018-03-01

    Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson's disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson's disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, Western blot and activity measurements, to assess complex I quantity and function in multiple brain regions from an extensively characterized population-based cohort of idiopathic Parkinson's disease (n = 18) and gender and age matched healthy controls (n = 11). Mitochondrial DNA was assessed in single neurons from the same areas by real-time PCR. Immunohistochemistry showed that neuronal complex I deficiency occurs throughout the Parkinson's disease brain, including areas spared by the neurodegenerative process such as the cerebellum. Activity measurements in brain homogenate confirmed a moderate decrease of complex I function, whereas Western blot was less sensitive, detecting only a mild reduction, which did not reach statistical significance at the group level. With the exception of the substantia nigra, neuronal complex I loss showed no correlation with the load of somatic mitochondrial DNA damage. Interestingly, α-synuclein aggregation was less common in complex I deficient neurons in the substantia nigra. We show that neuronal complex I deficiency is a widespread phenomenon in the Parkinson's disease brain which, contrary to mainstream theory, does not follow the anatomical distribution of neurodegeneration and is not associated with the neuronal load of mitochondrial DNA mutation. Our findings suggest that complex I deficiency in Parkinson's disease can

  12. The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases

    NARCIS (Netherlands)

    Heidema, A.G.; Boer, J.M.A.; Nagelkerke, N.; Mariman, E.C.M.; A, van der D.L.; Feskens, E.J.M.

    2006-01-01

    Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods

  13. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options.

    NARCIS (Netherlands)

    Nouws, J.; Nijtmans, L.G.J.; Smeitink, J.A.M.; Vogel, R.O.

    2012-01-01

    Complex I deficiency is the most frequent cause of oxidative phosphorylation disorders. The disease features a large diversity of clinical symptoms often leading to progressive encephalomyopathies with a fatal outcome. There is currently no cure, and although disease-causing mutations have been

  14. Limited value of transbronchial lung biopsy for diagnosing Mycobacterium avium complex lung disease.

    Science.gov (United States)

    Sekine, Akimasa; Saito, Takefumi; Satoh, Hiroaki; Morishita, Yukio; Tsunoda, Yoshiya; Tanaka, Toru; Yatagai, Yohei; Lin, Shih-Yuen; Miyazaki, Kunihiko; Miura, Yukiko; Hayashihara, Kenji

    2017-11-01

    It remains unclear whether transbronchial lung biopsy (TBLB) is useful for diagnosing Mycobacterium avium complex (MAC) lung disease. Thirty-eight consecutive patients with MAC lung disease, who were evaluated with TBLB tissue culture between June 2006 and May 2010, were included. Bronchial washing (BW) and histopathological evaluation were performed in all patients. The positivity rates of BW and TBLB tissue culture, and typical histopathological findings for MAC disease were investigated. Furthermore, all patients were divided into two groups according to the presence of intrabronchial purulent or mucopurulent secretion and the clinical, bacteriological and pathological characteristics were compared between the two groups. The positive culture rates of BW and TBLB specimens for MAC were 100% (38 patients) and 28.9% (11 patients). BW materials were much more sensitive for culture positivity than TBLB specimens (P present in the TBLB specimens of only 11 patients (28.9%). Intrabronchial secretion was identified in 15 patients (39.5%, secretion-positive group) and absent in 23 patients (60.5%, secretion-negative group). Typical histopathological findings for MAC disease were more common in the secretion-positive group than in the secretion-negative group (53.3% vs 13.0%, P = 0.01), although the radiological classification and smear positivity of BW were not different between the two groups. TBLB for pathological and bacterial investigations would provide only a limited value for MAC diagnosis. Moreover, the presence of intrabronchial secretion may be an important manifestation of ongoing airway damage, which would require early treatment. © 2016 John Wiley & Sons Ltd.

  15. Modeling infectious disease dynamics in the complex landscape of global health

    Science.gov (United States)

    Heesterbeek, Hans; Anderson, Roy; Andreasen, Viggo; Bansal, Shweta; De Angelis, Daniela; Dye, Chris; Eames, Ken; Edmunds, John; Frost, Simon; Funk, Sebastian; Hollingsworth, Deirdre; House, Thomas; Isham, Valerie; Klepac, Petra; Lessler, Justin; Lloyd-Smith, James; Metcalf, Jessica; Mollison, Denis; Pellis, Lorenzo; Pulliam, Juliet; Roberts, Mick; Viboud, Cecile

    2015-01-01

    Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational and spatial scales, which even within a single pathogen often span hours to months, cellular to ecosystem levels, and local to pandemic spread. Some pathogens are directly transmitted between individuals of a single species, while others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity, and dynamic human behavior, raise prevention and control from formerly national to international issues. In the face of this complexity, mathematical models offer essential tools for synthesizing information to understand epidemiological patterns, and for developing the quantitative evidence base for decision-making in global health. PMID:25766240

  16. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

    Directory of Open Access Journals (Sweden)

    Laurel J Gershwin

    Full Text Available Bovine respiratory disease complex (BRDC is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus, which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

  17. Global Dynamics of Infectious Disease with Arbitrary Distributed Infectious Period on Complex Networks

    Directory of Open Access Journals (Sweden)

    Xiaoguang Zhang

    2014-01-01

    Full Text Available Most of the current epidemic models assume that the infectious period follows an exponential distribution. However, due to individual heterogeneity and epidemic diversity, these models fail to describe the distribution of infectious periods precisely. We establish a SIS epidemic model with multistaged progression of infectious periods on complex networks, which can be used to characterize arbitrary distributions of infectious periods of the individuals. By using mathematical analysis, the basic reproduction number R0 for the model is derived. We verify that the R0 depends on the average distributions of infection periods for different types of infective individuals, which extend the general theory obtained from the single infectious period epidemic models. It is proved that if R0<1, then the disease-free equilibrium is globally asymptotically stable; otherwise the unique endemic equilibrium exists such that it is globally asymptotically attractive. Finally numerical simulations hold for the validity of our theoretical results is given.

  18. Genetics of graft-versus-host disease: the major histocompatibility complex.

    Science.gov (United States)

    Petersdorf, Effie W

    2013-01-01

    Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic cell transplantation. Many genes are presumed to be involved in GVHD, but the best characterized genetic system is that of the human major histocompatibility complex (MHC) located on chromosome 6. Among the hundreds of genes located within the MHC region, the best known and characterized are the classical HLA genes, HLA-A, C, B, DRB1, DQB1, and DPB1. They play a fundamental role in T cell immune responses, and HLA-A, C, and B also function as ligands for the natural killer cell immunoglobulin-like receptors involved in innate immunity. This review highlights the state-of-the art in the field of histocompatibility and immunogenetics of the MHC with respect to genetic risk factors for GVHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. The major histocompatibility complex: a model for understanding graft-versus-host disease.

    Science.gov (United States)

    Petersdorf, Effie W

    2013-09-12

    Acute graft-versus-host disease (GVHD) afflicts as much as 80% of all patients who receive an unrelated donor hematopoietic cell transplant (HCT) for the treatment of blood disorders, even with optimal donor HLA matching and use of prophylactic immunosuppressive agents. Of patients who develop acute GVHD, many are at risk for chronic GVHD and bear the burden of considerable morbidity and lowered quality of life years after transplantation. The immunogenetic basis of GVHD has been the subject of intensive investigation, with the classic HLA genetic loci being the best-characterized determinants. Recent information on the major histocompatibility complex (MHC) region of chromosome 6 as an important source of untyped genetic variation has shed light on novel GVHD determinants. These data open new paradigms for understanding the genetic basis of GVHD.

  20. Evolution in health and medicine Sackler colloquium: Consanguinity, human evolution, and complex diseases.

    Science.gov (United States)

    Bittles, A H; Black, M L

    2010-01-26

    There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F >or= 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is approximately 3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates.

  1. From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

    Directory of Open Access Journals (Sweden)

    Knox Sarah S

    2010-04-01

    Full Text Available Abstract Background Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. Hypothesis The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. Conclusion Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression.

  2. Social ecosystem health: confronting the complexity and emergence of infectious diseases

    Directory of Open Access Journals (Sweden)

    Cristina de Albuquerque Possas

    2001-02-01

    Full Text Available The emergence and re-emergence of infectious diseases and their rapid dissemination worldwide are challenging national health systems, particularly in developing countries affected by extreme poverty and environmental degradation. The expectations that new vaccines and drugs and global surveillance would help reverse these trends have been frustrated thus far by the complexity of the epidemiological transition, despite promising prospects for the near future in biomolecular research and genetic engineering. This impasse raises crucial issues concerning conceptual frameworks supporting priority-setting, risk anticipation, and the transfer of science and technology's results to society. This article discusses these issues and the limitations of social and economic sciences on the one hand and ecology on the other as the main theoretical references of the health sciences in confronting the complexity of these issues on their own. The tension between these historically dissociated paradigms is discussed and a transdisciplinary approach is proposed, that of social ecosystem health, incorporating these distinct perspectives into a comprehensive framework.

  3. Synonymous codon usage of genes in polymerase complex of Newcastle disease virus.

    Science.gov (United States)

    Kumar, Chandra Shekhar; Kumar, Sachin

    2017-06-01

    Newcastle disease virus (NDV) is pathogenic to both avian and non-avian species but extensively finds poultry as its primary host and causes heavy economic losses in the poultry industry. In this study, a total of 186 polymerase complex comprising of nucleoprotein (N), phosphoprotein (P), and large polymerase (L) genes of NDV was analyzed for synonymous codon usage. The relative synonymous codon usage and effective number of codons (ENC) values were used to estimate codon usage variation in each gene. Correspondence analysis (COA) was used to study the major trend in codon usage variation. Analyzing the ENC plot values against GC3s (at synonymous third codon position) we concluded that mutational pressure was the main factor determining codon usage bias than translational selection in NDV N, P, and L genes. Moreover, correlation analysis indicated, that aromaticity of N, P, and L genes also influenced the codon usage variation. The varied distribution of pathotypes for N, P, and L gene clearly suggests that change in codon usage for NDV is pathotype specific. The codon usage preference similarity in N, P, and L gene might be detrimental for polymerase complex functioning. The study represents a comprehensive analysis to date of N, P, and L genes codon usage pattern of NDV and provides a basic understanding of the mechanisms for codon usage bias. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Segregation analysis suggests that keratoconus is a complex non-mendelian disease.

    Science.gov (United States)

    Kriszt, Agnes; Losonczy, Gergely; Berta, András; Vereb, György; Takács, Lili

    2014-11-01

    Complex segregation analysis of 60 unrelated sporadic keratoconus (KC) families was performed to reveal the presumed mode of inheritance in our dataset. Sixty probands, 212 family members and 212 age and gender matched healthy controls underwent clinical and videokeratographic examination. Family aggregation and distribution of videokeratography parameters were examined. Segregation of KSI, KISA and 6mm Fourier asymmetry alone or in covariate analysis with gender or the presence of Fleischer ring, exploring mendelian and non-mendelian models of inheritance was tested using complex segregation analysis with the S.A.G.E. program package. In 145 relatives of probands, the estimated prevalence of manifest KC was 7.6% (95% CI: 3.3-11.9) based on KISA index, indicating strong familial aggregation. All examined videokeratography indices were able to differentiate between KC and non-KC family members as well as normal controls (anova p 0.1) for all indices indicated the presence of a non-mendelian major gene effect (MG). Inclusion of Fleischer ring as covariate improved the fit of MG models. Mendelian, Sporadic and polygenic models were consistently rejected. Complex segregation analysis indicates a strong genetic contribution to the transmission of keratoconus. Inheritance is most probably due to a non-mendelian major gene effect. Low genotype-phenotype correlation in sporadic KC families can make linkage studies difficult, thus genome wide association studies, epigenetic and pathway analyses may provide more information on disease pathogenesis in non-familial keratoconus. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Towards structural systems pharmacology to study complex diseases and personalized medicine.

    Directory of Open Access Journals (Sweden)

    Lei Xie

    2014-05-01

    Full Text Available Genome-Wide Association Studies (GWAS, whole genome sequencing, and high-throughput omics techniques have generated vast amounts of genotypic and molecular phenotypic data. However, these data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery, which continues along a one-drug-one-target-one-disease paradigm. As a partial consequence, both the cost to launch a new drug and the attrition rate are increasing. Systems pharmacology and pharmacogenomics are emerging to exploit the available data and potentially reverse this trend, but, as we argue here, more is needed. To understand the impact of genetic, epigenetic, and environmental factors on drug action, we must study the structural energetics and dynamics of molecular interactions in the context of the whole human genome and interactome. Such an approach requires an integrative modeling framework for drug action that leverages advances in data-driven statistical modeling and mechanism-based multiscale modeling and transforms heterogeneous data from GWAS, high-throughput sequencing, structural genomics, functional genomics, and chemical genomics into unified knowledge. This is not a small task, but, as reviewed here, progress is being made towards the final goal of personalized medicines for the treatment of complex diseases.

  6. Osteomeatal complex obstruction is not associated with adjacent sinus disease in chronic rhinosinusitis with polyps.

    Science.gov (United States)

    Leung, Randy M; Kern, Robert C; Conley, David B; Tan, Bruce K; Chandra, Rakesh K

    2011-01-01

    It is universally accepted that osteomeatal complex (OMC) disease is linked to the subsequent development of chronic rhinosinusitis without nasal polyps (CRSsNPs) via postobstructive mechanisms. The role of OMC obstruction in the pathogenesis of CRSwNPs is less clear. This study was designed to identify if there is an association between OMC obstruction and inflammation of the adjacent sinuses, when patients are stratified by polyp status. This is a follow-up and expanded series of a previous pilot study from our group. CT scans of 144 patients with CRSsNPs and 123 patients with CRS with nasal polyps (CRSwNPs) were evaluated for each sinus and OMC. Patients had no previous surgeries for NPs. CT scans were obtained after a trial of maximal medical therapy. Increasing OMC involvement was associated with increasing Lund-Mackay score for both CRSsNPs and CRSwNPs. In CRSsNP patients, OMC status significantly correlated with adjacent sinus status (p OMC status does not correlate with adjacent sinus status (p = 0.328). OMC obstruction in the setting of CRSwNP may be a barometer of the overall disease process, but in this scenario, paranasal sinus inflammation can not be classified as a postobstructive phenomenon. These findings question the role of minimally invasive procedures in the management of CRSwNPs.

  7. The synergy factor: a statistic to measure interactions in complex diseases

    Directory of Open Access Journals (Sweden)

    Combarros Onofre

    2009-06-01

    Full Text Available Abstract Background One challenge in understanding complex diseases lies in revealing the interactions between susceptibility factors, such as genetic polymorphisms and environmental exposures. There is thus a need to examine such interactions explicitly. A corollary is the need for an accessible method of measuring both the size and the significance of interactions, which can be used by non-statisticians and with summarised, e.g. published data. The lack of such a readily available method has contributed to confusion in the field. Findings The synergy factor (SF allows assessment of binary interactions in case-control studies. In this paper we describe its properties and its novel characteristics, e.g. in calculating the power to detect a synergistic effect and in its application to meta-analyses. We illustrate these functions with real examples in Alzheimer's disease, e.g. a meta-analysis of the potential interaction between a BACE1 polymorphism and APOE4: SF = 2.5, 95% confidence interval: 1.5–4.2; p = 0.0001. Conclusion Synergy factors are easy to use and clear to interpret. Calculations may be performed through the Excel programmes provided within this article. Unlike logistic regression analysis, the method can be applied to datasets of any size, however small. It can be applied to primary or summarised data, e.g. published data. It can be used with any type of susceptibility factor, provided the data are dichotomised. Novel features include power estimation and meta-analysis.

  8. Passive Immunotherapy for Retroviral Disease: Influence of Major Histocompatibility Complex Type and T-Cell Responsiveness

    Science.gov (United States)

    Hasenkrug, Kim J.; Brooks, Diane M.; Chesebro, Bruce

    1995-11-01

    Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibody-mediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4^+ and CD8^+ T lymphocytes. Thus, cell-mediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed.

  9. Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

    Directory of Open Access Journals (Sweden)

    Chris Wallace

    2015-06-01

    Full Text Available Identification of candidate causal variants in regions associated with risk of common diseases is complicated by linkage disequilibrium (LD and multiple association signals. Nonetheless, accurate maps of these variants are needed, both to fully exploit detailed cell specific chromatin annotation data to highlight disease causal mechanisms and cells, and for design of the functional studies that will ultimately be required to confirm causal mechanisms. We adapted a Bayesian evolutionary stochastic search algorithm to the fine mapping problem, and demonstrated its improved performance over conventional stepwise and regularised regression through simulation studies. We then applied it to fine map the established multiple sclerosis (MS and type 1 diabetes (T1D associations in the IL-2RA (CD25 gene region. For T1D, both stepwise and stochastic search approaches identified four T1D association signals, with the major effect tagged by the single nucleotide polymorphism, rs12722496. In contrast, for MS, the stochastic search found two distinct competing models: a single candidate causal variant, tagged by rs2104286 and reported previously using stepwise analysis; and a more complex model with two association signals, one of which was tagged by the major T1D associated rs12722496 and the other by rs56382813. There is low to moderate LD between rs2104286 and both rs12722496 and rs56382813 (r2 ≃ 0:3 and our two SNP model could not be recovered through a forward stepwise search after conditioning on rs2104286. Both signals in the two variant model for MS affect CD25 expression on distinct subpopulations of CD4+ T cells, which are key cells in the autoimmune process. The results support a shared causal variant for T1D and MS. Our study illustrates the benefit of using a purposely designed model search strategy for fine mapping and the advantage of combining disease and protein expression data.

  10. Integrating genome-wide association study summaries and element-gene interaction datasets identified multiple associations between elements and complex diseases.

    Science.gov (United States)

    He, Awen; Wang, Wenyu; Prakash, N Tejo; Tinkov, Alexey A; Skalny, Anatoly V; Wen, Yan; Hao, Jingcan; Guo, Xiong; Zhang, Feng

    2018-03-01

    Chemical elements are closely related to human health. Extensive genomic profile data of complex diseases offer us a good opportunity to systemically investigate the relationships between elements and complex diseases/traits. In this study, we applied gene set enrichment analysis (GSEA) approach to detect the associations between elements and complex diseases/traits though integrating element-gene interaction datasets and genome-wide association study (GWAS) data of complex diseases/traits. To illustrate the performance of GSEA, the element-gene interaction datasets of 24 elements were extracted from the comparative toxicogenomics database (CTD). GWAS summary datasets of 24 complex diseases or traits were downloaded from the dbGaP or GEFOS websites. We observed significant associations between 7 elements and 13 complex diseases or traits (all false discovery rate (FDR) elements and complex diseases. © 2017 WILEY PERIODICALS, INC.

  11. Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in Voltage-Gated Potassium Channel-Complex Antibodies Encephalitis: A Case Report.

    Science.gov (United States)

    Savard, Martin; Irani, Sarosh R; Guillemette, Annie; Gosselin-Lefebvre, Stéphanie; Geschwind, Michael; Jansen, Gerard H; Gould, Peter V; Laforce, Robert

    2016-02-01

    Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis. A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased. This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease.

  12. The effect of the physical activity on polymorphic premature ventricular complexes in chronic kidney disease

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    Márcio G. Kiuchi

    2017-06-01

    Full Text Available Background: Polymorphic premature ventricular complexes (PVCs are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Endurance exercise training clearly lowers sympathetic activity in sympatho-excitatory disease states and may be tolerated by patients with chronic kidney disease (CKD. Methods: We assessed 40 CKD patients with hypertension with polymorphic PVCs. Patients underwent a complete medical history and physical examination. We evaluated the effectiveness of β blocker only or β blocker + exercise during 12 months of follow-up regarding the changes of the numbers of PVCs and mean heart rate (HR by 24-hour-Holter. Results: We observed in the β blocker group a significant decrease in the number of polymorphic PVCs from baseline 36,515 ± 3,518 to 3, 6, 9 and 12 months of follow-up, 28,314 ± 2,938, 23,709 ± 1,846, 22,564 ± 1,673, and 22,725 ± 1,415, respectively (P < 0.001. In the β blocker + exercise group a significant decrease in the number of polymorphic PVCs also occurred from baseline 36,091 ± 3,327 to 3, 6, 9 and 12 months of follow-up, 29,252 ± 3,211, 20,948 ± 2,386, 14,238 ± 3,338, and 6,225 ± 2,319, respectively (P < 0.001. Comparisons between the two groups at the same time point showed differences from the sixth month onwards: the 6th (Δ = −2,761, P = 0.045, 9th (Δ = −8,325, P < 0.001 and 12th (Δ = −16,500, P < 0.001 months. There was an improvement during the 12 months of follow-up vs. baseline, after the β blocker or β blocker + exercise in mean 24-hour HR Holter monitoring, creatinine values, eGFR, and ACR. Conclusion: Polymorphic PVCs may be modifiable by physical activity in CKD patients with hypertension without structural heart disease.

  13. HYBRID TREATMENT OF COMPLEX COMBINED CORONARY AND VALVE DISEASE FOR PATIENTS WITH HIGH LEVEL OF OPERATIONAL RISK

    Directory of Open Access Journals (Sweden)

    G. V. Aniskevich

    2011-01-01

    Full Text Available The analysis of results of hybrid treatment of complex combined coronary and valve disease at patients with high level of operational risk between January 2005 and December 2010. The hybrid treatment of complex combined coronary and valve disease, provides performance of percutaneous coronary interventions (PCI in a combinati- on valve surgery. 118 patients, with a median age 64.4 ± 8.9 years, are included in research. 2 approaches of a hy- brid method of treatment – 2-Staged (n = 86 and a method «1-stop» (n = 32 are applied. The оperative mortality has made 4.2%. On the basis of the received results were the conclusion is drawn that at high-risk patients with complex combined coronary and valve disease the hybrid method of treatment allows to lower risk of operation. 

  14. Management of chronic obstructive pulmonary disease exacerbations at the Nasser Medical Complex: a clinical audit.

    Science.gov (United States)

    Al-Faqawi, Maha; Abuowda, Yousef; Elmassry, Alaa Eldeen; Böttcher, Bettina

    2018-02-21

    The frequency and severity of chronic obstructive pulmonary disease (COPD) exacerbations are the most important determinants of prognosis in COPD. The aim of this study was to assess the management of patients presenting with COPD exacerbations at the Nasser Medical Complex in the Gaza Strip and to compare the management with the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD 2015). We reviewed the medical records of all patients admitted to Nasser Medical Complex and diagnosed with COPD exacerbation between Jan 1, 2014, and Dec 31, 2016. Clinical practice was compared with GOLD guidelines. Ethical approval was obtained from the General Directorate of Human Resources. 55 patient records were reviewed. The mean age was 66·4 years (SD 8·5), and 54 (98%) patients were male. All patients received inhaled bronchodilators. 36 (65%) patients received short-acting β agonists (SABA), 43 (78%) received short-acting muscarinic agonists (SAMA), 13 (24%) received long-acting muscarinic agonists (LAMA), one (2%) received long-acting beta-agonists (LABA), and 22 (40%) received both SABA and SAMA. 53 (96%) patients received systemic corticosteroids. 43 (78%) patients took more than the recommended 40 mg prednisolone daily. Only 12 (22%) patients received prednisolone as the recommended 5 day treatment course, whereas most patients received a shorter course. Other treatments included oxygen (51 [93%] patients), antibiotics (55 [100%]), antiviral medication (three [6%]), and theophylline (two [4%]). Overall adherence to guidelines was moderately good. All patients received antibiotics, and most patients received oxygen, which are both recommended for all patients. Less useful therapies were rarely prescribed. However, more patients received SAMA than SABA, although SABA is more effective and therefore the first-line treatment for COPD exacerbation. The dose of the most prescribed drug (prednisolone) exceeded the recommended dose. Generally, awareness and

  15. THE POLYPEPTIDE STIMULATOR APPLICATION IN COMPLEX TREATMENT OF COGNITIVE DISORDERS IN CHILDREN WITH DISEASES OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    S. A. Nemkova

    2012-01-01

    Full Text Available The results of the review of studies on the polypeptide nootropic neurometabolic stimulator in a complex correction of cognitive impairment in children with diseases of the central nervous system are given in the article. It is shown that cognitive-modulating effect is the leading feature of the drug, and in a combination with nootropic, neurotrophic, neuroprotective, reparative and anticonvulsive effects, as well as antioxidant, anti-stress and metabolic actions, which determines its high therapeutic efficacy in a complex correction of cognitive impairment in various central nervous system diseases in children.

  16. The 'sialo-microbial-dental complex' in oral health and disease.

    Science.gov (United States)

    Kaidonis, John; Townsend, Grant

    2016-01-01

    Biofilms are naturally found in all wet environments including the oral structures of nearly all species. Human oral biofilms have existed since our earliest ancestors and have evolved symbiotically with the dentition over many millennia within a Palaeolithic, hunter-gatherer setting. Irrespective of the plant-animal ratio, it can be argued that the Palaeolithic diet was essentially acidic, and acted as a selective force for much of the evolution of the stomatognathic system. The relationship between saliva, biofilm and teeth, the 'sialo-microbial-dental complex', provides oral health benefits and offers a different perspective to the old dental paradigm that only associated oral biofilms (plaque) with disease (caries). This new paradigm emphasises that oral biofilms are essential for the 'mineral maintenance' of teeth. Oral biofilms provide physical protection from dietary acid and together with bacterial metabolic acids cause the resting pH of the biofilm to fall below neutral. This is then followed by the re-establishment of a neutral environment by chemical interactions mediated by the saliva within the biofilm. Such pH fluctuations are often responsible for the cyclic demineralisation, then remineralisation of teeth, a process necessary for tooth maturation. However, since the advent of farming and especially since the industrial revolution, the increase in consumption of carbohydrates, refined sugars and acidic drinks has changed the ecology of biofilms. Biofilm biodiversity is significantly reduced together with a proliferation of acidogenic and aciduric organisms, tipping the balance of the 'demin-remin' cycle towards net mineral loss and hence caries. In addition, the consumption of acidic drinks in today's societies has removed the protective nature of the biofilm, leading to erosion. Erosion and caries are 'modern-day' diseases and reflect an imbalance within the oral biofilm resulting in the demineralisation of teeth. Copyright © 2015 The Authors

  17. Single ventricle, bicuspid aorta and interatrial wall aneurysm as a rare complex adult congenital heart disease: a case report

    OpenAIRE

    Berisha, Blerim; Krasniqi, Xhevdet; Thaqi, Agim; Gashi, Masar; Ko?inaj, Dardan

    2009-01-01

    Background Single ventricle, bicuspid aortic valve and interatrial wall aneurysm in adulthood are a rare and unique case in medical literature. This presented case with congenital heart disease has never been treated surgically and clinical consequences seriously presented in adulthood. Case presentation A 27 year old man with complex congenital heart disease presented. At the age of six, the single ventricle was ultrasonographly diagnosed, but at age 27 clinical consequences started to be se...

  18. [Case management and complex chronic diseases: concepts, models, evidence and uncertainties].

    Science.gov (United States)

    Morales-Asencio, José Miguel

    2014-01-01

    Chronic diseases are the greatest challenge for Health Care, but the conventional health care models have failed noticeably. Nurses are one of the main providers of the services developed to tackle this challenge, with special emphasis on case management, as one of the most common forms. But, one of the key problems is that case management is poorly conceptualized, and with the diversity of experience available, make its development and comparative evaluation difficult. An in-depth review on case management definition and concepts is presented in this article, with a description of the models, ingredients and the effectiveness reported in various studies. The remaining uncertainties in case management, such as the heterogeneity of designs and target populations, the weak description of the components, and the scarce use of research models for complex interventions, are also discussed. Finally, some key factors for a successful implementation of case management are detailed, such as a clear definition of accountability and roles, the existence of support to guarantee the competence of case managers, the use of valid mechanisms for case finding, adjusted caseload, accessible and team-shared record systems, or the integration of health and social services. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  19. The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease.

    Science.gov (United States)

    Traish, Abdulmaged M; Zitzmann, Michael

    2015-09-01

    Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle, which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributiong to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. In this review, we discuss the relationship between TD and obesity and highlight the contemporary advancement in management of obesity with pharmacological and surgical approaches, as well as utilization of T therapy and how this intervention may evolve as a novel approach to treatment of obesity in men with TD .

  20. Genetic architecture of the F7 gene in a Spanish population: implication for mapping complex diseases and for functional assays.

    Science.gov (United States)

    Sabater-Lleal, M; Almasy, L; Martínez-Marchán, E; Martínez-Sánchez, E; Souto, R; Blangero, J; Souto, Jc; Fontcuberta, J; Soria, J M

    2006-05-01

    Delineating the genetic variability of loci coding for complex diseases helps to understand the individual variation in disease susceptibility and drug response. We present the allelic architecture of the F7 gene. This gene is the major determinant of FVII plasma levels, and these plasma levels constitute an important intermediate risk factor for cardiovascular disease. As part of the Genetic Analysis of Idiopathic Thrombophila Project, we completely re-sequenced the F7 locus (promoter, exons, introns, and 3'-untranslated region) in 40 unrelated individuals. We found 49 polymorphisms with only two amino acid changes suggesting that regulatory non-coding and intronic variants are responsible for the FVII variability. These results are important for mapping susceptibility alleles of complex diseases, because differences in pair-wise linkage disequilibrium patterns between DNA variants and haplotype frequency distributions may help to detect disease-associated alleles. In addition, we present the results of an in silico search that established genomic comparisons among different species. In conclusion, our study of the F7 DNA sequence variations is an example of a strategy for analyzing the genetic architecture of a quantitative trait locus. Furthermore, it provides a model for future analyses of genetic factors that contribute to the susceptibility of complex diseases in humans.

  1. Plasma levels of nucleosomes and nucleosome-autoantibody complexes in murine lupus: effects of disease progression and lipopolyssacharide administration.

    NARCIS (Netherlands)

    Licht, R.; Bruggen, M.C.J. van; Oppers-Walgreen, B.; Rijke, T.P.M.; Berden, J.H.M.

    2001-01-01

    OBJECTIVE: To evaluate the effect of disease progression and lipopolysaccharide (LPS) administration on the presence of nucleosomes, antinucleosome reactivity, and nucleosome-Ig complexes in the circulation of MRL and control mice. METHODS: Plasma samples from lupus-prone (MRL/lpr and MRL/+) and

  2. Local immune-complexes and inflammatory response in patients with chronic interstitial pulmonary disorders associated with collagen vascular diseases

    NARCIS (Netherlands)

    Jansen, H. M.; Schutte, A. J. H.; Elema, J. D.; van der Giessen, M.; Reig, R. P.; van Leeuwen, M. A.; Sluiter, H. J.; The, T. Hauw

    Evidence is accumulating that the lung injury in collagen vascular diseases (CVD) is triggered by immune complexes (IC). These reactions are neutrophil- and complement-dependent. The direct, in vivo phagocytosis of IC by bronchoalveolar lavage polymorphonuclear leucocytes (BAL-PMN), was studied in

  3. Health related quality of life and health status in adult survivors with previously operated complex congenital heart disease

    NARCIS (Netherlands)

    Kamphuis, M.; Ottenkamp, J.; Vliegen, H. W.; Vogels, T.; Zwinderman, K. H.; Kamphuis, R. P.; Verloove-Vanhorick, S. P.

    2002-01-01

    To examine the impact of previously operated complex congenital heart disease on health related quality of life and subjective health status and to determine the relation between these parameters and physical status. Cross sectional; information on medical follow up was sought retrospectively.

  4. Mutation of C20orf7 Disrupts Complex I Assembly and Causes Lethal Neonatal Mitochondrial Disease

    NARCIS (Netherlands)

    Sugiana, Canny; Pagliarini, David J.; McKenzie, Matthew; Kirby, Denise M.; Salemi, Renato; Abu-Amero, Khaled K.; Dahl, Hans-Henrik M.; Hutchison, Wendy M.; Vascotto, Katherine A.; Smith, Stacey M.; Newbold, Robert F.; Christodoulou, John; Calvo, Sarah; Mootha, Vamsi K.; Ryan, Michael T.; Thorburn, David R.

    2008-01-01

    Complex I (NADH:ubiquinone oxidoreductase) is the first and largest multimeric complex of the mitochondrial respiratory chain. Human complex I comprises seven Subunits encoded by mitochondrial DNA and 38 nuclear-encoded subunits that are assembled together in a process that is only partially

  5. The human RNase MRP complex : composition, assembly and role in human disease

    NARCIS (Netherlands)

    Eenennaam, Hans van

    2002-01-01

    Not all RNA molecules in human cells are being translated into proteins. Some of them function in binding proteins, thereby forming so-called RNA-protein complexes. The RNase MRP complex is an example of such an RNA-protein complex. In this thesis two new protein components of the human RNase MRP

  6. Evaluation of the Aristotle complexity models in adult patients with congenital heart disease.

    Science.gov (United States)

    Hörer, Jürgen; Vogt, Manfred; Wottke, Michael; Cleuziou, Julie; Kasnar-Samprec, Jelena; Lange, Rüdiger; Schreiber, Christian

    2013-01-01

    The adult congenital heart disease (CHD) population has surpassed the paediatric CHD population. Half of all mortality caused by CHD occurs in adulthood; in some patients, it occurs during surgery. We sought to assess the potential risk factors for adverse outcome after cardiac operations in adults with CHD, and to evaluate the predictive power of the Aristotle score models for hospital mortality. Procedure-dependent and independent factors, as well as the outcome factors of all consecutive patients aged 16 or more who underwent surgery for CHD between 2005 and 2008 at our institution were evaluated according to the European Association for Cardio-Thoracic Surgery Congenital Database nomenclature. An Aristotle basic complexity (ABC) and an Aristotle comprehensive complexity (ACC) score were assigned to each operation. The discriminatory power of the scores was assessed using the area under the receiver operating characteristics (AuROC) curve. During 542 operations, 773 procedures were performed. The early mortality rate was 2.4%, and the early complication rate was 53.7%. Tricuspid valve replacement (P = 0.009), mitral valve replacement (P < 0.001), elevated lung resistances (P = 0.002), hypothyroidism (P = 0.002) and redosternotomy (P = 0.003) emerged as risk factors for 30-day mortality. Tricuspid valve replacement (P < 0.001), tricuspid valvuloplasty (P = 0.006), mitral valve replacement (P = 0.003), shunt implantation (P = 0.009), surgical ablation (P = 0.024), myocardial dysfunction (P = 0.014), elevated lung resistances (P = 0.004), hypothyroidism (P = 0.002) and redosternotomy (P < 0.001) emerged as risk factors for complications. Mean ABC and ACC scores were 6.6 ± 2.3, and 9.0 ± 3.7, respectively. The AuROCs of the ABC and the ACC scores for 30-day mortality were 0.663 (P = 0.044), and 0.755 (P = 0.002), respectively. The AuROCs of the ABC and the ACC scores for complications were 0.634 (P < 0.001), and 0.670 (P < 0.001), respectively. Surgery for adults

  7. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

    Science.gov (United States)

    Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

    2015-05-01

    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

  8. Complex Regional Pain Syndrome Caused by Lumbar Herniated Intervertebral Disc Disease.

    Science.gov (United States)

    Kim, Se Hee; Choi, Sang Sik; Lee, Mi Kyung; Kin, Jung Eun

    2016-07-01

    Most cases of complex regional pain syndrome (CRPS) occur after some inciting injury. There are a few cases of CRPS after an operation for disc disease. CRPS from a mild herniated intervertebral disc (HIVD) without surgical intervention is even rarer than CRPS after an operation for disc disease.A 22-year-old man was transferred to a pain clinic. He had continuously complained about back and right leg pain. He presented with a skin color change in the right lower leg, intermittent resting tremor, stiffness, and swelling in the right leg. He complained of a pulling sensation and numbness in his right buttock, posterior thigh, lateral calf, and ankle. This symptom was in accordance with L4/5 radiculopathy. Magnetic resonance imaging (MRI) also showed L4/5 HIVD that was central to the bilateral subarticular protrusion.He was diagnosed as having CRPS, which fits the revised International Association for the Study of Pain (IASP) criteria. He fulfilled 4 symptom categories (allodynia, temperature asymmetry and skin color change, sweating changes, decreased range of motion and motor dysfunction) and 3 of 4 sign categories (allodynia, temperature asymmetry and skin color changes, decreased range of motion and motor dysfunction). The bone scan and thermography also revealed CRPS.For the past 2 months, we have performed intensive treatments. But, he never became pain-free and walking for 5 minutes led to persistent leg pain. We decided to perform percutaneous nucleoplasty, which can directly decompress a HIVD. On the next day, he achieved dramatic symptom relief. The visual analog scale (VAS) score improved to 3, compared to the VAS score of 9 at the first visit. The skin color change, allodynia, and tremor in the right leg disappeared, and the temperature asymmetry normalized. Motor weakness of the right leg also recovered.We report an unusual case of CRPS that was caused by L4/5 HIVD without a history of trauma or surgery. It has a clear causal relationship between HIVD

  9. EFFICACY AND SAFETY OF IRRIGATION SPRAY APPLICATION FOR THE THROAT IN COMPLEX THERAPY OF INFLAMMATORY OROPHARYNX DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu.L. Soldatskiy

    2011-01-01

    Full Text Available Inflammatory diseases of the oropharynx manifested with pain or discomfort in the throat, is a frequent pathology in children. Traditionally, patients with acute and exacerbation of chronic tonsillitis and pharyngitis are prescribed gargarism. In recent years, the use of sea water-based throat sprays have been allowed for irrigation therapy. Their use as part of the complex treatment of inflammatory oropharynx diseases statistically reliably decreases the intensity of pain reaction on the 10th–24th day of treatment compared to conventional gargarism and is comparable with conventional therapy when assessing other clinical symptoms. It is therefore possible to recommend using sea water-based substance as a initial means of irrigation therapy in the complex treatment of inflammatory oropharynx diseases in children.Key words: pharyngitis, tonsillitis, throat pain, irrigation therapy, children.

  10. Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease.

    Science.gov (United States)

    Baddeley, Thomas C; McCaffrey, Jennifer; Storey, John M D; Cheung, John K S; Melis, Valeria; Horsley, David; Harrington, Charles R; Wischik, Claude M

    2015-01-01

    Methylthioninium (MT) is a tau aggregation inhibitor with therapeutic potential in Alzheimer's disease (AD). MT exists in equilibrium between reduced [leucomethylthioninium (LMT)] and oxidized (MT(+)) forms; as a chloride salt [methylthioninium chloride (MTC), "methylene blue"], it is stabilized in its MT(+) form. Although the results of a phase 2 study of MTC in 321 mild/moderate AD subjects identified a 138-mg MT/day dose as the minimum effective dose on cognitive and imaging end points, further clinical development of MT was delayed pending resolution of the unexpected lack of efficacy of the 228-mg MT/day dose. We hypothesized that the failure of dose response may depend on differences known at the time in dissolution in simulated gastric and intestinal fluids of the 100-mg MTC capsules used to deliver the 228-mg dose and reflect previously unsuspected differences in redox processing of MT at different levels in the gut. The synthesis of a novel chemical entity, LMTX (providing LMT in a stable anhydrous crystalline form), has enabled a systematic comparison of the pharmacokinetic properties of MTC and LMTX in preclinical and clinical studies. The quantity of MT released in water or gastric fluid within 60 minutes proved in retrospect to be an important determinant of clinical efficacy. A further factor was a dose-dependent limitation in the ability to absorb MT in the presence of food when delivered in the MT(+) form as MTC. A model is presented to account for the complexity of MT absorption, which may have relevance for other similar redox molecules. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex.

    Science.gov (United States)

    Shoemake, B M; Vander Ley, B L; Newcomer, B W; Heller, M C

    2018-01-01

    The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations. Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H 2 O 2 /I - ) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo. Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd. In vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H 2 O 2 /I - system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo-controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I - concentration. Bovine herpesvirus-1, parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H 2 O 2 /I - reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a C max  = 181 (1,420 μM I), T 12 , a sufficient concentration to inactivate these pathogens in vitro. In vitro, the LPO/H 2 O 2 /I - system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  12. The care delivery experience of hospitalized patients with complex chronic disease.

    Science.gov (United States)

    Kuluski, Kerry; Hoang, Sylvia N; Schaink, Alexis K; Alvaro, Celeste; Lyons, Renee F; Tobias, Roy; Bensimon, Cécile M

    2013-12-01

    This study investigated what is important in care delivery from the perspective of hospital inpatients with complex chronic disease, a currently understudied population. One-on-one semi-structured interviews were conducted with inpatients at a continuing care/rehabilitation hospital (n = 116) in Canada between February and July 2011. The study design was mixed methods and reports on patient characteristics and care delivery experiences. Basic descriptive statistics were run using SPSS version 17, and thematic analysis on the transcripts was conducted using NVivo9 software. Patients had an average of 5 morbidities and several illness symptoms including activity of daily living impairments, physical pain and emotional disturbance. Three broad themes (each with one or more subthemes) were generated from the data representing important components of care delivery: components of the care plan (a comprehensive assessment, supported transitions and a bio-psycho-social care package); care capacity and quality (optimal staff to patient ratios, quicker response times, better patient-provider communication and consistency between providers) and the patient-provider relationships (characterized by respect and dignity). As health systems throughout the industrialized world move to sustain health budgets while optimizing quality of care, it is critical to better understand this population, so that appropriate metrics, services and policies can be developed. The study has generated a body of evidence on the important components of care delivery from the perspectives of a diverse group of chronically ill individuals who have spent a considerable amount of time in the health-care system. Moving forward, exploration around the appropriate funding models and skill mix is needed to move the evidence into changed practice. © 2013 John Wiley & Sons Ltd.

  13. Magnetic resonance imaging planning in children with complex congenital heart disease – A new approach

    Directory of Open Access Journals (Sweden)

    Israel Valverde

    2017-04-01

    Full Text Available Objectives To compare a standard sequential 2D Planning Method (2D-PM with a 3D offline Planning Method (3D-PM based on 3D contrast-enhanced magnetic resonance angiography (CE-MRA in children with congenital heart disease (CHD. Design In 14 children with complex CHD (mean: 2.6 years, range: 3 months to 7.6 years, axial and coronal cuts were obtained with single slice spin echo sequences to get the final double oblique longitudinal cut of the targeted anatomical structure (2D-PM, n = 31. On a separate workstation, similar maximal intensity projection (MIP images were generated offline from a 3D CE-MRA. MIP images were localizers for repeated targeted imaging using the previous spin echo sequence (3D-PM. Finally, image coverage, spatial orientation and acquisition time were compared for 2D-PM and 3D-PM. Main outcome measures 2D-PM and 3D-PM images were similar: both perfectly covered the selected anatomic regions and no spatial differences were found (p>0.05. The mean time for creation of the final imaging plane was 241 ± 31 s (2D-PM compared to 71 ± 18 s (3D-PM (p<0.05. Conclusions 3D-PM shows similar results compared to 2D-PM, but allows faster and offline planning thereby reducing the scan time significantly. As newly developed high-resolution 3D datasets can also be used further improvement of this technology is expected.

  14. The clinical efficacy of a clarithromycin-based regimen for Mycobacterium avium complex disease: A nationwide post-marketing study.

    Science.gov (United States)

    Kadota, Jun-Ichi; Kurashima, Atsuyuki; Suzuki, Katsuhiro

    2017-05-01

    The revised 2007 American Thoracic Society/Infectious Diseases Society of America statement recommend clarithromycin-based combination therapy for treatment of Mycobacterium avium complex lung disease and stipulates approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient. Our objective was to obtain data on the clinical outcome of clarithromycin-based daily regimens by conducting a nationwide retrospective post-marketing study of M. avium complex lung disease. In accordance with the Japanese guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multidrug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin-based regimen) until bacilli negative conversion, and the treatment was continued for approximately 1 year after the initial conversion. Data were collected before administration, at the time of bacilli negative conversion, at the end of treatment, and at 6 months after the end of treatment. Of the 466 subjects enrolled in the study, 271 patients who received clarithromycin at 800 mg/day underwent evaluation for M. avium complex disease. The final bacilli negative conversion rate in those patients was 94.7%. The bacteriological relapse rate was 5.0% (5/100 patients). Bacteriological relapse was noted in patients treated for less than 15 months after conversion. No life-threatening or serious adverse drug reactions were observed. This study demonstrated that a clarithromycin-based daily regimen can yield a high bacteriological conversion rate in M. avium complex disease. After conversion, treatment for less than 15 months might be insufficient to prevent bacteriological relapse. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

    International Nuclear Information System (INIS)

    Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

    1979-01-01

    Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

  16. Determination of immune complexes in sera from dogs with various diseases by mastocytoma cell assay.

    OpenAIRE

    Targowski, S

    1982-01-01

    Canine immunoglobulin G complexed with particulate or soluble antigen can bind to the Fc receptors on the mastocytoma cells. Attachment of immune complexes composed of immunoglobulin G and soluble antigen (ovalbumin) to mastocytoma cells was detected by an inhibition of rosette formation with indicator cells (sensitized sheep erythrocytes). Therefore, canine circulating immune complexes may also attach to mastocytoma cells and inhibit rosette formation (mastocytoma cell assay). Sera from 326 ...

  17. Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease

    KAUST Repository

    Vangone, Anna

    2014-07-30

    Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. © 2014 Vangone et al.

  18. Effectiveness of bronchoscopy in the diagnosis of bronchial-type mycobacterium avium-intracellulare complex pulmonary disease

    International Nuclear Information System (INIS)

    Sato, Kazuhiro; Kourakata, Hiroyo

    2004-01-01

    Mycobacterium avium-intracellulare complex (MAC) pulmonary disease with associated nodules and bronchiectasis is an increasingly prevalent condition. This condition is often difficult to diagnose in the early stages of the disease, because of the limited effectiveness of sputum culture cytology. The effectiveness of bronchoscopy in the isolation and diagnosis of MAC in respiratory secretions is still unclear. Over a three-year period, we examined the effectiveness of bronchoscopy in 45 non-HIV-infected patients who had clusters of small peripheral lung nodules. These nodules were associated with changes of the draining bronchi detected by high-resolution CT (HRCT). A total of 22 of 45 patients (48.9%) had cultures positive for MAC. In the MAC-positive group, 10 patients tested positive for disease in sputum and 22 tested positive for disease in bronchial washings. A total of 13 of 45 patients (28.9%) fulfilled the American Thoracic Society criteria for pulmonary MAC disease, and 9 (20.0%) others with cultures positive for MAC did not fulfill the criteria. Radiographic measures and sputum cultures of 13 of 16 patients (81.3%) with negative cultures revealed no further disease progression. We found that HRCT was a useful technique in the diagnosis of MAC-pulmonary disease. We also found that bronchoscopy was a more sensitive diagnostic technique than sputum culture, analysis in the differential diagnosis of MAC pulmonary diseases. (author)

  19. Tedizolid is highly bactericidal in the treatment of pulmonary Mycobacterium avium complex disease.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G; Lee, Pooi S; Gumbo, Tawanda

    2017-09-01

    To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden. We identified the 0-24 h area under the concentration-time curves to MIC (AUC0-24/MIC) ratios associated with the following targets: 80% of maximal kill (EC80), bacteriostasis, and 1.0 and 2.0 log10 cfu/mL kill. We then performed 10 000 patient Monte Carlo simulations to identify the optimal dose for each of the exposure targets. Tedizolid achieved the feat of 2.0 log10 cfu/mL kill below initial bacterial burden, an effect not seen before in this model with other antibiotics. The tedizolid exposure associated with 1.0 log10 cfu/mL kill was a non-protein bound AUC0-24/MIC ratio of 23.46, while that associated with 2.0 log10 cfu/mL kill was 37.50, and the EC80 was 21.71. The clinical dose of 200 mg achieved each of these targets in ∼100% of the 10 000 patients, except the 2.0 log10 cfu/mL kill which required 300 mg/day. A tedizolid susceptibility MIC breakpoint of 1 mg/L is proposed. Tedizolid, at standard clinical doses, is expected to be bactericidal, and even achieved an unprecedented 2.0 log10 cfu/mL kill of MAC as monotherapy. We propose it as the backbone of short-course anti-MAC chemotherapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Hypoxic Challenge Testing (Fitness to Fly) in children with complex congenital heart disease.

    Science.gov (United States)

    Naqvi, Nitha; Doughty, Victoria L; Starling, Luke; Franklin, Rodney C; Ward, Simon; Daubeney, Piers E F; Balfour-Lynn, Ian M

    2018-02-14

    Commercial airplanes fly with an equivalent cabin fraction of inspired oxygen of 0.15, leading to reduced oxygen saturation (SpO 2 ) in passengers. How this affects children with complex congenital heart disease (CHD) is unknown. We conducted Hypoxic Challenge Testing (HCT) to assess need for inflight supplemental oxygen. Children aged <16 years had a standard HCT. They were grouped as (A) normal versus abnormal baseline SpO 2 (≥95% vs <95%) and (B) absence versus presence of an actual/potential right-to-left (R-L) shunt. We measured SpO 2 , heart rate, QT interval corrected for heart rate and partial pressure of carbon dioxide measured transcutaneously (PtcCO 2 ). A test failed when children with (1) normal baseline SpO 2 desaturated to 85%, (2) baseline SpO 2 85%-94% desaturated by 15% of baseline; and (3) baseline SpO 2 75%-84% desaturated to 70%. There were 68 children, mean age 3.3 years (range 10 weeks-14.5 years). Children with normal (n=36) baseline SpO 2 desaturated from median 99% to 91%, P<0.0001, and 3/36 (8%) failed the test. Those with abnormal baseline SpO 2 (n=32) desaturated from median 84% to 76%, P<0.0001, and 5/32 (16%) failed (no significant difference between groups). Children with no R-L shunt (n=25) desaturated from median 99% to 93%, P<0.0001, but 0/25 failed. Those with an actual/potential R-L shunt (n=43) desaturated from median 87% to 78%, P<0.0001, and 8/43 (19%) failed (difference between groups P<0.02). PtcCO 2 , heart rate and QT interval corrected for heart rate were unaffected by the hypoxic state. This is the first evidence to help guide which children with CHD need a preflight HCT. We suggest all children with an actual or potential R-L shunt should be tested. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. [Terminal complement complex (TCC) levels in urine in patients with renal diseases].

    Science.gov (United States)

    Yasuda, K

    2001-03-01

    The terminal complement complex (TCC) has been reported to play an important role in the pathogenesis of proteinuria not only in experimental nephritis but also in human glomerulonephritis. In order to clarify the clinical significance of TCC, the author investigated a total of 129 pediatric patients with the following glomerular diseases: idiopathic nephrotic syndrome (INS; 40 cases), IgA nephropathy (IgAN; 48 cases), mesangio-capillary glomerulonephritis (MPGN; 16 cases), lupus nephritis (LN; 16 cases), purpura nephritis (5 cases) and membranous nephritis (4 cases). Results were analyzed in relation to the responsiveness to steroid treatment in INS and the degree of proteinuria and histopathologic severity in glonerulonephritis groups. In 40 patients who underwent renal biopsy, the localizations of vitronectin and clusterin, both of which are regulatory proteins for TCC, were examined by immunofluorescence microscopy in conjunction with that of TCC for the study of the mechanism of local defense in glomerulonephritis. The urinary TCC levels were elevated in 9 (90%) of 10 patients with steroid-resistant INS, while they were elevated only in 2 of 30 steroid-responsive patients. In glomerulonephritis groups, urinary TCC levels were elevated in 13 of 48 patients with IgAN, 6 of 16 with MPGN, 8 of 16 with LN, 2 of 5 purpural nephritis and 1 of 4 with membranous nephritis. Urinary TCC levels correlated with histological severity in IgAN and showed a reciprocal relation to C3 levels in MPGN and LN. Immunofluorescence findings showed that localization of TCC was quite similar to that of C3 in glomerulonephritis groups. Vitronectin and clusterin were also demonstrated to deposit in similar pattern to TCC. These results suggest that in INS urinary TCC levels could predict the responsiveness to steroid therapy and might be useful as a non-invasive diagnostic method in differential diagnosis of INS. In IgAN, urinary TCC could be a useful marker of histologic severity. The

  2. Therapeutic application of new holmium-166 chitosan complex in malignant and benign diseases

    International Nuclear Information System (INIS)

    Park, K.B.; Kim, Y.M.; Shin, B.C.; Kim, J.R.; Ryu, J.M.; Lim, S.M.

    1998-01-01

    The new holmium-166 chitosan complex ( 166 Ho-CHICO, DW- 166 HC) was prepared by reacting the aqueous acidic solution of chitosan with 166 Ho(NO 3 ) 3 at room temperature with quantitative labelling yield. The progress of the reaction and labelling yield were determined by instant this layer chromatography using silicic acid impregnated glass fiber (ITLC-SA) and developing solvent of MeOH:H 2 O:HAC (49:49:2). The high labelling yield of more than 99% was obtained by reacting chitosan solution (35 mg/4 ml) with 166 Ho(NO 3 ) 3 in which 7 mg of 165 Ho+ 166 Ho were contained as a maximum content. The labelling yield was highly dependent on the pH of the chitosan solution. The optimal labelling could be obtained at pH 2.5∼3.5 The characteristics of 166 Ho-CHICO were similar to those of chitosan, which is biocompatible, biodegradable, non-toxic, soluble and viscous in acidic condition but geltatinuous at pH 6.0 and precipitating in alkaline conditions. 166 Ho-CHICO can be easily prepared by reconstituting freeze-dried chitosan (kit A) with 166 Ho(NO 3 ) 3 solution (kit B) just prior to use. After intrahepatic administration of 166 Ho-CHICO to male rats, the radioactivity concentrations in blood were low and the cumulative urinary and fecal excretion over a period of 0 to 72 hours were 0.53% and 0.54%, respectively. the radioactivity concentration in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administered site, and only slight radioactivity was detected from the liver, spleen, lungs, and bones. An autoradiograph after intratumoral administration of 166 Ho-CHICO showed that radioactivity was localized at the administered site of the lesion without distribution to other organs and tissues. A biodistribution study in normal rabbits with 166 Ho-CHICO showed that most of the radioactivities were retained in the knee joint with negligible extra leakage at 72 hours after intra

  3. [Change of paradigms in the surgical treatment of complex thoracic aortic disease].

    Science.gov (United States)

    Herold, Ulf; Tsagakis, Konstantinos; Kamler, Markus; Massoudy, Parwis; Assenmacher, Eva; Eggebrecht, Holger; Buck, Thomas; Jakob, Heinz

    2006-08-01

    One of the main issues in complex thoracic aortic disease, requiring the replacement of the ascending aorta, the entire aortic arch and the descending aorta, is the vast amount of surgery necessary to cure the patient. Though one-stage repair is feasible by a clamshell thoracotomy, the associated surgical trauma and perioperative morbidity limit this approach to younger patients only. Classic surgical repair consist of a two-stage strategy, whereby, in the first step, the ascending aorta and the aortic arch are replaced via a midline sternotomy. In the second step, via a lateral thoracotomy, the descending aorta is replaced. The two stages may sum up to a mortality of 20%; furthermore, the waiting period between the stages is associated with a mortality rate of 10% of its own. Additionally, the two-stage strategy has an inherent limitation, due to the comorbidity and advanced age of the majority of patients. Therefore, the second stage cannot be offered to up to 30% of patients. New developments and improvements in aortic surgery were introduced to overcome these shortcomings and to simplify the surgical repair. The "elephant trunk" principle, introduced by Borst et al. in 1983, was an important step to facilitate surgical repair, but still required the second step. With the introduction of endovascular repair of thoracic aortic disease with stent grafts implanted retrograde via the femoral artery, new therapeutic concepts emerged. In the late 1990s, two Japanese groups reported first trials to stabilize the free-floating "elephant trunk" prosthesis by implantation of nitinol stent grafts into the vascular graft. The applied devices were purely custom-made and nonstandardized. The availability of industrially made and CE-marked stent-graft devices raised the possibility to apply them in open aortic arch surgery. The experience with stent-graft devices implanted antegrade into the descending aorta (Medtronic Talent) was reported first by the Essen and the Vienna

  4. Detecting the tipping points in a three-state model of complex diseases by temporal differential networks

    Directory of Open Access Journals (Sweden)

    Pei Chen

    2017-10-01

    Full Text Available Abstract Background The progression of complex diseases, such as diabetes and cancer, is generally a nonlinear process with three stages, i.e., normal state, pre-disease state, and disease state, where the pre-disease state is a critical state or tipping point immediately preceding the disease state. Traditional biomarkers aim to identify a disease state by exploiting the information of differential expressions for the observed molecules, but may fail to detect a pre-disease state because there are generally little significant differences between the normal and pre-disease states. Thus, it is challenging to signal the pre-disease state, which actually implies the disease prediction. Methods In this work, by exploiting the information of differential associations among the observed molecules between the normal and pre-disease states, we propose a temporal differential network based computational method to accurately signal the pre-disease state or predict the occurrence of severe disease. The theoretical foundation of this work is the quantification of the critical state using dynamical network biomarkers. Results Considering that there is one stationary Markov process before reaching the tipping point, a novel index, inconsistency score (I-score, is proposed to quantitatively measure the change of the stationary processes from the normal state so as to detect the onset of pre-disease state. In other words, a drastic increase of I-score implies the high inconsistency with the preceding stable state and thus signals the upcoming critical transition. This approach is applied to the simulated and real datasets of three diseases, which demonstrates the effectiveness of our method for predicting the deterioration into disease states. Both functional analysis and pathway enrichment also validate the computational results from the perspectives of both molecules and networks. Conclusions At the molecular network level, this method provides a

  5. Social behavior and the superorganism: Implications for disease and stability in complex animal societies and Colony Collapse Disorder in Honeybees

    Directory of Open Access Journals (Sweden)

    Niccolo Caldararo

    2015-01-01

    Full Text Available Sociability, mass response to threat, food production and food sharing and an adaptable communication system are a suite of traits involved in the evolution of complex society in animals. Cycles of interaction characterize members of such societies and those of species in association that can affect disease structure in time and virulence. Colony Collapse Disorder (in North America, Honey Bee Depopulation Syndrome, or HBDS elsewhere shows similarity to a number of mass behavioural responses in other social animals, especially in ants. A number of questions regarding the cause of CCD continues to make progress in fighting the disease difficult. Here information is provided that may result in an isolation of factors to identify the syndrome of effects that lead to the disease, based on studies of disease avoidance and illness behaviour in other animal species. Most of the work to date to discover a cause has focused on a direct relationship between a pathogen or parasite or environmental condition and the Disorder. Dysfunctional mass behaviour is even seen in humans, as during the Black Plague. Disease avoidance is an important survival tactic for many animals and if the mechanism is modified by a pathogen or toxin unusual outcomes may result. In complex animal societies the opportunity for other forms of disruption of social life are numerous.

  6. "It's not all in my head!" - The complex relationship between rare diseases and mental health problems.

    Science.gov (United States)

    Nunn, Rebecca

    2017-02-27

    The incidence of mental health disorders is significantly higher in individuals with a rare disease, compared to the general population. This letter considers the possible reasons for this in terms of the many ways in which a rare disease impacts on an individual's life, and how these impacts can be strongly related to factors which predispose to mental health difficulties.Furthermore, issues surrounding mental health can also play a significant role in the process of diagnosing a rare disease. The unusual nature of such diseases intrinsically predisposes an individual to obtain an inaccurate diagnosis of a psychosomatic disorder, a diagnosis which can often be further complicated by the presence of genuine psychiatric symptoms.This letter argues that these common experiences of rare disease patients have impacts upon the way in which their psychiatric care should be offered and managed, and that sensitivity and understanding surrounding these issues should be considered a necessary part of effective care for rare disease patients.

  7. [Adequacy of clinical interventions in patients with advanced and complex disease. Proposal of a decision making algorithm].

    Science.gov (United States)

    Ameneiros-Lago, E; Carballada-Rico, C; Garrido-Sanjuán, J A; García Martínez, A

    2015-01-01

    Decision making in the patient with chronic advanced disease is especially complex. Health professionals are obliged to prevent avoidable suffering and not to add any more damage to that of the disease itself. The adequacy of the clinical interventions consists of only offering those diagnostic and therapeutic procedures appropriate to the clinical situation of the patient and to perform only those allowed by the patient or representative. In this article, the use of an algorithm is proposed that should serve to help health professionals in this decision making process. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

  8. Fungal pathogen complexes associated with rambutan, longan and mango diseases in Puerto Rico

    Science.gov (United States)

    Different fungi have been associated with diseased inflorescences, leaves, and fruits of mango, rambutan and longan. During a fungal disease survey conducted between 2008 and 2013 at six orchards of rambutan and longan, and one orchard of mango in Puerto Rico, symptoms such as fruit rot, infloresc...

  9. Selection for immunoresponsiveness in chickens : effects of the major histocompatibility complex and resistance to Marek's disease

    NARCIS (Netherlands)

    Pinard, M.H.

    1992-01-01

    Improving genetic disease resistance may be an attractive preventive measure in the control of infectious diseases in livestock production. Chickens were selected for high and low antibody response to sheep red blood cells for ten generations. Divergent selection was successfully achieved

  10. The influence of major histocompatibility complex and vaccination with turkey herpesvirus on Marek's disease virus evolution

    Science.gov (United States)

    Over the last five decades, the pathogenicity of the Marek’s disease virus (MDV) has evolved from the relatively mild strains (mMDV) observed in the 1960s to the more severe very-virulent-plus strains currently observed in today’s outbreaks. The use of vaccines to control Marek’s disease (MD), but n...

  11. 'MHC-I-opathy'-unified concept for spondyloarthritis and Behçet disease.

    Science.gov (United States)

    McGonagle, Dennis; Aydin, Sibel Zehra; Gül, Ahmet; Mahr, Alfred; Direskeneli, Haner

    2015-12-01

    The spondyloarthropathies comprise ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA) and arthritis associated with inflammatory bowel disease. In this Perspectives article, we describe how Behçet disease and several clinically distinct spondyloarthropathies-all associated with MHC class I (MHC-I) alleles such as HLA-B(*)51, HLA-C(*)0602 and HLA-B(*)27 and epistatic ERAP-1 interactions-have a shared immunopathogenetic basis. As a unifying concept, we propose that barrier dysfunction in environmentally exposed organs such as the skin, and aberrant innate immune reactions at sites of mechanical stress, can often trigger secondary adaptive immune CD8(+) T-cell responses with prominent neutrophilic inflammation that culminate in exacerbation and recurrence of these diseases. Of note, these 'MHC-I-opathies' show a differential immunopathology, probably reflecting antigenic differences within target tissues: HLA-B(*)51 is linked to ocular and mucocutaneous disease but not gut involvement, and HLA-C(*)0602 is linked to type I psoriasis but not scalp or nail disease.

  12. Temporal Sampling of White Band Disease Infected Corals Reveals Complex and Dynamic Bacterial Communities

    Science.gov (United States)

    Gignoux-Wolfsohn, S.; Vollmer, S. V.; Aronson, F. M.

    2016-02-01

    White band disease (WBD) is a coral disease that is currently decimating populations of the endangered staghorn coral, Acropora cervicornis and elkhorn coral, A. palmata across the Caribbean. Since it was first reported in 1979, WBD has killed 95% of these critical reef-building Caribbean corals. WBD is infectious; it can be transmitted through the water column or by a corallivorous snail. While previous research shows that WBD is likely caused by bacteria, identification of a specific pathogen or pathogens has remained elusive. Much of the difficulty of understanding the etiology of the disease comes from a lack of information about how existing bacterial communities respond to disease and separating initial from secondary colonizers. In order to address this lack of information, we performed a fully-crossed tank infection experiment. We exposed healthy corals from two different sites to disease and healthy (control) homogenates from both sites, replicating genotype across tanks. We sampled every coral at three time points: before inoculation with the homogenate, after inoculation, and when the coral showed signs of disease. We then performed 16S rRNA gene sequencing on the Illumina HiSeq 2000. We saw significant differences between time points and disease state. Interestingly, at the first time point (time one) we observed differences between genotypes: every fragment from some genotypes was dominated by Endozoicomonas, while other genotypes were not dominated by one family. At time two we saw an increase in abundance of Alteromonadaceae and Flavobacteriaceae in all corals, and a larger increase in disease-exposed corals. At time three, we saw another increase in Flavobacteriaceae abundance in diseased corals, as well as an introduction of Francisella to diseased corals. While Flavobacteriaceae and Francisella were proposed as potential pathogens, their increase at time three suggests they may be secondary colonizers or opportunists. In genotypes that were

  13. Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases

    NARCIS (Netherlands)

    Koene, S.; Rodenburg, R.J.; van der Knaap, M.S.; Willemsen, M.A.A.P.; Sperl, W.; Laugel, V.; Ostergaard, E.; Tarnopolsky, M.; Martin, M.A.; Nesbitt, V.; Fletcher, J.; Edvardson, S.; Procaccio, V.; Slama, A.; van den Heuvel, L.P.W.J.; Smeitink, J.A.M.

    2012-01-01

    Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new

  14. Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases.

    NARCIS (Netherlands)

    Koene, S.; Rodenburg, R.J.T.; Knaap, M.S. van der; Willemsen, M.A.A.P.; Sperl, W.; Laugel, V.; Ostergaard, E.; Tarnopolsky, M.; Martin, M.A.; Nesbitt, V.; Fletcher, J.; Edvardson, S.; Procaccio, V.; Slama, A.; Heuvel, L.P.W.J. van den; Smeitink, J.A.M.

    2012-01-01

    Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new

  15. Immune complex modulation by plasma proteins. With special reference to the complement system and autoimmune diseases

    DEFF Research Database (Denmark)

    Baatrup, G

    1989-01-01

    of IC in the circulation or tissues, this activation may lead to chronic inflammatory disease. This thesis reviews certain aspects of the interactions between IC and C. The earlier work describes our development of an assay for measuring the C activity in patient sera by its ability to solubilize...... were performed to characterize the reaction. The CMS assay, showed that serum from patients with SLE and other systemic persistent inflammatory diseases and infections exhibited a reduced capacity to solubilize IC. The CMS values correlated inversely to the disease activity in SLE patients. It was also...

  16. Unveiling Members of Colletotrichum acutatum Species Complex Causing Colletotrichum Leaf Disease of Hevea brasiliensis in Sri Lanka.

    Science.gov (United States)

    Hunupolagama, D M; Chandrasekharan, N V; Wijesundera, W S S; Kathriarachchi, H S; Fernando, T H P S; Wijesundera, R L C

    2017-06-01

    Colletotrichum is an important fungal genus with great diversity, which causes anthracnose of a variety of crop plants including rubber trees. Colletotrichum acutatum and Colletotrichum gloeosporioides have been identified as the major causative agents of Colletotrichum leaf disease of rubber trees in Sri Lanka based on morphology, pathogenicity, and the analysis of internally transcribed spacer sequences of the nuclear ribosomal DNA. This study has been conducted to investigate the members of the C. acutatum species complex causing rubber leaf disease using a morphological and multi gene approach. For the first time in Sri Lanka, Colletotrichum simmondsii, Colletotrichum laticiphilum, Colletotrichum nymphaeae, and Colletotrichum citri have been identified as causative agents of Colletotrichum leaf disease in addition to C. acutatum s. str. Among them, C. simmondsii has been recognized as the major causative agent.

  17. 'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Walor, David M.; Berdon, Walter E. [Columbia University Medical Center, Department of Radiology Children' s Hospital of New York, New York, NY (United States); Westra, Sjirk J. [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

    2005-07-01

    ''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

  18. 'Hair-on-end' skull changes resembling thalassemia caused by marrow expansion in uncorrected complex cyanotic heart disease

    International Nuclear Information System (INIS)

    Walor, David M.; Berdon, Walter E.; Westra, Sjirk J.

    2005-01-01

    ''Hair-on-end'' skull changes resembling thalassemia were rarely described in the 1950s and 1960s in children with cyanotic congenital heart diseases; these changes were described almost entirely in patients with tetralogy of Fallot or D-transposition of the great arteries. As these lesions have become correctable, the osseous changes, never common, seem now only to exist in a small number of patients with uncorrectable complex cyanotic congenital heart disease who survive in a chronic hypoxic state. We present two cases: a case of marked marrow expansion in the skull of a 5-year-old boy with uncorrectable cyanotic heart disease studied by CT, and a second case of an 8-year-old with tetralogy of Fallot and pulmonary atresia studied by plain skull radiographs. The true incidence of these findings is unknown. (orig.)

  19. Characteristics of Mycobacterium avium complex (MAC pulmonary disease in previously treated lung cancer patients

    Directory of Open Access Journals (Sweden)

    Erin Meier

    2017-01-01

    Conclusion: MAC pulmonary disease in previously treated lung cancer can occur without apparent risk factors for this NTM infection. Symptomatic improvement with MAC antimicrobial therapy appears to be lower than expected but comorbidities might influence outcomes in this patient population.

  20. ROLE OF AZITHROMYCIN IN COMPLEX TREATMENT OF RESPIRATORY DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    E.V. Sereda

    2008-01-01

    Full Text Available The article contains the analysis of the role of azithromycin (sumamed in treatment of respiratory diseases in children. It is noted that azithromycin is an efficient antibacterial drug for treatment of extramural and uncomplicated pneumonia and is the drug of choice for atypical mycoplasmal and chlamidia trachomatis pneumonia, as well as for relapses of chronic bronchopulmonary diseases in children. High sensitivity to azithromycin of main pneumotropic and atypical agents, convenience of application, presence of children's pharmaceutical forms, reduction of administration to 1 time per day in case of short treatment schedules, high efficiency and absence of serious adverse events make it possible to recommend this antibiotic as an available means for treatment of respiratory diseases in infants and senior children not only as in patients but as out patients as well.Key words: children, azithromycin, treatment, respiratory diseases.

  1. Charcot Marie Tooth disease type 4J with complex central nervous system features.

    Science.gov (United States)

    Orengo, James P; Khemani, Pravin; Day, John W; Li, Jun; Siskind, Carly E

    2018-02-01

    We describe a family with Charcot Marie Tooth disease type 4J presenting with features of Charcot Marie Tooth disease plus parkinsonism and aphemia. Genetic testing found two variants in the FIG4 gene: c.122T>C (p.I41T) - the most common Charcot Marie Tooth disease type 4J variant - and c.1949-10T>G (intronic). Proband fibroblasts showed absent FIG4 protein on western blot, and skipping of exon 18 by RT-PCR. As most patients with Charcot Marie Tooth disease type 4J do not have central nervous system deficits, we postulate the intronic variant and I41T mutation together are causing loss of FIG4 protein and subsequently the central nervous system findings in our family.

  2. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions

    Science.gov (United States)

    Bingham, Clifton O.; Moni, Malini

    2015-01-01

    Purpose of review This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. Recent findings There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. Summary Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions. PMID:23455329

  3. “BIRD BITING” MOSQUITOES AND HUMAN DISEASE: A REVIEW OF THE ROLE OF CULEX PIPIENS COMPLEX MOSQUITOES IN EPIDEMIOLOGY

    Science.gov (United States)

    Farajollahi, Ary; Fonseca, Dina M.; Kramer, Laura D.; Kilpatrick, A. Marm

    2011-01-01

    The transmission of vector-borne pathogens is greatly influenced by the ecology of their vector, which is in turn shaped by genetic ancestry, the environment, and the hosts it feeds on. One group of vectors, the mosquitoes in the Culex pipiens complex, play key roles in the transmission of a range of pathogens including several viruses such as West Nile and St. Louis encephalitis viruses, avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex includes Cx. pipiens pipiens with two forms, pipiens and molestus, Cx. pipiens pallens, Cx. quinquefasciatus, Cx. australicus, and Cx. globocoxitus. While several members of the complex have limited geographic distributions, Cx. pipiens pipiens and Cx. quinquefasciatus are found in all known urban and sub-urban temperate and tropical regions, respectively, across the world, where they are often principal disease vectors. In addition, hybrids are common in areas of overlap. Although gaps in our knowledge still remain, the advent of genetic tools has greatly enhanced our understanding of the history of speciation, domestication, dispersal, and hybridization. We review the taxonomy, genetics, evolution, behavior, and ecology, of members of the Cx. pipiens complex and their role in the transmission of medically important pathogens. The adaptation of Cx. pipiens complex mosquitoes to human-altered environments led to their global distribution through dispersal via humans and, combined with their mixed feeding patterns on birds and mammals (including humans), increased the transmission of several avian pathogens to humans. We highlight several unanswered questions that will increase our ability to control diseases transmitted by these mosquitoes. PMID:21875691

  4. Strategies for overcoming tropical disease by ruthenium complexes with purine analog: Application against Leishmania spp. and Trypanosoma cruzi.

    Science.gov (United States)

    Fandzloch, Marzena; Arriaga, José Manuel Méndez; Sánchez-Moreno, Manuel; Wojtczak, Andrzej; Jezierska, Julia; Sitkowski, Jerzy; Wiśniewska, Joanna; Salas, Juan Manuel; Łakomska, Iwona

    2017-11-01

    Tropical diseases currently constitute a major health problem and thus a challenge in the field of drug discovery. The current treatments show serious disadvantages due to cost, toxicity, long therapy duration and resistance, and the use of metal complexes as chemotherapeutic agents against these ailments appears to be a very attractive alternative. Herein, we describe three newly synthesized ruthenium complexes with a bioactive molecule, the purine analogue 5,6,7-trimethyl-1,2,4-triazolo[1,5-a]pyrimidine (tmtp): cis,fac-[RuCl 2 (dmso) 3 (tmtp)] (1), mer-[RuCl 3 (dmso)(H 2 O)(tmtp)]·2H 2 O (2) and fac,cis-[RuCl 3 (H 2 O)(tmtp) 2 ] (3). Their structures were characterized using X-ray and spectroscopic methods (IR, NMR or EPR). The stability of the synthesized complexes 1-3 in various buffered solutions (pH=3-7.4) was monitored using conventional and stopped-flow techniques. The in vitro antiproliferative activity of all ruthenium complexes against promastigote forms of Leishmania spp. (L. infantum, L. braziliensis, and L. donovani) and epimastigote forms of Trypanosoma cruzi was investigated. Notably, the results showed that the activity of 1 against L. brasiliensis was more than three-fold higher than that of glucantime, and 1 showed no appreciable toxicity towards J774.2 macrophages. Additionally, 2 displayed even 141-fold lower toxicity against host cells than glucantime, demonstrating significantly higher selectivity than the reference drug. Therefore, 1 and 2 appear to be excellent candidates for further development as potential drugs for the effective treatment of leishmaniasis and Chagas disease. All novel complexes were also shown to be potent inhibitors of Fe-SOD in the studied species, while their effects on human CuZn-SOD were very low. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Management of complex urethral stricture disease: Algorithm and experience from a single institute

    Directory of Open Access Journals (Sweden)

    Yu-Hua Shau

    2015-09-01

    Conclusion: Complex urethral strictures can be managed by a variety of surgical techniques according to specific stricture locations. However, a careful postoperative follow-up for recurrences is mandatory, since ∼40% of patients undergoing buccal mucosal graft-augmented urethroplasties were expected to have additional procedures after the index urethroplasty.

  6. Species of the Colletotrichum acutatum complex associated with anthracnose diseases of fruit in Brazil

    NARCIS (Netherlands)

    Bragança, Carlos A.D.; Damm, Ulrike; Baroncelli, Riccardo; Massola Júnior, Nelson S.; Crous, Pedro W.

    Abstract Although Colletotrichum acutatum was recently investigated and shown to be a species complex comprising about 30 species, the name is still used in its broad sense for anthracnose pathogens of fruits in Brazil. In this study, a multilocus molecular analysis was carried out based on a

  7. Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease

    NARCIS (Netherlands)

    Keller, Margaux F.; Saad, Mohamad; Bras, Jose; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Büchel, Finja; Sharma, Manu; Gibbs, J. Raphael; Schulte, Claudia; Moskvina, Valentina; Durr, Alexandra; Holmans, Peter; Kilarski, Laura L.; Guerreiro, Rita; Hernandez, Dena G.; Brice, Alexis; Ylikotila, Pauli; Stefánsson, Hreinn; Majamaa, Kari; Morris, Huw R.; Williams, Nigel; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Hardy, John; Martinez, Maria; Singleton, Andrew B.; Nalls, Michael A.; Plagnol, Vincent; Sheerin, Una-Marie; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Segalen, Victor; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Montpied, Gabriel; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Goate, Alison; Gray, Emma; Gústafsson, Omar; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Steinberg, Stacy; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Sabatier, Paul; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Su, Zhan; Vukcevic, Damjan; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela

    2012-01-01

    Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait

  8. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    Directory of Open Access Journals (Sweden)

    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  9. Phosphorylated α-Synuclein-Copper Complex Formation in the Pathogenesis of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Juan Antonio Castillo-Gonzalez

    2017-01-01

    Full Text Available Parkinson’s disease is the second most important neurodegenerative disorder worldwide. It is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein and ubiquitin-bound proteins. Both the ubiquitin proteasome system (UPS and autophagy-lysosomal pathway (ALS are altered in Parkinson’s disease, leading to aggregation of proteins, particularly α-synuclein. Interestingly, it has been observed that copper promotes the protein aggregation process. Additionally, phosphorylation of α-synuclein along with copper also affects the protein aggregation process. The interrelation among α-synuclein phosphorylation and its capability to interact with copper, with the subsequent disruption of the protein degradation systems in the neurodegenerative process of Parkinson’s disease, will be analyzed in detail in this review.

  10. Human experimental endotoxemia in modeling the pathophysiology, genomics, and therapeutics of innate immunity in complex cardiometabolic diseases.

    Science.gov (United States)

    Patel, Parth N; Shah, Rhia Y; Ferguson, Jane F; Reilly, Muredach P

    2015-03-01

    Inflammation is a fundamental feature of several complex cardiometabolic diseases. Indeed, obesity, insulin resistance, metabolic dyslipidemia, and atherosclerosis are all closely linked inflammatory states. Increasing evidence suggests that the infectious, biome-related, or endogenous activation of the innate immune system may contribute to the development of metabolic syndrome and cardiovascular disease. Here, we describe the human experimental endotoxemia model for the specific study of innate immunity in understanding further the pathogenesis of cardiometabolic disease. In a controlled, experimental setting, administration of an intravenous bolus of purified Escherichia coli endotoxin activates innate immunity in healthy human volunteers. During endotoxemia, changes emerge in glucose metabolism, lipoprotein composition, and lipoprotein functions that closely resemble those observed chronically in inflammatory cardiovascular disease risk states. In this review, we describe the transient systemic inflammation and specific metabolic consequences that develop during human endotoxemia. Such a model provides a controlled induction of systemic inflammation, eliminates confounding, undermines reverse causation, and possesses unique potential as a starting point for genomic screening and testing of novel therapeutics for treatment of the inflammatory underpinning of cardiometabolic disease. © 2014 American Heart Association, Inc.

  11. Elevation of soluble major histocompatibility complex class I related chain A protein in malignant and infectious diseases in Chinese patients

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoxin

    2012-11-01

    Full Text Available Abstract Background Elevation of soluble major histocompatibility complex class I chain-related gene A (sMICA products in serum has been linked to tissue/organ transplantation, autoimmune diseases and some malignant disorders. Cells infected by microbiological pathogens may release sMICA, whereas less is known whether and to what extent serum sMICA levels may change in infectious diseases. Methods The present study determined serum sMICA levels by enzyme-linked immunosorbent assay (ELISA in a southern China population, including patients (n = 1041 suffering from several types of malignant and infectious diseases and healthy controls (n = 141. Results Relative to controls, serum sMICA elevation was significant in patients of hepatic cancer, and was approaching statistical significance in patients with lung, gastric and nasopharyngeal cancers. sMICA elevation was also associated with some bacterial (Enterobacteriaceae, Mycobacterium tuberculosis, non-fermenting Gram-negative bacteria and Gram-positive cocci, viral (hepatitis B and C and the Microspironema pallidum infections. Conclusion Serum sMICA levels may be informative for the diagnosis of some malignant and infectious diseases. The results also indicate that microbiological infections should be considered as a potential confounding clinical condition causing serum sMICA elevation while using this test to evaluate the status of other disorders, such as cancers, host-graft response and autoimmune diseases.

  12. Public health impact of disease-behavior dynamics. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

    Science.gov (United States)

    Wells, Chad R.; Galvani, Alison P.

    2015-12-01

    In a loop of dynamic feedback, behavior such as the decision to vaccinate, hand washing, or avoidance influences the progression of the epidemic, yet behavior is driven by the individual's and population's perceived risk of infection during an outbreak. In what we believe will become a seminal paper that stimulates future research as well as an informative teaching aid, Wang et. al. comprehensively review methodological advances that have been used to incorporate human behavior into epidemiological models on the effects of coupling disease transmission and behavior on complex social networks [1]. As illustrated by the recent outbreaks of measles and Middle Eastern Respiratory Syndrome (MERS), here we highlight the importance of coupling behavior and disease transmission that Wang et al. address.

  13. A case study of infant physiologic response to skin-to-skin contact following surgery for complex congenital heart disease

    Science.gov (United States)

    Harrison, Tondi M.; Ludington-Hoe, Susan

    2014-01-01

    Background Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care immediately after birth. Skin to skin contact (SSC) is well-accepted and practiced as a positive therapeutic intervention in premature infants, but is not routinely offered to infants in cardiac intensive care units. Physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. Objective The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Methods Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes prior to SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. Results All physiologic parameters were clinically acceptable throughout the 135-minute observation. Conclusion This case study provides beginning evidence that SSC is safe in full-term infants following surgery for complex congenital heart disease. Further research with a larger sample is needed to examine effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment. PMID:25325374

  14. Ruthenium complex with benznidazole and nitric oxide as a new candidate for the treatment of chagas disease.

    Directory of Open Access Journals (Sweden)

    Renata Sesti-Costa

    2014-10-01

    Full Text Available Chagas disease remains a serious medical and social problem in Latin America and is an emerging concern in nonendemic countries as a result of population movement, transfusion of infected blood or organs and congenital transmission. The current treatment of infected patients is unsatisfactory due to strain-specific drug resistance and the side effects of the current medications. For this reason, the discovery of safer and more effective chemotherapy is mandatory for the successful treatment and future eradication of Chagas disease.We investigated the effect of a ruthenium complex with benznidazole and nitric oxide (RuBzNO2 against Trypanosoma cruzi both in vitro and in vivo. Our results demonstrated that RuBzNO2 was more effective than the same concentrations of benznidazole (Bz in eliminating both the extracellular trypomastigote and the intracellular amastigote forms of the parasite, with no cytotoxic effect in mouse cells. In vivo treatment with the compound improved the survival of infected mice, inhibiting heart damage more efficiently than Bz alone. Accordingly, tissue inflammation and parasitism was significantly diminished after treatment with RuBzNO2 in a more effective manner than that with the same concentrations of Bz.The complexation of Bz with ruthenium and nitric oxide (RuBzNO2 increases its effectiveness against T. cruzi and enables treatment with lower concentrations of the compound, which may reduce the side effects of Bz. Our findings provide a new potential candidate for the treatment of Chagas disease.

  15. Development of an integrated genome informatics, data management and workflow infrastructure: A toolbox for the study of complex disease genetics

    Directory of Open Access Journals (Sweden)

    Burren Oliver S

    2004-01-01

    Full Text Available Abstract The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D, chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.

  16. The economic implications of the enteric disease complex and its control by the utilization of pleuromutillins in swine

    Directory of Open Access Journals (Sweden)

    Veturia Ileana Nueleanu

    2007-12-01

    Full Text Available The enteric disease complex may have a great economic impact by decreasing the growth of the animals, the conversion-rate of the fodder and, implicitly, the quality of carcass. That results in low production values, in correlation with low costs of production and decreased profitability. A therapeutic protocol was established, being administered tiamullin in the period of maximum incidence ofthe disease –5 days before and after weaning in pig youth, and the same period of time for the fatten pigs. The average meat production increased with 37.04% in youth pigs and 29.23% in fat pigs, in comparison with the period before the therapy. The profit that was achieved in youth pigs was 95 %, in comparison with the investment (the medication that was 5 %. The value of the investment was 27% in fat pigs, in comparison with the materialized profit of 73 %. The ratio between the total investment values (tiamullin medication and the benefit obtained in posttherapeutic period was 1:3.76, for the enteric disease complex in swine.

  17. Congenital anomalies of coronary arteries in complex congenital heart disease: diagnosis and analysis with dual-source CT.

    Science.gov (United States)

    Yu, Fang-fang; Lu, Bin; Gao, Yang; Hou, Zhi-hui; Schoepf, U Joseph; Spearman, James V; Cao, Hui-li; Sun, Ming-li; Jiang, Shi-liang

    2013-01-01

    Congenital heart diseases (CHDs) are sometimes associated with coronary artery anomalies (CAAs). Accurate preoperative evaluation of coronary artery anatomy is essential for successful surgical repair of complex CHD. The aim of this study was to evaluate the incidence of congenital CAAs in patients with complex CHD at dual-source CT. Four hundred seventeen consecutive patients with complex CHD underwent contrast-enhanced cardiac CT angiography. The results were retrospectively analyzed, including the types and incidences of CAAs in various forms of complex CHD. Each patient was analyzed independently by 2 experienced cardiovascular radiologists. Image quality of coronary arteries was assessed on a 5-point scale with 2 or less being nondiagnostic. Thirty-five of 417 studies were nondiagnostic (8.39%). Sixty-three cases of CAA (15.11%) were detected by anomalous ostia and coronary arteries. CAA was involved in 6 of 108 patients with tetralogy of Fallot (5.56%), 18 of 84 patients with double outlet right ventricle (21.43%), 11 of 97 patients with pulmonary artery atresia (11.34%), 7 of 36 patients with transposition of the great arteries (22.22%), 15 of 41 patients with single ventricle (36.59%), 4 of 12 patients with truncus arteriosus/aortopulmonary window (33.33%), and 2 of 39 patients with interruption of the aortic arch/coarctation of the aorta (5.13%). Twenty of these were accompanied with an anomalous coronary course (31.74%). Patients with complex CHD have a higher prevalence of CAAs, which should be considered before surgery. Dual-source CT is an effective technique to visualize and evaluate complex CHD. Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  18. Huntington Disease: The Complexities of Making and Disclosing a Clinical Diagnosis After Premanifest Genetic Testing.

    Science.gov (United States)

    McCusker, Elizabeth A; Loy, Clement T

    2017-01-01

    The management of patients and families affected by Huntington disease (HD) is complicated by several factors, both practical and ethical. It can be difficult to determine the onset of clinically manifest HD (mHD). In addition, it can be challenging to decide when to disclose the diagnosis to the affected individual. Firstly, the features of HD, an incurable, inherited, neurocognitive disorder that often manifests in young adulthood, influence how the person presents and accepts a diagnosis. Secondly, a positive genetic test for HD may result in a genetic diagnosis, sometimes years before the development of clinical features and the diagnosis of mHD. Thirdly, observational studies of unaffected gene expansion carriers documented HD manifestations up to 10 years before the typical presentation for diagnosis. These developments may permit earlier genetic diagnosis and information regarding the patient's likely status with respect to the development of clinical disease. Making the genetic diagnosis of HD and providing information regarding disease status, earlier rather than later, respects the person's right to know and preserves honesty in the doctor/patient relationship. Conversely, delaying the diagnosis respects the right not to know, avoids potential discrimination, and permits the person to live a "normal" life for longer, in the context of a disease without cure. This discussion has implications for other inherited and neurocognitive disorders.

  19. Modeling infectious disease dynamics in the complex landscape of global health

    DEFF Research Database (Denmark)

    Heesterbeek, Hans; Anderson, Roy; Andreasen, Viggo

    2015-01-01

    The spread of infectious diseases can be unpredictable. With the emergence of antibiotic resistance and worrying new viruses, and with ambitious plans for global eradication of polio and the elimination of malaria, the stakes have never been higher. Anticipation and measurement of the multiple...

  20. Complexity Analysis of Resting-State MEG Activity in Early-Stage Parkinson's Disease Patients

    NARCIS (Netherlands)

    Gómez, C.; Olde Dubbelink, K.T.E.; Stam, C.J.; Abasolo, D.; Berendse, H.W.; Hornero, R.

    2011-01-01

    The aim of the present study was to analyze resting-state brain activity in patients with Parkinson's disease (PD), a degenerative disorder of the nervous system. Magnetoencephalography (MEG) signals were recorded with a 151-channel whole-head radial gradiometer MEG system in 18 early-stage

  1. The Viral Replication Complex Is Associated with the Virulence of Newcastle Disease Virus

    NARCIS (Netherlands)

    Dortmans, J.C.F.M.; Rottier, P.J.M.; Koch, G.; Peeters, B.P.H.

    2010-01-01

    Virulent strains of Newcastle disease virus ([NDV] also known as avian paramyxovirus type 1) can be discriminated from low-virulence strains by the presence of multiple basic amino acid residues at the proteolytic cleavage site of the fusion (F) protein. However, some NDV variants isolated from

  2. A robust GWSS method to simultaneously detect rare and common variants for complex disease.

    Directory of Open Access Journals (Sweden)

    Chung-Feng Kao

    Full Text Available The rapid advances in sequencing technologies and the resulting next-generation sequencing data provide the opportunity to detect disease-associated variants with a better solution, in particular for low-frequency variants. Although both common and rare variants might exert their independent effects on the risk for the trait of interest, previous methods to detect the association effects rarely consider them simultaneously. We proposed a class of test statistics, the generalized weighted-sum statistic (GWSS, to detect disease associations in the presence of common and rare variants with a case-control study design. Information of rare variants was aggregated using a weighted sum method, while signal directions and strength of the variants were considered at the same time. Permutations were performed to obtain the empirical p-values of the test statistics. Our simulation showed that, compared to the existing methods, the GWSS method had better performance in most of the scenarios. The GWSS (in particular VDWSS-t method is particularly robust for opposite association directions, association strength, and varying distributions of minor-allele frequencies. It is therefore promising for detecting disease-associated loci. For empirical data application, we also applied our GWSS method to the Genetic Analysis Workshop 17 data, and the results were consistent with the simulation, suggesting good performance of our method. As re-sequencing studies become more popular to identify putative disease loci, we recommend the use of this newly developed GWSS to detect associations with both common and rare variants.

  3. Japanese Alzheimer’s Disease and Other Complex Disorders Diagnosis Based on Mitochondrial SNP Haplogroups

    Directory of Open Access Journals (Sweden)

    Shigeru Takasaki

    2012-01-01

    Full Text Available This paper first explains how the relations between Japanese Alzheimer’s disease (AD patients and their mitochondrial SNP frequencies at individual mtDNA positions examined using the radial basis function (RBF network and a method based on RBF network predictions and that Japanese AD patients are associated with the haplogroups G2a and N9b1. It then describes a method for the initial diagnosis of Alzheimer’s disease that is based on the mtSNP haplogroups of the AD patients. The method examines the relations between someone’s mtDNA mutations and the mtSNPs of AD patients. As the mtSNP haplogroups thus obtained indicate which nucleotides of mtDNA loci are changed in the Alzheimer’s patients, a person’s probability of becoming an AD patient can be predicted by comparing those mtDNA mutations with that person’s mtDNA mutations. The proposed method can also be used to diagnose diseases such as Parkinson’s disease and type 2 diabetes and to identify people likely to become centenarians.

  4. Modeling infectious disease dynamics in the complex landscape of global health

    NARCIS (Netherlands)

    Heesterbeek, Hans; Anderson, Roy M; Andreasen, Viggo; Bansal, Shweta; De Angelis, Daniela; Dye, Chris; Eames, Ken T D; Edmunds, W John; Frost, Simon D W; Funk, Sebastian; Hollingsworth, T Deirdre; House, Thomas; Isham, Valerie; Klepac, Petra; Lessler, Justin; Lloyd-Smith, James O; Metcalf, C Jessica E; Mollison, Denis; Pellis, Lorenzo; Pulliam, Juliet R C; Roberts, Mick G; Viboud, Cecile

    2015-01-01

    Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales,

  5. Neuroinflammation and Complexes of 17 beta-Hydroxysteroid Dehydrogenase type 10-Amyloid beta in Alzheimer's Disease

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Řípová, D.; Bartoš, A.; Bocková, Markéta; Hegnerová, Kateřina; Říčný, J.; Čechová, L.; Vrajová, M.; Homola, Jiří

    2013-01-01

    Roč. 10, č. 2 (2013), s. 165-173 ISSN 1567-2050 R&D Projects: GA MZd(CZ) NT11225 Institutional support: RVO:67985882 Keywords : Amyloid beta * mitochondrial enzyme * Alzheimer 's disease Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 3.796, year: 2013

  6. USE OF NEXT-GENERATION SEQUENCING FOR GENOMIC ANALYSIS IN COMPLEX DISEASES

    OpenAIRE

    Sana, Maria Elena

    2013-01-01

    Since the early 1990s, Sanger method has been the gold standard methodology for sequencing analysis of DNA. Next-generation sequencing (NGS) approaches revolutionized the field of genomics over the last 5 years. These new sequencing technologies make feasible the direct and cost-effective sequencing of genomes at unprecedented scale and speed. Furthermore, the applications of these technologies are wide-spread and have been developed to explore the complex biological systems, among which RNA ...

  7. Surgical management of congenital heart disease: correlation between hospital costs and the Aristotle complexity score.

    Science.gov (United States)

    Sinzobahamvya, N; Kopp, T; Photiadis, J; Arenz, C; Schindler, E; Haun, C; Hraska, V; Asfour, B

    2010-09-01

    Hospital costs are expected to correlate with clinical complexity. Do costs for congenital heart surgery correlate with Aristotle complexity scores? 442 inpatient stays in 2008 were evaluated. Aristotle scores and levels were determined. Costs were estimated according to the German Institute for Hospital Reimbursement system. Pearson and Spearman R correlation coefficients and corresponding goodness-of-fit regression coefficients R2 were calculated. Mean basic and comprehensive Aristotle scores were 7.60 +/- 2.74 and 9.23 +/- 2.94 points, respectively. Mean expenses per hospital stay amounted to 29,369 +/- 30,823 Euros. Aristotle basic and comprehensive scores and levels were positively correlated with hospital costs. With a Spearman R of 1 and related R2 of 0.9436, scores of the 6 Aristotle comprehensive levels correlated best. Mean hospital reimbursement was 26,412 +/- 17,962 Euros. Compensation was higher than expenses for patients in comprehensive levels 1 to 3, but much lower for those in levels 4 to 6. Aristotle comprehensive complexity scores were highly correlated with hospital costs. The Aristotle score could be used as a scale to establish the correct reimbursement after congenital heart surgery. Georg Thieme Verlag KG Stuttgart, New York.

  8. Modulation of Mitochondrial Complex I Activity Averts Cognitive Decline in Multiple Animal Models of Familial Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Liang Zhang

    2015-04-01

    Full Text Available Development of therapeutic strategies to prevent Alzheimer's disease (AD is of great importance. We show that mild inhibition of mitochondrial complex I with small molecule CP2 reduces levels of amyloid beta and phospho-Tau and averts cognitive decline in three animal models of familial AD. Low-mass molecular dynamics simulations and biochemical studies confirmed that CP2 competes with flavin mononucleotide for binding to the redox center of complex I leading to elevated AMP/ATP ratio and activation of AMP-activated protein kinase in neurons and mouse brain without inducing oxidative damage or inflammation. Furthermore, modulation of complex I activity augmented mitochondrial bioenergetics increasing coupling efficiency of respiratory chain and neuronal resistance to stress. Concomitant reduction of glycogen synthase kinase 3β activity and restoration of axonal trafficking resulted in elevated levels of neurotrophic factors and synaptic proteins in adult AD mice. Our results suggest that metabolic reprogramming induced by modulation of mitochondrial complex I activity represents promising therapeutic strategy for AD.

  9. Ecologies of complexity: Tropical environments, African trypanosomiasis, and the science of disease control in British colonial Africa, 1900-1940.

    Science.gov (United States)

    Tilley, Helen

    2004-01-01

    Tropical Africa was one of the last regions of the world to experience formal European colonialism, a process that coincided with the advent of a range of new scientific specialties and research methods. The history of British attempts to understand and control African trypanosomiasis (sleeping sickness in humans and nagana in cattle), following the intense human epidemics that broke out between 1895 and 1910, reveals hitherto ignored scientific research in the fields of ecology, epidemiology, and tropical medicine that helped produce a new understanding of the "ecology of disease." Often generated within a transnational and inter-disciplinary context, this knowledge increasingly assumed that vector-borne diseases in tropical environments were highly complex, dynamic, and interrelated phenomena. Thus while many people continued to hope that trypanosomiasis could be eradicated, research results made this prospect seem unlikely, if not impossible.

  10. Complex temporal climate signals drive the emergence of human water-borne disease

    OpenAIRE

    Morris, Aaron; Gozlan, Rodolphe E; Hassani, Hossein; Andreou, Demetra; Couppié, Pierre; Guégan, Jean-François

    2014-01-01

    International audience; Predominantly occurring in developing parts of the world, Buruli ulcer is a severely disabling mycobacterium infection which often leads to extensive necrosis of the skin. While the exact route of transmission remains uncertain, like many tropical diseases, associations with climate have been previously observed and could help identify the causative agent's ecological niche. In this paper, links between changes in rainfall and outbreaks of Buruli ulcer in French Guiana...

  11. “Touching Triton”: Building Student Understanding of Complex Disease Risk

    OpenAIRE

    Loftin, Madelene; East, Kelly; Hott, Adam; Lamb, Neil

    2016-01-01

    Life science classrooms often emphasize the exception to the rule when it comes to teaching genetics, focusing heavily on rare single-gene and Mendelian traits. By contrast, the vast majority of human traits and diseases are caused by more complicated interactions between genetic and environmental factors. Research indicates that students have a deterministic view of genetics, generalize Mendelian inheritance patterns to all traits, and have unrealistic expectations of genetic technologies. T...

  12. Complex educational and care (gerontechnology for elderly individuals/families experiencing Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Silomar Ilha

    Full Text Available ABSTRACT Objective: To describe the contributions of the Integrated Multidisciplinary Care Group for Caregivers of Individuals with Alzheimer's Disease as an educational and care (gerontechnology in the context of Alzheimer's disease in elderly individuals from the perspective of family members/caregivers. Method: Exploratory, descriptive study with a qualitative approach conducted with 13 family members/caregivers of elderly people participating in the support group of a university institution of the state of Rio Grande do Sul, Brazil. Data collected between January and April 2016 through a semi-structured interview were submitted to discursive textual analysis. Results: Family members/caregivers pointed out education and care as contributions of the group; education for care and for the future; exchange, socialization, and development of knowledge through the range of knowledge existing in the Group. Conclusion: The Group contributes as a (gerontechnology of care and education for care in which knowledge is built and applied in practice, supporting the experienced disorders and improving the quality of care provided for elderly individuals with Alzheimer's disease.

  13. Major histocompatibility complex (MHC) molecules: their common characteristics and relations with diseases

    OpenAIRE

    Başak Yalçın

    2013-01-01

    Major histocompatibility complex (MHC) molecules or human leukocyte antigens (HLA) are the cell surface molecules responsible from antigen presentation and activation of T cells. At the same time MHC molecules determine direction of T cell response. Unlike T cells, antigen specificity of MHC molecules is not high and they can not differenciate self and non-self antigens from each other. MHC molecules are classified as MHC I (HLA- A, B, C) and MHC II (HLA-DP, DR, DQ) molecules which are struct...

  14. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

    Science.gov (United States)

    Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J; Sterk, Peter J; Yiallouros, Panayiotis; Roca, Josep; Van de Perre, Philippe; Mercier, Jacques

    2014-01-01

    Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

  15. Climate impact on spreading of airborne infectious diseases. Complex network based modeling of climate influences on influenza like illnesses

    Science.gov (United States)

    Brenner, Frank; Marwan, Norbert; Hoffmann, Peter

    2017-06-01

    In this study we combined a wide range of data sets to simulate the outbreak of an airborne infectious disease that is directly transmitted from human to human. The basis is a complex network whose structures are inspired by global air traffic data (from openflights.org) containing information about airports, airport locations, direct flight connections and airplane types. Disease spreading inside every node is realized with a Susceptible-Exposed-Infected-Recovered (SEIR) compartmental model. Disease transmission rates in our model are depending on the climate environment and therefore vary in time and from node to node. To implement the correlation between water vapor pressure and influenza transmission rate [J. Shaman, M. Kohn, Proc. Natl. Acad. Sci. 106, 3243 (2009)], we use global available climate reanalysis data (WATCH-Forcing-Data-ERA-Interim, WFDEI). During our sensitivity analysis we found that disease spreading dynamics are strongly depending on network properties, the climatic environment of the epidemic outbreak location, and the season during the year in which the outbreak is happening.

  16. Gene-Environment Interplay in Common Complex Diseases: Forging an Integrative Model—Recommendations From an NIH Workshop

    Science.gov (United States)

    Bookman, Ebony B.; McAllister, Kimberly; Gillanders, Elizabeth; Wanke, Kay; Balshaw, David; Rutter, Joni; Reedy, Jill; Shaughnessy, Daniel; Agurs-Collins, Tanya; Paltoo, Dina; Atienza, Audie; Bierut, Laura; Kraft, Peter; Fallin, M. Daniele; Perera, Frederica; Turkheimer, Eric; Boardman, Jason; Marazita, Mary L.; Rappaport, Stephen M.; Boerwinkle, Eric; Suomi, Stephen J.; Caporaso, Neil E.; Hertz-Picciotto, Irva; Jacobson, Kristen C.; Lowe, William L.; Goldman, Lynn R.; Duggal, Priya; Gunnar, Megan R.; Manolio, Teri A.; Green, Eric D.; Olster, Deborah H.; Birnbaum, Linda S.

    2011-01-01

    Although it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene-environment interaction remain a challenge and have had limited success to date. Given the current state-of-the-science, NIH sought input on ways to accelerate investigations of gene-environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene-environment interaction studies. Participants of the NIH Gene-Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene-environment interactions. Further, participants also emphasized the continued need for high-quality measures of environmental exposures and new genomic technologies in ongoing and new studies. PMID:21308768

  17. The power of gene-based rare variant methods to detect disease-associated variation and test hypotheses about complex disease.

    Directory of Open Access Journals (Sweden)

    Loukas Moutsianas

    2015-04-01

    Full Text Available Genome and exome sequencing in large cohorts enables characterization of the role of rare variation in complex diseases. Success in this endeavor, however, requires investigators to test a diverse array of genetic hypotheses which differ in the number, frequency and effect sizes of underlying causal variants. In this study, we evaluated the power of gene-based association methods to interrogate such hypotheses, and examined the implications for study design. We developed a flexible simulation approach, using 1000 Genomes data, to (a generate sequence variation at human genes in up to 10K case-control samples, and (b quantify the statistical power of a panel of widely used gene-based association tests under a variety of allelic architectures, locus effect sizes, and significance thresholds. For loci explaining ~1% of phenotypic variance underlying a common dichotomous trait, we find that all methods have low absolute power to achieve exome-wide significance (~5-20% power at α = 2.5 × 10(-6 in 3K individuals; even in 10K samples, power is modest (~60%. The combined application of multiple methods increases sensitivity, but does so at the expense of a higher false positive rate. MiST, SKAT-O, and KBAC have the highest individual mean power across simulated datasets, but we observe wide architecture-dependent variability in the individual loci detected by each test, suggesting that inferences about disease architecture from analysis of sequencing studies can differ depending on which methods are used. Our results imply that tens of thousands of individuals, extensive functional annotation, or highly targeted hypothesis testing will be required to confidently detect or exclude rare variant signals at complex disease loci.

  18. Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada

    Directory of Open Access Journals (Sweden)

    R. Michele Anholt

    2017-12-01

    Full Text Available Bovine respiratory disease (BRD is the most important illness of feedlot cattle. Disease management targets the associated bacterial pathogens, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni, and Trueperella pyogenes. We conducted a cross-sectional study to measure the frequencies of antimicrobial-resistant BRD pathogens using a collaborative network of veterinarians, industry, government, and a diagnostic laboratory. Seven private veterinary practices in southern Alberta collected samples from both living and dead BRD-affected animals at commercial feedlots. Susceptibility testing of 745 isolates showed that 100% of the M. haemolytica, M. bovis, P. multocida, and T. pyogenes isolates and 66.7% of the H. somni isolates were resistant to at least one antimicrobial class. Resistance to macrolide antimicrobials (90.2% of all isolates was notable for their importance to beef production and human medicine. Multidrug resistance (MDR was high in all target pathogens with 47.2% of the isolates resistant to four or five antimicrobial classes and 24.0% resistance to six to nine classes. We compared the MDR profiles of isolates from two feedlots serviced by different veterinary practices. Differences in the average number of resistant classes were found for M. haemolytica (p < 0.001 and P. multocida (p = 0.002. Compared to previous studies, this study suggests an increasing trend of resistance in BRD pathogens against the antimicrobials used to manage the disease in Alberta. For the veterinary clinician, the results emphasize the importance of ongoing susceptibility testing of BRD pathogens to inform treatment protocols. Surveillance studies that collect additional epidemiological information and manage sampling bias will be necessary to develop strategies to limit the spread of resistance.

  19. Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada.

    Science.gov (United States)

    Anholt, R Michele; Klima, Cassidy; Allan, Nick; Matheson-Bird, Heather; Schatz, Crystal; Ajitkumar, Praseeda; Otto, Simon Jg; Peters, Delores; Schmid, Karin; Olson, Merle; McAllister, Tim; Ralston, Brenda

    2017-01-01

    Bovine respiratory disease (BRD) is the most important illness of feedlot cattle. Disease management targets the associated bacterial pathogens, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni , and Trueperella pyogenes . We conducted a cross-sectional study to measure the frequencies of antimicrobial-resistant BRD pathogens using a collaborative network of veterinarians, industry, government, and a diagnostic laboratory. Seven private veterinary practices in southern Alberta collected samples from both living and dead BRD-affected animals at commercial feedlots. Susceptibility testing of 745 isolates showed that 100% of the M. haemolytica, M. bovis, P. multocida , and T. pyogenes isolates and 66.7% of the H. somni isolates were resistant to at least one antimicrobial class. Resistance to macrolide antimicrobials (90.2% of all isolates) was notable for their importance to beef production and human medicine. Multidrug resistance (MDR) was high in all target pathogens with 47.2% of the isolates resistant to four or five antimicrobial classes and 24.0% resistance to six to nine classes. We compared the MDR profiles of isolates from two feedlots serviced by different veterinary practices. Differences in the average number of resistant classes were found for M. haemolytica ( p  BRD pathogens against the antimicrobials used to manage the disease in Alberta. For the veterinary clinician, the results emphasize the importance of ongoing susceptibility testing of BRD pathogens to inform treatment protocols. Surveillance studies that collect additional epidemiological information and manage sampling bias will be necessary to develop strategies to limit the spread of resistance.

  20. Kahlbaum, Hecker, and Kraepelin and the Transition From Psychiatric Symptom Complexes to Empirical Disease Forms.

    Science.gov (United States)

    Kendler, Kenneth S; Engstrom, Eric J

    2017-02-01

    The nosology for major psychiatric disorders developed by Emil Kraepelin in the 1890s has substantially shaped psychiatry. His theories, however, did not arise de novo, being strongly influenced by Karl Kahlbaum and Ewald Hecker. From the 1860-1880s, they articulated a paradigm shift in the conceptualization of psychiatric diagnosis, from symptom-based syndromes, popular since the late 18th century, to proto-disease entities. This effort was influenced by parallel developments in general medicine, especially the rise of bacterial theories of disease where different syndromes had distinctive symptoms, courses, and etiologies. Their thinking was particularly shaped by the increasing understanding of general paresis of the insane. Indeed, this disorder, with its distinct course and characteristic symptoms, was paradigmatic for them. Their hope was that a similar progression of medical understanding would evolve for the other major psychiatric syndromes. Their thinking and its connection with Kraepelin's nosology are illustrated through a close reading of their essays on hebephrenia, catatonia, and cyclic insanity. Kahlbaum, Hecker, and Kraepelin shared both a commitment to a clinical research agenda for psychiatry (to utilize methods of clinical assessment and follow-up to help define disease forms) and a skepticism for the brain-based neuropathological paradigm of psychiatric research then dominant in most European centers. Understanding the historical origins of our key diagnostic concepts can help us to evaluate their strengths and limitations. It remains to be determined whether this "Kahlbaum-Hecker-Kraepelin paradigm"-defining disorders based on distinctive symptoms and course-will produce psychiatric syndromes of sufficient homogeneity to yield their etiologic secrets.

  1. Twin-based DNA methylation analysis takes the center stage of studies of human complex diseases

    DEFF Research Database (Denmark)

    Zhang, Dongfeng; Li, Shuxia; Tan, Qihua

    2012-01-01

    -related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Various study designs and application issues will be highlighted and discussed with aim at making uses of twins in assessing the environmental impact on epigenetic changes during the development...... understanding of the epigenetic processes remains limited. Twins are special samples in genetic studies due to their genetic similarity and rearing-environment sharing. In the past decades, twins have made a great contribution in dissecting the genetic and environmental contributions to human diseases...

  2. The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases.

    Science.gov (United States)

    Heidema, A Geert; Boer, Jolanda M A; Nagelkerke, Nico; Mariman, Edwin C M; van der A, Daphne L; Feskens, Edith J M

    2006-04-21

    Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods have been developed for analyzing the relation between large numbers of genetic and environmental predictors to disease or disease-related variables in genetic association studies. In this commentary we discuss logistic regression analysis, neural networks, including the parameter decreasing method (PDM) and genetic programming optimized neural networks (GPNN) and several non-parametric methods, which include the set association approach, combinatorial partitioning method (CPM), restricted partitioning method (RPM), multifactor dimensionality reduction (MDR) method and the random forests approach. The relative strengths and weaknesses of these methods are highlighted. Logistic regression and neural networks can handle only a limited number of predictor variables, depending on the number of observations in the dataset. Therefore, they are less useful than the non-parametric methods to approach association studies with large numbers of predictor variables. GPNN on the other hand may be a useful approach to select and model important predictors, but its performance to select the important effects in the presence of large numbers of predictors needs to be examined. Both the set association approach and random forests approach are able to handle a large number of predictors and are useful in reducing these predictors to a subset of predictors with an important contribution to disease. The combinatorial methods give more insight in combination patterns for sets of genetic and/or environmental predictor variables that may be related to the outcome variable. As the non-parametric methods have different strengths and weaknesses we conclude that to approach genetic association

  3. Computational modeling and statistical analyses on individual contact rate and exposure to disease in complex and confined transportation hubs

    Science.gov (United States)

    Wang, W. L.; Tsui, K. L.; Lo, S. M.; Liu, S. B.

    2018-01-01

    Crowded transportation hubs such as metro stations are thought as ideal places for the development and spread of epidemics. However, for the special features of complex spatial layout, confined environment with a large number of highly mobile individuals, it is difficult to quantify human contacts in such environments, wherein disease spreading dynamics were less explored in the previous studies. Due to the heterogeneity and dynamic nature of human interactions, increasing studies proved the importance of contact distance and length of contact in transmission probabilities. In this study, we show how detailed information on contact and exposure patterns can be obtained by statistical analyses on microscopic crowd simulation data. To be specific, a pedestrian simulation model-CityFlow was employed to reproduce individuals' movements in a metro station based on site survey data, values and distributions of individual contact rate and exposure in different simulation cases were obtained and analyzed. It is interesting that Weibull distribution fitted the histogram values of individual-based exposure in each case very well. Moreover, we found both individual contact rate and exposure had linear relationship with the average crowd densities of the environments. The results obtained in this paper can provide reference to epidemic study in complex and confined transportation hubs and refine the existing disease spreading models.

  4. Functional interrelations between the lumbosacral, sacroiliac and coxofemoral complex in dogs as denoted by degenerative joint diseases

    International Nuclear Information System (INIS)

    Kuenzel, W.; Breit, S.; Knaus, I.

    2002-01-01

    Functional interrelations between coxofemoral joint, sacroiliac joint and the lumbosacral junction were investigated in Rottweilers, Golden Retriever and German Shepherd dogs. The study was based on sample of 120 ventrodorsal radiographs of the pelvis, which was assessed for evidence of hip dysplasia, alterations of the synovial and extrasynovial components of the sacroiliac joints, and osteophyte formation at the lumbosacral junction. Alteration of the extrasynovial component of the sacroiliac joint was the disease most commonly observed. Such degenerative alterations of the sacroiliac joint were noted to be associated with osteophyte formation at the lumbosacral junction. Both diseases were associated with age and German Shepherd dogs were most frequently affected. Results obtained by the additional evaluation of the coxofemoral joints suggest two mechanisms inducing degenerative alterations at the joint complex investigated. Based on changes in collagen composition, congenitally determined insufficiency of the supporting connective tissue may be responsible for the coincidence of alterations of all joint components of the lumbosacral - sacroilia - coxofemoral complex as noted in one group of dogs. In contrast, pre-dominant affection of the sacroiliac amphiarthosis and the lumbosacral intervertebral disc space is supposed to result from cumulative overloading. (author)

  5. @neurIST: infrastructure for advanced disease management through integration of heterogeneous data, computing, and complex processing services.

    Science.gov (United States)

    Benkner, Siegfried; Arbona, Antonio; Berti, Guntram; Chiarini, Alessandro; Dunlop, Robert; Engelbrecht, Gerhard; Frangi, Alejandro F; Friedrich, Christoph M; Hanser, Susanne; Hasselmeyer, Peer; Hose, Rod D; Iavindrasana, Jimison; Köhler, Martin; Iacono, Luigi Lo; Lonsdale, Guy; Meyer, Rodolphe; Moore, Bob; Rajasekaran, Hariharan; Summers, Paul E; Wöhrer, Alexander; Wood, Steven

    2010-11-01

    The increasing volume of data describing human disease processes and the growing complexity of understanding, managing, and sharing such data presents a huge challenge for clinicians and medical researchers. This paper presents the @neurIST system, which provides an infrastructure for biomedical research while aiding clinical care, by bringing together heterogeneous data and complex processing and computing services. Although @neurIST targets the investigation and treatment of cerebral aneurysms, the system's architecture is generic enough that it could be adapted to the treatment of other diseases. Innovations in @neurIST include confining the patient data pertaining to aneurysms inside a single environment that offers clinicians the tools to analyze and interpret patient data and make use of knowledge-based guidance in planning their treatment. Medical researchers gain access to a critical mass of aneurysm related data due to the system's ability to federate distributed information sources. A semantically mediated grid infrastructure ensures that both clinicians and researchers are able to seamlessly access and work on data that is distributed across multiple sites in a secure way in addition to providing computing resources on demand for performing computationally intensive simulations for treatment planning and research.

  6. [Psychiatry and occupational diseases act in Chile: historical and critical review of a complex relationship].

    Science.gov (United States)

    Almonte, Juan C; Mena, Cristián; Ortiz, Sofía; Osorio, Juan P

    2016-12-01

    The Work Accidents and Occupational Diseases Act exists in Chile since 1968. It uses a single model for the understanding and management of both somatic diseases like silicosis and psychiatric disorders. During the last decade in Chile, the consultation rates due to psychiatric conditions of probable labor origin has rose over 1,000%, a factor that underscored the deficiencies of this model. The aim of this paper is to analyze the consequences of the application of this act in the psychiatric field for almost 50 years after its promulgation. This article contains an historical overview and an epistemological debate based on the authors’ experience dealing with clinical and administrative work both in occupational psychiatry departments and in regulatory entities. The development of occupational mental health in Chile is examined as part of an historical process that initially did not consider the relationship between work and mental suffering as relevant. The application of a single causality model in psychiatry, as well as the effects of building a psychiatric nosology upon legal rather than medical criteria is contested.

  7. Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

    Science.gov (United States)

    Disanto, Giulio; Berlanga, Antonio J.; Handel, Adam E.; Para, Andrea E.; Burrell, Amy M.; Fries, Anastasia; Handunnetthi, Lahiru; De Luca, Gabriele C.; Morahan, Julia M.

    2011-01-01

    Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research. PMID:21197462

  8. Cutaneous Disseminated and Extracutaneous Sporotrichosis: Current Status of a Complex Disease

    Directory of Open Access Journals (Sweden)

    Alexandro Bonifaz

    2017-02-01

    Full Text Available Sporotrichosis is an implantation or inoculation mycosis caused by species of Sporothrix schenckii complex; its main manifestations are limited to skin; however, cutaneous-disseminated, disseminated (visceral and extracutaneous variants of sporotrichosis can be associated with immunosuppression, including HIV-AIDS, chronic alcoholism or more virulent strains. The most common extracutaneous form of sporotrichosis includes pulmonary, osteoarticular and meningeal. The laboratory diagnosis requires observing yeast forms and isolating the fungus; the two main causative agents are Sporothrix schenckii (ss and Sporothrix brasiliensis. Antibody levels and species recognition by Polimerase Chain Reaction using biological samples or cultures are also useful. The treatment of choice for most cases is amphotericin B and subsequent itraconazole for maintenance therapy.

  9. Treatment of Children with Protein – Losing Enteropathy After Fontan and Other Complex Congenital Heart Disease Procedures in Condition with Limited Human and Technical Resources

    OpenAIRE

    Bejiqi, Ramush; Retkoceri, Ragip; Zeka, Naim; Bejiqi, Hana; Vuqiterna, Armend; Maloku, Arlinda

    2014-01-01

    Background Protein-losing enteropathy (PLE) is a disorder characterized by abnormal and often profound enteric protein loss. It’s relatively uncommon complication of Fontan and other complex congenital heart disease (CCHD) procedures. Because of the complexity and rarity of this disease process, the pathogenesis and pathophysiology of protein-losing enteropathy remain poorly understood, and attempts at treatment seldom yield long-term success. Aim of presentation is to describe single centre ...

  10. APP/Go protein Gβγ-complex signaling mediates Aβ degeneration and cognitive impairment in Alzheimer's disease models.

    Science.gov (United States)

    Bignante, Elena Anahi; Ponce, Nicolás Eric; Heredia, Florencia; Musso, Juliana; Krawczyk, María C; Millán, Julieta; Pigino, Gustavo F; Inestrosa, Nibaldo C; Boccia, Mariano M; Lorenzo, Alfredo

    2018-04-01

    Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation. Gallein, a selective pharmacological inhibitor of Gβγ complex, inhibited Aβ-induced dendritic and axonal dystrophy, abnormal tau phosphorylation, synaptic loss, and neuronal cell death in hippocampal neurons expressing endogenous protein levels. In the 3xTg-AD mice, intrahippocampal application of gallein reversed memory impairment associated with early Aβ pathology. Our data provide further evidence for the involvement of APP/Go protein in Aβ-induced degeneration and reveal that Gβγ complex is a signaling target potentially relevant for developing therapies for halting Aβ degeneration in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Complex Interactions between Fungal Avirulence Genes and Their Corresponding Plant Resistance Genes and Consequences for Disease Resistance Management

    Directory of Open Access Journals (Sweden)

    Yohann Petit-Houdenot

    2017-06-01

    Full Text Available During infection, pathogens secrete an arsenal of molecules, collectively called effectors, key elements of pathogenesis which modulate innate immunity of the plant and facilitate infection. Some of these effectors can be recognized directly or indirectly by resistance (R proteins from the plant and are then called avirulence (AVR proteins. This recognition usually triggers defense responses including the hypersensitive response and results in resistance of the plant. R—AVR gene interactions are frequently exploited in the field to control diseases. Recently, the availability of fungal genomes has accelerated the identification of AVR genes in plant pathogenic fungi, including in fungi infecting agronomically important crops. While single AVR genes recognized by their corresponding R gene were identified, more and more complex interactions between AVR and R genes are reported (e.g., AVR genes recognized by several R genes, R genes recognizing several AVR genes in distinct organisms, one AVR gene suppressing recognition of another AVR gene by its corresponding R gene, two cooperating R genes both necessary to recognize an AVR gene. These complex interactions were particularly reported in pathosystems showing a long co-evolution with their host plant but could also result from the way agronomic crops were obtained and improved (e.g., through interspecific hybridization or introgression of resistance genes from wild related species into cultivated crops. In this review, we describe some complex R—AVR interactions between plants and fungi that were recently reported and discuss their implications for AVR gene evolution and R gene management.

  12. The role of 3D printing in preoperative planning for heart transplantation in complex congenital heart disease.

    Science.gov (United States)

    Smith, M L; McGuinness, J; O'Reilly, M K; Nolke, L; Murray, J G; Jones, J F X

    2017-08-01

    The presence of a structural cardiac defect in the setting of dextrocardia is extremely rare. Graspable models allow enhanced appreciation of aberrant structures and vascular relations, particularly in rare and complex cases. This is the first case report of the use of a replica of a patients' anatomy to plan the surgical strategy in the setting of dextrocardia. We intend to demonstrate the benefit of three-dimensional printing to enhance preoperative planning in complex congenital heart disease undergoing heart transplantation. The anomalous structures encountered include situs inversus dextrocardia, transposition of the great vessels, a single atrium and a dilated double-outlet single right ventricle. Computed Tomography acquisition was performed with the use of ECG multiphase gating technology and contrast enhancement. The structures of interest were segmented and the generated 3D mesh was exported as a stereolithographic (STL) file. The model was printed on a Z-Corp 250 binder jetting printer. Post processing techniques were used to enhance model strength. Pre-operative 3D visualisation of the patients' anatomy allowed for a more comprehensive surgical strategy to be planned, thus reducing the intra-operative duration and cross-clamp time which are recognised to correlate with reduced patient morbidity. The ongoing advances in medical image procurement and 3D processing software and printing technology will continue to enhance preoperative planning and thereby improve patient care. We demonstrate the pivotal role played by such technologies in advancing spatial comprehension of complex aberrant anatomy.

  13. Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

    Science.gov (United States)

    Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

    2016-07-01

    Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

  14. Reflex sympathetic dystrophy: complex regional pain syndrome type I in children with mitochondrial disease and maternal inheritance.

    Science.gov (United States)

    Higashimoto, T; Baldwin, E E; Gold, J I; Boles, R G

    2008-05-01

    Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy (RSD), is an idiopathic condition characterised by localised, abnormally intense and prolonged pain, allodynia and autonomic nervous system changes (ie, swelling, skin colour and temperature changes and altered perspiration) that usually appear following a "noxious" trigger such as trauma or surgery. The objective of this report is to demonstrate that children with CRPS-I can have additional dysautonomic conditions secondary to an underlying maternally inherited mitochondrial disease, an association not previously published. Medical records of about 500 patients seen by one paediatric metabolic geneticist were reviewed to identify children meeting established CRPS diagnostic criteria. CRPS-I was present in eight children in seven families, each of which also had additional functional/dysautonomic conditions, the most common (> or = 4 cases per condition) being gastrointestinal dysmotility, migraine, cyclic vomiting and chronic fatigue. All seven probands studied met Nijmegen (2002) diagnostic criteria for definite mitochondrial disease on the basis of the clinical signs and symptoms and biochemical analyses. Six of the seven families met our pedigree-based criteria for probable maternal inheritance. In one tertiary-care paediatric genetics practice, children meeting the CRPS-I diagnostic criteria frequently had additional autonomic-related conditions secondary to maternally inherited mitochondrial disease, suggesting that mitochondrial DNA sequence variants can predispose children towards the development of CRPS-I and other dysautonomias. CRPS-I should be considered in patients with mitochondrial disease who complain of idiopathic pain. Maternally inherited mitochondrial disease may not be a rare cause of CRPS-I, especially in children who present with other manifestations of dysautonomia.

  15. Complex educational and care (geron)technology for elderly individuals/families experiencing Alzheimer's disease.

    Science.gov (United States)

    Ilha, Silomar; Santos, Silvana Sidney Costa; Backes, Dirce Stein; Barros, Edaiane Joana Lima; Pelzer, Marlene Teda; Costenaro, Regina Gema Santini

    2017-01-01

    To describe the contributions of the Integrated Multidisciplinary Care Group for Caregivers of Individuals with Alzheimer's Disease as an educational and care (geron)technology in the context of Alzheimer's disease in elderly individuals from the perspective of family members/caregivers. Exploratory, descriptive study with a qualitative approach conducted with 13 family members/caregivers of elderly people participating in the support group of a university institution of the state of Rio Grande do Sul, Brazil. Data collected between January and April 2016 through a semi-structured interview were submitted to discursive textual analysis. Family members/caregivers pointed out education and care as contributions of the group; education for care and for the future; exchange, socialization, and development of knowledge through the range of knowledge existing in the Group. The Group contributes as a (geron)technology of care and education for care in which knowledge is built and applied in practice, supporting the experienced disorders and improving the quality of care provided for elderly individuals with Alzheimer's disease. Descrever as contribuições do Grupo de Assistência Multidisciplinar Integrada aos Cuidadores de Pessoas com a Doença de Alzheimer como (geronto)tecnologia cuidativo-educacional no contexto da doença de Alzheimer em pessoas idosas, na perspectiva de familiares/cuidadores. Pesquisa exploratório-descritiva, qualitativa, realizada com 13 familiares/cuidadores de pessoas idosas, participantes do grupo de apoio de uma instituição universitária do Rio Grande do Sul, Brasil. Os dados coletados entre janeiro a abril/2016, com uma entrevista semiestruturada, foram submetidos à análise textual discursiva. Os familiares/cuidadores referiram como contribuições do Grupo a educação e o cuidado; a educação para o cuidado e para o futuro; a troca, socialização e construção do conhecimento por meio dos diversos saberes existentes no Grupo. O

  16. Association of satellites with a mastrevirus in natural infection: complexity of Wheat dwarf India virus disease.

    Science.gov (United States)

    Kumar, Jitendra; Kumar, Jitesh; Singh, Sudhir P; Tuli, Rakesh

    2014-06-01

    (WDIV), isolated from two distant locations in India. This study reports the first identification of the satellites in a monocot plant. The satellites enhanced accumulation of WDIV and severity of disease symptoms. The satellites lowered the concentration of virus-specific small RNAs in wheat plants, indicating their silencing suppressor activity. The involvement of the satellites in symptom severity of the mastrevirus can have implications in the form of economic impact of the virus on crop yield. Understanding the role of the satellites in disease severity is important for developing disease management strategies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. Results of clinical approbation of new local treatment method in the complex therapy of inflammatory parodontium diseases

    Directory of Open Access Journals (Sweden)

    Yu. G. Romanova

    2017-08-01

    Full Text Available Treatment and prevention of inflammatory diseases of parodontium are one of the most difficult problems in stomatology today. Purpose of research: estimation of clinical efficiency of local combined application of developed agent apigel for oral cavity care and low-frequency electromagnetic field magnetotherapy at treatment of inflammatory diseases of parodontium. Materials and methods: 46 patients with chronic generalized catarrhal gingivitis and chronic generalized periodontitis of 1st degree were included into the study. Patients were divided into 2 groups depending on treatment management: basic (n = 23 and control (n = 23. Conventional treatment with the local use of the dental gel with camomile was used in the control group. Patients of the basic group were treated with local combined application of apigel and magnetotherapy. Efficiency was estimated with clinical, laboratory, microbiological and functional (ultrasonic Doppler examination methods of examination. Results: The application of the apigel and pulsating electromagnetic field in the complex medical treatment of patients with chronic generalized periodontitis (GhGP caused positive changes in clinical symptom and condition of parodontal tissues, that was accompanied by decline of hygienic and parodontal indexes. As compared with patients who had traditional anti-inflammatory therapy, patients who were treated with local application of apigel and magnetoterapy had decline of edema incidence. It was revealed that decrease of the pain correlated with improvement of hygienic condition of oral cavity and promoted prevention of bacterial contamination of damaged mucous membranes. Estimation of microvasculatory blood stream with the method of ultrasonic doppler flowmetry revealed more rapid normalization of volume and linear high systole, speed of blood stream in the parodontal tissues in case of use of new complex local method. Conclusions: Effect of the developed local agent in patients

  18. Role of H3K4 demethylases in complex neurodevelopmental diseases.

    Science.gov (United States)

    Wynder, Christopher; Stalker, Leanne; Doughty, Martin L

    2010-06-01

    Significant neurological disorders can result from subtle perturbations of gene regulation that are often linked to epigenetic regulation. Proteins that regulate the methylation of lysine 4 of histone H3 (H3K4) and play a central role in epigenetic regulation, and mutations in genes encoding these enzymes have been identified in both autism and Rett syndrome. The H3K4 demethylases remove methyl groups from lysine 4 leading to loss of RNA polymerase binding and transcriptional repression. When these proteins are mutated, brain development is altered. Currently, little is known regarding how these gene regulators function at the genomic level. In this article, we will discuss findings that link H3K4 demethylases to neurodevelopment and neurological disease.

  19. Stenting and overdilating small Gore-Tex vascular grafts in complex congenital heart disease.

    Science.gov (United States)

    Penford, Gemma; Quandt, Daniel; Mehta, Chetan; Bhole, Vinay; Dhillon, Rami; Seale, Anna; Stumper, Oliver

    2018-01-01

    Gore-Tex ® grafts are integral in the management of congenital heart disease. Issues of graft stenosis or somatic outgrowth may precipitate high-risk early surgery, and catheter intervention is a relatively under-reported management option. To assess efficacy, safety, and outcomes of stenting and overdilating small Gore-Tex ® vascular grafts with the aim of optimizing surgical timing. Retrospective analysis of single-center, 13-year experience of 93 graft stenting interventions or reintervention in 80 patients, with the aim of relieving stenosis ± overdilation, to depose surgical graft revision or optimize surgical timing and candidacy. Median preintervention graft diameter was 52% (IQR 43-63) of nominal size, postintervention this increased to median 102% (IQR 96-120) [P Gore-Tex ® vascular grafts can be stented effectively and expanded beyond nominal diameters by around +26%. This improves oxygen saturations, providing excellent palliation and optimized surgical timing. Adverse events are most frequent in precavopulmonary shunt patients. Gore-Tex ® grafts are widely used in the palliation of cyanotic congenital heart disease. Grafts may become stenosed and do not allow for somatic growth. Over a 13 year period, graft stenting was performed in 80 patients (93 technically successful interventions, 4 unsuccessful.) Median internal lumen change was +50% (of nominal graft size), mean oxygen saturation change +13%. Over-dilation was performed in more than half of the cohort, with a median gain of +26% on nominal graft size. In precavopulmonary shunt patients, there was a moderate incidence of serious complications. Clinically useful deferral of surgery was achieved for the majority. © 2018 Wiley Periodicals, Inc.

  20. The impact of complex chronic diseases on care utilization among assisted living residents.

    Science.gov (United States)

    McNabney, Matthew K; Onyike, Chiadi; Johnston, Deirdre; Mayer, Lawrence; Lyketsos, Constantine; Brandt, Jason; Rosenblatt, Adam; Samus, Quincy

    2014-01-01

    Many residents of assisted living (AL) have chronic diseases that are difficult to manage, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). We estimated the amount and intensity of care delivered by the staff for residents with these conditions. We performed a secondary data analysis from the Maryland Assisted Living (MDAL) Study (399 residents, 29 facilities). In-person assessments included measures of cognition, function, depression, and general medical health. Diagnosis of CHF, COPD, and DM, as well as current medications was abstracted from AL medical charts. Measures of care utilization were operationalized at the resident level as: 1) minutes per day of direct care (caregiver activity scale [CAS]), 2) subjective staff ratings of care burden, and 3) assigned AL "level of care" (based on state regulatory criteria). In best fit regression models, CHF and DM were not significant predictors of the evaluated care utilization measures; however, COPD was independently associated with increased minutes per day of direct care - 34% of the variance in the caregiver activity scale was explained by degree of functional dependency, cognitive impairment, age, and presence of COPD. Functional dependency, depressive symptoms, and age explained almost a quarter (23%) of the variance of staff care burden rating. For the AL level of care intensity rating, degree of functional dependency, level of cognition, and age were significant correlates, together explaining about 28% of the variance. The presence of COPD was a significant predictor of time per day of direct care. However, CHF and DM were not correlates of care utilization measures. Functional and cognitive impairment was associated with measures of care utilization, reiterating the importance of these characteristics in the utilization and intensity of care consumed by AL residents. Further study of this population could reveal other forms and amounts of

  1. Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease.

    Science.gov (United States)

    Crowe, Sonya; Knowles, Rachel; Wray, Jo; Tregay, Jenifer; Ridout, Deborah A; Utley, Martin; Franklin, Rodney; Bull, Catherine L; Brown, Katherine L

    2016-06-06

    Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3-5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. UK. A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

    2015-03-01

    Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

  3. Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

    International Nuclear Information System (INIS)

    Back, Susan J.; Andronikou, Savvas; Kilborn, Tracy; Kaplan, Bernard S.; Darge, Kassa

    2015-01-01

    Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

  4. Broncho-pleural fistula with hydropneumothorax at CT: Diagnostic implications in mycobacterium avium complex lung disease with pleural involvement

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Park, Hye Yun; Koh, Won Jung [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jung Soo [Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2016-04-15

    To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion.

  5. Broncho-pleural fistula with hydropneumothorax at CT: Diagnostic implications in mycobacterium avium complex lung disease with pleural involvement

    International Nuclear Information System (INIS)

    Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Park, Hye Yun; Koh, Won Jung; Kim, Jung Soo

    2016-01-01

    To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion

  6. Thousand Cankers Disease Complex: A Forest Health Issue that Threatens Juglans Species across the U.S.

    Directory of Open Access Journals (Sweden)

    Dixie A. Daniels

    2016-11-01

    Full Text Available Thousand Cankers Disease (TCD is a disease complex wherein the fungus (Geosmithia morbida is vectored by the walnut twig beetle (WTB, Pityophthorus juglandis. The disease causes mortality primarily of eastern black walnut (Juglans nigra, although other walnut and wingnut (Pterocarya species are also susceptible. Black walnut is native to the Eastern and Midwestern U.S. but is widely planted in western states. Total standing volume in both urban and forested settings is approximately 96 million cubic meters, and is valued at $539 billion. Although native to the Southwestern U.S., the range of WTB has expanded considerably. The spread of G. morbida coincides with that of WTB. TCD was introduced into Tennessee in 2010, and has spread to seven eastern states. Trees infected with TCD exhibit drought-like symptoms, making field detection difficult without molecular and/or morphological methods. The recently sequenced G. morbida genome will provide valuable research tools focused on understanding gene interactions between organisms involved in TCD and mechanisms of pathogenicity. With no chemical treatments available, quarantine and sanitation are preeminent options for slowing the spread of TCD, although biological control agents have been discovered. High levels of black walnut mortality due to TCD will have far-reaching implications for both eastern and western states.

  7. Fractional flow reserve for the assessment of complex multivessel disease in a patient after hybrid coronary revascularization.

    Science.gov (United States)

    Corban, Michel T; Eshtehardi, Parham; Samady, Habib

    2013-06-01

    We present a case of a 43-year-old woman with history of hybrid coronary revascularization [endoscopic atraumatic coronary artery bypass (ACAB)] of left internal mammary artery (LIMA) to the left anterior descending artery (LAD) and stent implantation in right coronary artery (RCA), who presented 6 years later with recurrent atypical angina. Coronary angiography revealed patent LIMA to LAD and RCA stent, with a new lesion in an obtuse marginal artery and significant progression of disease in the proximal/mid LAD proximal to LIMA touchdown. To further evaluate the hemodynamic significance of these new disease segments, the patient underwent fractional flow reserve (FFR) assessment of the left coronary system with subsequent stent implantation in the proximal/mid LAD. This case illustrates (1) the critical value of FFR assessment in determining the ischemia provoking lesions in this post ACAB patient with complex multivessel coronary artery disease; and (2) the accelerated progression of atherosclerosis in bypassed segments as compared to segments proximal to stents. Copyright © 2012 Wiley Periodicals, Inc.

  8. Pathway analysis of complex diseases for GWAS, extending to consider rare variants, multi-omics and interactions.

    Science.gov (United States)

    Kao, Patrick Y P; Leung, Kim Hung; Chan, Lawrence W C; Yip, Shea Ping; Yap, Maurice K H

    2017-02-01

    Genome-wide association studies (GWAS) is a major method for studying the genetics of complex diseases. Finding all sequence variants to explain fully the aetiology of a disease is difficult because of their small effect sizes. To better explain disease mechanisms, pathway analysis is used to consolidate the effects of multiple variants, and hence increase the power of the study. While pathway analysis has previously been performed within GWAS only, it can now be extended to examining rare variants, other "-omics" and interaction data. 1. Factors to consider in the choice of software for GWAS pathway analysis. 2. Examples of how pathway analysis is used to analyse rare variants, other "-omics" and interaction data. To choose appropriate software tools, factors for consideration include covariate compatibility, null hypothesis, one- or two-step analysis required, curation method of gene sets, size of pathways, and size of flanking regions to define gene boundaries. For rare variants, analysis performance depends on consistency between assumed and actual effect distribution of variants. Integration of other "-omics" data and interaction can better explain gene functions. Pathway analysis methods will be more readily used for integration of multiple sources of data, and enable more accurate prediction of phenotypes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease

    Energy Technology Data Exchange (ETDEWEB)

    Tumbale, Percy; Appel, C Denise; Kraehenbuehl, Rolf; Robertson, Patrick D; Williams, Jessica S; Krahn, Joe; Ahel, Ivan; Williams, R Scott [NIEHS; (Manchester)

    2012-09-17

    DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn2+ complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C2HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

  10. Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

    Directory of Open Access Journals (Sweden)

    Ivo D Dinov

    Full Text Available A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI. The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data.Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i introduce methods for rebalancing imbalanced cohorts, (ii utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model

  11. Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

    Science.gov (United States)

    Dinov, Ivo D; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W; Price, Nathan D; Van Horn, John D; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M; Dauer, William; Toga, Arthur W

    2016-01-01

    A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model-based predictive approaches

  12. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies

    NARCIS (Netherlands)

    Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M.; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J.; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H.; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M.; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J.; Sterk, Peter J.; Yiallouros, Panayiotis; Roca, Josep; van de Perre, Philippe; Mercier, Jacques

    2014-01-01

    Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the

  13. Mental stress and ischemic heart disease: evolving awareness of a complex association.

    Science.gov (United States)

    Proietti, Riccardo; Mapelli, Daniela; Volpe, Biancarosa; Bartoletti, Stefano; Sagone, Antonio; Dal Bianco, Lucia; Daliento, Luciano

    2011-05-01

    The connection between cardiovascular disease and psychosocial risk factors has been the subject of an ever-growing body of literature over the last 50 years. Studies on the role of negative emotions, personality traits, chronic stress and social determinants have brought to light their possible role in triggering acute coronary syndromes, although further studies are required to clarify controversial results regarding the association between cardiovascular risk and important psychological problems such as depression and anxiety. The recognition of the role of emotional events in acute coronary syndromes paved the way for provocation experiments, aimed at inducing mental stress in a controlled setting and then documenting reversible impairment of myocardial perfusion, depolarization anomalies and arrhythmias. This ultimately led to the formalization of the concept of mental stress-induced myocardial ischemia. Accumulating evidence on the mechanistic bases of such phenomena outline a wide range of central and peripheral physiological changes associated with emotions and behaviors, whose effects are exerted on the cardiovascular system, sympathetic nervous system and the hypothalamus-hypophysis neuroendocrine axis. This article outlines the main steps in the identification of psychological aspects as cardiovascular risk factors and emphasizes the relevance of emotional stress as a trigger of acute cardiovascular events. Finally, a description is provided of the pathophysiological mechanisms behind mental stress-induced myocardial ischemia and pathways connecting the heart and brain.

  14. Complex temporal climate signals drive the emergence of human water-borne disease.

    Science.gov (United States)

    Morris, Aaron; Gozlan, Rodolphe E; Hassani, Hossein; Andreou, Demetra; Couppié, Pierre; Guégan, Jean-François

    2014-08-01

    Predominantly occurring in developing parts of the world, Buruli ulcer is a severely disabling mycobacterium infection which often leads to extensive necrosis of the skin. While the exact route of transmission remains uncertain, like many tropical diseases, associations with climate have been previously observed and could help identify the causative agent's ecological niche. In this paper, links between changes in rainfall and outbreaks of Buruli ulcer in French Guiana, an ultraperipheral European territory in the northeast of South America, were identified using a combination of statistical tests based on singular spectrum analysis, empirical mode decomposition and cross-wavelet coherence analysis. From this, it was possible to postulate for the first time that outbreaks of Buruli ulcer can be triggered by combinations of rainfall patterns occurring on a long (i.e., several years) and short (i.e., seasonal) temporal scale, in addition to stochastic events driven by the El Niño-Southern Oscillation that may disrupt or interact with these patterns. Long-term forecasting of rainfall trends further suggests the possibility of an upcoming outbreak of Buruli ulcer in French Guiana.

  15. PROTEIN COMPLEX OF WHEAT, BUCKWHEAT AND MAIZE IN RELATION TO CELIAC DISEASE

    Directory of Open Access Journals (Sweden)

    Milan Chňapek

    2014-02-01

    Full Text Available Cereals are the most wide spread and very important plants utilized as a food source for mankind and for animals where they play role in energetical metabolism and proteosynthesis. Cereals contain proteins with unique properties. These properties allow us to produce leavened bread. Technological characteristic of cereal grain is determined by quantity and quality of storage proteins which represent alcohol soluble prolamins and glutenins soluble in acids and basis solutions. Celiac disease is one of the most frequent food intolerance caused by cereal storage proteins. Therapy consists of strict diet without consumptions of cereals or gluten. Pseudocereals are very perspective groups of plants in gluten free diet, due to absence of celiac active proteins, but on the other hand, flour from pseudocereals is not very suitable for baking. There are a lot of analytical methods applicable for detection of celiac active proteins in cereal and pseudocereal grain. Electrophoretical and immunochemical methods are the most utilized. Genotypes of wheat and maize were homogeneous and singlelined in contrast with genotypes of buckwheat. Average content of HMW-GS was highest in genotypes of bread wheat and lowest in buckwheat varieties. A celiac active fraction of storage proteins (LMW-GS and gliadins was detected at the highest content level in wheat genotypes. Genotypes of buckwheat and maize showed similar low content of this protein fraction. Presence of residual albumins and globulins in buckwheat varieties showed the highest value.

  16. Understanding the complexities of functional ability in Alzheimer's disease: more than just basic and instrumental factors.

    Science.gov (United States)

    Kahle-Wrobleski, Kristin; Coley, Nicola; Lepage, Benoit; Cantet, Christelle; Vellas, Bruno; Andrieu, Sandrine

    2014-05-01

    Dementia of the Alzheimer's type (AD) is defined by both cognitive and functional decline; new criteria allow for identification of milder, non-functionally impaired patients. Understanding loss of autonomy in AD is essential, as later stages represent a significant burden and cost to patients, their families, and society. The purpose of the present analyses was to determine the factor structure of the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) in a cohort of AD patients. Baseline ADCS-ADL assessments of 734 AD patients from the PLASA study were included in an exploratory factor analysis (EFA). Because the ADCS-ADL was designed to assess change over time, change from baseline scores over 2 years were also analyzed using an EFA. Factorial solutions were evaluated based on cross-loading, non-loadings, and number of items per factor. Mean age at baseline was 79.3, mean MMSE was 19.8 and 73.3% of participants were female. Baseline data suggested a 4-factor solution that included factors for basic ADLs (BADLs), domestic/household activities, communication/engagement with the environment, and outside activities. The change scores EFA suggested a 2-factor solution of BADLs and instrumental ADLs (IADLs). Distinct factors of IADLs should be considered for further validation as areas of attention to catch early functional decline.

  17. Inflammatory bowel diseases influence major histocompatibility complex class I (MHC I) and II compartments in intestinal epithelial cells.

    Science.gov (United States)

    Bär, F; Sina, C; Hundorfean, G; Pagel, R; Lehnert, H; Fellermann, K; Büning, J

    2013-05-01

    Antigen presentation by intestinal epithelial cells (IEC) is crucial for intestinal homeostasis. Disturbances of major histocompatibility complex class I (MHC I)- and II-related presentation pathways in IEC appear to be involved in an altered activation of CD4(+) and CD8(+) T cells in inflammatory bowel disease. However, a comprehensive analysis of MHC I- and II-enriched compartments in IEC of the small and large bowel in the healthy state as opposed to inflammatory bowel diseases is lacking. The aim of this study was to characterize the subcellular expression of MHC I and II in the endocytic pathway of IEC throughout all parts of the intestinal tract, and to identify differences between the healthy state and inflammatory bowel diseases. Biopsies were taken by endoscopy from the duodenum, jejunum, ileum and colon in healthy individuals (n = 20). In Crohn's disease (CD), biopsies were obtained from the ileum and colon and within the colon from ulcerative colitis (UC) patients (n = 15). Analysis of IEC was performed by immunoelectron microscopy. MHC I and II were identified in early endosomes and multi-vesicular, multi-lamellar, electrondense and vacuolar late endosomes. Both molecules were enriched in multi-vesicular bodies. No differences were found between the distinct parts of the gut axis. In CD and UC the expression of MHC I and II showed a shift from multi-vesicular bodies towards the basolateral membranes. Within the multi-vesicular bodies, MHC I and II moved from internal vesicles to the limiting membranes upon inflammation in CD and UC. MHC I- and II-enriched compartments in IEC were identical in all parts of the small and large bowel. CD and UC appear to modulate the MHC I- and II-related presentation pathways of exogenous antigens in IEC. © 2012 British Society for Immunology.

  18. Grapevine leaf stripe disease symptoms (esca complex are reduced by a nutrients and seaweed mixture

    Directory of Open Access Journals (Sweden)

    Francesco CALZARANO

    2015-01-01

    Full Text Available Grapevine leaf stripe disease (GLSD seriously reduces the quality and quantity of grape production, and results in a shorter lifespan of vineyards. Recent research has shown that foliar applications of nutrients influence the development of GLSD foliar symptoms. Based on this knowledge the effect of foliar applications of a mixture of calcium chloride, magnesium nitrate and Fucales seaweed extract on the development of leaf symptoms was evaluated over a 3-year period from 2010 to 2012. Nine foliar applications of the full mixture and its individual mineral components, also in different combinations, were tested in three different vineyards, one of cv. Trebbiano d’Abruzzo and two of cv. Montepulciano d’Abruzzo in the Teramo province (Abruzzo, Italy. Treatments were applied every 10 days from the beginning of vegetative growth to pre-bunch closure. The final results were similar in all the three vineyards and in the three years leading to a significant reduction of symptom development in the vines treated with the full mixture, while lower effects were obtained by applying partial combinations or single components. Both quantity and quality of grapes from the treated vines increased, while no phytotoxic or other unwanted effects on grape growth were detected. Vines treated with the full mixture showed an increase in trans-resveratrol and flavonoids content, and a higher accumulation of calcium oxalate in crystal druses in the leaf mesophyll. These data can be a useful base to set up a control strategy against GLSD and give some input for better understanding the mechanisms involved in foliar symptom expression in GLSD.

  19. 3-D volumetric MRI evaluation of the placenta in fetuses with complex congenital heart disease.

    Science.gov (United States)

    Andescavage, Nickie; Yarish, Alexa; Donofrio, Mary; Bulas, Dorothy; Evangelou, Iordanis; Vezina, Gilbert; McCarter, Robert; duPlessis, Adre; Limperopoulos, Catherine

    2015-09-01

    Placental insufficiency remains a common cause of perinatal mortality and neurodevelopmental morbidity. Congenital heart disease (CHD) in the fetus and its relationship to placental function is unknown. This study explores placental health and its relationship to neonatal outcomes by comparing placental volumes in healthy pregnancies and pregnancies complicated by CHD using in vivo three-dimensional MRI studies. In a prospective observational study, pregnant women greater than 18 weeks gestation with normal pregnancies or pregnancies complicated by CHD were recruited and underwent fetal MR imaging. The placenta was manually outlined and the volume was calculated in cm(3). Brain volume was also calculated and clinical data were also collected. Relationships, including interactive effects, between placental and fetal growth, including brain growth, were evaluated using longitudinal multiple linear regression analysis. 135 women underwent fetal MRI between 18 and 39 weeks gestation (mean 31.6 ± 4.4). Placental volume increased exponentially with gestational age (p = 0.041). Placental volume was positively associated with birth weight (p < 0.001) and increased more steeply with birth weight in CHD-affected fetuses (p = 0.046). Total brain and cerebral volumes were smaller in the CHD group (p < 0.001), but brainstem volume (p < 0.001) was larger. Placental volumes were not associated with brain volumes. Impaired placental growth in CHD is associated with gestational age and birth weight at delivery. Abnormalities in placental development may contribute to the significant morbidity in this high-risk population. Assessment of placental volume by MRI allows for in vivo assessments of placental development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Diabetes, kidney disease and cardiovascular disease patients. Assessing care of complex patients using outpatient testing and visits: additional metrics by which to evaluate health care system functioning.

    Science.gov (United States)

    Levin, Adeera; Chaudhry, Munaza R; Djurdjev, Ognjenka; Beaulieu, Monica; Komenda, Paul

    2009-09-01

    The triad of cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetes mellitus (DM) share many fundamental disease pathways. Patients with these conditions contribute excessively to health care costs. Opportunities for system redesign require metrics by which to evaluate the impact. Using a provincial comprehensive set of administrative billing databases (outpatient visits, laboratory tests, pharmacy and hospital inpatient services), we itemized the prevalence of each and combination of conditions, resource utilization associated with each condition and combinations, using ICD 9-10 billing codes and standard definitions. Three consecutive years (2003-2005) were used to establish stability of findings. CKD, CVD and DM diagnoses are found in 422 124 persons within a province of 4.3 million individuals (10%); 1.7% had all three conditions. The median age of each cohort varied significantly between those with multiple conditions (67-79 years) versus those with single condition (56-72 years). The median number of physician visits was 26 per patient year. Duplicate testing accounted for expenditures of $3 million/annum; 7.55% of patients accounted for 34.4% of duplicate tests. Those with DM or CKD had similar use of medications, physician visits and hospital days. Those with all conditions (CVD-CKD-DM) had a median of 6 in-hospital days/year. A significant proportion were not on ACE/ARB or statin medications (30 and 45%, respectively). Patients with chronic, complex conditions consume a large number of outpatient and inpatient resources. Documenting these allows identification of a set of metrics by which to design and measure health care system redesign initiatives. Potential targets to benchmark in designing more effective systems have been identified.

  1. Vector capacity of members of Triatoma brasiliensis species complex: The need to extend Chagas disease surveillance to Triatoma melanica.

    Science.gov (United States)

    Folly-Ramos, Elaine; Dornak, L Lynnette; Orsolon, Guilherme; Gonçalves, Teresa Cristina Monte; Lilioso, Mauricio; Costa, Jane; Almeida, Carlos Eduardo

    2016-06-01

    We conducted a lab-based comparative study on vector capacity features of two species of triatomines: Triatoma brasiliensis and T. melanica. Both are members of the T. brasiliensis species complex. The former is the most important Chagas disease vector in the northeastern region of Brazil. To date, no transmission via T. melanica has been recorded. Immature insects exhibited distinct intermoult periods without a direct relationship to a given species. Females of T. brasiliensis consumed an average of 1.9 times more meals (mean = 12.92 vs 6.63) and survived for a shorter period (mean =330.8 days) than T. melanica (mean = 365.2 days), probably due to the cost of reproduction (all significant at P39%) of insects defecated rapidly (<30 s) after feeding. Overall, results highlight the need to extend vector surveillance to T. melanica. © 2016 The Society for Vector Ecology.

  2. Neuropsychological syndromes in patients with Parkinson’s disease after deep electric stimulation of pallidar complex structures

    Directory of Open Access Journals (Sweden)

    Yu V Mikadze

    2013-01-01

    Full Text Available The paper provides the results of neuropsychological examinations in 10 patients with Parkinson’s disease who underwent deep electrical stimulation of pallidar complex structures. The general neuropsychological test battery that had been developed by A.R. Luria and allowed the qualitative classification of the cognitive impairment symptoms detectable on examination to be made was used to study cognitive functions. The patients were examined before and just after surgery and in the late period (following 1—2 years. The examinations have shown that the syndromes indicative of dysfunctions in the deep, parietal, and occipital and prefrontal regions of the left hemisphere and in the parietooccipital regions of the right hemisphere are stable components that determine the pattern of cognitive disorders and are preserved throughout all examinations.

  3. Factors associated with development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics.

    Science.gov (United States)

    Joffe, Daniel J; Lelewski, Roxana; Weese, J Scott; Mcgill-Worsley, Jamie; Shankel, Catharine; Mendonca, Sonia; Sager, Tara; Smith, Michael; Poljak, Zvonimir

    2016-01-01

    This study investigated the association between presence of respiratory pathogens and development of Canine Infectious Respiratory Disease Complex (CIRDC) in dogs in 5 Canadian small animal clinics. In total, 86 dogs were tested using a commercial PCR respiratory panel; 64 dogs were considered as cases and 22 were control dogs matched by veterinary clinic. No control animals (0/22) were positive for canine parainfluenza virus (CPIV), whereas 27/64 (42%) CIRDC cases were positive. Furthermore, 81% of case dogs tested positive for Mycoplasma cynos, compared with 73% of control dogs. Canine respiratory corona virus (CRCoV) was detected in no control dogs compared with 9.4% of clinical dogs. No animals were positive for any influenza virus type A present in the diagnostic panel. Presence of CPIV was associated (P < 0.01) with the occurrence of CIRDC after adjustment for demographic factors and presence of CRCoV (P = 0.09).

  4. Gait Complexity and Regularity Are Differently Modulated by Treadmill Walking in Parkinson's Disease and Healthy Population

    Directory of Open Access Journals (Sweden)

    Thibault Warlop

    2018-02-01

    Full Text Available Variability raises considerable interest as a promising and sensitive marker of dysfunction in physiology, in particular in neurosciences. Both internally (e.g., pathology and/or externally (e.g., environment generated perturbations and the neuro-mechanical responses to them contribute to the fluctuating dynamics of locomotion. Defective internal gait control in Parkinson's disease (PD, resulting in typical timing gait disorders, is characterized by the breakdown of the temporal organization of stride duration variability. Influence of external cue on gait pattern could be detrimental or advantageous depending on situations (healthy or pathological gait pattern, respectively. As well as being an interesting rehabilitative approach in PD, treadmills are usually implemented in laboratory settings to perform instrumented gait analysis including gait variability assessment. However, possibly acting as an external pacemaker, treadmill could modulate the temporal organization of gait variability of PD patients which could invalidate any gait variability assessment. This study aimed to investigate the immediate influence of treadmill walking (TW on the temporal organization of stride duration variability in PD and healthy population. Here, we analyzed the gait pattern of 20 PD patients and 15 healthy age-matched subjects walking on overground and on a motorized-treadmill (randomized order at a self-selected speed. The temporal organization and regularity of time series of walking were assessed on 512 consecutive strides and assessed by the application of non-linear mathematical methods (i.e., the detrended fluctuation analysis and power spectral density; and sample entropy, for the temporal organization and regularity of gait variability, respectively. A more temporally organized and regular gait pattern seems to emerge from TW in PD while no influence was observed on healthy gait pattern. Treadmill could afford the necessary framework to regulate gait

  5. Ensemble Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Complex Graph Measures from Diffusion Tensor Images

    Science.gov (United States)

    Ebadi, Ashkan; Dalboni da Rocha, Josué L.; Nagaraju, Dushyanth B.; Tovar-Moll, Fernanda; Bramati, Ivanei; Coutinho, Gabriel; Sitaram, Ranganatha; Rashidi, Parisa

    2017-01-01

    The human brain is a complex network of interacting regions. The gray matter regions of brain are interconnected by white matter tracts, together forming one integrative complex network. In this article, we report our investigation about the potential of applying brain connectivity patterns as an aid in diagnosing Alzheimer's disease and Mild Cognitive Impairment (MCI). We performed pattern analysis of graph theoretical measures derived from Diffusion Tensor Imaging (DTI) data representing structural brain networks of 45 subjects, consisting of 15 patients of Alzheimer's disease (AD), 15 patients of MCI, and 15 healthy subjects (CT). We considered pair-wise class combinations of subjects, defining three separate classification tasks, i.e., AD-CT, AD-MCI, and CT-MCI, and used an ensemble classification module to perform the classification tasks. Our ensemble framework with feature selection shows a promising performance with classification accuracy of 83.3% for AD vs. MCI, 80% for AD vs. CT, and 70% for MCI vs. CT. Moreover, our findings suggest that AD can be related to graph measures abnormalities at Brodmann areas in the sensorimotor cortex and piriform cortex. In this way, node redundancy coefficient and load centrality in the primary motor cortex were recognized as good indicators of AD in contrast to MCI. In general, load centrality, betweenness centrality, and closeness centrality were found to be the most relevant network measures, as they were the top identified features at different nodes. The present study can be regarded as a “proof of concept” about a procedure for the classification of MRI markers between AD dementia, MCI, and normal old individuals, due to the small and not well-defined groups of AD and MCI patients. Future studies with larger samples of subjects and more sophisticated patient exclusion criteria are necessary toward the development of a more precise technique for clinical diagnosis. PMID:28293162

  6. GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.

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    Yutao Liu

    Full Text Available DNA copy number variants (CNVs have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC. This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1. (p = 0.017, fisher's exact test. It was validated with array comparative genomic hybridization (arrayCGH and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio = 3.5, 95% CI -1.1-12.0. Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4. Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

  7. Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

    Science.gov (United States)

    Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza

    2016-11-01

    We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Evaluation of obstructive airway lesions in complex congenital heart disease using composite volume-rendered images from multislice CT

    International Nuclear Information System (INIS)

    Choo, Ki Seok; Kim, Chang Won; Lee, Tae Hong; Kim, Suk; Kim, Kun Il; Lee, Hyoung Doo; Ban, Ji Eun; Sung, Si Chan; Chang, Yun Hee

    2006-01-01

    Multislice CT (MSCT) allows high-quality volume-rendered (VR) and composite volume-rendered images. To investigate the clinical usefulness of composite VR images in the evaluation of the relationship between cardiovascular structures and the airway in children with complex congenital heart disease (CHD). Four- or 16-slice MSCT scanning was performed consecutively in 77 children (mean age 6.4 months) with CHD and respiratory symptoms, a chest radiographic abnormality, or abnormal course of the pulmonary artery on ECHO. MSCT scanning was performed during breathing or after sedation. Contrast medium (2 ml/kg) was administered through a pedal venous route or arm vein in all patients. The VR technique was used to reconstruct the cardiovascular structures and airway, and then both VR images were composed using the commercial software (VoxelPlus 2 ; Daejeon, Korea). Stenoses were seen in the trachea in 1 patient and in the bronchi in 14 patients (19%). Other patients with complex CHD did not have significant airway stenoses. Composite VR images with MSCT can provide more exact airway images in relationship to the surrounding cardiovascular structures and thus help in optimizing management strategies in treating CHD. (orig.)

  9. Safety, bioavailability and mechanism of action of nitric oxide to control Bovine Respiratory Disease Complex in calves entering a feedlot.

    Science.gov (United States)

    Regev-Shoshani, G; Vimalanathan, S; Prema, D; Church, J S; Reudink, M W; Nation, N; Miller, C C

    2014-04-01

    Bovine Respiratory Disease Complex (BRDc), a multi-factorial disease, negatively impacts the cattle industry. Nitric oxide (NO), a naturally occurring molecule, may have utility controlling incidence of BRDc. Safety, bioavailability, toxicology and tolerance/stress of administering NO to cattle is evaluated herein. Thirteen, crossbred, multiple-sourced, commingled commercial weaned beef calves were treated multiple times intranasally over a 4 week period with either a nitric oxide releasing solution (treatment) or saline (control). Exhaled NO, methemoglobin percent (MetHg) and serum nitrites demonstrated biological availability as a result of treatment. Cortisol levels, tissue nitrites, behavior and gross and macroscopic pathology of organs were all normal. Moreover, preliminary in vitro studies using Mannheimia haemolytica, Infectious Bovine Rhinotracheitis, Bovine Parainfluenza-3 and Bovine Respiratory Syncytial Virus, suggest a potential explanation for the previously demonstrated efficacy for BRDc. These data confirm the bioavailability, safety and lack of residual of NO treatment to cattle, along with the bactericidal and virucidal effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The role of complex networks in behavior epidemiology. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

    Science.gov (United States)

    Zhao, Dawei; Wang, Lianhai

    2015-12-01

    Outbreaks of disease can trigger spontaneous behavioral response of individuals to consider prevention measures (mainly including medical cure and non-pharmaceutical intervention), which usually in turn influence the diffusion of epidemic, namely, forming the interplay between individual behaviors and epidemic dynamics. During the past decade, understanding such coupled disease-behavior dynamics in population has become a critical tool for predicting the disease evolution and designing effective prevention strategies [1-3].

  11. The genetic and environmental bases of complex human-disease: extending the utility of twin-studies.

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    Douglas S Goodin

    Full Text Available Making only the assumption that twins are representative of the population from which they are drawn, we here develop a simple mathematical model (using widely available epidemiological information that sheds considerable light on the pathogenesis of complex human diseases. Specifically, for the case of multiple sclerosis (MS, we demonstrate that the vast majority of patients (≥94%, possibly all, require genetic susceptibility in order to get MS. Nevertheless, only a tiny fraction of the population (≤2.2% is actually susceptible to getting this disease; a finding which is highly consistent in all of the studied populations across both North America and Europe. Men are more likely to be susceptible than women although susceptible women are more than twice as likely to actually develop MS compared to susceptible men (i.e., they have a greater disease penetrance. This is because women are more responsive to the environmental factors involved in MS pathogenesis than men. These differences account for the current gender-ratio (3∶1, favoring women and also for the increasing incidence of MS in women around the world. By contrast, the most important genetic marker for MS susceptibility (DRB1*1501 influences the likelihood of susceptibility but not the penetrance of the disease. Nevertheless, even for this major susceptibility allele, only a very small fraction of DRB1*1501carriers (<5% are susceptible to getting MS and for only a minority of MS patients (∼41% does this allele contribute to their susceptibility. Moreover, each copy of this allele seems to make an independent contribution to susceptibility. Finally, at least three environmental events are necessary for MS pathogenesis and, during the course of their lives, the large majority of the population (≥69% experiences an environmental exposure, which is sufficient to produce MS in, at least, some susceptible genotypes. Also, susceptible men (compared to susceptible women have a lower

  12. Radiological imaging in pediatric rheumatic diseases

    International Nuclear Information System (INIS)

    Matuszewska, Genowefa; Zaniewicz-Kaniewska, Katarzyna; Włodkowska-Korytkowska, Monika; Smorawińska, Patrycja; Saied, Fadhil; Kunisz, Wojciech; Sudoł-Szopińska, Iwona

    2014-01-01

    Radiological imaging plays a fundamental role in the diagnosis and monitoring of rheumatic diseases. The basic method of imaging is a classic X-ray picture, which for many years has been used as a single method for the recognition and evaluation of the effects of disease management. In today’s modern day treatment of rheumatic diseases, ultrasonography and magnetic resonance are more commonly performed for early detection of inflammatory changes in the region of soft tissue, subchondral bone and bone marrow. In spite of their usefulness and fundamental role in the diagnosis, X-ray still remains an essential tool in the diagnosis of rheumatoid arthritis in children and is complementary to today’s methods of imaging diagnostics. In clinical practice, X-ray imaging is still an important examination performed not only to recognize the disorders, but also to provide a differential diagnosis. It helps estimate disease progression and is used to monitor the effects of treatment and the development of possible complications. Differential diagnosis of rheumatic diseases is performed on the basis of localization and type of radiographic changes. The surrounding periarticular soft tissues, bone structures, joint space, with special attention to articular bone surfaces and epiphyses, are analyzed. The aim of this work is to describe characteristic inflammatory changes present on X-ray imaging typical for the most commonly diagnosed rheumatic diseases in children, such as juvenile idiopathic arthritis, systemic lupus erythematosus, systemic scleroderma, mixed connective tissue disease, juvenile dermatomyositis, juvenile spondyloarthropathy and systemic vascular disease

  13. Phylogeographic Pattern and Extensive Mitochondrial DNA Divergence Disclose a Species Complex within the Chagas Disease Vector Triatoma dimidiata

    Science.gov (United States)

    Monteiro, Fernando A.; Peretolchina, Tatiana; Lazoski, Cristiano; Harris, Kecia; Dotson, Ellen M.; Abad-Franch, Fernando; Tamayo, Elsa; Pennington, Pamela M.; Monroy, Carlota; Cordon-Rosales, Celia; Salazar-Schettino, Paz Maria; Gómez-Palacio, Andrés; Grijalva, Mario J.; Beard, Charles B.; Marcet, Paula L.

    2013-01-01

    Background Triatoma dimidiata is among the main vectors of Chagas disease in Latin America. However, and despite important advances, there is no consensus about the taxonomic status of phenotypically divergent T. dimidiata populations, which in most recent papers are regarded as subspecies. Methodology and Findings A total of 126 cyt b sequences (621 bp long) were produced for specimens from across the species range. Forty-seven selected specimens representing the main cyt b clades observed (after a preliminary phylogenetic analysis) were also sequenced for an ND4 fragment (554 bp long) and concatenated with their respective cyt b sequences to produce a combined data set totalling 1175 bp/individual. Bayesian and Maximum-Likelihood phylogenetic analyses of both data sets (cyt b, and cyt b+ND4) disclosed four strongly divergent (all pairwise Kimura 2-parameter distances >0.08), monophyletic groups: Group I occurs from Southern Mexico through Central America into Colombia, with Ecuadorian specimens resembling Nicaraguan material; Group II includes samples from Western-Southwestern Mexico; Group III comprises specimens from the Yucatán peninsula; and Group IV consists of sylvatic samples from Belize. The closely-related, yet formally recognized species T. hegneri from the island of Cozumel falls within the divergence range of the T. dimidiata populations studied. Conclusions We propose that Groups I–IV, as well as T. hegneri, should be regarded as separate species. In the Petén of Guatemala, representatives of Groups I, II, and III occur in sympatry; the absence of haplotypes with intermediate genetic distances, as shown by multimodal mismatch distribution plots, clearly indicates that reproductive barriers actively promote within-group cohesion. Some sylvatic specimens from Belize belong to a different species – likely the basal lineage of the T. dimidiata complex, originated ∼8.25 Mya. The evidence presented here strongly supports the proposition that T

  14. Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata.

    Directory of Open Access Journals (Sweden)

    Fernando A Monteiro

    Full Text Available BACKGROUND: Triatoma dimidiata is among the main vectors of Chagas disease in Latin America. However, and despite important advances, there is no consensus about the taxonomic status of phenotypically divergent T. dimidiata populations, which in most recent papers are regarded as subspecies. METHODOLOGY AND FINDINGS: A total of 126 cyt b sequences (621 bp long were produced for specimens from across the species range. Forty-seven selected specimens representing the main cyt b clades observed (after a preliminary phylogenetic analysis were also sequenced for an ND4 fragment (554 bp long and concatenated with their respective cyt b sequences to produce a combined data set totalling 1175 bp/individual. Bayesian and Maximum-Likelihood phylogenetic analyses of both data sets (cyt b, and cyt b+ND4 disclosed four strongly divergent (all pairwise Kimura 2-parameter distances >0.08, monophyletic groups: Group I occurs from Southern Mexico through Central America into Colombia, with Ecuadorian specimens resembling Nicaraguan material; Group II includes samples from Western-Southwestern Mexico; Group III comprises specimens from the Yucatán peninsula; and Group IV consists of sylvatic samples from Belize. The closely-related, yet formally recognized species T. hegneri from the island of Cozumel falls within the divergence range of the T. dimidiata populations studied. CONCLUSIONS: We propose that Groups I-IV, as well as T. hegneri, should be regarded as separate species. In the Petén of Guatemala, representatives of Groups I, II, and III occur in sympatry; the absence of haplotypes with intermediate genetic distances, as shown by multimodal mismatch distribution plots, clearly indicates that reproductive barriers actively promote within-group cohesion. Some sylvatic specimens from Belize belong to a different species - likely the basal lineage of the T. dimidiata complex, originated ~8.25 Mya. The evidence presented here strongly supports the proposition

  15. Sero-diagnosis of Mycobacterium avium complex lung disease using serum immunoglobulin A antibody against glycopeptidolipid antigen in Taiwan.

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    Chin-Chung Shu

    Full Text Available BACKGROUND: Lung disease (LD due to non-tuberculous mycobacteria is an important clinical concern. Mycobacterium avium complex (MAC is one of the most common causative agents but the diagnosis of MAC-LD remains challenging. Detection of serum IgA antibody against MAC glycopeptidolipid (GPL has recently been shown to improve the diagnosis of MAC-LD, but has yet to be validated worldwide. METHODS: This prospective study was conducted in a tertiary referral center in northern Taiwan and enrolled patients with MAC-LD, MAC contamination, other lung diseases, and control subjects. Serum immunoglobulin A (IgA antibody against MAC-GPL was detected in the participants and its specificity and sensitivity was assessed. RESULTS: There were 56 patients with MAC-LD, 11 with MAC contamination, 13 M. kansasii-LD, 26 LD due to rapidly-growing mycobacteria (RGM, 48 pulmonary tuberculosis, and 42 household contacts of patients with TB. Patients with MAC-LD were older and 32% of them had an underlying co-morbidity. By logistic regression, serum MAC-GPL IgA level was an independent predictor of MAC-LD among the study subjects and those with culture-positive specimens for MAC. By the receiver operating characteristic curve, serum MAC-GPL IgA had a good power to discriminate MAC-LD from MAC contamination. Under the optimal cut-off value of 0.73 U/mL, its sensitivity and specificity were 60% and 91%, respectively. Among MAC-LD patients, presence of co-morbidity was associated with MAC-GPL <0.73 U/ml in logistic regression analysis. CONCLUSIONS: Measurement of serum anti-MAC-GPL IgA level is useful for the diagnosis of MAC-LD. However, its implement in clinical practice for immuno-compromised hosts needs careful consideration.

  16. Classical determinants of coronary artery disease as predictors of complexity of coronary lesions, assessed with the SYNTAX score.

    Science.gov (United States)

    Montero-Cabezas, J M; Karalis, I; Wolterbeek, R; Kraaijeveld, A O; Hoefer, I E; Pasterkamp, G; Pijls, N H; Doevendans, P A; Walterberger, J; Kuiper, J; van Zonneveld, A J; Jukema, J W

    2017-09-01

    We need new biomarkers that can predict cardiovascular disease to improve both diagnosis and therapeutic strategies. The CIRCULATING CELLS study was designed to study the role of several cellular mediators of atherosclerosis as biomarkers of coronary artery disease (CAD). An objective and reproducible method for the quantification of CAD extension is required to establish relationships with these potential biomarkers. We sought to analyse the correlation of the SYNTAX score with known CAD risk factors to test it as a valid marker of CAD extension. A subgroup of 279 patients (67.4% males) were included in our analysis. Main exclusion criteria were a history of previous percutaneous coronary intervention or surgical revascularisation that prevent an accurate assessment of the SS. Diabetes mellitus, smoking, renal insufficiency, body mass index and a history of CAD and myocardial infarction were all positively and strongly associated with a higher SYNTAX score after adjustment for the non-modifiable biological factors (age and sex). In the multivariate model, age and male sex, along with smoking and renal insufficiency, remain statistical significantly associated with the SYNTAX score. In a selected cohort of revascularisation-naive patients with CAD undergoing coronary angiography, non-modifiable cardiovascular risk factors such as advanced age, male sex, as well as smoking and renal failure were independently associated with CAD complexity assessed by the SYNTAX score. The SYNTAX score may be a valid marker of CAD extension to establish relationships with potential novel biomarkers of coronary atherosclerosis.

  17. Voltage-Dependent Anion Channel 1 Interacts with Ribonucleoprotein Complexes To Enhance Infectious Bursal Disease Virus Polymerase Activity.

    Science.gov (United States)

    Han, Chunyan; Zeng, Xiangwei; Yao, Shuai; Gao, Li; Zhang, Lizhou; Qi, Xiaole; Duan, Yulu; Yang, Bo; Gao, Yulong; Liu, Changjun; Zhang, Yanping; Wang, Yongqiang; Wang, Xiaomei

    2017-08-15

    Infectious bursal disease virus (IBDV) is a double-stranded RNA (dsRNA) virus. Segment A contains two overlapping open reading frames (ORFs), which encode viral proteins VP2, VP3, VP4, and VP5. Segment B contains one ORF and encodes the viral RNA-dependent RNA polymerase, VP1. IBDV ribonucleoprotein complexes are composed of VP1, VP3, and dsRNA and play a critical role in mediating viral replication and transcription during the virus life cycle. In the present study, we identified a cellular factor, VDAC1, which was upregulated during IBDV infection and found to mediate IBDV polymerase activity. VDAC1 senses IBDV infection by interacting with viral proteins VP1 and VP3. This association is caused by RNA bridging, and all three proteins colocalize in the cytoplasm. Furthermore, small interfering RNA (siRNA)-mediated downregulation of VDAC1 resulted in a reduction in viral polymerase activity and a subsequent decrease in viral yield. Moreover, overexpression of VDAC1 enhanced IBDV polymerase activity. We also found that the viral protein VP3 can replace segment A to execute polymerase activity. A previous study showed that mutations in the C terminus of VP3 directly influence the formation of VP1-VP3 complexes. Our immunoprecipitation experiments demonstrated that protein-protein interactions between VDAC1 and VP3 and between VDAC1 and VP1 play a role in stabilizing the interaction between VP3 and VP1, further promoting IBDV polymerase activity. IMPORTANCE The cellular factor VDAC1 controls the entry and exit of mitochondrial metabolites and plays a pivotal role during intrinsic apoptosis by mediating the release of many apoptogenic molecules. Here we identify a novel role of VDAC1, showing that VDAC1 interacts with IBDV ribonucleoproteins (RNPs) and facilitates IBDV replication by enhancing IBDV polymerase activity through its ability to stabilize interactions in RNP complexes. To our knowledge, this is the first report that VDAC1 is specifically involved in

  18. Scaling up complexity in host-pathogens interaction models. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

    Science.gov (United States)

    Aguiar, Maíra

    2015-12-01

    Caused by micro-organisms that are pathogenic to the host, infectious diseases have caused debilitation and premature death to large portions of the human population, leading to serious social-economic concerns. The persistence and increase in the occurrence of infectious diseases as well the emergence or resurgence of vector-borne diseases are closely related with demographic factors such as the uncontrolled urbanization and remarkable population growth, political, social and economical changes, deforestation, development of resistance to insecticides and drugs and increased human travel. In recent years, mathematical modeling became an important tool for the understanding of infectious disease epidemiology and dynamics, addressing ideas about the components of host-pathogen interactions. Acting as a possible tool to understand, predict the spread of infectious diseases these models are also used to evaluate the introduction of intervention strategies like vector control and vaccination. Many scientific papers have been published recently on these topics, and most of the models developed try to incorporate factors focusing on several different aspects of the disease (and eventually biological aspects of the vector), which can imply rich dynamic behavior even in the most basic dynamical models. As one example to be cited, there is a minimalistic dengue model that has shown rich dynamic structures, with bifurcations (Hopf, pitchfork, torus and tangent bifurcations) up to chaotic attractors in unexpected parameter regions [1,2], which was able to describe the large fluctuations observed in empirical outbreak data [3,4].

  19. Delayed vaccine virus replication in chickens vaccinated subcutaneously with an immune complex infectious bursal disease vaccine: Quantification of vaccine virus by real-time polymerase chain reaction

    OpenAIRE

    Iván, Judit; Velhner, Maja; Ursu, Krisztina; Germán, Péter; Mató, Tamás; Drén, Csaba Nick; Mészáros, János

    2005-01-01

    The distribution of the immune complex vaccine virus for infectious bursal disease (IBD) in tissue was examined and the viral loads of the organs were quantitatively compared. One-day-old specific pathogen free (SPF) and maternally immune broiler chickens were injected subcutaneously with the vaccine. Lymphoid and non-lymphoid tissues were collected at various time intervals during the experiment to test for infectious bursal disease virus (IBDV)-RNA by using reverse transcriptase-polymerase ...

  20. Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex.

    Science.gov (United States)

    Kishimoto, Mai; Tsuchiaka, Shinobu; Rahpaya, Sayed Samim; Hasebe, Ayako; Otsu, Keiko; Sugimura, Satoshi; Kobayashi, Suguru; Komatsu, Natsumi; Nagai, Makoto; Omatsu, Tsutomu; Naoi, Yuki; Sano, Kaori; Okazaki-Terashima, Sachiko; Oba, Mami; Katayama, Yukie; Sato, Reiichiro; Asai, Tetsuo; Mizutani, Tetsuya

    2017-03-18

    Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.

  1. Infection of differentiated airway epithelial cells from caprine lungs by viruses of the bovine respiratory disease complex.

    Science.gov (United States)

    Kirchhoff, Jana; Uhlenbruck, Sabine; Keil, Günther M; Schwegmann-Wessels, Christel; Ganter, Martin; Herrler, Georg

    2014-05-14

    Bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus type 3 (BPIV3) and bovine herpesvirus type 1 (BHV-1) are important pathogens associated with the bovine respiratory disease complex (BRDC). Non-bovine ruminants such as goats may also be infected and serve as a virus reservoir to be considered in the development of control strategies. To evaluate the susceptibility of caprine airway epithelial cells to infection by viruses of BRDC, we established a culture system for differentiated caprine epithelial cells. For this purpose, we generated precision-cut lung slices (PCLS), in which cells are retained in their original structural configuration and remain viable for more than a week. The three bovine viruses were found to preferentially infect different cell types. Ciliated epithelial cells were the major target cells of BPIV3, whereas BHV-1 preferred basal cells. Cells infected by BRSV were detected in submucosal cell layers. This spectrum of susceptible cells is the same as that reported recently for infected bovine PCLS. While infection of caprine cells by BRSV and BPIV3 was as efficient as that reported for bovine cells, infection of caprine cells by BHV-1 required a tenfold higher dose of infectious virus as compared to infection of bovine airway cells. These results support the notion that non-bovine ruminants may serve as a reservoir for viruses of BRDC and introduce a culture system to analyze virus infection of differentiated airway epithelial cells from the caprine lung. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The Effects of Chunghyul-Dan (A Korean Medicine Herbal Complex on Cardiovascular and Cerebrovascular Diseases: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Woo-Sang Jung

    2016-01-01

    Full Text Available Chunghyul-dan (CHD is a herbal complex containing 80% ethanol extract and is composed of Scutellariae Radix, Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, and Rhei Rhizoma. We have published several experimental and clinical research articles on CHD. It has shown antilipidemic, antihypertensive, antiatherosclerotic, and inhibitory effects on ischemic stroke recurrence with clinical safety in the previous studies. The antilipidemic effect of CHD results from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase and pancreatic lipase-inhibitory activity. The antihypertensive effect likely results from the inhibitory effect on endogenous catecholamine(s release and harmonization of all components showing the antihypertensive effects. Furthermore, anti-inflammatory and antioxidant effects on endothelial cells are implicated to dictate the antiatherosclerotic effects of CHD. It also showed neuroprotective effects on cerebrovascular and parkinsonian models. These effects of CHD could be helpful for the prevention of the recurrence of ischemic stroke. Therefore, we suggest that CHD could be a promising medication for treating and preventing cerebrovascular and cardiovascular diseases. However, to validate and better understand these findings, well-designed clinical studies are required.

  3. Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

    Science.gov (United States)

    Orekhov, Alexander N.; Bobryshev, Yuri V.; Sobenin, Igor A.; Melnichenko, Alexandra A.; Chistiakov, Dimitry A.

    2014-01-01

    In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. PMID:25050779

  4. One-year experience of a regional service model of teleconsultation for planning and treatment of complex thoracoabdominal aortic disease.

    Science.gov (United States)

    Chisci, Emiliano; de Donato, Gianmarco; Fargion, Aaron; Ventoruzzo, Giorgio; Parlani, Gianbattista; Setacci, Carlo; Ercolini, Leonardo; Michelagnoli, Stefano

    2018-03-01

    The objective of this study was to report the methodology and 1-year experience of a regional service model of teleconsultation for planning and treatment of complex thoracoabdominal aortic disease (TAAD). Complex TAADs without a feasible conventional surgical repair were prospectively evaluated by vascular surgeons of the same public health service (National Health System) located in a huge area of 22,994 km 2 with 3.7 million inhabitants and 11 tertiary hospitals. Surgeons evaluated computed tomography scans and clinical details that were placed on a web platform (Google Drive; Google, Mountain View, Calif) and shared by all surgeons. Patients gave informed consent for the teleconsultation. The surgeon who submits a case discusses in detail his or her case and proposes a possible therapeutic strategy. The other surgeons suggest other solutions and options in terms of grafts, techniques, or access to be used. Computed tomography angiography, angiography, and clinical outcomes of cases are then presented at the following telemeetings, and a final agreement of the operative strategy is evaluated. Teleconsultation is performed using a web conference service (WebConference.com; Avaya Inc, Basking Ridge, NJ) every month. An inter-rater agreement statistic was calculated, and the κ value was interpreted according to Altman's criteria for computed tomography angiography measurements. The rate of participation was constant (mean number of surgeons, 11; range, 9-15). Twenty-four complex TAAD cases were discussed for planning and operation during the study period. The interobserver reliability recorded was moderate (κ = 0.41-0.60) to good (κ = 0.61-0.80) for measurements of proximal and distal sealing and very good (κ = 0.81-1) for detection of any target vessel angulation >60 degrees, significant calcification (circumferential), and thrombus presence (>50%). The concordance for planning and therapeutic strategy among all participants was complete in 16 cases. In

  5. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

    2004-01-01

    B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...

  6. An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial

    NARCIS (Netherlands)

    K. Dulfer (Karolijn)

    2014-01-01

    markdownabstract__Abstract__ A 12-week standardized exercise program improved self-reported cognitive functioning, and parent-reported social functioning in children and adolescents with complex congenital heart disease. Furthermore, it resulted in a decrease in passive leisure time spending.

  7. Complexity of program and clinical outcomes of heart failure disease management incorporating specialist nurse-led heart failure clinics. A meta-regression analysis

    NARCIS (Netherlands)

    Phillips, CO; Singa, RM; Rubin, HR; Jaarsma, T

    2005-01-01

    Objectives: To determine whether a hierarchy of effectiveness exists with respect to complexity of published protocols of heart failure (HF) disease management (DM) incorporating specialist nurse-led HF clinics. Data sources and study selection: We searched MEDLINE (1966-November 2004), the Cochrane

  8. Using multidetector-row CT in neonates with complex congenital heart disease to replace diagnostic cardiac catheterization for anatomical investigation: initial experiences in technical and clinical feasibility

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Tain; Tsai, I.C.; Chen, Min-Chi [Taichung Veterans General Hospital, 407 Department of Radiology, Taichung (Taiwan); Medical College of Chung Shan Medical University, Faculty of Medicine, Taichung (Taiwan); National Yang Ming University School of Medicine, Department of Medicine, Taipei (Taiwan); Fu, Yun-Ching; Jan, Sheng-Lin [Taichung Veterans General Hospital, Department of Paediatrics, Taichung (Taiwan); National Yang-Ming University, Institute of Clinical Medicine, Taipei (Taiwan); Wang, Chung-Chi; Chang, Yen [Taichung Veterans General Hospital, Section of Cardiovascular Surgery, Department of Surgery, Taichung (Taiwan)

    2006-12-15

    Echocardiography is the first-line modality for the investigation of neonatal congenital heart disease. Diagnostic cardiac catheterization, which has a small but recognized risk, is usually performed if echocardiography fails to provide a confident evaluation of the lesions. To verify the technical and clinical feasibilities of replacing diagnostic cardiac catheterization with multidetector-row CT (MDCT) in neonatal complex congenital heart disease. Over a 1-year period we prospectively enrolled all neonates with complex congenital heart disease referred for diagnostic cardiac catheterization after initial assessment by echocardiography. MDCT was performed using a 40-detector-row CT scanner with dual syringe injection. A multidisciplinary congenital heart disease team evaluated the MDCT images and decided if further diagnostic cardiac catheterization was necessary. The accuracy of MDCT in detecting separate cardiovascular anomalies and bolus geometry of contrast enhancement were calculated. A total of 14 neonates were included in the study. No further diagnostic cardiac catheterization was needed in any neonate. The accuracy of MDCT in diagnosing separate cardiovascular anomalies was 98% (53/54) with only one atrial septal defect missed in a patient with coarctation syndrome. The average cardiovascular enhancement in evaluated chambers was 471 HU. No obvious beam-hardening artefact was observed. The technical and clinical feasibility of MDCT in complex congenital heart disease in neonates is confirmed. After initial assessment with echocardiography, MDCT could probably replace diagnostic cardiac catheterization for further anatomical clarification in neonates. (orig.)

  9. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

    2004-01-01

    B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto's thyroidi......B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...... of Tg by boiling reduced the proliferative responses. The data indicate that anti-Tg antibodies associated with AITD facilitate the formation of complement-activating Tg/anti-Tg complexes, binding of IC to B cells, and the subsequent proliferation of B and T cell subsets. This represents a novel...

  10. Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa

    Directory of Open Access Journals (Sweden)

    Clement Nyamunura Mweya

    2013-10-01

    Full Text Available Background: The East African region has experienced several Rift Valley fever (RVF outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. Methods: Diverse ecological niche modelling techniques have been developed for this purpose: we present a maximum entropy (Maxent approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Results: Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Conclusion: Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

  11. Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa.

    Science.gov (United States)

    Mweya, Clement Nyamunura; Kimera, Sharadhuli Iddi; Kija, John Bukombe; Mboera, Leonard E G

    2013-01-01

    The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

  12. Significant elevation and correlation of plasma neutrophil gelatinase associated lipocalin and its complex with matrix metalloproteinase-9 in patients with pelvic inflammatory disease.

    Science.gov (United States)

    Tsai, Hsiu-Ting; Su, Pen-Hua; Lee, Tsung-Hsien; Tee, Yi-Torng; Lin, Long-Yau; Yang, Shun-Fa; Wang, Po-Hui

    2011-06-11

    To detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID). Enzyme-linked immunosorbent assay was used to measure the levels of plasma NGAL and NGAL/MMP-9 complex. The levels of plasma NGAL or NGAL/MMP-9 complex were increased in patients with PID compared with those in normal controls and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In patients with PID, plasma level of NGAL/MMP-9 complex was correlated with plasma level of NGAL or MMP-9 significantly. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%; the negative predictive values, 72.7% and 74.5%. Plasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. In patients with PID, about 80% have plasma levels of NGAL or NGAL/MMP-9 complex level >10.04 ng/ml or 2.33 ng/ml, respectively. Copyright © 2011. Published by Elsevier B.V.

  13. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

    Directory of Open Access Journals (Sweden)

    Mark Preciados

    2016-12-01

    Full Text Available During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA, polychlorinated biphenyls (PCBs, phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1 signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2 and

  14. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.

    Science.gov (United States)

    Preciados, Mark; Yoo, Changwon; Roy, Deodutta

    2016-12-13

    During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of

  15. Immune complexes in chronic Chagas disease patients are formed by exovesicles from Trypanosoma cruzi carrying the conserved MASP N-terminal region

    Science.gov (United States)

    Díaz Lozano, Isabel María; de Pablos, Luis Miguel; Longhi, Silvia Andrea; Zago, María Paola; Schijman, Alejandro Gabriel; Osuna, Antonio

    2017-03-01

    The exovesicles (EVs) are involved in pathologic host-parasite immune associations and have been recently used as biomarkers for diagnosis of infectious diseases. The release of EVs by Trypanosoma cruzi, the causative agent of Chagas disease, has recently been described, with different protein cargoes including the MASP multigene family of proteins MASPs are specific to this parasite and characterized by a conserved C-terminal (C-term) region and an N-terminal codifying for a signal peptide (SP). In this investigation, we identified immature MASP proteins containing the MASP SP in EVs secreted by the infective forms of the parasite. Those EVs are responsible for the formation of immune complexes (ICs) containing anti-MASP SP IgGs in patients with different (cardiac, digestive and asymptomatic) chronic Chagas disease manifestations. Moreover, purified EVs as well as the MASP SP inhibit the action of the complement system and also show a significant association with the humoral response in patients with digestive pathologies. These findings reveal a new route for the secretion of MASP proteins in T. cruzi, which uses EVs as vehicles for immature and misfolded proteins, forming circulating immune complexes. Such complexes could be used in the prognosis of digestive pathologies of clinical forms of Chagas disease.

  16. Disease flare of ankylosing spondylitis presenting as reactive arthritis with seropositivity: a case report

    Directory of Open Access Journals (Sweden)

    Manoj EM

    2012-02-01

    Full Text Available Abstract Introduction Concurrent rheumatoid factor seropositivity is occasionally detected in ankylosing spondylitis and often causes confusion in clinical routine. Overlap between various seronegative arthritides is a known but uncommon association. Differentiation of spondyloarthropathy from rheumatoid arthritis is important, since the natural history, complications, treatments and prognosis of the two diseases differ significantly. Case presentation Here, we report the case of a 47-year-old Sri Lankan man who had a long history of intermittent joint pains worsening following a recent episode of self-resolving non-bloody diarrhea. Subsequently, he developed a skin rash suggestive of keratoderma blenorrhagica and circinate balanitis. He had classical radiological evidence of ankylosing spondylosis (previously undiagnosed associated with human leukocyte antigen B27 antigen, but was positive for rheumatoid factor. Conclusions A disease flare of ankylosing spondylitis prompted by a minor diarrheal illness showing well documented features of reactive arthritis is remarkable. The prognostic implications of seropositivity in spondyloarthritis are discussed.

  17. 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...

  18. Towards a phylogenetic approach to the composition of species complexes in the North and Central American Triatoma, vectors of Chagas disease.

    Science.gov (United States)

    de la Rúa, Nicholas M; Bustamante, Dulce M; Menes, Marianela; Stevens, Lori; Monroy, Carlota; Kilpatrick, C William; Rizzo, Donna; Klotz, Stephen A; Schmidt, Justin; Axen, Heather J; Dorn, Patricia L

    2014-06-01

    Phylogenetic relationships of insect vectors of parasitic diseases are important for understanding the evolution of epidemiologically relevant traits, and may be useful in vector control. The sub-family Triatominae (Hemiptera:Reduviidae) includes ∼140 extant species arranged in five tribes comprised of 15 genera. The genus Triatoma is the most species-rich and contains important vectors of Trypanosoma cruzi, the causative agent of Chagas disease. Triatoma species were grouped into complexes originally by morphology and more recently with the addition of information from molecular phylogenetics (the four-complex hypothesis); however, without a strict adherence to monophyly. To date, the validity of proposed species complexes has not been tested by statistical tests of topology. The goal of this study was to clarify the systematics of 19 Triatoma species from North and Central America. We inferred their evolutionary relatedness using two independent data sets: the complete nuclear internal transcribed spacer-2 ribosomal DNA (ITS-2 rDNA) and head morphometrics. In addition, we used the Shimodaira-Hasegawa statistical test of topology to assess the fit of the data to a set of competing systematic hypotheses (topologies). An unconstrained topology inferred from the ITS-2 data was compared to topologies constrained based on the four-complex hypothesis or one inferred from our morphometry results. The unconstrained topology represents a statistically significant better fit of the molecular data than either the four-complex or the morphometric topology. We propose an update to the composition of species complexes in the North and Central American Triatoma, based on a phylogeny inferred from ITS-2 as a first step towards updating the phylogeny of the complexes based on monophyly and statistical tests of topologies. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibroblasts.

    Science.gov (United States)

    Fujita, Naonobu; Saitoh, Tatsuya; Kageyama, Shun; Akira, Shizuo; Noda, Takeshi; Yoshimori, Tamotsu

    2009-11-20

    A single nucleotide polymorphism in Atg16L1, an autophagy-related gene (ATG), is a risk factor for Crohn disease, a major form of chronic inflammatory bowel disease. However, it is still unknown how the Atg16L1 variant contributes to disease development. The Atg16L1 protein possesses a C-terminal WD repeat domain whose function is entirely unknown, and the Crohn disease-associated mutation (T300A) is within this domain. To elucidate the function of the WD repeat domain, we established an experimental system in which a WD repeat domain mutant of Atg16L1 is stably expressed in Atg16L1-deficient mouse embryonic fibroblasts. Using the system, we show that the Atg16L1 complex forms a dimeric complex and that the total Atg16L1 protein level is strictly maintained, possibly by the ubiquitin proteasome system. Furthermore, we show that an Atg16L1 WD repeat domain deletion and the T300A mutant have little impact on canonical autophagy and autophagy against Salmonella enterica serovar Typhimurium. Therefore, we propose that Atg16L1 T300A is differentially involved in Crohn disease and canonical autophagy.

  20. Framework for Smart Electronic Health Record-Linked Predictive Models to Optimize Care for Complex Digestive Diseases

    Science.gov (United States)

    2014-07-01

    Atherosclerosis 2012; 224: 480–5. 5. Choi S-Y, Kim D, Kim HJ, et al. The relation between non - alcoholic fatty liver disease and the risk of...Ito H, Komatsu Y, et al. Non - alcoholic fatty liver disease is an independent predictor for macroangiop- athy in Japanese type 2 diabetic patients: a...population including the rise in obesity have impacted IBD and patterns of associated liver disease . We evaluated a prospective IBD patient registry

  1. Simple deterministic models and applications. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

    Science.gov (United States)

    Yang, Hyun Mo

    2015-12-01

    Currently, discrete modellings are largely accepted due to the access to computers with huge storage capacity and high performance processors and easy implementation of algorithms, allowing to develop and simulate increasingly sophisticated models. Wang et al. [7] present a review of dynamics in complex networks, focusing on the interaction between disease dynamics and human behavioral and social dynamics. By doing an extensive review regarding to the human behavior responding to disease dynamics, the authors briefly describe the complex dynamics found in the literature: well-mixed populations networks, where spatial structure can be neglected, and other networks considering heterogeneity on spatially distributed populations. As controlling mechanisms are implemented, such as social distancing due 'social contagion', quarantine, non-pharmaceutical interventions and vaccination, adaptive behavior can occur in human population, which can be easily taken into account in the dynamics formulated by networked populations.

  2. The amount of C1q-adiponectin complex is higher in the serum and the complex localizes to perivascular areas of fat tissues and the intimal-medial layer of blood vessels of coronary artery disease patients.

    Science.gov (United States)

    Hong, Eun Shil; Lim, Cheong; Choi, Hye Yeon; Ku, Eu Jeong; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Jang, Hak Chul; Choi, Sung Hee

    2015-05-09

    The complement component C1q triggers activation of the classical immune pathway and can bind to adiponectin (APN). Recently, some studies have been reported that serum C1q-APN/total APN ratio correlates with atherosclerosis and coronary artery disease (CAD). We assessed the relationships between C1q related variables and the severity of CAD, and investigated the localization of the C1q-APN complex. The sample included 153 subjects comprising healthy controls and patients with subclinical or overt CAD. We measured the serum concentrations of C1q, total APN, and high-molecular weight (HMW)-APN, and the amount of C1q-APN complex. We identified the sites of C1q-APN complex deposition in various adipose tissues and blood vessels. Serum concentrations of C1q and HMW-APN and the C1q/HMW-APN ratio were independently associated with the severity of coronary stenosis. The amount of C1q-APN complex was significantly higher in patients with CAD compared with controls. C1q and APN co-localized in perivascular areas of subcutaneous, visceral, and pericardial fat tissues, and the internal mammary artery of patients with severe CAD. Serum C1q concentration and the C1q/HMW-APN ratio were independent markers of coronary artery stenosis. The amount of C1q-APN complex was significantly greater in serum from CAD patients. C1q and APN co-localized to perivascular areas in adipose tissue and blood vessels. The association between the increased amount of the C1q-APN complex and CAD should be investigated further.

  3. Complex Interplay of Future Climate Levels of CO2, Ozone and Temperature on Susceptibility to Fungal Diseases in Barley

    DEFF Research Database (Denmark)

    Mikkelsen, Bolette Lind

    Climate change will modify the environmental growth conditions for plants, and consequently also their physiology and susceptibility to diseases. However, there is a lack of experimental studies on the effect of climate change on plant diseases, which include several climatic factors in order...

  4. Caenorhabditis elegans expressing the Saccharomyces cerevisiae NADH alternative dehydrogenase Ndi1p, as a tool to identify new genes involved in complex I related diseases

    Directory of Open Access Journals (Sweden)

    Raynald eCossard

    2015-06-01

    Full Text Available Isolated complex I deficiencies are one of the most commonly observed biochemical features in patients suffering from mitochondrial disorders. In the majority of these clinical cases the molecular bases of the diseases remain unknown suggesting the involvement of unidentified factors that are critical for complex I function.The Saccharomyces cerevisiae NDI1 gene, encoding the mitochondrial internal NADH dehydrogenase was previously shown to complement a complex I deficient strain in Caenorhabitis elegans with notable improvements in reproduction, whole organism respiration. These features indicate that Ndi1p can functionally integrate the respiratory chain, allowing complex I deficiency complementation. Taking into account the Ndi1p ability to bypass complex I, we evaluate the possibility to extend the range of defects/mutations causing complex I deficiencies that can be alleviated by NDI1 expression.We report here that NDI1 expressing animals unexpectedly exhibit a slightly shortened lifespan, a reduction in the progeny and a depletion of the mitochondrial genome. However, Ndi1p is expressed and targeted to the mitochondria as a functional protein that confers rotenone resistance to those animals and without affecting their respiration rate and ATP content.We show that the severe embryonic lethality level caused by the RNAi knockdowns of complex I structural subunit encoding genes (e.g. NDUFV1, NDUFS1, NDUFS6, NDUFS8 or GRIM-19 human orthologs in wild type animals is significantly reduced in the Ndi1p expressing worm.All together these results open up the perspective to identify new genes involved in complex I function, assembly or regulation by screening an RNAi library of genes leading to embryonic lethality that should be rescued by NDI1 expression.

  5. Examining the use of process evaluations of randomised controlled trials of complex interventions addressing chronic disease in primary health care-a systematic review protocol.

    Science.gov (United States)

    Liu, Hueiming; Muhunthan, Janini; Hayek, Adina; Hackett, Maree; Laba, Tracey-Lea; Peiris, David; Jan, Stephen

    2016-08-15

    Randomised controlled trials (RCTs) of complex interventions in primary health care (PHC) are needed to provide evidence-based programmes to achieve the Declaration of Alma Ata goal of making PHC equitable, accessible and universal and to effectively address the rising burden from chronic disease. Process evaluations of these RCTs can provide insight into the causal mechanisms of complex interventions, the contextual factors, and inform as to whether an intervention is ineffective due to implementation failure or failure of the intervention itself. To build on this emerging body of work, we aim to consolidate the methodology and methods from process evaluations of complex interventions in PHC and their findings of facilitators and barriers to intervention implementation in this important area of health service delivery. Systematic review of process evaluations of randomised controlled trials of complex interventions which address prevalent major chronic diseases in PHC settings. Published process evaluations of RCTs will be identified through database and clinical trial registry searches and contact with authors. Data from each study will be extracted by two reviewers using standardised forms. Data extracted include descriptive items about (1) the RCT, (2) about the process evaluations (such as methods, theories, risk of bias, analysis of process and outcome data, strengths and limitations) and (3) any stated barriers and facilitators to conducting complex interventions. A narrative synthesis of the findings will be presented. Process evaluation findings are valuable in determining whether a complex intervention should be scaled up or modified for other contexts. Publishing this protocol serves to encourage transparency in the reporting of our synthesis of current literature on how process evaluations have been conducted thus far and a deeper understanding of potential challenges and solutions to aid in the implementation of effective interventions in PHC beyond

  6. Global epidemiology of capsular group W meningococcal disease (1970-2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex.

    Science.gov (United States)

    Mustapha, Mustapha M; Marsh, Jane W; Harrison, Lee H

    2016-03-18

    Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease: The PReVaiL randomized clinical trial.

    Science.gov (United States)

    Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars; Jakobsen, Janus Christian; Zoffmann, Vibeke; Dideriksen, Kasper; Kruse, Anne; Mikkelsen, Ulla Ramer; Wetterslev, Jørn

    2016-10-15

    To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. Randomized clinical trial. Denmark. A total of 158 adolescents aged 13-16years with no physical activity restrictions after repaired complex congenital heart disease. PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. The primary outcome was maximal oxygen uptake (VO2 peak) at 52weeks after randomization. The secondary outcome was physical activity. Exploratory outcomes were generic and disease-specific questionnaires. In the intervention group, 58 patients (72%) completed the final test, but of those, only 46 (57%) fulfilled the compliance criteria of using the eHealth application for at least 2 consecutive weeks. In the control group, 61 patients (79%) completed both exercise tests. Adjusted for baseline values, the difference between the intervention group and the control group in mean VO2 peak at 1year was -0.65ml·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. Adding a tailored eHealth intervention to health education and individual counseling did not affect outcomes among adolescents with congenital heart disease. Our results do not support the use of this eHealth intervention in adolescents with complex congenital heart disease. Clinical trials.gov identifier: NCT01189981. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Motor output complexity in Parkinson's disease during quiet standing and walking: Analysis of short-term correlations using the entropic half-life.

    Science.gov (United States)

    Pasluosta, C; Hannink, J; Gaßner, H; Von Tscharner, V; Winkler, J; Klucken, J; Eskofier, B M

    2018-02-16

    Parkinson's disease (PD) is associated with alterations in motor outputs such as center of pressure (CoP) adjustments during quiet standing and foot kinematics during walking. Previous research suggests that the complexity of motor outputs reflects the number of control processes stabilizing a specific movement, providing a measure that is linked to the neurological control of the movement. The Entropic Half Life (EnHL) represents a new method for assessing motor output complexity. We hypothesized that there will be a lack of neuromuscular control pathways for PD patients, resulting in a decrease in motor output complexity. We computed the EnHL of CoP adjustments during quiet standing and foot kinematics during walking of 70 PD patients and 33 age-matched controls. Patients with PD showed longer EnHL values compared to controls, suggesting a tighter motor control. Excluding vision led to a decrease of EnHL of CoP in both groups. EnHL was correlated with spatio-temporal gait parameters. We compared EnHL with the pull test and the timed up-and-go test. No significant differences were present in the pull test, yet motor output complexity was correlated with the timed up-and-go test. The results suggest a reduced complexity in motor outputs of PD patients affecting distinct motor functions. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.

    Science.gov (United States)

    van der Kammen, Rob; Song, Ji-Ying; de Rink, Iris; Janssen, Hans; Madonna, Stefania; Scarponi, Claudia; Albanesi, Cristina; Brugman, Wim; Innocenti, Metello

    2017-12-15

    The Arp2/3 complex assembles branched actin filaments, which are key to many cellular processes, but its organismal roles remain poorly understood. Here, we employed conditional A rpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis. We found that depletion of the Arp2/3 complex by knockout of Arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of Arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2 target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistent with this, we revealed that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocyte shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. © 2017. Published by The Company of Biologists Ltd.

  10. A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets.

    Directory of Open Access Journals (Sweden)

    Jaleal S Sanjak

    2017-01-01

    Full Text Available The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation.

  11. Sacroiliitis in children with spondyloarthropathy: therapeutic effect of CT-guided intra-articular corticosteroid injection; Sakroiliitis bei Kinder mit Spondylarthropathie: Therapeutischer Effekt der CT-gestuetzten intraartikulaeren Kortikosteroid-Injektionen

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, T.; Hermann, K.G.A.; Diekmann, F.; Hamm, B. [Humboldt-Universitaet, Berlin (Germany). Universitaetsklinikum Charite, Inst. fuer Radiologie; Biedermann, T. [HELIOS Klinikum Berlin (Germany). II. Klinik fuer Kinderheilkunde und Jugendmedizin, Abt. Kinderrheumatologie; Braun, J. [Rheumazentrum Ruhrgebiet, St. Josefs-Krankenhaus (Germany); Bollow, M. [Augusta-Krankenhaus, Bochum (Germany). Inst. fuer Radiologie

    2003-06-01

    Purpose: The prospective investigation of the therapeutic effect of CT-guided intra-articular corticosteroid injection into inflammatory sacroiliac (SI) joints compared to conventional treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) in children with juvenile spondyloarthropathy (jSpA) and the determination of the role of dynamic magnetic resonance imaging (MRI) in establishing the indication and monitoring the therapy. Materials and Methods: The study comprises 89 children with known jSpA who were diagnosed by MRI to have a unilateral or bilateral sacroiliitis. Therapy with NSAIDS was initiated or continued in all 89 patients. Four weeks after the diagnostic MRI, two groups were distinguished according to the clinical response of NSAIDS, with group 1 consisting of 22 responders and group 2 of 56 non-responders. The patients of group 2 were treated with CT-guided intra-articular corticosteroid injection (low-dose injection) while the therapy with NSAIDS was continued. A total of 83 SI joints were punctured without complications, 27 bilaterally and 29 unilaterally. The indication for the intervention was based on inflammatory activity as determined by MRI. The therapy was monitored by clinical follow-up every 8 to 12 weeks over a period of 20 months. Follow-up by dynamic MRI was performed in all 56 children of group 2 and 15 of the 33 children of group 1 within 8{+-}4 months of the initial examination. Results: A total of 87.5% of the children in group 2 showed a statistically signficant decrease in their subjective complaints from 6.9{+-}3.4 to 1.8{+-}1.7 (p<0.05) as measured on a visual analog scale (VAS from 0 to 10). Improvement was seen as early as 1.5{+-}1.0 weeks after the intervention and lasted for a mean of 12{+-}6 months. The children in group 1 already showed similar improvement of the VAS from 6.8{+-}3.2 to 1.5{+-}1.4 (p<0.05) during the initial four weeks of NSAIDS therapy, with the improvement lasting for the 20-month observation period

  12. Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

    Directory of Open Access Journals (Sweden)

    Brafman-Kennedy Barbara

    2011-05-01

    Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

  13. Effect of exercise training on sports enjoyment and leisure-time spending in adolescents with complex congenital heart disease: the moderating effect of health behavior and disease knowledge.

    Science.gov (United States)

    Dulfer, Karolijn; Duppen, Nienke; Blom, Nico A; van Dijk, Arie P J; Helbing, Wim A; Verhulst, Frank C; Utens, Elisabeth M W J

    2014-01-01

    The aim of this study was to evaluate the effects of a standardized exercise program on sports enjoyment and leisure-time spending in adolescents with congenital heart disease and to know what the moderating impact of their baseline health behavior and disease knowledge is. Included were 93 patients, aged 10 to 25, with surgical repair for tetralogy of Fallot or with a Fontan circulation for single-ventricle physiology, of 5 participating centers of pediatric cardiology in The Netherlands. They were randomly allocated, stratified for age, gender, and type of congenital heart disease to a 12-week period with either: (1) three times per week standardized exercise training or (2) care as usual (randomization ratio 2:1). At baseline and after 12 weeks, participants completed Web-based questionnaires and were interviewed by phone. Primary analyses tested changes from baseline to follow-up in sports enjoyment and leisure-time spending in the exercise group vs. control group. Secondary analyses concerned the moderating influence of baseline health behavior and disease knowledge on changes from baseline to follow-up, and comparison with normative data. At follow-up, the exercise group reported a decrease in passive leisure-time spending (watching television and computer usage) compared with controls. Exercise training had no effect on sports enjoyment and active leisure-time spending. Disease knowledge had a moderating effect on improvement in sports enjoyment, whereas health behavior did not. Compared with normative data, patients obtained similar leisure time scores and lower frequencies as to drinking alcohol and smoking. Exercise training decreased passive, but not active, leisure-time spending. It did not influence sports enjoyment. © 2013 Wiley Periodicals, Inc.

  14. Demonstrating freedom from disease using multiple complex data sources 2: Case study-Classical swine fever in Denmark

    DEFF Research Database (Denmark)

    Martin, P.A.J.; Cameron, A.R.; Barfod, Kristen

    2007-01-01

    A method for quantitative evaluation of surveillance for disease freedom has been presented in the accompanying paper (Martin et al., 2007). This paper presents an application of the methods, using as an example surveillance for classical swine fever (CSF) in Denmark in 2005. A scenario tree model......) associated with age and location (county), and disease clustering within herds. A surveillance time period of one month was used in the analysis. Records for the year 2005 were analysed, representing 25,332 samples from 3528 herds; all were negative for CSF-specific antibodies. Design prevalences of 0...

  15. Porcine respiratory disease complex: Interaction of vaccination and porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, and Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Chae, Chanhee

    2016-06-01

    Porcine respiratory disease is a multifactorial and complex disease caused by a combination of infectious pathogens, environmental stressors, differences in production systems, and various management practices; hence the name porcine respiratory disease complex (PRDC) is used. Porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and Mycoplasma hyopneumoniae are considered to be the most important pathogens that cause PRDC. Although interactions among the three major respiratory pathogens are well documented, it is also necessary to understand the interaction between vaccines and the three major respiratory pathogens. PRRSV and M. hyopneumoniae are well known to potentiate PCV2-associated lesions; however, PRRSV and mycoplasmal vaccines can both enhance PCV2 viraemia regardless of the effects of the actual PRRSV or M. hyopneumoniae infection. On the other hand, M. hyopneumoniae potentiates the severity of pneumonia induced by PRRSV, and vaccination against M. hyopneumoniae alone is also able to decrease PRRSV viraemia and PRRSV-induced lung lesions in dually infected pigs. This review focuses on (1) interactions between PCV2, PRRSV, and M. hyopneumoniae; and (2) interactions between vaccines and the three major respiratory pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. DISEASES

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease.

    Science.gov (United States)

    Rodríguez-Ruiz, Mar; Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Mallol, Josefa; Cortés, Antonio; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Franco, Rafael

    2017-08-01

    Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D 1 , histamine H 3 , and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H 3 receptor agonists, via negative cross-talk, and H 3 receptor antagonists, via cross-antagonism, decreased D 1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D 1 receptor-mediated excitotoxic cell death. Both D 1 and H 3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D 1 -H 3 receptor heteromer function. Likely due to heteromerization, H 3 receptors act as allosteric regulator for D 1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D 1 or H 3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D 1 -H 3 -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H 3 receptor antagonists reduced NMDA or D 1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H 3 receptor antagonists reverted the toxicity induced by ß 1-42 -amyloid peptide. Thus, histamine H 3 receptors in D 1 -H 3 -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration.

  18. Most of rare missense alleles in humans are deleterious:implications for evolution of complex disease and associationstudies

    Energy Technology Data Exchange (ETDEWEB)

    Kryukov, Gregory V.; Pennacchio, Len A.; Sunyaev, Shamil R.

    2006-10-24

    The accumulation of mildly deleterious missense mutations inindividual human genomes has been proposed to be a genetic basis forcomplex diseases. The plausibility of this hypothesis depends onquantitative estimates of the prevalence of mildly deleterious de novomutations and polymorphic variants in humans and on the intensity ofselective pressure against them. We combined analysis of mutationscausing human Mendelian diseases, human-chimpanzee divergence andsystematic data on human SNPs and found that about 20 percent of newmissense mutations in humans result in a loss of function, while about 27percent are effectively neutral. Thus, more than half of new missensemutations have mildly deleterious effects. These mutations give rise tomany low frequency deleterious allelic variants in the human populationas evident from a new dataset of 37 genes sequenced in over 1,500individual human chromosomes. Surprisingly, up to 70 percent of lowfrequency missense alleles are mildly deleterious and associated with aheterozygous fitness loss in the range 0.001-0.003. Thus, the low allelefrequency of an amino acid variant can by itself serve as a predictor ofits functional significance. Several recent studies have reported asignificant excess of rare missense variants in disease populationscompared to controls in candidate genes or pathways. These studies wouldbe unlikely to work if most rare variants were neutral or if rarevariants were not a significant contributor to the genetic component ofphenotypic inheritance. Our results provide a justification for thesetypes of candidate gene (pathway) association studies and imply thatmutation-selection balance may be a feasible mechanism for evolution ofsome common diseases.

  19. The use of laser therapy in complex treatment of ulcer diseases in participants of Chernobyl accident clean-up

    International Nuclear Information System (INIS)

    Simonova, L.Yi.; Rozdyil's'kij, S.Yi.; Kulyinyich, G.V.; Fertman, V.Z.; Krapivnij, O.O.; Abramova, L.P.; Byilogurova, L.V.; Levchenko, A.P.

    2001-01-01

    The study involved 59 male patients with relapsing duodenal ulcer who had participated in Chernobyl accident clean-up. Laser therapy was administrated daily on the projection of the zone of the ulcer and acupuncture zones. The obtained results allow to conclude that transcutaneous laser therapy is an effective method of treatment of ulcer disease

  20. Mycoplasma detection by triplex real-time PCR in bronchoalveolar lavage fluid from bovine respiratory disease complex cases

    NARCIS (Netherlands)

    Cornelissen, Jan B.W.J.; Bree, de Freddy M.; Wal, van der Fimme J.; Kooij, Engbert A.; Koene, Miriam G.J.; Bossers, Alex; Smid, Bregtje; Antonis, Adriaan F.; Wisselink, Henk J.

    2017-01-01

    Background: In this study we evaluated the RespoCheck Mycoplasma triplex real-time PCR for the detection in bronchoalveolar lavage fluid (BALF) of Mycoplasma (M.) dispar, M. bovis and M. bovirhinis, all three associated with bovine respiratory disease (BRD). Primers and probes of the RespoCheck

  1. Developing Scenarios for Uncertain Complex Risks : Using SD to Explore Futures of Lyme Disease in the Netherlands

    NARCIS (Netherlands)

    Pruyt, E.; Coumou, J.

    2012-01-01

    Lyme disease due to infection with Lyme borreliosis poses an uncertain dynamic threat to the Dutch and their public health system. This risk was used to develop and illustrate two variants of a National Risk Assessment approaches for slumbering/latent risks. This paper explains and illustrates the

  2. THE AROMATIC PHYTO-BATHS ARE AN EFFECTIVE METHOD OF HYDROTHERAPY IN COMPLEX REHABILITATIVE TREATMENT OF CHILDREN WITH DIFFERENT DISEASES

    Directory of Open Access Journals (Sweden)

    O. M. Konova

    2014-01-01

    Full Text Available The drugs and phytoaromatic substances increases the efficacy of balneotherapy. Mineral, medicinal and aromatic baths are widely used in complex rehabilitation of patients from 1 month of age. Aromatic phyto-baths have a complex mechanism of action and a wide variety of therapeutic effects. Today special products based on natural plant components and essential oilsare are developed to prepare the aromatic phyto-baths. Only officially registered industrial drugs with clinical efficacy and safety were proven by clinical researches can be recommended for the pediatric using. Our studies demonstrated a positive impact aromatic phyto-baths to the dynamics of clinical symptoms at the patients with acute respiratory infections, atopic dermatitis; and also were revealed an increase of adaptive organism reserves.

  3. The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?

    Directory of Open Access Journals (Sweden)

    Kostikas K

    2016-06-01

    Full Text Available Konstantinos Kostikas, Andreas Clemens, Francesco Patalano Novartis Pharma AG, Basel, Switzerland Abstract: The term asthma–COPD overlap syndrome (ACOS is one of multiple terms used to describe patients with characteristics of both COPD and asthma, representing ~20% of patients with obstructive airway diseases. The recognition of both sets of morbidities in patients is important to guide practical treatment decisions. It is widely recognized that patients with COPD and coexisting asthma present with a higher disease burden, despite the conceptual expectation that the “reversible” or “treatable” component of asthma would allow for more effective management and better outcomes. However, subcategorization into terms such as ACOS is complicated by the vast spectrum of heterogeneity that is encapsulated by asthma and COPD, resulting in different clinical clusters. In this review, we discuss the possibility that these different clusters are suboptimally described by the umbrella term “ACOS”, as this additional categorization may lead to clinical confusion and potential inappropriate use of resources. We suggest that a more clinically relevant approach would be to recognize the extreme variability and the numerous phenotypes encompassed within obstructive airway diseases, with various degrees of overlapping in individual patients. In addition, we discuss some of the evidence to be considered when making practical decisions on the treatment of patients with overlapping characteristics between COPD and asthma, as well as the potential options for phenotype and biomarker-driven management of airway disease with the aim of providing more personalized treatment for patients. Finally, we highlight the need for more evidence in patients with overlapping disease characteristics and to facilitate better characterization of potential treatment responders. Keywords: emphysema, chronic bronchitis, COPD, asthma, ACOS, overlap syndrome

  4. Preserving Posterior Complex Can Prevent Adjacent Segment Disease following Posterior Lumbar Interbody Fusion Surgeries: A Finite Element Analysis.

    Science.gov (United States)

    Huang, Yun-Peng; Du, Cheng-Fei; Cheng, Cheng-Kung; Zhong, Zheng-Cheng; Chen, Xuan-Wei; Wu, Gui; Li, Zhe-Cheng; Ye, Jin-Duo; Lin, Jian-Hua; Wang, Li Zhen

    2016-01-01

    To investigate the biomechanical effects of the lumbar posterior complex on the adjacent segments after posterior lumbar interbody fusion (PLIF) surgeries. A finite element model of the L1-S1 segment was modified to simulate PLIF with total laminectomy (PLIF-LAM) and PLIF with hemilaminectomy (PLIF-HEMI) procedures. The models were subjected to a 400N follower load with a 7.5-N.m moment of flexion, extension, torsion, and lateral bending. The range of motion (ROM), intradiscal pressure (IDP), and ligament force were compared. In Flexion, the ROM, IDP and ligament force of posterior longitudinal ligament, intertransverse ligament, and capsular ligament remarkably increased at the proximal adjacent segment in the PLIF-LAM model, and slightly increased in the PLIF-HEMI model. There was almost no difference for the ROM, IDP and ligament force at L5-S1 level between the two PLIF models although the ligament forces of ligamenta flava remarkably increased compared with the intact lumbar spine (INT) model. For the other loading conditions, these two models almost showed no difference in ROM, IDP and ligament force on the adjacent discs. Preserved posterior complex acts as the posterior tension band during PLIF surgery and results in less ROM, IDP and ligament forces on the proximal adjacent segment in flexion. Preserving the posterior complex during decompression can be effective on preventing adjacent segment degeneration (ASD) following PLIF surgeries.

  5. Complex self-management interventions in chronic disease unravelled: a review of lessons learned from an individual patient data meta-analysis.

    Science.gov (United States)

    Jonkman, Nini H; Groenwold, Rolf H H; Trappenburg, Jaap C A; Hoes, Arno W; Schuurmans, Marieke J

    2017-03-01

    Meta-analyses using individual patient data (IPD) rather than aggregated data are increasingly applied to analyze sources of heterogeneity between trials and have only recently been applied to unravel multicomponent, complex interventions. This study reflects on methodological challenges encountered in two IPD meta-analyses on self-management interventions in patients with heart failure or chronic obstructive pulmonary disease. Critical reflection on prior IPD meta-analyses and discussion of literature. Experience from two IPD meta-analyses illustrates methodological challenges. Despite close collaboration with principal investigators, assessing the effect of characteristics of complex interventions on the outcomes of trials is compromised by lack of sufficient details on intervention characteristics and limited data on fidelity and adherence. Furthermore, trials collected baseline variables in a highly diverse way, limiting the possibilities to study subgroups of patients in a consistent manner. Possible solutions are proposed based on lessons learnt from the methodological challenges. Future researchers of complex interventions should pay considerable attention to the causal mechanism underlying the intervention and conducting process evaluations. Future researchers on IPD meta-analyses of complex interventions should carefully consider their own causal assumptions and availability of required data in eligible trials before undertaking such resource-intensive IPD meta-analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Is the reduction of dimensionality to a small number of features always necessary in constructing predictive models for analysis of complex diseases or behaviours?

    Science.gov (United States)

    Zollanvari, Amin; Saccone, Nancy L; Bierut, Laura J; Ramoni, Marco F; Alterovitz, Gil

    2011-01-01

    Gene expression and genome wide association data have provided researchers the opportunity to study many complex traits and diseases. When designing prognostic and predictive models capable of phenotypic classification in this area, significant reduction of dimensionality through stringent filtering and/or feature selection is often deemed imperative. Here, this work challenges this presumption through both theoretical and empirical analysis. This work demonstrates that by a proper compromise between structure of the selected model and the number of features, one is able to achieve better performance even in large dimensionality. The inclusion of many genes/variants in the classification rules can help shed new light on the analysis of complex traitstraits that are typically determined by many causal variants with small effect size.

  7. Three-Year Major Clinical Outcomes of Angiography-Guided Single Stenting Technique in Non-Complex Left Main Coronary Artery Diseases.

    Science.gov (United States)

    Kim, Yong Hoon; Her, Ae-Young; Rha, Seung-Woon; Choi, Byoung Geol; Shim, Minsuk; Choi, Se Yeon; Byun, Jae Kyeong; Li, Hu; Kim, Woohyeun; Kang, Jun Hyuk; Choi, Jah Yeon; Park, Eun Jin; Park, Sung Hun; Lee, Sunki; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo

    2017-10-12

    There is limited long-term comparative clinical outcome data concerning angiography- versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in non-complex left main coronary artery (LMCA) disease treated with the single stenting technique in the drug-eluting stent (DES) era.The aim of this study was to investigate whether angiography-guided stenting is comparable to IVUS-guided stenting during 3-year clinical follow-up periods in patients with non-complex LM disease treated with the single stenting technique.A total of 196 patients treated with either angiography-guided (n = 74) or IVUS-guided (n = 122) PCI were included. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-target vessel revascularization (Non-TVR). To adjust for any potential confounders, propensity score (PS) adjusted analysis was performed.During 3-year follow-up, the PS adjusted Cox-proportional hazard ratio (HR) was not significantly different between the two groups for total death, cardiac death, and MI. Also, TLR and the combined rates of TVR and non-TVR were not significantly different. Finally, MACE was not significantly different between the two groups (HR: 0.63, 95% Confidence interval (CI): 0.33-1.17; P = 0.149).Angiography-guided PCI for non-complex LMCA diseases treated with the single stenting technique showed comparable results compared with IVUS-guided PCI in reducing clinical events during 3-year clinical follow-up in the DES era. Although IVUS guided PCI is the ideal strategy, angiography-guided PCI can be an option for LMCA PCI in some selected cases.

  8. CD147 is a regulatory subunit of the gamma-secretase complex inAlzheimer's disease amyloid beta-peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Shuxia; Zhou, Hua; Walian, Peter J.; Jap, Bing K.

    2005-04-06

    {gamma}-secretase is a membrane protein complex that cleaves the {beta}-amyloid precursor protein (APP) within the transmembrane region, following prior processing by {beta}-secretase, producing amyloid {beta}-peptides (A{beta}{sub 40} and A{beta}{sub 42}). Errant production of A{beta}-peptides that substantially increases A{beta}{sub 42} production has been associated with the formation of amyloid plaques in Alzheimer's disease patients. Biophysical and genetic studies indicate that presenilin-1 (Psn-1), which contains the proteolytic active site, and three other membrane proteins, nicastrin (Nct), APH-1, and PEN-2 are required to form the core of the active {gamma}-secretase complex. Here, we report the purification of the native {gamma}-secretase complexes from HeLa cell membranes and the identification of an additional {gamma}-secretase complex subunit, CD147, a transmembrane glycoprotein with two immunoglobulin-like domains. The presence of this subunit as an integral part of the complex itself was confirmed through co-immunoprecipitation studies of the purified protein from HeLa cells and solubilized complexes from other cell lines such as neural cell HCN-1A and HEK293. Depletion of CD147 by RNA interference was found to increase the production of A{beta} peptides without changing the expression level of the other {gamma}-secretase components or APP substrates while CD147 overexpression had no statistically significant effect on amyloid {beta}-peptide production, other {gamma}-secretase components or APP substrates, indicating that the presence of the CD147 subunit within the {gamma}-secretase complex directly down-modulates the production of A{beta}-peptides. {gamma}-secretase was first recognized through its role in the production of the A{beta} peptides that are pathogenic in Alzheimer's disease (AD) (1). {gamma}-secretase is a membrane protein complex with unusual aspartyl protease activity that cleaves a variety of type I membrane proteins

  9. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records

    DEFF Research Database (Denmark)

    Jiang, Li; Edwards, Stefan M.; Thomsen, Bo

    2014-01-01

    Background: Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic...... from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining...... of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known...

  10. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records

    DEFF Research Database (Denmark)

    Jiang, Li; Edwards, Stefan M.; Thomsen, Bo

    2014-01-01

    Background: Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic...... from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining...... causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. Conclusion: We have implemented and validated a network-based approach to prioritize genes for human diseases based...

  11. Structural biology of disease-associated repetitive DNA sequences and protein-DNA complexes involved in DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, G.; Santhana Mariappan, S.V.; Chen, X.; Catasti, P.; Silks, L.A. III; Moyzis, R.K.; Bradbury, E.M.; Garcia, A.E.

    1997-07-01

    This project is aimed at formulating the sequence-structure-function correlations of various microsatellites in the human (and other eukaryotic) genomes. Here the authors have been able to develop and apply structure biology tools to understand the following: the molecular mechanism of length polymorphism microsatellites; the molecular mechanism by which the microsatellites in the noncoding regions alter the regulation of the associated gene; and finally, the molecular mechanism by which the expansion of these microsatellites impairs gene expression and causes the disease. Their multidisciplinary structural biology approach is quantitative and can be applied to all coding and noncoding DNA sequences associated with any gene. Both NIH and DOE are interested in developing quantitative tools for understanding the function of various human genes for prevention against diseases caused by genetic and environmental effects.

  12. [Antimicrobial efficacy of systemic antibiotics of different groups in the complex treatment of patients with chronic periodontal disease].

    Science.gov (United States)

    Zorina, O A; Berkutova, I S; Basova, A A

    2014-01-01

    Among microorganisms found in the oral cavity there are several kinds of periodontopathogenic bacteria having higher adhesive, invasive and toxic properties. Eighty patients with moderate and severe chronic generalized periodontitis were included in the study. The choice of treatment regimen depended on real-time PCR values of pathogenic microorganisms in periodontal pockets. Data on composition of periodontal pockets microflora by moderate and severe periodontal disease allow prompt target antimicrobial therapy.

  13. Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-evaluation is needed

    OpenAIRE

    Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K. Ray

    2017-01-01

    Holistic management of Parkinson’s disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson’s from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson’s which may manifest in a motor dominant or nonmotor do...

  14. Regulatory MicroRNA Networks: Complex Patterns of Target Pathways for Disease-related and Housekeeping MicroRNAs

    Directory of Open Access Journals (Sweden)

    Sachli Zafari

    2015-06-01

    Full Text Available Blood-based microRNA (miRNA signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behind respective miRNA patterns is only partially understood. Moreover, “preserved” miRNAs, i.e., miRNAs that are not dysregulated in any disease, and their biological impact have been explored to a very limited extent. We set out to systematically determine their role in regulatory networks by defining groups of highly-dysregulated miRNAs that contribute to a disease signature as opposed to preserved housekeeping miRNAs. We further determined preferential targets and pathways of both dysregulated and preserved miRNAs by computing multi-layer networks, which were compared between housekeeping and dysregulated miRNAs. Of 848 miRNAs examined across 1049 blood samples, 8 potential housekeepers showed very limited expression variations, while 20 miRNAs showed highly-dysregulated expression throughout the investigated blood samples. Our approach provides important insights into miRNAs and their role in regulatory networks. The methodology can be applied to systematically investigate the differences in target genes and pathways of arbitrary miRNA sets.

  15. Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

    Directory of Open Access Journals (Sweden)

    Tracy A Nichols

    Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

  16. Modifying the Interagency Emergency Health Kit to include treatment for non-communicable diseases in natural disasters and complex emergencies.

    Science.gov (United States)

    Tonelli, Marcello; Wiebe, Natasha; Nadler, Brian; Darzi, Ara; Rasheed, Shahnawaz

    2016-01-01

    The Interagency Emergency Health Kit (IEHK) provides a standard package of medicines and simple medical devices for aid agencies to use in emergencies such as disasters and armed conflicts. Despite the increasing burden of non-communicable diseases (NCDs) in such settings, the IEHK includes few drugs and devices for management of NCDs. Using published data to model the population burden of acute and chronic presentations of NCDs in emergency-prone regions, we estimated the quantity of medications and devices that should be included in the IEHK. NCDs considered were cardiovascular diseases, diabetes, hypertension and chronic respiratory disease. In scenario 1 (the primary scenario), we assumed that resources in the IEHK would only include those needed to manage acute life-threatening conditions. In scenario 2, we included resources required to manage both acute and chronic presentations of NCDs. Drugs and devices that might be required included amlodipine, aspirin, atenolol, beclomethasone, dextrose 50%, enalapril, furosemide, glibenclamide, glyceryl trinitrate, heparin, hydralazine, hydrochlorothiazide, insulin, metformin, prednisone, salbutamol and simvastatin. For scenario 1, the number of units required ranged from 12 (phials of hydralazine) to ∼15 000 (tablets of enalapril). Space and weight requirements were modest and total cost for all drugs and devices was approximately US$2078. As expected, resources required for scenario 2 were much greater. Space and cost requirements increased proportionately: estimated total cost of scenario 2 was $22 208. The resources required to treat acute NCD presentations appear modest, and their inclusion in the IEHK seems feasible.

  17. WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.

    Science.gov (United States)

    Covone, A E; Fiorillo, C; Acquaviva, M; Trucco, F; Morana, G; Ravazzolo, R; Minetti, C

    2016-08-01

    We have performed whole-exome sequencing in a family trio with a 16-year-old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans-phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Revascularization heart team recommendations as an adjunct to appropriate use criteria for coronary revascularization in patients with complex coronary artery disease.

    Science.gov (United States)

    Sanchez, Carlos E; Dota, Anthony; Badhwar, Vinay; Kliner, Dustin; Smith, A J Conrad; Chu, Danny; Toma, Catalin; Wei, Lawrence; Marroquin, Oscar C; Schindler, John; Lee, Joon S; Mulukutla, Suresh R

    2016-10-01

    To evaluate how a comprehensive evidence-based clinical review by a multidisciplinary revascularization heart team on treatment decisions for revascularization in patients with complex coronary artery disease using SYNTAX scores combined with Society of Thoracic Surgeons-derived clinical variables can be additive to the utilization of Appropriate Use Criteria for coronary revascularization. Decision-making regarding the use of revascularization for coronary artery disease has come under major scrutiny due to inappropriate overuse of revascularization. There is little data in routine clinical practice evaluating how a structured, multidisciplinary heart team approach may be used in combination with the Appropriate Use Criteria for revascularization. From May 1, 2012 to January 1, 2015, multidisciplinary revascularization heart team meetings were convened to discuss evidence-based management of 301 patients with complex coronary artery disease. Heart team recommendations were adjudicated with the Appropriate Use Criteria for coronary revascularization for each clinical scenario using the Society for Cardiovascular Angiography and Interventions' Quality Improvement Toolkit (SCAI-QIT) Appropriate Use Criteria App. Concordance of the Heart Team to Appropriate Use Criteria had a 99.3% appropriate primary indication for coronary revascularization. Among patients who underwent percutaneous revascularization, 34.9% had an inappropriate or uncertain indication as recommended by the Heart Team. Patients with uncertain or inappropriate percutaneous coronary interventions had significantly higher SYNTAX score (27.3 ± 6.6; 28.5 ± 5.5; 19.2 ± 6; P coronary artery disease. A formal, multidisciplinary revascularization heart team can provide proper validation for clinical decisions and should be considered in combination with the Appropriate Use Criteria for coronary revascularization to formulate revascularization strategies for individuals in a patient

  19. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

    Science.gov (United States)

    Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

    2015-01-01

    Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully

  20. Effects of genetic changes to the begomovirus/betasatellite complex causing cotton leaf curl disease in South Asia post-resistance breaking.

    Science.gov (United States)

    Briddon, Rob W; Akbar, Fazal; Iqbal, Zafar; Amrao, Luqman; Amin, Imran; Saeed, Muhammad; Mansoor, Shahid

    2014-06-24

    Cotton leaf curl disease (CLCuD) has been a problem for cotton production across Pakistan and north-eastern India since the early 1990s. The appearance of the disease has been attributed to the introduction, and near monoculture of highly susceptible cotton varieties. During the intervening period the genetic make-up of the virus(es) causing the disease has changed dramatically. The most prominent of these changes has been in response to the introduction of CLCuD-resistant cotton varieties in the late 1990s, which provided a brief respite from the losses due to the disease. During the 1990s the disease was shown to be caused by multiple begomoviruses and a single, disease-specific betasatellite. Post-resistance breaking the complex encompassed only a single begomovirus, Cotton leaf curl Burewala virus (CLCuBuV), and a recombinant version of the betasatellite. Surprisingly CLCuBuV lacks an intact transcriptional-activator protein (TrAP) gene. The TrAP gene is found in all begomoviruses and encodes a product of ∼134 amino acids that is important in virus-host interactions; being a suppressor of post-transcriptional gene silencing (host defence) and a transcription factor that modulates host gene expression, including microRNA genes. Recent studies have highlighted the differences between CLCuBuV and the earlier viruses that are part of on-going efforts to define the molecular basis for resistance breaking in cotton. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Retinal nerve fiber layer and ganglion cell complex thickness assessment in patients with Alzheimer disease and mild cognitive impairment. Preliminary results

    Directory of Open Access Journals (Sweden)

    A. S. Tiganov

    2014-07-01

    Full Text Available Purpose: to investigate the retinal nerve fiber layer (RNFL and the macular ganglion cell complex (GCC in patients with Alzheimer`s disease and mild cognitive impairment.Methods: this study included 10 patients (20 eyes with Alzheimer`s disease, 10 patients with mild cognitive impairment and 10 age- and sex-matched healthy controls that had no history of dementia. All the subjects underwent psychiatric examination, including the Mini-Mental State Examination (MMSE, and complete ophthalmological examination, comprising optical coherence tomography and scanning laser polarimetry.Results: there was a significant decrease in GCC thickness in patients with Alzheimer`s disease compared to the control group, global loss volume of ganglion cells was higher than in control group. there was no significant difference among the groups in terms of RNFL thickness. Weak positive correlation of GCC thickness and MMSE results was observed.Conclusion: Our data confirm the retinal involvement in Alzheimer`s disease, as reflected by loss of ganglion cells. Further studies will clear up the role and contribution of dementia in pathogenesis of optic neuropathy.

  2. [Alzheimer's disease cerebro-spinal fluid biomarkers: A clinical research tool sometimes useful in daily clinical practice of memory clinics for the diagnosis of complex cases].

    Science.gov (United States)

    Magnin, E; Dumurgier, J; Bouaziz-Amar, E; Bombois, S; Wallon, D; Gabelle, A; Lehmann, S; Blanc, F; Bousiges, O; Hannequin, D; Jung, B; Miguet-Alfonsi, C; Quillard, M; Pasquier, F; Peoc'h, K; Laplanche, J-L; Hugon, J; Paquet, C

    2017-04-01

    The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  3. Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease

    Science.gov (United States)

    1993-01-01

    How peptide-major histocompatibility complex (MHC) class II complexes are naturally generated is still unknown, but accumulating evidence suggests that unfolding proteins or long peptides can become bound to class II molecules at the dominant determinant before proteolytic cleavage. We have compared the immunogenicity of hen egg-white lysozyme (HEL) in nonobese diabetic (NOD), (NOD x BALB/c)F1, and E(d) alpha transgenic NOD mice. We find that a response to the subdominant ANOD- restricted determinant disappears upon introduction of an E(d) molecule, and is restored when scission of HEL separates this determinant from its adjoining, competitively dominant, E(d)-restricted determinant. This suggests that the E(d) molecule binds and protects its dominant determinant on a long peptide while captured neighboring determinants are lost during proteolysis. These results provide clear evidence for "determinant capture" as a mechanism of determinant selection during antigen processing and a possible explanation for MHC- protective effects in insulin-dependent diabetes mellitus. PMID:8228814

  4. A randomized controlled trial of nurses vs. doctors in the resolution of acute disease of low complexity in primary care.

    Science.gov (United States)

    Iglesias, Begoña; Ramos, Francisca; Serrano, Beatriz; Fàbregas, Mireia; Sánchez, Carmen; García, María José; Cebrian, Hèlia Marta; Aragonés, Rosa; Casajuana, Josep; Esgueva, Neus

    2013-11-01

    To compare the effectiveness of care delivered by nurses to the usual care delivered by general practitioners, in adult patients requesting same day appointments in primary care practices in Catalonia (Spain). Same day appointments conducted by nurses are characterized by high patient satisfaction and a high resolution index. The profile of nursing and the organization of primary care services in our country differ from other countries. Multicentre, randomized, unblinded clinical trial with two parallel groups. Patients were randomized to an intervention group (seen by nurses trained to respond to low complexity problems) or a control group (seen by the general practitioner) using an automatic probabilistic function. 38 primary care practices in Catalonia, 142 general practitioners and 155 nurses participated. Population study: ≥ 18-year-old patients who requested a same day consultation. Recruitment period: January-May, 2009. Of the 1,461 randomized patients, 92.5% completed the study. resolution of symptoms and patient satisfaction 2 weeks after the visit. Seven hundred and fifty-three patients were assigned to the intervention group and 708 to the control group. Nurses successfully solved 86.3% of the cases. We did not observe any differences in resolution of symptoms or patient satisfaction between the groups. Nurses trained specifically to resolve acute health problems of low complexity give comparable quality of care to that provided by general practitioners in terms of resolution of the problem 15 days after the visit and in patient satisfaction with the visit. © 2013 Blackwell Publishing Ltd.

  5. Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

    Science.gov (United States)

    Grissett, G P; White, B J; Larson, R L

    2015-01-01

    Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. Dembo-PCR technique for the detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs.

    Science.gov (United States)

    Rahpaya, Sayed Samim; Tsuchiaka, Shinobu; Kishimoto, Mai; Oba, Mami; Katayama, Yukie; Nunomura, Yuki; Kokawa, Saki; Kimura, Takashi; Kobayashi, Atsushi; Kirino, Yumi; Okabayashi, Tamaki; Nonaka, Nariaki; Mekata, Hirohisa; Aoki, Hiroshi; Shiokawa, Mai; Umetsu, Moeko; Morita, Tatsushi; Hasebe, Ayako; Otsu, Keiko; Asai, Tetsuo; Yamaguchi, Tomohiro; Makino, Shinji; Murata, Yoshiteru; Abi, Ahmad Jan; Omatsu, Tsutomu; Mizutani, Tetsuya

    2017-12-28

    The bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds and rodents. However, experimental data that supports this possibility are scarce. We collected total 117 samples and screened for 44 bovine abortive, diarrheal and respiratory disease complex pathogens by using Dembo-PCR, based on TaqMan real-time PCR. Fifty-seven samples showed positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, salmonella enterica ser. Typhimurium, and Neospora caninum ; some samples contained multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus represented the most frequently detected pathogens, especially in flies, suggesting the important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggests that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of the abortion, diarrhea, and respiratory infectious agents and that they may transmit more than one pathogen at the same time.

  7. Complex interplay of future climate levels of CO2, ozone and temperature on susceptibility to fungal diseases in barley

    DEFF Research Database (Denmark)

    Mikkelsen, Bolette Lind; Bagger Jørgensen, Rikke; Lyngkjær, Michael Foged

    2015-01-01

    Barley (Hordeum vulgare) was grown in different climatic environments with elevated [CO2] (700 vs 385 ppm), [O3] (60/90 vs 20 ppb) and temperature (24/19 vs 19/12°C day/night) as single factors and in combinations, to evaluate the impact of these climatic factors on photosynthesis and susceptibil......Barley (Hordeum vulgare) was grown in different climatic environments with elevated [CO2] (700 vs 385 ppm), [O3] (60/90 vs 20 ppb) and temperature (24/19 vs 19/12°C day/night) as single factors and in combinations, to evaluate the impact of these climatic factors on photosynthesis...... and susceptibility to powdery mildew and spot blotch disease. No significant increase in net CO2 assimilation rate was observed in barley grown under elevated [CO2] at ambient temperature. However, this rate was positively stimulated under elevated temperature together with a slightly higher potential quantum...... efficiency of PSII, both at ambient and elevated [CO2], suggesting that photosynthesis was not limited by [CO2] at ambient temperature. When growing under elevated temperature or [O3], infection by the biotrophic powdery mildew fungus decreased, whereas disease symptoms and growth of the toxin...

  8. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    International Nuclear Information System (INIS)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-01-01

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface

  9. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, Edward I. [Charles Sturt University, School of Animal and Veterinary Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Dombrovski, Andrew K. [Charles Sturt University, School of Biomedical Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Swarbrick, Crystall M.D. [Charles Sturt University, School of Biomedical Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Raidal, Shane R. [Charles Sturt University, School of Animal and Veterinary Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Forwood, Jade K., E-mail: jforwood@csu.edu.au [Charles Sturt University, School of Biomedical Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia)

    2013-09-06

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.

  10. Vitamin D receptor expression levels determine the severity and complexity of disease progression among leprosy reaction patients

    Directory of Open Access Journals (Sweden)

    D. Mandal

    2015-07-01

    Full Text Available We studied the roles of vitamin D and its receptor, VDR, in the progression of leprosy. The majority of individuals with leprosy from Kolkata, India, with a type 1 or type 2 reaction have low levels of vitamin D3 in serum samples. Interestingly, individuals with a type 2 reaction associated with neuritis/erythema nodosum leprosum had very low VDR mRNA expression levels, ranging from 5% to 10%, compared to that of healthy control subjects; these patients also had a high bacilli index, ranging from 3+ to 5+. This is the first report to indicate that VDR expression levels may determine the complexity and severity of the progression of leprosy.

  11. Synthesis and characterization of (68)Ga-labeled curcumin and curcuminoid complexes as potential radiotracers for imaging of cancer and Alzheimer's disease.

    Science.gov (United States)

    Asti, Mattia; Ferrari, Erika; Croci, Stefania; Atti, Giulia; Rubagotti, Sara; Iori, Michele; Capponi, Pier C; Zerbini, Alessandro; Saladini, Monica; Versari, Annibale

    2014-05-19

    Curcumin (CUR) and curcuminoids complexes labeled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Gallium-68 is a positron-emitting, generator-produced radionuclide, and its properties can be exploited in situ in medical facilities without a cyclotron. Moreover, CUR showed a higher uptake in tumor cells compared to normal cells, suggesting potential diagnostic applications in this field. In spite of this, no studies using labeled CUR have been performed in this direction, so far. Herein, (68)Ga-labeled complexes with CUR and two curcuminoids, namely diacetyl-curcumin (DAC) and bis(dehydroxy)curcumin (bDHC), were synthesized and characterized by means of experimental and theoretical approaches. Moreover, a first evaluation of their affinity to synthetic β-amyloid fibrils and uptake by A549 lung cancer cells was performed to show the potential application of these new labeled curcuminoids in these diagnostic fields. The radiotracers were prepared by reacting (68)Ga(3+) obtained from a (68)Ge/(68)Ga generator with 1 mg/mL curcuminoids solutions. Reaction parameters (precursor amount, reaction temperature, and pH) were optimized to obtain high and reproducible radiochemical yield and purity. Stoichiometry and formation of the curcuminoid complexes were investigated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, NMR, ultraviolet-visible, and fluorescence spectroscopy on the equivalent (nat)Ga-curcuminoids (nat = natural) complexes, and their structure was computed by theoretical density functional theory calculations. The analyses evidenced that CUR, DAC, and bDHC were predominantly in the keto-enol form and attested to Ga(L)2(+) species formation. Identity of the (68)Ga(L)2(+) complexes was confirmed by coelution with the equivalent (nat)Ga(L)2(+) complexes in ultrahigh-performance liquid chromatography analyses.(68)Ga(CUR)2(+), (68)Ga(DAC)2(+), and (68)Ga(bDHC)2

  12. Increase in endemic Neisseria meningitidis capsular group W sequence type 11 complex associated with severe invasive disease in England and Wales.

    Science.gov (United States)

    Ladhani, Shamez N; Beebeejaun, Kazim; Lucidarme, Jay; Campbell, Helen; Gray, Steve; Kaczmarski, Ed; Ramsay, Mary E; Borrow, Ray

    2015-02-15

    In England and Wales, the incidence of invasive meningococcal disease has been declining for more than a decade, but meningococcal group W (MenW) cases have been increasing since 2009. Public Health England conducts enhanced national surveillance of invasive meningococcal disease in England and Wales. Detailed clinical information was obtained for all laboratory-confirmed MenW cases diagnosed during 3 epidemiologic years (2010-2011 to 2012-2013), alongside whole-genome sequencing analysis of the clinical isolates. The year-on-year increase in invasive MenW disease across all age groups since 2009-2010 was due to rapid endemic expansion of a single clone belonging to the sequence type 11 complex (cc11). In 2013-2014, MenW was responsible for 15% of all invasive meningococcal disease. All but 1 of the recent MenW:cc11 isolates were very closely related, consistent with recent clonal expansion. Clinical follow-up of all 129 MenW cases diagnosed during 2010-2011 to 2012-2013 revealed that most patients were previously healthy (n = 105 [81%]), had not travelled abroad prior to illness and the majority presented with septicemia (n = 63 [49%]), meningitis (n = 16 [12%]) or both (n = 21 [16%]); however, one-quarter had atypical presentations including pneumonia (n = 15 [12%]), septic arthritis (n = 9 [7%]), and epiglottitis/supraglottitis (n = 5 [4%]). Forty-eight (37%) required intensive care and 15 (12%) died. There was no association between infecting strain, clinical disease, or outcome. The recent increase in invasive MenW disease in England and Wales is due to rapid endemic expansion of a single clone belonging to cc11 and is associated with severe disease with unusual clinical presentations. This increase will require careful monitoring in the coming years. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Modeling fall propensity in Parkinson's disease: deficits in the attentional control of complex movements in rats with cortical-cholinergic and striatal-dopaminergic deafferentation.

    Science.gov (United States)

    Kucinski, Aaron; Paolone, Giovanna; Bradshaw, Marc; Albin, Roger L; Sarter, Martin

    2013-10-16

    Cognitive symptoms, complex movement deficits, and increased propensity for falls are interrelated and levodopa-unresponsive symptoms in patients with Parkinson's disease (PD). We developed a test system for the assessment of fall propensity in rats and tested the hypothesis that interactions between loss of cortical cholinergic and striatal dopaminergic afferents increase fall propensity. Rats were trained to traverse stationary and rotating rods, placed horizontally or at inclines, and while exposed to distractors. Rats also performed an operant Sustained Attention Task (SAT). Partial cortical cholinergic and/or caudate dopaminergic deafferentation were produced by bilateral infusions of 192 IgG-saporin (SAP) into the basal forebrain and/or 6-hydroxydopamine (6-OHDA) into the caudate nucleus, respectively, modeling the lesions seen in early PD. Rats with dual cholinergic-dopaminergic lesions (DL) fell more frequently than SAP or 6-OHDA rats. Falls in DL rats were associated with incomplete rebalancing after slips and low traversal speed. Ladder rung walking and pasta handling performance did not indicate sensorimotor deficits. SAT performance was impaired in DL and SAP rats; however, SAT performance and falls were correlated only in DL rats. Furthermore, in DL rats, but not in rats with only dopaminergic lesions, the placement and size of dopaminergic lesion correlated significantly with fall rates. The results support the hypothesis that after dual cholinergic-dopaminergic lesions, attentional resources can no longer be recruited to compensate for diminished striatal control of complex movement, thereby "unmasking" impaired striatal control of complex movements and yielding falls.

  14. Connecting human behavior and infectious disease spreading. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Wang et al.

    Science.gov (United States)

    Holme, Petter

    2015-12-01

    Vaccination against measles is one of the great success stories of 20th century medicine. In the USA, before the introduction of the vaccine in 1963, three to four million adolescents were infected annually, around 500 died, around 5000 got serious complications (primarily encephalitis, swelling of the brain), and around 50,000 were hospitalized [7]. With the vaccine, measles virtually vanished and by 2000 it was declared extinct from the USA. This was, however, not the end of the story. There is still a small fraction of parents who do not let their children be vaccinated. The reasons vary-fear of side effects, an aversion of exposing children to something ;unnatural;, and a large number of other ideas. (For a non-academic account of the psychology of vaccination, we recommend Eula Biss's On Immunity[3].) The last few decades, anti-vaccination ideas have been spreading in social media and united people opposing vaccination into something of a movement [4]. In December 2014 there was a first larger outbreak (over 500 cases) of the century, centered around Disneyland (Anaheim, California) [10], and the anti-vaccination movement got much of the blame [4]. This example illustrates how ideas and opinions-that just like diseases are spreading over networks of people-can facilitate outbreaks. The reverse is, thankfully, more common-people, aware of an emerging outbreak, try to lower the chance of contagion by improving hygiene etc., which impedes the outbreak.

  15. Properties and modeling of GWAS when complex disease risk is due to non-complementing, deleterious mutations in genes of large effect.

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    Kevin R Thornton

    Full Text Available Current genome-wide association studies (GWAS have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE. This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders, and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated.

  16. Classical nuclear hormone receptor activity as a mediator of complex biological responses: a look at health and disease.

    Science.gov (United States)

    Yen, Paul Michael

    2015-08-01

    Nuclear hormone receptors are a large family of receptors that bind a wide range of lipolic hormones and intracellular ligands. They act as ligand-inducible transcription factors to regulate the expression of target genes and play important roles in normal development, reproduction, and metabolism. NRs bind to hormones steroids, thyroid hormone, and vitamin D as well as metabolites of fatty acids, cholesterol, and bild acids. Orphan receptors are another group of NRs for which no known ligands have been identified yet but appear to have major roles in regulating intracellular metabolism. Targeting NRs has been a major source for the development of new drugs, particularly selective agonists and antagonists for cancer and metabolic diseases. Additionally, hormone resistance syndromes in man have enlarged our understanding of the functions of specific NRs and their isoforms as well as genetic mechanisms for phenotype expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Mycoplasma detection by triplex real-time PCR in bronchoalveolar lavage fluid from bovine respiratory disease complex cases.

    Science.gov (United States)

    Cornelissen, Jan B W J; de Bree, Freddy M; van der Wal, Fimme J; Kooi, Engbert A; Koene, Miriam G J; Bossers, Alex; Smid, Bregtje; Antonis, Adriaan F; Wisselink, Henk J

    2017-04-08

    In this study we evaluated the RespoCheck Mycoplasma triplex real-time PCR for the detection in bronchoalveolar lavage fluid (BALF) of Mycoplasma (M.) dispar, M. bovis and M. bovirhinis, all three associated with bovine respiratory disease (BRD). Primers and probes of the RespoCheck Mycoplasma triplex real-time PCR are based on the V3/V4 region of the 16S rRNA gene of the three Mycoplasma species. The analytical sensitivity of the RespoCheck triplex real-time PCR was, as determined by spiking experiments of the Mycoplasma strains in Phosphate Buffered Saline, 300 colony forming units (cfu)/mL for M. dispar, and 30 cfu/mL for M. bovis or M. bovirhinis. The analytical sensitivity of the RespoCheck Mycoplasma triplex real-time PCRwas, as determined on purified DNA, 10 fg DNA per assay for M. dispar and 100 fg fo rM. bovis and M. bovirhinis. The analytical specificity of the RespoCheck Mycoplasma triplex real-time PCR was, as determined by testing Mycoplasmas strains (n = 17) and other bacterial strains (n = 107), 100, 98.2 and 99.1% for M. bovis, M. dispar and M. bovirhinis respectively. The RespoCheck Mycoplasma triplex real-time PCR was compared with the PCR/DGGE analysis for M. bovis, M. dispar and M. bovirhinis respectively by testing 44 BALF samples from calves. In conclusion, the RespoCheck PCR assay can be a valuable tool for timely and accurate detection of three Mycoplasma species associated with in bovine respiratory disease.

  18. A meta-review of evidence on heart failure disease management programs: the challenges of describing and synthesizing evidence on complex interventions

    Directory of Open Access Journals (Sweden)

    Thompson David R

    2011-08-01

    Full Text Available Abstract Background Despite favourable results from past meta-analyses, some recent large trials have not found Heart Failure (HF disease management programs to be beneficial. To explore reasons for this, we evaluated evidence from existing meta-analyses. Methods Systematic review incorporating meta-review was used. We selected meta-analyses of randomized controlled trials published after 1995 in English that examined the effects of HF disease management programs on key outcomes. Databases searched: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR, DARE, NHS EED, NHS HTA, Ageline, AMED, Scopus, Web of Science and CINAHL; cited references, experts and existing reviews were also searched. Results 15 meta-analyses were identified containing a mean of 18.5 randomized trials of HF interventions +/- 10.1 (range: 6 to 36. Overall quality of the meta-analyses was very mixed (Mean AMSTAR Score = 6.4 +/- 1.9; range 2-9. Reporting inadequacies were widespread around populations, intervention components, settings and characteristics, comparison, and comparator groups. Heterogeneity (statistical, clinical, and methodological was not taken into account sufficiently when drawing conclusions from pooled analyses. Conclusions Meta-analyses of heart failure disease management programs have promising findings but often fail to report key characteristics of populations, interventions, and comparisons. Existing reviews are of mixed quality and do not adequately take account of program complexity and heterogeneity.

  19. Studying the Efficiency of “Bilator-6” Complex Preparation Against Fungoid Diseases of Garden Strawberry and Common Barberry

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    Fomichev Valeriy Tarasovich

    2014-04-01

    Full Text Available The article aims at studying the produced complex preparation “Bilator” characterized by multifunctional effect. Bilator is a nano-structured water solution of bischofite salts (MgCl2 subjected to electrochemical processing with the use of copper anode. In order to activate the efficiency of this solution at the level of a cellular membrane the authors propose the technology of its electrochemical processing as a result of which qualitative characteristics change: the solution turns heterogeneous where the substance is connected in the colloidal nanostructures (micelles representing neutral particles with the sizes of 20-250 nanometers. The colloidal (micellar form of solution structure eliminates coagulation processes, reduces the size of a gradient of osmotic pressure on border of a cell and, thereby, provides better delivery of active agents at cellular level. The structure of a cellular membrane, having the sizes of carrying-out channels of 30-40 nanometers, provides penetration into the cell only to those elements whose sizes do not exceed this range. It gives the chance to use each ingredient with maximum efficiency, facilitates their penetration and provides the synergism. The conducted research proved the efficiency of Bilator-6 preparation for protecting a common barberry and a garden strawberry from mealy dew. The data allowed to assume the positive influence of the preparation on intensity of blossoming of these plants.

  20. Cotton leaf curl Burewala virus with intact or mutant transcriptional activator proteins: complexity of cotton leaf curl disease.

    Science.gov (United States)

    Kumar, Jitendra; Gunapati, Samatha; Alok, Anshu; Lalit, Adarsh; Gadre, Rekha; Sharma, Naresh C; Roy, Joy K; Singh, Sudhir P

    2015-05-01

    Cotton leaf curl disease (CLCuD) is a serious disease of cotton on the Indian subcontinent. In the present study, three cotton leaf curl viruses, cotton leaf curl Burewala virus (CLCuBuV), cotton leaf curl Kokhran virus (CLCuKoV) and cotton leaf curl Multan virus (CLCuMV), and their associated satellites, cotton leaf curl Multan betasatellite (CLCuMB) and cotton leaf curl Multan alphasatellite (CLCuMA), were detected. CLCuBuV with either intact (CLCuBuV-1) or mutant (CLCuBuV-2) transcriptional activator protein (TrAP) were detected in different plants. Agroinoculation with CLCuBuV-1 or CLCuBuV-2 together with CLCuMB and CLCuMA, resulted in typical leaf curling and stunting of tobacco plants. Inoculation with CLCuKoV or an isolate of CLCuMV (CLCuMV-2), together with CLCuMB and CLCuMA, induced severe leaf curling, while the other isolate of CLCuMV (CLCuMV-1), which was recombinant in origin, showed mild leaf curling in tobacco. To investigate the effect of intact or mutant TrAP and also the recombination events, CLCuBuV-1, CLCuBuV-2, CLCuMV-1 or CLCuMV-2 together with the satellites (CLCuMA and CLCuMB) were transferred to cotton via whitefly-mediated transmission. Cotton plants containing CLCuBuV-1, CLCuBuV-2 or CLCuMV-2 together with satellites showed curling and stunting, whereas the plants having CLCuMV-1 and the satellites showed only mild and indistinguishable symptoms. CLCuBuV-1 (intact TrAP) showed severe symptoms in comparison to CLCuBuV-2 (mutant TrAP). The present study reveals that two types of CLCuBuV, one with an intact TrAP and the other with a mutant TrAP, exist in natural infection of cotton in India. Additionally, CLCuMuV-1, which has a recombinant origin, induces mild symptoms in comparison to the other CLCuMV isolates.

  1. Predictive Big Data Analytics: A Study of Parkinson’s Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations

    Science.gov (United States)

    Dinov, Ivo D.; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W.; Price, Nathan D.; Van Horn, John D.; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M.; Dauer, William; Toga, Arthur W.

    2016-01-01

    Background A unique archive of Big Data on Parkinson’s Disease is collected, managed and disseminated by the Parkinson’s Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson’s disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data–large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources–all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Methods and Findings Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several

  2. Social workers' roles in addressing the complex end-of-life care needs of elders with advanced chronic disease.

    Science.gov (United States)

    Kramer, Betty J

    2013-01-01

    This study examined social workers' roles in caring for low-income elders with advanced chronic disease in an innovative, community-based managed care program, from the perspective of elders, family, team members, and social workers. The results are drawn from a larger longitudinal, multimethod case study. Sources of data include survey reports of needs addressed by social workers for 120 deceased elders, five focus groups with interdisciplinary team members, and in-depth interviews with 14 elders and 10 of their family caregivers. A thematic conceptual matrix was developed to detail 32 distinctive social work roles that address divergent needs of elders, family, and team members. Distinctive perceptions of social workers' roles were identified for the different stakeholder groups (i.e., elders, family caregivers, team members, and social workers). Findings from this study may inform supervisors and educators regarding training needs of those preparing to enter the rapidly growing workforce of gerontological social workers who may be called upon to care for elders at the end of life. Training is particularly warranted to help social workers gain the skills needed to more successfully treat symptom management, depression, anxiety, agitation, grief, funeral planning, and spiritual needs that are common to the end of life.

  3. Working memory in mild cognitive impairment and Alzheimer's disease: contribution of forgetting and predictive value of complex span tasks.

    Science.gov (United States)

    Gagnon, Lyssa G; Belleville, Sylvie

    2011-03-01

    This study examines working memory (WM) in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Performances on sentence span and operation span were measured in individuals meeting criteria for MCI (n = 20) and AD (n = 16) as well as in healthy older adults (n = 20). In addition, the effect of retention interval was assessed by manipulating the length of first and last items of trials (long-short vs. short-long), as forgetting might contribute to impaired performance in AD and MCI. Results show a group effect (p deterioration or progression to AD were more affected by retention interval (p < .05, η² = .28) than were those who remained stable. Furthermore, deficits in AD are associated with a higher proportion of intrusion errors, particularly those from the current trial (p < .05, η² = .15), which could reflect inhibitory processes. Overall, these results indicate impaired WM in age-related disorders with a gradient between MCI and AD. Retention interval increases deficit in persons with AD. It also shows potential in predicting a negative prognosis in those with MCI. (c) 2011 APA, all rights reserved

  4. Durable diagnosis of seminal vesicle and sexual gland diseases using the nano optical sensor thin film Sm-doxycycline complex.

    Science.gov (United States)

    Attia, M S; Youssef, A O; El-Sherif, R H

    2014-07-04

    A new method in which a nano optical sensor for diagnosis of different diseases of seminal vesicle and sexual gland was prepared. The working principle of the method depends on the determination of the fructose concentration in semen of different patients by using nano optical sensor thin film Sm-doxycycline doped in sol-gel matrix. The assay is based on the quenching of the characteristic emission bands of Sm(3+) present in silica doped Sm-doxycycline nanooptode thin film by different fructose concentrations in acetonitrile at λex = 400 nm. This method was optimized for parameters, such as, solvent effect, operational stability, shelf life and interference parameters. Good and reproducible linearity (1 × 10(-9) - 5.0 × 10(-5) mol L(-1)) with a detection limit of 9.0 × 10(-10) mol L(-1) and quantification limit of detection (LOQ) 2.7 × 10(-9) mol L(-1) were obtained. Seminal fructose determination in different patient samples after appropriate dilutions confirmed the reliability of this technique. The method was successfully applied for routine fructose monitoring in human semen samples of different cases such as; obstructive and non-obstructive azoospermia, inflammation of male accessory glands, atrophy of seminal vesicle, congenital vas deferens and retrograde ejaculation. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Modifiers of stress related to timing of diagnosis in parents of children with complex congenital heart disease.

    Science.gov (United States)

    Pinto, Nelangi M; Weng, Cindy; Sheng, Xiaoming; Simon, Kimberly; Byrne, Janice B; Miller, Thomas; Puchalski, Michael D

    2016-10-01

    Prenatal diagnosis of congenital heart disease (CHD) reportedly increases parental stress compared with postnatal diagnosis. We investigated the association of timing of diagnosis with parental stress and modifiers of this relationship. We enrolled parents with a fetus/infant diagnosed prenatally (Group 1) or postnatally (Group 2) with CHD requiring intervention prior to newborn discharge. Parents completed a Basic Symptom Inventory (BSI) - at diagnosis, birth, and follow-up. Adjusted mixed effects regression models compared scores. The BSI was completed by 105 families (Group 1, n = 60 and Group 2, n = 45). On regression modeling, anxiety and global stress were lower in Group 1 (effect size -0.19 to -0.62) at diagnosis and birth though not at follow-up. When stratified by gender, Group 1 scores for anxiety and stress were primarily lower in fathers. Within Group 1, mothers scored higher in all domains and later gestational age at diagnosis was associated with higher anxiety and stress. Contrary to prior reports, parents of prenatally diagnosed infants with CHD had lower anxiety and stress than those diagnosed postnatally after adjusting for severity. Identifying those most vulnerable and modifiable risk factors will allow us to appropriately target psychosocial services for families with a CHD diagnosis.

  6. The prevalence of radiographic sacroiliitis in patients affected by inflammatory bowel disease with inflammatory low back pain

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    A. Lo Nigro

    2011-09-01

    Full Text Available Inflammatory bowel diseases (IBD, are Crohn’s disease (CD or ulcerative colitis (UC, are frequently complicated by joint complaints with prevalence that varies between 10 and 28 %. The IBD related arthropathy may be expressed as peripheral arthritis or axial one frequently indistinguishable from the classical ankylosing spondylitis (AS. According to ESSG criteria for spondyloarthropathy, the presence of synovitis or the inflammatory back pain (IBP in IBD patients is diagnostic for spondyloarthropathy, but for diagnosis of as also radiological criteria must be fulfilled. There are few studies regarding the radiological prevalence of sacroiliitis in patients with IBD. We examined, by plain film radiograms of pelvis, 100 sacroiliac joints (SJ of 50 IBD patients with IBP. The New York (1984 SJ radiological score with gradation from 0 to 4 was applied. Total sacroiliac score (SJS was summarized between left and right side (from 0 to 8. Fourteen patients fulfilled New York modified criteria for AS and 8 patients had unilateral 2nd grade sacroiliitis. Only 4 of 14 AS patients (28% were HLA B27 positive. Thirty patients had localized IBP, 10 extended to buttock and 4 extended to sacrum. Sixteen patients had sciatica-like extension of back pain. A difference in SJS between left and right side were observed only in CD patients (1,3± 0,8 e 0,8± 0,9 respectively; p<0,05, but not in UC (1,5± 1,2 vs 1,5± 1,3; p=ns nor in total IBD patients (1,4± 1 vs 1,2± 1,2; p=ns. Total SJS was higher in UC respect CD, but not significantly (2,9± 2,3 vs 2,1± 1,5; p=ns. Our data confirm the importance of these symptoms in patients with IBD, who need to be carefully investigated also for these aspects.

  7. Genetic identity of the Bemisia tabaci species complex and association with high cotton leaf curl disease (CLCuD) incidence in Pakistan.

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    Ahmed, Muhammad Z; De Barro, Paul J; Greeff, Jaco M; Ren, Shun-Xiang; Naveed, Muhammad; Qiu, Bao-Li

    2011-03-01

    The cotton whitefly, Bemisia tabaci (Gennadius), is a cryptic species complex, and members of the complex have become serious pests in Pakistan because of their feeding and their ability to transmit cotton leaf curl virus (CLCuV). Here, an analysis was made of the identity of B. tabaci collected from cotton and a range of non-cotton hosts in the cotton-growing zones in Punjab and Sindh, the main cotton-producing provinces of Pakistan, using a portion of the mitochondrial cytochrome oxidase 1 gene. The geographic distribution of the different members of the complex was then compared with the incidence of CLCuD. Using the Dinsdale nomenclature, the results revealed three putative species, Asia 1, Asia II 1 and Middle East-Asia Minor 1. Asia II 1 (also referred to in the literature as biotypes K, P, PCG-1, PK1, SY and ZHJ2) was only recorded from Punjab cotton plants, whereas Asia 1 (also referred to in the literature as biotypes H, M, NA and PCG-2) was found in both Sindh and Punjab. Middle East-Asia Minor 1 (commonly known as biotype B and B2) was found only in Sindh. Moreover, Asia II 1 was associated with high incidences of CLCuD, whereas regions where Middle East-Asia Minor 1 was present had a lower incidence. Phylogenetic analysis showed that the Middle East-Asia Minor 1 population in Sindh formed a distinct genetic subgroup within the putative species, suggesting that the Sindh province of Pakistan may form part of its home range. So far, no individuals from the putative species Mediterranean (commonly known as biotypes Q, J and L) have been found in Pakistan. The capacity to manage pests and disease effectively relies on knowledge of the identity of the agents causing the damage. In the case of CLCuD in Pakistan, this knowledge has been obscured to some extent because of the inconsistent approach to identifying and distinguishing the different B. tabaci associated with CLCuD. The situation has now been clarified, and a strong association between disease

  8. The Preferred Substrates for Transglutaminase 2 in a Complex Wheat Gluten Digest Are Peptide Fragments Harboring Celiac Disease T-Cell Epitopes

    Science.gov (United States)

    Dørum, Siri; Arntzen, Magnus Ø.; Qiao, Shuo-Wang; Holm, Anders; Koehler, Christian J.; Thiede, Bernd; Sollid, Ludvig M.; Fleckenstein, Burkhard

    2010-01-01

    Background Celiac disease is a T-cell mediated chronic inflammatory disorder of the gut that is induced by dietary exposure to gluten proteins. CD4+ T cells of the intestinal lesion recognize gluten peptides in the context of HLA-DQ2.5 or HLA-DQ8 and the gluten derived peptides become better T-cell antigens after deamidation catalyzed by the enzyme transglutaminase 2 (TG2). In this study we aimed to identify the preferred peptide substrates of TG2 in a heterogeneous proteolytic digest of whole wheat gluten. Methods A method was established to enrich for preferred TG2 substrates in a complex gluten peptide mixture by tagging with 5-biotinamido-pentylamine. Tagged peptides were isolated and then identified by nano-liquid chromatography online-coupled to tandem mass spectrometry, database searching and final manual data validation. Results We identified 31 different peptides as preferred substrates of TG2. Strikingly, the majority of these peptides were harboring known gluten T-cell epitopes. Five TG2 peptide substrates that were predicted to bind to HLA-DQ2.5 did not contain previously characterized sequences of T-cell epitopes. Two of these peptides elicited T-cell responses when tested for recognition by intestinal T-cell lines of celiac disease patients, and thus they contain novel candidate T-cell epitopes. We also found that the intact 9mer core sequences of the respective epitopes were not present in all peptide substrates. Interestingly, those epitopes that were represented by intact forms were frequently recognized by T cells in celiac disease patients, whereas those that were present in truncated versions were infrequently recognized. Conclusion TG2 as well as gastrointestinal proteolysis play important roles in the selection of gluten T-cell epitopes in celiac disease. PMID:21124911

  9. Rheumatic manifestations of inflammatory bowel disease.

    Science.gov (United States)

    Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo

    2009-11-28

    This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-alpha blocking agents should be considered as first-line therapy.

  10. Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Priscila Camillo Teixeira

    2011-06-01

    Full Text Available BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC and ischemic (IC cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS: Myocardium homogenates from CCC (N=5, IC (N=5 and IDC (N=5 patients, as well as from heart donors (N=5 were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit and muscular creatine kinase (CKM and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.

  11. A glimpse into the regulation of the Wilson disease protein, ATP7B, sheds light on the complexity of mammalian apical trafficking pathways.

    Science.gov (United States)

    Gupta, Arnab; Das, Santanu; Ray, Kunal

    2018-03-01

    Wilson disease (WD), a Mendelian disorder of copper metabolism caused by mutations in the ATP7B gene, manifests a large spectrum of phenotypic variability. This phenomenon of extensive symptom variation is not frequently associated with a monogenic disorder. We hypothesize that the phenotypic variability in WD is primarily driven by the variations in interacting proteins that regulate the ATP7B function and localization in the cell. Based on existing literature, we delineated a potential molecular mechanism for ATP7B mediated copper transport in the milieu of its interactome, its dysfunction in WD and the resulting variability in the phenotypic manifestation. Understanding the copper-induced apical trafficking of ATP7B also significantly contributes to the appreciation of the complexities of the ligand-induced transport pathway. We believe that this holistic view of WD will pave the way for a better opportunity for rational drug design and therapeutics.

  12. [Identification of gene-gene interactions related to the etiology of complex disease: a multifactor dimensionality reduction-genotype pedigree disequilibrium test].

    Science.gov (United States)

    Li, Na; Tang, Xun; Chen, Da-fang; Hu, Yong-hua

    2007-10-01

    To introduce the application of a multifactor dimensionality reduction-genotype pedigree disequilibrium test (MDR-PDT) for detecting gene-gene interactions in the etiology of complex disease. A brief overview on the basic theory, implementing steps and features of MDR-PDT were described, and a practical research case was demonstrated to application of MDR-PDT in nuclear family studies. The MDR-PDT approach was the extension or development of conventional MDR method which could be used for detecting gene-gene interactions in families of diverse structure. MDR-PDT was a new nonparametric and model-free method which might use additional family members in the nuclear families and had a good power to identify gene-gene interactions.

  13. Complex Interaction of Hb Q-Thailand (HBA1: c.223G>C) with β-Thalassemia/Hb E (HBB: c.79G>A) Disease.

    Science.gov (United States)

    Panyasai, Sitthichai; Satthakarn, Surada; Pornprasert, Sakorn

    2018-01-01

    Hb Q-Thailand [α74(EF3)Asp→His (α1), GAC>CAC, HBA1: c.223G>C] is an abnormal hemoglobin (Hb) frequently found in Thailand and Southeast Asian countries. The association of the α Q-Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report how to diagnose the coinheritance of Hb Q-Thailand with β-thalassemia (β-thal)/Hb E disease in four Thai samples from high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) testing results. Understanding of the HPLC chromatogram and CE electropherogram patterns of this complex mutation is important for interpretation of testing results and providing genetic counseling.

  14. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems.

    LENUS (Irish Health Repository)

    Corrrigan, Mairead

    2006-01-01

    BACKGROUND: Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. METHODS: In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis. RESULTS: Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration

  15. Safety and efficacy of implementing a multidisciplinary heart team approach for revascularization in patients with complex coronary artery disease: an observational cohort pilot study.

    Science.gov (United States)

    Chu, Danny; Anastacio, Melissa M; Mulukutla, Suresh R; Lee, Joon S; Smith, A J Conrad; Marroquin, Oscar C; Sanchez, Carlos E; Morell, Victor O; Cook, Chris C; Lico, Serrie C; Wei, Lawrence M; Badhwar, Vinay

    2014-11-01

    Since the advent of transcatheter aortic valve replacement, the multidisciplinary heart team (MHT) approach has rapidly become the standard of care for patients undergoing the procedure. However, little is known about the potential effect of MHT on patients with coronary artery disease (CAD). To determine the safety and efficacy of implementing the MHT approach for patients with complex CAD. Observational cohort pilot study of 180 patients with CAD involving more than 1 vessel in a single major academic tertiary/quaternary medical center. From May 1, 2012, through May 31, 2013, MHT meetings were convened to discuss evidence-based management of CAD. All cases were reviewed by a team of interventional cardiologists and cardiac surgeons within 72 hours of angiography. All clinical data were reviewed by the team to adjudicate optimal treatment strategies. Final recommendations were based on a consensus decision. Outcome measures were tracked for all patients to determine the safety and efficacy profile of this pilot program. Multidisciplinary heart team meeting. Thirty-day periprocedural mortality and rate of major adverse cardiac events. Most of the patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG); a small percentage of patients underwent a hybrid procedure or medical management. Incidence of 30-day periprocedural mortality was low across all groups of patients (PCI group, 5 of 64 [8%]; CABG group, 1 of 87 [1%]). The rate of major adverse cardiac events during a median follow-up of 12.1 months ranged from 12 of 87 patients (14%) in the CABG group to 15 of 64 (23%) in the PCI group. Outcomes of patients with complex CAD undergoing the optimal treatment strategy recommended by the MHT were similar to those of published national standards. Implementation of the MHT approach for patients with complex CAD is safe and efficacious.

  16. Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia

    Energy Technology Data Exchange (ETDEWEB)

    Demircioglu, F. Esra; Sosa, Brian A.; Ingram, Jessica; Ploegh, Hidde L.; Schwartz, Thomas U.

    2016-08-04

    The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.

  17. Endoplasmic reticulum aminopeptidase 1 function and its pathogenic role in regulating innate and adaptive immunity in cancer and major histocompatibility complex class I-associated autoimmune diseases.

    Science.gov (United States)

    Fruci, D; Romania, P; D'Alicandro, V; Locatelli, F

    2014-08-01

    Major histocompatibility complex (MHC) class I molecules present antigenic peptides on the cell surface to alert natural killer (NK) cells and CD8(+) T cells for the presence of abnormal intracellular events, such as virus infection or malignant transformation. The generation of antigenic peptides is a multistep process that ends with the trimming of N-terminal extensions in the endoplasmic reticulum (ER) by aminopeptidases ERAP1 and ERAP2. Recent studies have highlighted the potential role of ERAP1 in reprogramming the immunogenicity of tumor cells in order to elicit innate and adaptive antitumor immune responses, and in conferring susceptibility to autoimmune diseases in predisposed individuals. In this review, we will provide an overview of the current knowledge about the role of ERAP1 in MHC class I antigen processing and how its manipulation may constitute a promising tool for cancer immunotherapy and treatment of MHC class I-associated autoimmune diseases. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease

    Directory of Open Access Journals (Sweden)

    Raymond S.W. Tsang

    2018-04-01

    Full Text Available Objectives: This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW sequence type 11 (ST-11 clonal complex (CC isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Methods: Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Results: Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. Conclusions: The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Keywords: Neisseria meningitidis, Invasive meningococcal disease, Whole genome typing

  19. [Roles of Musculoskeletal Ultrasonography in the Management of Rheumatic Diseases].

    Science.gov (United States)

    Ikeda, Kei

    2015-05-01

    Inflammation of soft tissues and the subsequent structural damage are the characteristic features of many rheumatic conditions. However, the conventional measures to evaluate these features are not accurate, potentially causing under- and over-diagnosis or treatment. Musculoskeletal ultrasonography, on the other hand, directly visualizes features which are characteristic to rheumatic conditions, such as synovitis, tenosynovitis, bursitis, enthesitis, crystal depositions, bone erosions, and osteophytes/enthesophytes. By visualizing these key features, ultrasound facilitates a more accurate evaluation of rheumatic diseases such as rheumatoid arthritis (RA), spondyloarthropathy, crystal-induced arthritis, and osteoarthritis. For RA, we investigated the impact of ultrasound on the 2010 ACR/EULAR RA classification criteria when joint involvement was determined. We assessed 109 patients with early arthritis using ultrasound. When the presence of joint swelling and number of involved joints were determined by ultrasound, the classification of RA was different from that without ultrasound in approximately 20% of the patients. Moreover, the accuracy of the classification to identify patients who required methotrexate treatment within a year improved by ultrasound. In addition, we and other investigators demonstrated the advantage of ultrasound over conventional measures in the assessment of disease activity of RA. Ultrasound also supports the education of both physicians and patients and communication between them. The utilization of musculoskeletal ultrasonography in more hospitals and clinics is expected to improve the quality of daily practice for rheumatic diseases.

  20. Fourier analysis of multi-gated cardiac blood-pool data in patients with congenital heart diseases, (2). Assessment of diseases with complex cardiac anomalies, especially tetralogy of Fallot

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kan; Maeda, Hisato; Yamaguchi, Nobuo; Nakamura, Kazuyoshi; Matsumura, Kaname; Nakagawa, Tsuyoshi; Sakurai, Minoru; Aoki, Kenzo

    1985-04-01

    The clinical usefulness of Fourier analysis of multi-gated cardiac blood-pool data was evaluated in 18 subjects with normal cardiac functions and 14 patients with complex cardiac anomalies (ten with tetralogy of Fallot, two with tricuspid atresia (TA), one with double-outlet right ventricle (DORV), and one with Ebstein's anomaly (EA)). Using global ventricular time-activity curves, the phase and amplitude at fundamental frequency were calculated, and emptying patterns of the left and right ventricles (LV, RV) were evaluated by phase difference (D(phase)=RV phase minus LV phase) and amplitude ratio of RV to LV (R(amp)). In patients with TOF, mean values of D (phase) and R(amp) were 25.3 +- 10.5 degrees and 13.5 +- 0.49 respectively and significantly larger than those of normal subjects. D (phase) became larger in inverse proportion to the ratio of pulmonary-to-systemic blood flow and there was an inverse linear correlation between these two variables. On visual interpretation of functional images, the dynamic property of hypoplastic ventricles could be easily estimated in patients with TA or DORV. In a case with EA, the atrialized RV was shown clearly as a hypokinetic, atrial phase area. This method is valuable for pathophysiologic investigation of diseases with complex cardiac anomalies. (author).

  1. Treatment of Children with Protein – Losing Enteropathy After Fontan and Other Complex Congenital Heart Disease Procedures in Condition with Limited Human and Technical Resources

    Science.gov (United States)

    Bejiqi, Ramush; Retkoceri, Ragip; Zeka, Naim; Bejiqi, Hana; Vuqiterna, Armend; Maloku, Arlinda

    2014-01-01

    Background Protein-losing enteropathy (PLE) is a disorder characterized by abnormal and often profound enteric protein loss. It’s relatively uncommon complication of Fontan and other complex congenital heart disease (CCHD) procedures. Because of the complexity and rarity of this disease process, the pathogenesis and pathophysiology of protein-losing enteropathy remain poorly understood, and attempts at treatment seldom yield long-term success. Aim of presentation is to describe single centre experience in diagnosis, evaluation, management and treatment of children with protein-losing enteropathy after Fontan and other CCHD procedures in the current era and in centre with limited human and technical resources, follows with a comprehensive review of protein-losing enteropathy publications, and concludes with suggestions for prevention and treatment. Material and methodology Retrospectively we analyzed patients with CCHD and protein-losing enteropathy in our institution, starting from January 2000 to December 2012. The including criteria were age between two and 17 years, to have a complex congenital heart disease and available complete documentation of cardiac surgery under cardiopulmonary bypass. Results Of all patients we evaluated 18 cases with protein-losing enteropathy, aged 6 to 19 years (mean 14±9); there were three children who had undergone screening procedure for D-transposition, one Tetralogy of Fallot, and remaining 14 patients had undergone Fontan procedures; (anatomic diagnosis are: six with tricuspid atresia, seven with d-transposition, double outlet right ventricle and pulmonary atresia and two with hypoplastic left heart syndrome). The diagnosis of protein-losing enteropathy was made at median age of 5.6 years, ranging from 13 months to 15 years. Diagnosis was made using alpha 1-antitrypsin as a gold marker in stool. By physical examination in 14 patients edema was found, in three ascites, and six patients had pleural effusion. Laboratory findings

  2. Etiological studies in complex diseases

    NARCIS (Netherlands)

    Peeters, P.J.H.L.

    2016-01-01

    The incidence of a number