WorldWideScience

Sample records for connectivity sustains disease

  1. Undifferentiated Connective Tissue Disease

    Science.gov (United States)

    ... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

  2. Mixed Connective Tissue Disease

    Science.gov (United States)

    Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

  3. Resting-state connectivity of the sustained attention network correlates with disease duration in idiopathic generalized epilepsy.

    Directory of Open Access Journals (Sweden)

    Mona Maneshi

    Full Text Available INTRODUCTION: In idiopathic generalized epilepsy (IGE, a normal electroencephalogram between generalized spike and wave (GSW discharges is believed to reflect normal brain function. However, some studies indicate that even excluding GSW-related errors, IGE patients perform poorly on sustained attention task, the deficit being worse as a function of disease duration. We hypothesized that at least in a subset of structures which are normally involved in sustained attention, resting-state functional connectivity (FC is different in IGE patients compared to controls and that some of the changes are related to disease duration. METHOD: Seeds were selected based on a sustained attention study in controls. Resting-state functional magnetic resonance imaging (fMRI data was obtained from 14 IGE patients and 14 matched controls. After physiological noise removal, the mean time-series of each seed was used as a regressor in a general linear model to detect regions that showed correlation with the seed. In patients, duration factor was defined based on epilepsy duration. Between-group differences weighted by the duration factor were evaluated with mixed-effects model. Correlation was then evaluated in IGE patients between the FC, averaged over each significant cluster, and the duration factor. RESULTS: Eight of 18 seeds showed significant difference in FC across groups. However, only for seeds in the medial superior frontal and precentral gyri and in the medial prefrontal area, average FC taken over significant clusters showed high correlation with the duration factor. These 3 seeds showed changes in FC respectively with the premotor and superior frontal gyrus, the dorsal premotor, and the supplementary motor area plus precentral gyrus. CONCLUSION: Alterations of FC in IGE patients are not limited to the frontal areas. However, as indicated by specificity analysis, patients with long history of disease show changes in FC mainly within the frontal areas.

  4. Campus as a Living Laboratory for Sustainability: The Chemistry Connection

    Science.gov (United States)

    Lindstrom, Timothy; Middlecamp, Catherine

    2017-01-01

    In the undergraduate curriculum, chemistry and sustainability connect easily and well. Topics in chemistry provide instructors with opportunities to engage students in learning about sustainability; similarly, topics in sustainability provide instructors with opportunities to engage students in learning chemistry. One's own college or university…

  5. Radiotherapy in patients with connective tissue diseases.

    Science.gov (United States)

    Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

    2016-03-01

    The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Radiological approach to systemic connective tissue diseases

    International Nuclear Information System (INIS)

    Wiesmann, W.; Schneider, M.

    1988-01-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented. (orig.) [de

  7. Radiological approach to systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wiesmann, W; Schneider, M

    1988-07-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented.

  8. Pregnancy and autoimmune connective tissue diseases

    Science.gov (United States)

    Marder, Wendy; Littlejohn, Emily A

    2016-01-01

    The autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before and during pregnancy and the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  9. Pruritus in Autoimmune Connective Tissue Diseases.

    Science.gov (United States)

    Smith, Gideon P; Argobi, Yahya

    2018-07-01

    Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. [Pulmonary involvement in connective tissue disease].

    Science.gov (United States)

    Bartosiewicz, Małgorzata

    2016-01-01

    The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

  11. Sustaining forest landscape connectivity under different land cover change scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Rubio, L.; Rodriguez-Freire, M.; Mateo-Sanchez, M. C.; Estreguil, C.; Saura, S.

    2012-11-01

    Managing forest landscapes to sustain functional connectivity is considered one of the key strategies to counteract the negative effects of climate and human-induced changes in forest species pools. With this objective, we evaluated whether a robust network of forest connecting elements can be identified so that it remains efficient when facing different types of potential land cover changes that may affect forest habitat networks and ecological fluxes. For this purpose we considered changes both in the forested areas and in the non-forest intervening landscape matrix. We combined some of the most recent developments in graph theory with models of land cover permeability and least-cost analysis through the forest landscape. We focused on a case of study covering the habitat of a forest dwelling bird (nuthatch, Sitta europaea) in the region of Galicia (NW Spain). Seven land-use change scenarios were analysed for their effects on connecting forest elements (patches and links): one was the simplest case in which the landscape is represented as a binary forest/non-forest pattern (and where matrix heterogeneity is disregarded), four scenarios in which forest lands were converted to other cover types (to scrubland due to wildfires, to extensive and intensive agriculture, and to urban areas), and two scenarios that only involved changes in the non-forested matrix (re naturalization and intensification). Our results show that while the network of connecting elements for the species was very robust to the conversion of the forest habitat patches to different cover types, the different change scenarios in the landscape matrix could more significantly weaken its long-term validity and effectiveness. This is particularly the case when most of the key connectivity providers for the nuthatch are located outside the protected areas or public forests in Galicia, where biodiversity-friendly measures might be more easily implemented. We discuss how the methodology can be applied to

  12. Histopathology of lung disease in the connective tissue diseases.

    Science.gov (United States)

    Vivero, Marina; Padera, Robert F

    2015-05-01

    The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Health Systems Sustainability and Rare Diseases.

    Science.gov (United States)

    Ferrelli, Rita Maria; De Santis, Marta; Egle Gentile, Amalia; Taruscio, Domenica

    2017-01-01

    The paper is addressing aspects of health system sustainability for rare diseases in relation to the current economic crisis and equity concerns. It takes into account the results of the narrative review carried out in the framework of the Joint Action for Rare Diseases (Joint RD-Action) "Promoting Implementation of Recommendations on Policy, Information and Data for Rare Diseases", that identified networks as key factors for health systems sustainability for rare diseases. The legal framework of European Reference Networks and their added value is also presented. Networks play a relevant role for health systems sustainability, since they are based upon, pay special attention to and can intervene on health systems knowledge development, partnership, organizational structure, resources, leadership and governance. Moreover, sustainability of health systems can not be separated from the analysis of the context and the action on it, including fiscal equity. As a result of the financial crisis of 2008, cuts of public health-care budgets jeopardized health equity, since the least wealthy suffered from the greatest health effects. Moreover, austerity policies affected economic growth much more adversely than previously believed. Therefore, reducing public health expenditure not only is going to jeopardise citizens' health, but also to hamper fair and sustainable development.

  14. Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren's Disease)

    NARCIS (Netherlands)

    Karkampouna, S.; Kreulen, M.; Obdeijn, M. C.; Kloen, P.; Dorjée, A. L.; Rivellese, F.; Chojnowski, A.; Clark, I.; Kruithof-de Julio, Marianna

    2016-01-01

    Dupuytren's disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability. The aetiology of the disease is heterogeneous, with both genetic and environmental components. The connective tissue is abnormally infiltrated

  15. Autoimmune connective tissue diseases and vaccination

    Directory of Open Access Journals (Sweden)

    Ewa Więsik-Szewczyk

    2015-12-01

    Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  16. Vasculitis associated with connective tissue diseases.

    Science.gov (United States)

    Cozzani, E; Gasparini, G; Papini, M; Burlando, M; Drago, F; Parodi, A

    2015-04-01

    Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis.

  17. Silicone breast implants and connective tissue disease

    DEFF Research Database (Denmark)

    Lipworth, Loren; Holmich, Lisbet R; McLaughlin, Joseph K

    2011-01-01

    The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new "atypical" disease, which does not meet established diagnostic criteria for any known...... CTD, has been extensively studied. We have reviewed the epidemiologic literature regarding an association between cosmetic breast implants and CTDs, with particular emphasis on results drawn from the most recent investigations, many of which are large cohort studies with long-term follow-up, as well...... as on those studies that address some of the misinformation and historically widespread claims regarding an association between breast implants and CTDs. These claims have been unequivocally refuted by the remarkably consistent evidence from published studies, as well as numerous independent meta...

  18. Skin cancer risk in autoimmune connective tissue diseases.

    Science.gov (United States)

    Kostaki, D; Antonini, A; Peris, K; Fargnoli, M C

    2014-10-01

    Cutaneous malignancies have been significantly associated with autoimmune connective tissue diseases (ACTDs). This review focuses on the current state of knowledge on skin cancer risk in the most prevalent ACTDs in dermatology including lupus erythematosus, scleroderma, dermatomyositis and Sjögren syndrome. Potential pathogenetic mechanisms for the association between ACTDs and malignancy involve disease-related impairment of immune system, sustained cutaneous inflammation, drug-associated immune suppression and increased susceptibility to acquired viral infections. An additional causal role might be played by environmental factors such as UV exposure and smoking. The occurrence of skin cancer can have a profound impact on the already compromised quality of life of ACTD patients. Therefore, effective screening and monitoring strategies are essential for ACTD patients as early detection and prompt therapeutic intervention can reduce morbidity and mortality in these patients.

  19. Lung involvement in systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2008-01-01

    Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

  20. Generalized connective tissue disease in Crtap-/- mouse.

    Directory of Open Access Journals (Sweden)

    Dustin Baldridge

    2010-05-01

    Full Text Available Mutations in CRTAP (coding for cartilage-associated protein, LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1] or PPIB (coding for Cyclophilin B [CYPB] cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in alpha1(I and alpha1(II chains, there was also loss of 3Hyp at proline 986 in alpha2(V chains. In contrast, at two of the known 3Hyp sites in alpha1(IV chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin.

  1. Interstitial lung disease associated with connective tissue diseases

    International Nuclear Information System (INIS)

    Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

    2007-01-01

    An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

  2. Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

    Science.gov (United States)

    Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

    2018-01-03

    Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

  3. Campus as a Living Laboratory for Sustainability: The Physics Connection

    Science.gov (United States)

    Lindstrom, Timothy; Middlecamp, Catherine

    2018-01-01

    One of us is a physicist. The other is a chemist. For the past four years, we have been teaching a large introductory environmental science course that uses our campus as a lens through which to explore issues relating to sustainability. Our students "ask questions about the energy we use to heat and cool our buildings, the food we eat, the…

  4. Social-ecology networks : building connections for sustainable landscapes

    NARCIS (Netherlands)

    Opdam, P.F.M.

    2014-01-01

    Humans adapt their landscapes, their living environment. Sustainable use of the various landscape benefits requires that land owners and users collaborate in managing ecological networks. Because the government is stepping back as the organizer of coordinated landscape adaptation, we need new

  5. Design for sustainability: rural connectivity with village operators

    CSIR Research Space (South Africa)

    Roux, K

    2011-10-01

    Full Text Available South Africa has approximately 26500 primary and secondary schools, of which at least 17000 are in remote rural villages. None of these rural schools have any form of Internet connectivity. The same rural villages may have one health facility...

  6. Staying Connected: Sustaining Collaborative Care Models with Limited Funding.

    Science.gov (United States)

    Johnston, Brenda J; Peppard, Lora; Newton, Marian

    2015-08-01

    Providing psychiatric services in the primary care setting is challenging. The multidisciplinary, coordinated approach of collaborative care models (CCMs) addresses these challenges. The purpose of the current article is to discuss the implementation of a CCM at a free medical clinic (FMC) where volunteer staff provide the majority of services. Essential components of CCMs include (a) comprehensive screening and assessment, (b) shared development and communication of care plans among providers and the patient, and (c) care coordination and management. Challenges to implementing and sustaining a CCM at a FMC in Virginia attempting to meet the medical and psychiatric needs of the underserved are addressed. Although the CCM produced favorable outcomes, sustaining the model long-term presented many challenges. Strategies for addressing these challenges are discussed. Copyright 2015, SLACK Incorporated.

  7. Social-ecology networks : building connections for sustainable landscapes

    OpenAIRE

    Opdam, P.F.M.

    2014-01-01

    Humans adapt their landscapes, their living environment. Sustainable use of the various landscape benefits requires that land owners and users collaborate in managing ecological networks. Because the government is stepping back as the organizer of coordinated landscape adaptation, we need new landscape planning approaches that enhance collaboration by building social networks and link them to ecological networks. In this farewell address I will explain why the social-ecological network is a p...

  8. Connective tissue diseases, multimorbidity and the ageing lung.

    Science.gov (United States)

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

  9. Campus as a Living Laboratory for Sustainability: The Physics Connection

    Science.gov (United States)

    Lindstrom, Timothy; Middlecamp, Catherine

    2018-04-01

    One of us is a physicist. The other is a chemist. For the past four years, we have been teaching a large introductory environmental science course that uses our campus as a lens through which to explore issues relating to sustainability. Our students "ask questions about the energy we use to heat and cool our buildings, the food we eat, the air we breathe, the electricity to run light bulbs and appliances, the goods we purchase, and the waste we create." This course fits in the genre of using "campus as a living laboratory," a term we will discuss later.

  10. Combating plant diseases--the Darwin connection.

    Science.gov (United States)

    Hollomon, Derek W; Brent, Keith J

    2009-11-01

    Although Darwin knew of plant diseases, he did not study them as part of his analysis of natural selection. Effective plant disease control has only been developed after his death. This article explores the relevance of Darwin's ideas to three problem areas with respect to diseases caused by fungi: emergence of new diseases, loss of disease resistance bred into plants and development of fungicide resistance. Darwin's concept of change through natural or artificial selection relied on selection of many small changes, but subsequent genetic research has shown that change can also occur through large steps. Appearance of new diseases can involve gene duplication, transfer or recombination, but all evidence points to both host plant resistance and fungicide susceptibility being overcome through point mutations. Because the population size of diseases such as rusts and powdery and downy mildews is so large, all possible point mutations are likely to occur daily, even during moderate epidemics. Overcoming control measures therefore reflects the overall fitness of these mutants, and much resource effort is being directed towards assessment of their fitness, both in the presence and in the absence of selection. While recent developments in comparative genomics have caused some revision of Darwin's ideas, experience in managing plant disease control measures clearly demonstrates the relevance of concepts he introduced 150 years ago. It also reveals the remarkable speed and the practical impact of adaptation in wild microorganism populations to changes in their environment, and the difficulty of stopping or delaying such adaptation. (c) 2009 Society of Chemical Industry.

  11. Adipose tissue and sustainable development: a connection that needs protection

    Directory of Open Access Journals (Sweden)

    Angelo eTremblay

    2015-05-01

    Full Text Available Obesity is generally considered as an excess body fat that increases the risk to develop ergonomic, metabolic and psychosocial problems. As suggested in this paper, body fat gain is also a protective adaptation that prevents body lipotoxicity, contributes to the secretion of molecules involved in metabolic regulation, and dilutes lipid soluble persistent organic pollutants (POPs. Recent literature shows that this protective role of adipose tissue is more solicited in a modern context in which unsuspected factors can affect energy balance to a much greater extent than what is generally perceived by health care professionals. These factors include short sleep duration, demanding mental work, and chemical pollution whose impact is more detectable in a context dominated by economic productivity and competitiveness. Since these factors might also include the increase in atmospheric CO2, it is likely that obesity prevention will need the support of a promotion in sustainable development, whether it is for human health and well-being or global ecological protection.

  12. Oral manifestations of connective tissue disease and novel therapeutic approaches.

    Science.gov (United States)

    Heath, Kenisha R; Rogers, Roy S; Fazel, Nasim

    2015-10-16

    Connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren syndrome (SS) have presented many difficulties both in their diagnosis and treatment. Known causes for this difficulty include uncertainty of disease etiology, the multitude of clinical presentations, the unpredictable disease course, and the variable cell types, soluble mediators, and tissue factors that are believed to play a role in the pathogenesis of connective tissue diseases. The characteristic oral findings seen with these specific connective tissue diseases may assist with more swift diagnostic capability. Additionally, the recent use of biologics may redefine the success rate in the treatment and management of the disease. In this review we describe the oral manifestations associated with SLE, SSc, and SS and review the novel biologic drugs used to treat these conditions.

  13. [Rheumatoid arthritis as a connective tissue disease].

    Science.gov (United States)

    Targońska-Stępniak, Bożena

    2018-01-01

    The available data indicate that seropositive rheumatoid arthritis (RA) develops as a result of systemic, autoimmune reaction directed against a range of "self" peptides/proteins that have undergone specific forms of post-translational modification. The development and progress of autoimmunity may be triggered by non-specific, local inflammatory processes outside the joints, for example in the oral or respiratory mucous membrane. The disease occurs in genetically susceptible individuals under the influence of environmental risk factors that promote autoimmunity and consequently the inflammatory process. Smoking is particularly linked with RA pathogenesis. Synovitis of multiple, symmetrical, peripheral joints is the most typical feature of RA which results in irreversible damage to joints structure and as a consequence in disability of patients. However, the inflammatory process in the course of RA has a systemic, constitutional nature. Therefore, extra-articular symptoms with internal organ involvement may occur additionally to synovitis, what is an unfavorable prognostic factor. Extra-articular manifestations of RA are associated with the high disease activity both inflammatory and immunological. They occur in patients with severe form of the disease and contribute to a significant lifespan reduction. This is usually associated with progressive atherosclerosis and cardiovascular complications. The systemic inhibition of an abnormal immune system activity is the mainstay of the effective RA treatment. The currently used disease modifying antirheumatic drugs affect the activity and function of different constituents of the immune system, including B and T lymphocytes and the main pro-inflammatory cytokines, and contribute to autoimmune and inflammatory processes.

  14. Hyper-connectivity of functional networks for brain disease diagnosis.

    Science.gov (United States)

    Jie, Biao; Wee, Chong-Yaw; Shen, Dinggang; Zhang, Daoqiang

    2016-08-01

    Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer's disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also help

  15. Polycystic ovarian disease: the adrenal connection.

    Science.gov (United States)

    Marouliss, George B; Triantafillidis, Ioannis K

    2006-01-01

    Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

  16. Imaging of connective tissue diseases of the head and neck

    Science.gov (United States)

    2016-01-01

    We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren’s syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still’s disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders. PMID:26988082

  17. New perspectives on rare connective tissue calcifying diseases.

    Science.gov (United States)

    Rashdan, Nabil A; Rutsch, Frank; Kempf, Hervé; Váradi, András; Lefthériotis, Georges; MacRae, Vicky E

    2016-06-01

    Connective tissue calcifying diseases (CTCs) are characterized by abnormal calcium deposition in connective tissues. CTCs are caused by multiple factors including chronic diseases (Type II diabetes mellitus, chronic kidney disease), the use of pharmaceuticals (e.g. warfarin, glucocorticoids) and inherited rare genetic diseases such as pseudoxanthoma elasticum (PXE), generalized arterial calcification in infancy (GACI) and Keutel syndrome (KTLS). This review explores our current knowledge of these rare inherited CTCs, and highlights the most promising avenues for pharmaceutical intervention. Advancing our understanding of rare inherited forms of CTC is not only essential for the development of therapeutic strategies for patients suffering from these diseases, but also fundamental to delineating the mechanisms underpinning acquired chronic forms of CTC. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Facts and controversies in mixed connective tissue disease.

    Science.gov (United States)

    Martínez-Barrio, Julia; Valor, Lara; López-Longo, F Javier

    2018-01-12

    Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2016-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  20. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2009-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  1. Mixed connective tissue disease associated with noted pulmonary CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Souji; Tsukada, Atsuko; Furuya, Tatsutaka

    1984-10-01

    CT was performed in a 56-year-old woman with mixed connective tissue disease (MCTD). Much more definitive pulmonary findings were obtained by CT than by the conventional chest x-ray examination and pulmonary function test. CT findings disclosed pulmonary lesions extremely similar to those in cases of progressive systemic sclerosis. Pulmonary CT was considered useful in examining pulmonary lesions for MCTD.

  2. Achieving sustainable plant disease management through evolutionary principles.

    Science.gov (United States)

    Zhan, Jiasui; Thrall, Peter H; Burdon, Jeremy J

    2014-09-01

    Plants and their pathogens are engaged in continuous evolutionary battles and sustainable disease management requires novel systems to create environments conducive for short-term and long-term disease control. In this opinion article, we argue that knowledge of the fundamental factors that drive host-pathogen coevolution in wild systems can provide new insights into disease development in agriculture. Such evolutionary principles can be used to guide the formulation of sustainable disease management strategies which can minimize disease epidemics while simultaneously reducing pressure on pathogens to evolve increased infectivity and aggressiveness. To ensure agricultural sustainability, disease management programs that reflect the dynamism of pathogen population structure are essential and evolutionary biologists should play an increasing role in their design. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A Histopathological Study of Pulmonary Hypertension in Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Nobuhito Sasaki

    2011-01-01

    Full Text Available Connective tissue diseases (CTD, such as systemic sclerosis (SSc, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCTD, develop pulmonary hypertension (PH. Generally all PH cases associated with any CTD are classified into the same PH group. However, histological examination shows both common and specific lesions for each disease. In patients with SLE, fibrosis is generally rare and mild. The findings of PH in SLE are similar to those in primary pulmonary hypertension. Many cases of SSc are accompanied by fibrosis. MCTD is rather close to SSc. Arterial and arteriolar lesions of MCTD are characterized by fibrous intimal thickening. In this review, we describe the pathological features of PH associated with each CTD.

  4. Disease Definition for Schizophrenia by Functional Connectivity Using Radiomics Strategy.

    Science.gov (United States)

    Cui, Long-Biao; Liu, Lin; Wang, Hua-Ning; Wang, Liu-Xian; Guo, Fan; Xi, Yi-Bin; Liu, Ting-Ting; Li, Chen; Tian, Ping; Liu, Kang; Wu, Wen-Jun; Chen, Yi-Huan; Qin, Wei; Yin, Hong

    2018-02-17

    Specific biomarker reflecting neurobiological substrates of schizophrenia (SZ) is required for its diagnosis and treatment selection of SZ. Evidence from neuroimaging has implicated disrupted functional connectivity in the pathophysiology. We aimed to develop and validate a method of disease definition for SZ by resting-state functional connectivity using radiomics strategy. This study included 2 data sets collected with different scanners. A total of 108 first-episode SZ patients and 121 healthy controls (HCs) participated in the current study, among which 80% patients and HCs (n = 183) and 20% (n = 46) were selected for training and testing in intra-data set validation and 1 of the 2 data sets was selected for training and the other for testing in inter-data set validation, respectively. Functional connectivity was calculated for both groups, features were selected by Least Absolute Shrinkage and Selection Operator (LASSO) method, and the clinical utility of its features and the generalizability of effects across samples were assessed using machine learning by training and validating multivariate classifiers in the independent samples. We found that the accuracy of intra-data set training was 87.09% for diagnosing SZ patients by applying functional connectivity features, with a validation in the independent replication data set (accuracy = 82.61%). The inter-data set validation further confirmed the disease definition by functional connectivity features (accuracy = 83.15% for training and 80.07% for testing). Our findings demonstrate a valid radiomics approach by functional connectivity to diagnose SZ, which is helpful to facilitate objective SZ individualized diagnosis using quantitative and specific functional connectivity biomarker.

  5. Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement.

    Science.gov (United States)

    Vereckei, András; Fazakas, Adám; Baló, Timea; Fekete, Béla; Molnár, Mária Judit; Karádi, István

    2013-04-01

    The authors report a case of rare chloroquine cardiotoxicity mimicking connective tissue disease heart involvement in a 56-year-old woman with mixed connective tissue disease (MCTD) manifested suddenly as third degree A-V block with QT(c) interval prolongation and short torsade de pointes runs ultimately degenerating into ventricular fibrillation. Immunological tests suggested an MCTD flare, implying that cardiac arrest had resulted from myocardial involvement by MCTD. However, QT(c) prolongation is not a characteristic of cardiomyopathy caused by connective tissue disease, unless anti-Ro/SSA positivity is present, but that was not the case. Therefore, looking for another cause of QT(c) prolongation the possibility of chloroquine cardiotoxicity emerged, which the patient had been receiving for almost two years in supramaximal doses. Biopsy of the deltoid muscle was performed, because in chloroquine toxicity, specific lesions are present both in the skeletal muscle and in the myocardium, and electron microscopy revealed the accumulation of cytoplasmic curvilinear bodies, which are specific to antimalarial-induced myocyte damage and are absent in all other muscle diseases, except neuronal ceroid lipofuscinosis. Thus, the diagnosis of chloroquine cardiotoxicity was established. It might be advisable to supplement the periodic ophthalmological examination, which is currently the only recommendation for patients on long-term chloroquine therapy, with ECG screening.

  6. Mixed connective tissue disease associated with noted pulmonary CT findings

    International Nuclear Information System (INIS)

    Yamazaki, Souji; Tsukada, Atsuko; Furuya, Tatsutaka

    1984-01-01

    CT was performed in a 56-year-old woman with mixed connective tissue disease (MCTD). Much more definitive pulmonary findings were obtained by CT than by the conventional chest x-ray examination and pulmonary function test. CT findings disclosed pulmonary lesions extremely similar to those in cases of progressive systemic sclerosis. Pulmonary CT was considered useful in examining pulmonary lesions for MCTD. (Namekawa, K.)

  7. Sustainable control of white spot disease

    DEFF Research Database (Denmark)

    Heinecke, Rasmus Demuth; Buchmann, Kurt

    White spot disease caused by the ciliate Ichthyophthirius multifiliis Fouquet, 1876 is a serious problem in freshwater aquaculture worldwide. This parasitosis is of frequent occurrence in both conventional earth pond fish farms and in fish farms using new high technology re-circulation systems...

  8. The oral-systemic disease connection: a retrospective study.

    Science.gov (United States)

    Joseph, Bobby K; Kullman, Leif; Sharma, Prem N

    2016-11-01

    The study aimed at determining the association between oral disease and systemic health based on panoramic radiographs and general health of patients treated at Kuwait University Dental Center. The objective was to determine whether individuals exhibiting good oral health have lower propensity to systemic diseases. A total of 1000 adult patients treated at Kuwait University Dental Center were randomly selected from the patient's records. The general health of patients was assessed from the medical history of each patient recorded during their visit to the clinic. The number of reported diseases and serious symptoms were used to develop a medical index. The oral health of these patients was assessed from panoramic radiographs to create an oral index by evaluating such parameters as caries, periodontitis, periapical lesions, pericoronitis, and tooth loss. In a total of 887 patients, 43.8 % had an oral index between 3 and 8, of which significantly higher (62.1 %) patients were with medical conditions compared to those without (33.2 %; p relationship when the diagnosis of oral disease was based primarily on radiographic findings. Future research needs to include prospective clinical and interventional studies. The significance of the oral-systemic disease connection highlights the importance of preventing and treating oral disease which have profound medical implications on general health.

  9. Purpura fulminans in a patient with mixed connective tissue disease.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2013-01-01

    A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud\\'s syndrome and hypothyroidism. 2 days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made.

  10. Addison's disease secondary to connective tissue diseases: a report of six cases.

    Science.gov (United States)

    Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

    2009-04-01

    Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

  11. Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

    Science.gov (United States)

    Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

    2009-06-01

    Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

  12. Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

    Science.gov (United States)

    Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

    2017-01-01

    Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological

  13. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

    Science.gov (United States)

    Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

    2018-01-01

    Abstract Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2013-01-01

    Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer’s disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer’s disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer’s disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer’s disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer’s disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer’s disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer’s disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends

  16. Connecting Competences and Pedagogical Approaches for Sustainable Development in Higher Education: A Literature Review and Framework Proposal

    Directory of Open Access Journals (Sweden)

    Rodrigo Lozano

    2017-10-01

    Full Text Available Research into and practice of Higher Education for Sustainable Development (HESD have been increasing during the last two decades. These have focused on providing sustainability education to future generations of professionals. In this context, there has been considerable progress in the incorporation of SD in universities’ curricula. Most of these efforts have focussed on the design and delivery of sustainability-oriented competences. Some peer-reviewed articles have proposed different pedagogical approaches to better deliver SD in these courses; however, there has been limited research on the connection between how courses are delivered (pedagogical approaches and how they may affect sustainability competences. This paper analyses competences and pedagogical approaches, using hermeneutics to connect these in a framework based on twelve competences and twelve pedagogical approaches found in the literature. The framework connects the course aims to delivery in HESD by highlighting the connections between pedagogical approaches and competences in a matrix structure. The framework is aimed at helping educators in creating and updating their courses to provide a more complete, holistic, and systemic sustainability education to future leaders, decision makers, educators, and change agents. To better develop mind-sets and actions of future generations, we must provide students with a complete set of sustainability competences.

  17. Connective tissue diseases and noninvasive evaluation of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ardita G

    2014-06-01

    Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

  18. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Directory of Open Access Journals (Sweden)

    Seri Jeong

    Full Text Available This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCT. The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6, including SLE (24.3 vs. 10.7. The areas under the receiver operating characteristic curves (ROC-AUCs of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72 and MCT (0.85 than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  19. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Science.gov (United States)

    Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

    2017-01-01

    This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  20. The Concept of Directly Connected Impervious Areas and Its Implication on Sustainable Development in Urban Catchments

    Science.gov (United States)

    Seo, Yongwon; Hwang, Junsik; Choi, Hyun Il

    2017-04-01

    The concept of directly connected impervious area (DCIA) or efficient impervious areas (EIA) refers to a subset of impervious cover, which is directly connected to a drainage system or a water body via continuous impervious surfaces. The concept of DCIA is important in that it is regarded as a better predictor of stream ecosystem health than the total impervious area (TIA). DCIA is a key concept for a better assessment of green infrastructures introduced in urban catchments. Green infrastructure can help restore water cycle; it improves water quality, manages stormwater, provides recreational environment even at lower cost compared to conventional alternatives. In this study, we evaluated several methods to obtain the DCIA based on a GIS database and showed the importance of the accurate measurement of DCIA in terms of resulting hydrographs. We also evaluated several potential green infrastructure scenarios and showed how the spatial planning of green infrastruesture affects the shape of hydrographs and reduction of peak flows. These results imply that well-planned green infrastructure can be introduced to urban catchments for flood risk managements and quantitative assessment of spatial distribution of DCIA is crucial for sustainable development in urban environment.

  1. Training for Micrographia Alters Neural Connectivity in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Evelien Nackaerts

    2018-01-01

    Full Text Available Despite recent advances in clarifying the neural networks underlying rehabilitation in Parkinson's disease (PD, the impact of prolonged motor learning interventions on brain connectivity in people with PD is currently unknown. Therefore, the objective of this study was to compare cortical network changes after 6 weeks of visually cued handwriting training (= experimental with a placebo intervention to address micrographia, a common problem in PD. Twenty seven early Parkinson's patients on dopaminergic medication performed a pre-writing task in both the presence and absence of visual cues during behavioral tests and during fMRI. Subsequently, patients were randomized to the experimental (N = 13 or placebo intervention (N = 14 both lasting 6 weeks, after which they underwent the same testing procedure. We used dynamic causal modeling to compare the neural network dynamics in both groups before and after training. Most importantly, intensive writing training propagated connectivity via the left hemispheric visuomotor stream to an increased coupling with the supplementary motor area, not witnessed in the placebo group. Training enhanced communication in the left visuomotor integration system in line with the learned visually steered training. Notably, this pattern was apparent irrespective of the presence of cues, suggesting transfer from cued to uncued handwriting. We conclude that in early PD intensive motor skill learning, which led to clinical improvement, alters cortical network functioning. We showed for the first time in a placebo-controlled design that it remains possible to enhance the drive to the supplementary motor area through motor learning.

  2. Midcingulate cortex: Structure, connections, homologies, functions and diseases.

    Science.gov (United States)

    Vogt, Brent A

    2016-07-01

    Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms

  3. Significance of connective tissue diseases features in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Vincent Cottin

    2013-09-01

    Full Text Available Interstitial lung disease (ILD can occur in any of the connective tissue diseases (CTD with varying frequency and severity, and an overall long-term prognosis that is less severe than that of idiopathic pulmonary fibrosis (IPF. Because ILD may be the presenting manifestation of CTD and/or the dominant manifestation of CTD, clinical extra-thoracic manifestations should be systematically considered in the diagnostic approach of ILD. When present, autoantibodies strongly contribute to the recognition and classification of the CTD. Patients with clinical extrathoracic manifestations of CTD and/or autoantibodies (especially with a high titer and/or the antibody is considered “highly specific” of an autoimmune condition, but who do not fit with established international CTD criteria may be called undifferentiated CTD or “lung-dominant CTD”. Although it remains to be determined which combination of symptoms and serologic tests best identify the subset of patients with clinically relevant CTD features, available evidence suggests that such patients may have distinct clinical and imaging presentation and may portend a distinct clinical course. However, autoantibodies alone when present in IPF patients do not seem to impact prognosis or management. Referral to a rheumatologist and multidisciplinary discussion may contribute to management of patients with undifferentiated CTD.

  4. How are cancer and connective tissue diseases related to sarcoidosis?

    Science.gov (United States)

    Chopra, Amit; Judson, Marc A

    2015-09-01

    Several studies have suggested an association between sarcoidosis and cancer, and between sarcoidosis and connective tissue diseases (CTDs). In this review, we discuss the evidence supporting and refuting these associations. In terms of a cancer risk in sarcoidosis patients, the data are somewhat conflicting but generally show a very small increased risk. The data supporting an association between sarcoidosis and CTD are not as robust as for cancer. However, it appears that scleroderma is the CTD most strongly associated with sarcoidosis. There are several important clinical and research-related implications of the association of sarcoidosis and CTDs. First, rigorous efforts should be made to exclude alternative causes for granulomatous inflammation before establishing a diagnosis of sarcoidosis. Second, the association between sarcoidosis and both cancer and CTDs may yield important insights into the immunopathogenesis of all three diseases. Finally, these data provide insight in answering a common question asked by sarcoidosis patients, 'Am I at an increased risk of developing cancer?' We believe that although there is an increased (relative) risk of cancer in sarcoidosis patients compared with the general population, that increased risk is quite small (low absolute risk).

  5. Endodontic medicine: connections between apical periodontitis and systemic diseases.

    Science.gov (United States)

    Segura-Egea, J J; Martín-González, J; Castellanos-Cosano, L

    2015-10-01

    The prevalence of apical periodontitis (AP) in Europe has been reported to affect 61% of individuals and 14% of teeth, and increase with age. Likewise, the prevalence of root canal treatment (RCT) in Europe is estimated to be around 30-50% of individuals and 2-9% of teeth with radiographic evidence of chronic persistent AP in 30-65% of root filled teeth (RFT). AP is not only a local phenomenon and for some time the medical and dental scientific community have analysed the possible connection between apical periodontits and systemic health. Endodontic medicine has developed, with increasing numbers of reports describing the association between periapical inflammation and systemic diseases. The results of studies carried out both in animal models and humans are not conclusive, but suggest an association between endodontic variables, that is AP and RCT, and diabetes mellitus (DM), tobacco smoking, coronary heart disease and other systemic diseases. Several studies have reported a higher prevalence of periapical lesions, delayed periapical repair, greater size of osteolityc lesions, greater likelihood of asymptomatic infections and poorer prognosis for RFT in diabetic patients. On the other hand, recent studies have found that a poorer periapical status correlates with higher HbA1c levels and poor glycaemic control in type 2 diabetic patients. However, there is no scientific evidence supporting a causal effect of periapical inflammation on diabetes metabolic control. The possible association between smoking habits and endodontic infection has also been investigated, with controversial results. The aim of this paper was to review the literature on the association between endodontic variables and systemic health (especially DM and smoking habits). © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  6. Abnormalities of resting state functional connectivity are related to sustained attention deficits in MS.

    Directory of Open Access Journals (Sweden)

    Marisa Loitfelder

    Full Text Available OBJECTIVES: Resting state (RS functional MRI recently identified default network abnormalities related to cognitive impairment in MS. fMRI can also be used to map functional connectivity (FC while the brain is at rest and not adhered to a specific task. Given the importance of the anterior cingulate cortex (ACC for higher executive functioning in MS, we here used the ACC as seed-point to test for differences and similarities in RS-FC related to sustained attention between MS patients and controls. DESIGN: Block-design rest phases of 3 Tesla fMRI data were analyzed to assess RS-FC in 31 patients (10 clinically isolated syndromes, 16 relapsing-remitting, 5 secondary progressive MS and 31 age- and gender matched healthy controls (HC. Participants underwent extensive cognitive testing. OBSERVATIONS: In both groups, signal changes in several brain areas demonstrated significant correlation with RS-activity in the ACC. These comprised the posterior cingulate cortex (PCC, insular cortices, the right caudate, right middle temporal gyrus, angular gyri, the right hippocampus, and the cerebellum. Compared to HC, patients showed increased FC between the ACC and the left angular gyrus, left PCC, and right postcentral gyrus. Better cognitive performance in the patients was associated with increased FC to the cerebellum, middle temporal gyrus, occipital pole, and the angular gyrus. CONCLUSION: We provide evidence for adaptive changes in RS-FC in MS patients compared to HC in a sustained attention network. These results extend and partly mirror findings of task-related fMRI, suggesting FC may increase our understanding of cognitive dysfunction in MS.

  7. Mixed connective tissue disease: The King Faisal Specialist Hospital experience

    International Nuclear Information System (INIS)

    Al-Rayes, H.; Al-Sheikh, A.; Al-Dalaan, A.; Al-Saleh, S.

    2002-01-01

    The aim of this study was to assess the clinical presentation, complications and serological analysis of mixed connective tissue disease (MCTD) at King Faisal Specialist Hospital and Research Centre (KFSHRC), and to determine the long-term clinical and immunologic outcomes. This was a retrospective study with prospective follow-up of 18 patients with MCTD who were followed at KFSHRC between 1982 and 1999. The age at onset of the disease ranged from 6 to 44 years, with mean age of 17.9 years. The female to male ratio was 2.5:1 and the mean follow-up time was 5 years. The most frequent presenting symptoms were arthralgia in all patients, Raynaud's phenomenon in 16 patients (88%) and swollen hands in 11 patients (61%). Arthritis was seen in 12 patients in (67%) and definite myositis in 10 patients (58%). The most common skin rashes encountered included lupus-like rash in 8 patients (44%) and cutaneous vasculitis in 5 patients (28%). Pulmonary hypertension occurred in 4 patients (22%). Other clinical manifestations encountered were esophageal hypomotility in 10 patients (56%), myocarditis in 2 patients (11%) and proteinurea in 2 patients (11%), while various neurological manifestations were present in 7 patients (39%). All patients exhibited higher titer of ANA and anti-nRNP antibodies. Five of the 18 patients (28%) had marked reduction in the anti-nRNP during remission. Following treatment, features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension persisted. A favorable outcome was observed in 12 patients (67%), 3 patients (17%) had continued active disease, while 3 patients (17%) died, with death related to pulmonary hypertension occurring in 2 patients (11%). The studied patients demonstrated the typical clinical and serological findings of MCTD, which support the correlation between anti-nRNP antibody specificities and MCTD. Autoantibody reactivity against nRNP polypeptides tends to regress during

  8. Out of sight, out of mind: global connection, environmental discourse and the emerging field of sustainability education

    Science.gov (United States)

    Henderson, Joseph A.

    2015-09-01

    How might we understand the complex nature of our existence in the world, and what are the implications of such examination? Moreover, how might we go about engaging others in this practice and what are the complications of such an endeavor? Expanding on Quigley, Dogbey, Che and Hallo's findings, I consider the implications of human-environment connections and examine the difficulty of articulating such connections via photovoice methods in particular places. Further, I use a Foucauldian discourse lens to situate this connective process to larger political and social dynamics at work in their paper, and in environmental education in general. Implications for sustainability and sustainability education are then developed, along with suggestions for future research in this emerging field.

  9. Sustainability.

    Science.gov (United States)

    Chang, Chein-Chi; DiGiovanni, Kimberly; Mei, Ying; Wei, Li

    2016-10-01

    This review on Sustainability covers selected 2015 publications on the focus of Sustainability. It is divided into the following sections : • Sustainable water and wastewater utilities • Sustainable water resources management • Stormwater and green infrastructure • Sustainability in wastewater treatment • Life cycle assessment (LCA) applications • Sustainability and energy in wastewater industry, • Sustainability and asset management.

  10. Development and clinical course of diseases accompanied by connective tissue dysplasia in children of puberty age

    Directory of Open Access Journals (Sweden)

    Elizarova S.Yu.

    2011-03-01

    Full Text Available The risk of development and clinical course of somatic diseases have been analyzed in the research work. 111 adolescents suffering from connective tissue dysplasia have been under the study. It has been stated that the frequency of somatic diseases among adolescents with connective tissue dysplasia is higher than this frequency among adolescents without such disease. Phenotypic signs of connective tissue dysplasia have been revealed. They are responsible for the development of bronchial asthma and severe stomach ulcer

  11. Transient and sustained cortical activity elicited by connected speech of varying intelligibility

    Directory of Open Access Journals (Sweden)

    Tiitinen Hannu

    2012-12-01

    Full Text Available Abstract Background The robustness of speech perception in the face of acoustic variation is founded on the ability of the auditory system to integrate the acoustic features of speech and to segregate them from background noise. This auditory scene analysis process is facilitated by top-down mechanisms, such as recognition memory for speech content. However, the cortical processes underlying these facilitatory mechanisms remain unclear. The present magnetoencephalography (MEG study examined how the activity of auditory cortical areas is modulated by acoustic degradation and intelligibility of connected speech. The experimental design allowed for the comparison of cortical activity patterns elicited by acoustically identical stimuli which were perceived as either intelligible or unintelligible. Results In the experiment, a set of sentences was presented to the subject in distorted, undistorted, and again in distorted form. The intervening exposure to undistorted versions of sentences rendered the initially unintelligible, distorted sentences intelligible, as evidenced by an increase from 30% to 80% in the proportion of sentences reported as intelligible. These perceptual changes were reflected in the activity of the auditory cortex, with the auditory N1m response (~100 ms being more prominent for the distorted stimuli than for the intact ones. In the time range of auditory P2m response (>200 ms, auditory cortex as well as regions anterior and posterior to this area generated a stronger response to sentences which were intelligible than unintelligible. During the sustained field (>300 ms, stronger activity was elicited by degraded stimuli in auditory cortex and by intelligible sentences in areas posterior to auditory cortex. Conclusions The current findings suggest that the auditory system comprises bottom-up and top-down processes which are reflected in transient and sustained brain activity. It appears that analysis of acoustic features occurs

  12. The LncRNA Connectivity Map: Using LncRNA Signatures to Connect Small Molecules, LncRNAs, and Diseases.

    Science.gov (United States)

    Yang, Haixiu; Shang, Desi; Xu, Yanjun; Zhang, Chunlong; Feng, Li; Sun, Zeguo; Shi, Xinrui; Zhang, Yunpeng; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

    2017-07-27

    Well characterized the connections among diseases, long non-coding RNAs (lncRNAs) and drugs are important for elucidating the key roles of lncRNAs in biological mechanisms in various biological states. In this study, we constructed a database called LNCmap (LncRNA Connectivity Map), available at http://www.bio-bigdata.com/LNCmap/ , to establish the correlations among diseases, physiological processes, and the action of small molecule therapeutics by attempting to describe all biological states in terms of lncRNA signatures. By reannotating the microarray data from the Connectivity Map database, the LNCmap obtained 237 lncRNA signatures of 5916 instances corresponding to 1262 small molecular drugs. We provided a user-friendly interface for the convenient browsing, retrieval and download of the database, including detailed information and the associations of drugs and corresponding affected lncRNAs. Additionally, we developed two enrichment analysis methods for users to identify candidate drugs for a particular disease by inputting the corresponding lncRNA expression profiles or an associated lncRNA list and then comparing them to the lncRNA signatures in our database. Overall, LNCmap could significantly improve our understanding of the biological roles of lncRNAs and provide a unique resource to reveal the connections among drugs, lncRNAs and diseases.

  13. Declining functional connectivity and changing hub locations in Alzheimer's disease: an EEG study

    NARCIS (Netherlands)

    Engels, M.M.A.; Stam, C.J.; van der Flier, W.M.; Scheltens, P.; de Waal, H.; van Straaten, E.C.W.

    2015-01-01

    Background: EEG studies have shown that patients with Alzheimer's disease (AD) have weaker functional connectivity than controls, especially in higher frequency bands. Furthermore, active regions seem more prone to AD pathology. How functional connectivity is affected in AD subgroups of disease

  14. Breast implant rupture and connective tissue disease: a review of the literature

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Lipworth, Loren; McLaughlin, Joseph K

    2007-01-01

    Large-scale epidemiologic studies to date have not found any credible association between silicone breast implants and either well-defined connective tissue diseases or undefined or atypical connective tissue diseases. It has been hypothesized that implant rupture could prompt an immunologic reac...

  15. A framework of connections between soil and people can help improve sustainability of the food system and soil functions.

    Science.gov (United States)

    Ball, Bruce C; Hargreaves, Paul R; Watson, Christine A

    2018-04-01

    Globally soil quality and food security continue to decrease indicating that agriculture and the food system need to adapt. Improving connection to the soil by knowledge exchange can help achieve this. We propose a framework of three types of connections that allow the targeting of appropriate messages to different groups of people. Direct connection by, for example, handling soil develops soil awareness for management that can be fostered by farmers joining groups on soil-focused farming such as organic farming or no-till. Indirect connections between soil, food and ecosystem services can inform food choices and environmental awareness in the public and can be promoted by, for example, gardening, education and art. Temporal connection revealed from past usage of soil helps to bring awareness to policy workers of the need for the long-term preservation of soil quality for environmental conservation. The understanding of indirect and temporal connections can be helped by comparing them with the operations of the networks of soil organisms and porosity that sustain soil fertility and soil functions.

  16. Conceptualizing sustainable development. An assessment methodology connecting values, knowledge, worldviews and scenarios

    International Nuclear Information System (INIS)

    De Vries, Bert J.M.; Petersen, Arthur C.

    2009-01-01

    Sustainability science poses severe challenges to classical disciplinary science. To bring the perspectives of diverse disciplines together in a meaningful way, we describe a novel methodology for sustainability assessment of a particular social-ecological system, or country. Starting point is that a sustainability assessment should investigate the ability to continue and develop a desirable way of living vis-a-vis later generations and life elsewhere on the planet. Evidently, people hold different values and beliefs about the way societies sustain quality of life for their members. The first step, therefore, is to analyze people's value orientations and the way in which they interpret sustainability problems i.e. their beliefs. The next step is to translate the resulting worldviews into model-based narratives, i.e. scenarios. The qualitative and quantitative outcomes are then investigated in terms of associated risks and opportunities and robustness of policy options. The Netherlands Environmental Assessment Agency (PBL) has followed this methodology, using extensive surveys among the Dutch population. In its First Sustainability Outlook (2004), the resulting archetypical worldviews became the basis for four different scenarios for policy analysis, with emphases on the domains of transport, energy and food. The goal of the agency's Sustainability Outlooks is to show that choices are inevitable in policy making for sustainable development, to indicate which positive and negative impacts one can expect of these choices (trade-offs), and to identify options that may be robust under several worldviews. The conceptualization proposed here is both clear and applicable in practical sustainability assessments for policy making. (author)

  17. Disease emergence and resurgence—the wildlife-human connection

    Science.gov (United States)

    Friend, Milton; Hurley, James W.; Nol, Pauline; Wesenberg, Katherine

    2006-01-01

    In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network. Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.Aside from human disease concerns, H5N1 avian influenza has major economic consequences for the poultry industry worldwide. Many other emerging diseases, such as severe acute respiratory syndrome (SARS), monkeypox, Ebola fever, and West Nile fever, also have an important wildlife component. Despite these wildlife associations, the true integration of the wildlife component in approaches towards disease emergence remains elusive. This separation between wildlife and other species’ interests is counterproductive because the emergence of zoonotic viruses and other pathogens maintained by wildlife reservoir hosts is poorly understood.This book is about the wildlife component of emerging diseases. It is intended to enhance the reader’s awareness of the role of wildlife in disease emergence. By doing so, perhaps a more holistic approach to disease prevention and control will emerge for the benefit of human, domestic animal, and free-ranging wildlife populations alike. The perspectives offered are influenced by more than four decades of my experiences as a wildlife disease practitioner. Although wildlife are victims to many of the same disease agents affecting humans and domestic animals, many aspects of disease in free-ranging wildlife require different approaches than those commonly applied to address disease in humans or domestic animals. Nevertheless, the broader community of disease investigators and health care professionals has largely pursued a separatist approach for

  18. USDOT guidance for connected vehicle deployments : institutional and business models and financial sustainability.

    Science.gov (United States)

    2016-07-01

    This document provides guidance material in regards to Institutional and Business issues as well as Financial Sustainability for the CV Pilots Deployment Concept Development Phase. This material also provides part of the foundation for the Performanc...

  19. Green Connections and Emotional Wellbeing: Sustainability as a Factor of Occupational (Dis)Satisfaction in Catering

    OpenAIRE

    Mikkola, Minna; Post, Anna

    2012-01-01

    Catering in Finland and Sweden constitutes a large industry serving annually 800 million meals and 1,9 billion meals, respectively. On the sector public caterers constitute an influential professional subgroup responding to political pressures for sustainability and illustrating the use of local, organic and fairly traded food. However, heavy cost pressures and currently dilemmatic interpretations of sustainability present public caterers as objects of cultural expectations and arouse their e...

  20. SUSTAINABLE DEVELOPMENT – HUMAN DEVELOPMENT CONNECTIONS IN THE POST-TRUTH ERA

    Directory of Open Access Journals (Sweden)

    ANDREEA CONSTANTINESCU

    2017-08-01

    Full Text Available Following the distancing of current policy from economic rigors and ethical demands aimed at redistribution of wealth, modern societies are parasitized by post-truth of actual facts. It distorts the shape and content of general interest data, for example political distortion of scientific evidence proving anthropogenic climate change. Under these circumstances, the question "to what extent economist’s truth stating what you cannot measure you cannot manage is sustained?" becomes absolutely legitimate. Regarding sustainable development management, monitoring the degree of achievement of Sustainable Development Goals is no longer sufficient to track progress in this area. Therefore, experts propose to introduce as much as possible qualitative data which, combined with quantitative data, will enhance their relevance and make them harder to be diverted for political purposes. This paper follows this direction, trying to prove that protection of data’s real meaning can be achieved by systemic analysis of all data originating from monitoring certain processes, which can be aggregated, with applicability in sustainable development. Thus, analyzing together data on sustainable development and those that indicates the state of human development emphasizes on one hand, the intrinsic link between these concepts and, on the other, maintain the sense of sustainability even in the post-truth era.

  1. Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

    Science.gov (United States)

    Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

    To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  2. Kazakhstan: Sustainable Development in Transition and Connection to the EU’s Assistance

    Directory of Open Access Journals (Sweden)

    Sabina Chukayeva

    2016-06-01

    Full Text Available This year the World Leaders considered and adopted the new ambitious Sustainable Development Agenda “Transforming our World: The 2030 Agenda for Sustainable Development” to end poverty and universally promote shared economic prosperity, social development and environmental protection by 2030. This article explores new realities of the Sustainable Development agenda in the light of the transition from the Millennium Development Goals (MDGs to the Sustainable Development Goals (SDGs. It is clear today that the global development strategy requires a system renovation and new approaches, corresponding with the reality and challenges of the 21st century. Kazakhstan, being one of the 50 countries participating in the national consultations process on the post-2015 Agenda, brought its own contribution to “The Future We Want” programme. The fruitful cooperation with the European Union adds more perspectives for Kazakhstan as one of the most dynamic developing countries in the Central Asian region. The authors emphasized the importance of the United Nations Organization (UN leadership in the global strategic planning and controlling long-term strategies, including cooperation between states and civilizations, and inclusion of all points of view, especially that of the youth. This article is intended for specialists as well as a wider audience (e.g. students, who are interested in international relations and organizations, international cooperation, sustainable development, and foreign policy of the Republic of Kazakhstan.

  3. Connecting the nucleolus to the cell cycle and human disease.

    Science.gov (United States)

    Tsai, Robert Y L; Pederson, Thoru

    2014-08-01

    Long known as the center of ribosome synthesis, the nucleolus is connected to cell cycle regulation in more subtle ways. One is a surveillance system that reacts promptly when rRNA synthesis or processing is impaired, halting cell cycle progression. Conversely, the nucleolus also acts as a first-responder to growth-related stress signals. Here we review emerging concepts on how these "infraribosomal" links between the nucleolus and cell cycle progression operate in both forward and reverse gears. We offer perspectives on how new cancer therapeutic designs that target this infraribosomal mode of cell growth control may shape future clinical progress. © FASEB.

  4. The Estonian national program for sustainable resource development and its connection with teaching about fossil fuels in chemistry courses

    International Nuclear Information System (INIS)

    Karik, H.

    1996-01-01

    The conception of sustainable resource development worked out under the initiative of the United Nations (UN) actualizes ideas for improving the health of people and the environment. The needs of people are to he addressed and, simultaneously, natural resources preserved. That is ,why ecological and economic expenses are to he integrated and flow sheets of industrial plants are to be reorganized in order to utilize natural resources in a rational way. The association of Estonia with the resolution of the UN Conference on Environmental Development held in Rio de Janeiro and the resolution of the Estonian Parliament concerning The National Program of Sustainable Development require changes in our lifestyle. Chemical education in schools has to support a change in the way of thinking and many concrete subjects can be connected with the problems of sustainable development. Metallic elements get into the environment mostly with fuel combustion ashes. According to various prognoses, fossil fuel resources will last for a thousand years. This means that more and more metallic compounds are thrown into the environment. Dispersion of metals in the air, water bodies and soil is continuously increasing. Finally, they reach the food chain and to the human body. As a result, toxicosis, illnesses, and inadvisable dislocations in organic life may occur. The trend to use ash as a raw material for metal production is considered to have some prospective economically attractive application. This would be one possible way of sustainable resource development to avoid the increase of environmental pollution and increase production of the corresponding metals

  5. Detecting Parkinson's disease from sustained phonation and speech signals.

    Directory of Open Access Journals (Sweden)

    Evaldas Vaiciukynas

    Full Text Available This study investigates signals from sustained phonation and text-dependent speech modalities for Parkinson's disease screening. Phonation corresponds to the vowel /a/ voicing task and speech to the pronunciation of a short sentence in Lithuanian language. Signals were recorded through two channels simultaneously, namely, acoustic cardioid (AC and smart phone (SP microphones. Additional modalities were obtained by splitting speech recording into voiced and unvoiced parts. Information in each modality is summarized by 18 well-known audio feature sets. Random forest (RF is used as a machine learning algorithm, both for individual feature sets and for decision-level fusion. Detection performance is measured by the out-of-bag equal error rate (EER and the cost of log-likelihood-ratio. Essentia audio feature set was the best using the AC speech modality and YAAFE audio feature set was the best using the SP unvoiced modality, achieving EER of 20.30% and 25.57%, respectively. Fusion of all feature sets and modalities resulted in EER of 19.27% for the AC and 23.00% for the SP channel. Non-linear projection of a RF-based proximity matrix into the 2D space enriched medical decision support by visualization.

  6. Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

    Science.gov (United States)

    Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

    2015-08-01

    Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease

  7. Sustainability in Oceans Governance : Small Islands, Emerging Powers, and Connecting Regions

    NARCIS (Netherlands)

    Larik, J.E.; Singh, A.

    2017-01-01

    As evidenced by Goal No. 14 of the UN's Sustainable Development Goals, the importance of oceans governance as a matter of global policy can hardly be overstated. The unsustainable uses of their resources could lead to serious consequences, not only for coastal communities, but remote landlocked

  8. Guides to Sustainable Connections? Exploring Human-Nature Relationships among Wilderness Travel Leaders

    Science.gov (United States)

    Grimwood, Bryan S. R.; Haberer, Alexa; Legault, Maria

    2015-01-01

    This paper explores and critically interprets the role wilderness travel may play in fostering environmental sustainability. The paper draws upon two qualitative studies that sought to understand human-nature relationships as experienced by different groups of wilderness travel leaders in Canada. According to leaders involved in the studies,…

  9. How to connect bioethics and environmental ethics: health, sustainability, and justice.

    Science.gov (United States)

    Dwyer, James

    2009-11-01

    In this paper, I explore one way to bring bioethics and environmental ethics closer together. I focus on a question at the interface of health, sustainability, and justice: How well does a society promote health with the use of no more than a just share of environmental capacity? To address this question, I propose and discuss a mode of assessment that combines a measurement of population health, an estimate of environmental sustainability, and an assumption about what constitutes a fair or just share. This mode of assessment provides an estimate of the just and sustainable life expectancy of a population. It could be used to monitor how well a particular society promotes health within just environmental limits. It could also serve as a source of information that stakeholders use when they deliberate about programs, policies, and technologies. The purpose of this work is to focus attention on an ethical task: the need to fashion institutions and forms of life that promote health in ways that recognize the claims of sustainability and justice.

  10. Leadership and Context Connectivity: Merging Two Forces for Sustainable School Improvement

    Science.gov (United States)

    Marishane, Nylon Ramodikoe

    2016-01-01

    School improvement is admittedly the main business of school leadership. However, while there is agreement on the importance of school improvement, sustaining this improvement remains a challenge. The challenge seems to lie in the disconnection between the leader and the context in which the school operates. This chapter presents contextual…

  11. The Resource Buffer Theory: Connecting the Dots from Conservation to Sustainability

    Science.gov (United States)

    Peter E. Black

    2006-01-01

    Review of conservation history and scientific developments helps us understand relationships between humans, environment, and sustainability. Applying “conservation” to natural resources and practical resource management occurred early in the Twentieth Century; practical economic definitions of conservation and natural resource followed. Resource surpluses underpin the...

  12. Functional connectivity in cortical regions in dementia with Lewy bodies and Alzheimer's disease.

    Science.gov (United States)

    Kenny, Eva R; Blamire, Andrew M; Firbank, Michael J; O'Brien, John T

    2012-02-01

    Using resting-state functional magnetic resonance imaging, spontaneous low-frequency fluctuations in the blood oxygenation level-dependent signal were measured to investigate connectivity between key brain regions hypothesized to be differentially affected in dementia with Lewy bodies compared with Alzheimer's disease and healthy controls. These included connections of the hippocampus, because of its role in learning, and parietal and occipital areas involved in memory, attention and visual processing. Connectivity was investigated in 47 subjects aged 60 years and over: 15 subjects with dementia with Lewy bodies, 16 subjects with Alzheimer's disease and 16 control subjects. Subjects were scanned using a 3 Tesla magnetic resonance imaging system. The mean blood oxygenation level-dependent signal time series was extracted from seed regions in the hippocampus, posterior cingulate cortex, precuneus and primary visual cortex and correlated with all other brain voxels to determine functional connectivity. Both subjects with dementia with Lewy bodies and Alzheimer's disease showed greater connectivity than control subjects. Compared with controls, the dementia with Lewy bodies group had greater connectivity between the right posterior cingulate cortex and other brain areas. In dementia with Lewy bodies, there were no significant differences in hippocampal connectivity compared with controls, but in Alzheimer's disease left hippocampal connectivity was greater compared with controls. There were no significant differences between groups for precuneus or primary visual cortex connectivity. No seed regions showed significantly less connectivity in subjects with dementia with Lewy bodies or Alzheimer's disease compared with controls. We found greater connectivity with the posterior cingulate in dementia with Lewy bodies and with the hippocampus in Alzheimer's disease. Consistent with the known relative preservation of memory in dementia with Lewy bodies compared with Alzheimer

  13. Exposome: connecting the dots for effective prevention of disease

    NARCIS (Netherlands)

    Pronk, A.; Stierum, R.

    2018-01-01

    Our health is impacted by the environment we grow up, live, work, sport, sleep and relax in. The combination of exposures during daily activities and over the lifetime constitutes a major risk factor for disease. Many common disorders are closely linked to these exposures ranging from lifestyle

  14. The Middle-East connection of Wolman disease

    International Nuclear Information System (INIS)

    Shome, Durjoy K.; Das, Nagalla S.; Al-Jishi, E.; Zainaldeen, Hassan A.; Malik, N.; Greally, John F.

    2002-01-01

    The clinical, laboratory and cytological features of 2 Bahraini infants with Wolman's disease are described. While one of the cases showed the classical diagnostic features, the other case exhibited a few atypical features such as lack of adrenal calcification and unusual morphology of vacuolated marrow macrophages. Literature review shows that this disorder may not be rare in this region. (author)

  15. Migration, Mobility and Connection : Towards a Sustainable Model for the Preservation of Immigrant Cultural Heritage

    NARCIS (Netherlands)

    Arthur, Paul; Ensor, Jason; van Faassen, M.; Hoekstra, F.G.; 't Hart, M.; Peters, Nonja

    2016-01-01

    All over the world migrants have influenced and changed the cultures of the countries where they have settled, and they have built new communities that have retained connections, to differing degrees and by various means, with their original homelands. The multiple traces that they have left in

  16. Dry Eye Disease and Microbial Keratitis: Is There a Connection?

    Science.gov (United States)

    Narayanan, Srihari; Redfern, Rachel L.; Miller, William L.; Nichols, Kelly K.; McDermott, Alison M.

    2013-01-01

    Dry eye is a common ocular surface disease of multifactorial etiology characterized by elevated tear osmolality and inflammation leading to a disrupted ocular surface. The latter is a risk factor for ocular surface infection, yet overt infection is not commonly seen clinically in the typical dry eye patient. This suggests that important innate mechanisms operate to protect the dry eye from invading pathogens. This article reviews the current literature on epidemiology of ocular surface infection in dry eye patients and laboratory-based studies on innate immune mechanisms operating at the ocular surface and their alterations in human dry eye and animal models. The review highlights current understanding of innate immunity in dry eye and identifies gaps in our knowledge to help direct future studies to further unravel the complexities of dry eye disease and its sequelae. PMID:23583043

  17. Wnt pathway in Dupuytren disease: connecting profibrotic signals.

    Science.gov (United States)

    van Beuge, Marike M; Ten Dam, Evert-Jan P M; Werker, Paul M N; Bank, Ruud A

    2015-12-01

    A role of Wnt signaling in Dupuytren disease, a fibroproliferative disease of the hand and fingers, has not been fully elucidated. We examined a large set of Wnt pathway components and signaling targets and found significant dysregulation of 41 Wnt-related genes in tissue from the Dupuytren nodules compared with patient-matched control tissue. A large proportion of genes coding for Wnt proteins themselves was downregulated. However, both canonical Wnt targets and components of the noncanonical signaling pathway were upregulated. Immunohistochemical analysis revealed that protein expression of Wnt1-inducible secreted protein 1 (WISP1), a known Wnt target, was increased in nodules compared with control tissue, but knockdown of WISP1 using small interfering RNA (siRNA) in the Dupuytren myofibroblasts did not confirm a functional role. The protein expression of noncanonical pathway components Wnt5A and VANGL2 as well as noncanonical coreceptors Ror2 and Ryk was increased in nodules. On the contrary, the strongest downregulated genes in this study were 4 antagonists of Wnt signaling (DKK1, FRZB, SFRP1, and WIF1). Downregulation of these genes in the Dupuytren tissue was mimicked in vitro by treating normal fibroblasts with transforming growth factor β1 (TGF-β1), suggesting cross talk between different profibrotic pathways. Furthermore, siRNA-mediated knockdown of these antagonists in normal fibroblasts led to increased nuclear translocation of Wnt target β-catenin in response to TGF-β1 treatment. In conclusion, we have shown extensive dysregulation of Wnt signaling in affected tissue from Dupuytren disease patients. Components of both the canonical and the noncanonical pathways are upregulated, whereas endogenous antagonists are downregulated, possibly via interaction with other profibrotic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 75 FR 70162 - Presumptive Service Connection for Diseases Associated With Persian Gulf War Service: Functional...

    Science.gov (United States)

    2010-11-17

    ... Diseases Associated With Persian Gulf War Service: Functional Gastrointestinal Disorders AGENCY: Department... theater of operations during the Persian Gulf War. DATES: Comments must be received by VA on or before... Service Connection for Diseases Associated With Persian Gulf War Service: Functional Gastrointestinal...

  19. Magnetic resonance imaging of functional connectivity in Parkinson disease in the resting brain

    International Nuclear Information System (INIS)

    Liu Xian; Liu Bo; Luo Xiaodong; Li Ningna; Chen Zhiguang; Chen Jun

    2009-01-01

    Objective: To investigate functional connectivity changes in Parkinson disease in the resting brain using functional magnetic resonance imaging. Methods: Nine patients with Parkinson disease and eight age-matched healthy volunteers were entered into the study. The bilateral globus pallidus were chosen as seed points, the functional MR data acquired in the resting state were processed to investigate functional connectivity in PD patients and the results were compared with those of the controls. Results: In age-matched healthy controls, there are regions which had functional connectivity with bilateral globus pallidus, including bilateral temporal poles, bilateral hippocampus, bilateral thalami, posterior cingulate cortex, right middle occipital gyms and right superior parietal gyms. In PD patients, brain regions including bilateral cerebellum, left hippocampus, bilateral superior temporal gyri, left inferior frontal gyrus, left middle frontal gyrus, left precentral gyrus, left inferior parietal gyrus and left superior parietal gyrus, had functional connectivity with bilateral globus pallidus. Compared to healthy controls, increased functional connectivity in bilateral cerebellum, bilateral temporal lobes, left frontal lobe and left parietal lobe, and decreased functional connectivity in bilateral thalami were observed in PD patients. Conclusion: Abnormal changes of brain functional connectivity exists in Parkinson's disease in the resting state. (authors)

  20. Connecting the sustainable development goals by their energy inter-linkages

    Science.gov (United States)

    McCollum, David L.; Gomez Echeverri, Luis; Busch, Sebastian; Pachauri, Shonali; Parkinson, Simon; Rogelj, Joeri; Krey, Volker; Minx, Jan C.; Nilsson, Måns; Stevance, Anne-Sophie; Riahi, Keywan

    2018-03-01

    The United Nations’ Sustainable Development Goals (SDGs) provide guide-posts to society as it attempts to respond to an array of pressing challenges. One of these challenges is energy; thus, the SDGs have become paramount for energy policy-making. Yet, while governments throughout the world have already declared the SDGs to be ‘integrated and indivisible’, there are still knowledge gaps surrounding how the interactions between the energy SDG targets and those of the non-energy-focused SDGs might play out in different contexts. In this review, we report on a large-scale assessment of the relevant energy literature, which we conducted to better our understanding of key energy-related interactions between SDGs, as well as their context-dependencies (relating to time, geography, governance, technology, and directionality). By (i) evaluating the nature and strength of the interactions identified, (ii) indicating the robustness of the evidence base, the agreement of that evidence, and our confidence in it, and (iii) highlighting critical areas where better understanding is needed or context dependencies should be considered, our review points to potential ways forward for both the policy making and scientific communities. First, we find that positive interactions between the SDGs outweigh the negative ones, both in number and magnitude. Second, of relevance for the scientific community, in order to fill knowledge gaps in critical areas, there is an urgent need for interdisciplinary research geared toward developing new data, scientific tools, and fresh perspectives. Third, of relevance for policy-making, wider efforts to promote policy coherence and integrated assessments are required to address potential policy spillovers across sectors, sustainability domains, and geographic and temporal boundaries. The task of conducting comprehensive science-to-policy assessments covering all SDGs, such as for the UN’s Global Sustainable Development Report, remains manageable

  1. Water Sciences - Connecting the dots to achieve the 2030 Agenda for Sustainable Development

    Science.gov (United States)

    Uhlenbrook, Stefan; Ortigara, Angela; Minelli, Lucilla

    2017-04-01

    Land use change, urbanisation, climate change, demographic development and migration, conflicts and peace, change of diets, industry 4.0, globalisation etc. are among the challenges that water sciences need to address to serve societal needs. Water availability per capita is decreasing, water quality is deteriorating at many places, but water demand is continuously escalating. Business as usual in water science is not up to the related challenges. In fact, business as usual cannot be the answer in all aspects, i.e. also current policy making processes will need to improve and take stock of evidences provided by science in order to better address societal challenges. However, exciting developments have been taking place. The global community agreed on a new and ambitious agenda for development, which aims to be comprehensive and include the participation of all stakeholders in one integrated framework. The 2030 Agenda for Sustainable Development provides a stimulating new era, with unique opportunities to reconcile science, society and policy making. Hydrology and water management - in all its facets including wastewater - play a central role in the Agenda 2030, as it is not only central in Sustainable Development Goal (SDG) 6, but it is fundamental for the realization of other SDGs related to, for instance, poverty reduction, sustainable growth, health, food security, climate change, ecosystems (land and sea), gender equality, etc. Despite the recognition of the critical importance of water in this agenda, the implementation of related policies and use of scientific developments represent a difficult task. Two main challenges remain: (i) the utilization of the knowledge and developments already available, and (ii) the need to overcome current and future knowledge gaps ensuring that scientific results support sustainable development effectively. The UN system will produce a Synthesis Report for SDG 6, which is currently being prepared by a UN-Water Task Force that

  2. [Nailfold capillaroscopy in the evaluation of Raynaud's phenomenon and undifferentiated connective tissue disease].

    Science.gov (United States)

    Cortes, Sara; Clemente-Coelho, Paulo

    2008-01-01

    Microvascular abnormalities involved in the pathogenic mechanism of several connective tissue disorders can be detected by nailfold capillaroscopy. Evaluation of the interest of nailfold capillaroscopy results in patients with Raynaud s phenomenon or undifferentiated connective tissue disease and their correlation with diagnostic and therapeutical evolution. Selection of capillaroscopic and laboratory results of patients with the diagnosis of Raynaud s phenomenon (without defined connective tissue disease) or undifferentiated connective tissue disease. Evaluation of the present diagnosis and treatment comparing with the ones existed at the time of capillaroscopy performance. 80 patients were enrolled with an age of 51.4+/-14.3 years (mean+/-SD) 78 females (97.5%) with Raynaud s phenomenon and undifferentiated connective tissue disease 27 patients (33.8%); Raynaud s Phenomenon 46 patients (57.5%); undifferentiated connective tissue disease 7 patients (8.7%). The capillaroscopic results were normal 30 patients (37.5%); minor changes tortuosity enlargement 16 patients (20.0%) major changes 34 patients (42.5%) hemorrhages 25 patients (31.3%) megacapillaries 26 patients (32.5%) avascular areas 3 patients (3.8%). The introduction of new treatments after the capillaroscopy occurred in 32 patients (40.0%) and a new diagnosis was done in 39 patients (48.8%). Major changes in capillaroscopy correlated with the change of diagnosis and the introduction of a new treatment (pNailfold capillaroscopy performed in patients with isolated Raynaud s phenomenon or undifferentiated connective tissue disease has a role in the prognostic evaluation related to the possibility of an evolution of the diagnosis or to the need of the introduction of new treatments.

  3. Connecting cities and their environments: Harnessing the water-energy-food nexus for sustainable urban development

    Directory of Open Access Journals (Sweden)

    Chan Arthur

    2015-01-01

    Full Text Available Thousands of years of development have made the production and consumption of water, energy, and food for urban environments more complex. While the rise of cities has fostered social and economic progress, the accompanying environmental pressures threaten to undermine these benefits. The compounding effects of climate change, habitat loss, pollution, overexploitation (in addition to financial constraints make the individual management of these three vital resources incompatible with rapidly growing populations and resource-intensive lifestyles. Nexus thinking is a critical tool to capture opportunities for urban sustainability in both industrialised and developing cities. A nexus approach to water, energy, and food security recognises that conventional decisionmaking, strictly confined within distinct sectors, limits the sustainability of urban development. Important nexus considerations include the need to collaborate with a wide spectrum of stakeholders, and to “re-integrate” urban systems. This means recognising the opportunities coming from the interconnected nature of cities and metropolitan regions, including links with rural environments and wider biophysical dynamics.

  4. Everything is connected: social determinants of pediatric health and disease.

    Science.gov (United States)

    Tarazi, Carine; Skeer, Margie; Fiscella, Kevin; Dean, Stephanie; Dammann, Olaf

    2016-01-01

    Carine Tarazi, MA, is an Assistant Editor for Pediatric Research in Boston, Massachusetts, USA. Margie Skeer, ScD, MPH, MSW, served as a Guest Editor for this special issue. Dr. Skeer is Assistant Professor of Public Health and Community Medicine at Tufts University. Her research focuses on adolescent substance misuse and sexual risk prevention, both from epidemiologic and intervention-development perspectives. Kevin Fiscella, MD, MPH, served as a Guest Editor for this special issue. Dr. Fiscella is Tenured Professor of Family Medicine, Public Health Sciences and Community Health at the University of Rochester Medical Center. Dr. Fiscella's research focuses on health and health care disparities, particularly practical strategies to improve health equity. Stephanie Dean, MBA, is Managing Editor of Pediatric Research and is based out of editorial office in The Woodlands, Texas. Olaf Dammann, MD, served as a Guest Editor for this special issue. Dr. Dammann is a Professor of Public Health and Community Medicine, Pediatrics, and Ophthalmology at Tufts University School of Medicine in Boston, Massachusetts, USA, as well as Professor of Perinatal Neuroepidemiology at Hannover Medical School, Hannover, Germany. His research interests include the elucidation of risk factors for brain damage and retinopathy in preterm newborns, the theory of risk and causation in biomedical and public health research, and the development of computational chronic disease models.

  5. Disease epidemics: Lessons for resilience in an increasingly connected world

    Science.gov (United States)

    Allen, Craig R.; DeWitte, S.N.; Kurth, M.H.; Linkov, I.

    2016-01-01

    In public health, the term resilience often refers to the personality traits that individuals possess which help them endure and recover from stressors. However, resilience as a system characteristic, especially in regards to complex social-ecological systems, can be informative for public health at scales larger than the individual. Acute shocks to systems occur against a background of existing conditions, which are crucial determinants of the eventual public health outcomes of those shocks, and in the context of complex dependencies among and between ecological and societal elements. Many components of a system's baseline condition are chronic public health concerns themselves and diminish the capacity of the system to perform in the face of acute shocks. The emerging field of resilience management is concerned with holistically assessing and improving a system's ability to prepare for and absorb disruption, and then recover and adapt across physical, information, environmental and social domains. Integrating resilience considerations into current risk- and evidence-based approaches to disease control and prevention1 can move public health efforts toward more proactive and comprehensive solutions for protecting and improving the health of communities. Here, we look to the case of the Black Death as an illustrative case of a dramatic transformation in human history, an acute shock to a system that was underlain by chronic social maladies, to derive lessons about resilience management for public health in contemporary systems.

  6. Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease

    OpenAIRE

    Munoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

    2018-01-01

    Background Animal models of Alzheimer’s disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain c...

  7. Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain.

    Science.gov (United States)

    Hong, Jui-Yang; Kilpatrick, Lisa A; Labus, Jennifer S; Gupta, Arpana; Katibian, David; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

    2014-10-22

    Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis. Copyright © 2014 the authors 0270-6474/14/3414252-08$15.00/0.

  8. A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

    Science.gov (United States)

    Hafkemeijer, Anne; Möller, Christiane; Dopper, Elise G P; Jiskoot, Lize C; van den Berg-Huysmans, Annette A; van Swieten, John C; van der Flier, Wiesje M; Vrenken, Hugo; Pijnenburg, Yolande A L; Barkhof, Frederik; Scheltens, Philip; van der Grond, Jeroen; Rombouts, Serge A R B

    2017-01-01

    Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.

  9. Local Power -- Global Connections: linking the world to a sustainable future through decentralized energy technology

    Energy Technology Data Exchange (ETDEWEB)

    Brent, Richard; Sweet, David

    2007-07-01

    Various international dynamics are converging to increase the attractiveness of decentralized energy as a complement to existing centralized energy infrastructures. Decentralized energy (DE) technologies, including onsite renewables, high efficiency cogeneration and industrial energy recycling, offer considerable benefits to those seeking working alternatives to emerging challenges in the energy sector. DE is ideally suited to provide clean affordable energy to areas where modern energy services are currently lacking. Having smaller generators close to where energy is required ensures a safe, reliable and secure energy supply when the energy is required. Furthermore, because DE is a much cleaner alternative than conventional central power plants and the energy provided comes at a much smaller price tag DE is an increasingly acceptable alternative both in the developed and developing world. DE is sure to play a key role in any plan to build a sustainable energy future. (auth)

  10. Association between antinuclear antibody titers and connective tissue diseases in a Rheumatology Department.

    Science.gov (United States)

    Menor Almagro, Raúl; Rodríguez Gutiérrez, Juan Francisco; Martín-Martínez, María Auxiliadora; Rodríguez Valls, María José; Aranda Valera, Concepción; de la Iglesia Salgado, José Luís

    To determine the dilution titles at antinuclear antibodies (ANA) by indirect immunofluorescence observed in cell substrate HEp-2 and its association with the diagnosis of systemic connective tissue disease in ANA test requested by a Rheumatology Unit. Samples of patients attended for the first time in the rheumatology unit, without prior ANA test, between January 2010 and December 2012 were selected. The dilution titers, immunofluorescence patterns and antigen specificity were recorded. In January 2015 the diagnosis of the patients were evaluated and classified in systemic disease connective tissue (systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, undifferentiated connective, antiphospholipid syndrome, mixed connective tissue and inflammatory myophaty) or not systemic disease connective tissue. A total of 1282 ANA tests requested by the Rheumatology Unit in subjects without previous study, 293 were positive, predominance of women (81.9%). Patients with systemic connective tissue disease were recorded 105, and 188 without systemic connective tissue disease. For 1/640 dilutions the positive predictive value in the connective was 73.3% compared to 26.6% of non-connective, and for values ≥1/1,280 85% versus 15% respectively. When performing the multivariate analysis we observed a positive association between 1/320 dilution OR 3.069 (95% CI: 1.237-7.614; P=.016), 1/640 OR 12.570 (95% CI: 3.659-43.187; P=.000) and ≥1/1,280 OR 42.136 (95% CI: 8.604-206.345; P=.000). These results show association titles dilution ≥1/320 in ANA's first test requested by a Rheumatology Unit with patients with systemic connective tissue disease. The VPP in these patients was higher than previous studies requested by other medical specialties. This may indicate the importance of application of the test in a targeted way. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

    Science.gov (United States)

    Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

    2013-11-01

    Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (Preactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

  12. l-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

    Science.gov (United States)

    Akram, Harith; Wu, Chengyuan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Yousry, Tarek; Jahanshahi, Marjan; Hariz, Marwan; Behrens, Timothy; Ashburner, John; Zrinzo, Ludvic

    2017-06-01

    Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm 3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  13. Increased connectivity between sensorimotor and attentional areas in Parkinson's disease

    International Nuclear Information System (INIS)

    Onu, Mihaela; Badea, Liviu; Roceanu, Adina; Bajenaru, Ovidiu; Tivarus, Madalina

    2015-01-01

    Our study is using Independent Component Analysis (ICA) to evaluate functional connectivity changes in Parkinson's disease (PD) in an unbiased manner. Resting-state functional magnetic resonance imaging (rs-fMRI) data was collected for 27 PD patients and 16 healthy subjects. Differences for intra- and inter-network connectivity between healthy subjects and patients were investigated using FMRIB Software Library (FSL) tools (Melodic ICA, dual regression, FSLNets). Twenty-three ICA maps were identified as components of neuronal origin. For intra-network connectivity changes, eight components showed a significant connectivity increase in patients (p < 0.05); these were correlated with clinical scores and were largest for (sensori)motor networks. For inter-network connectivity changes, we found higher connectivity between the sensorimotor network and the spatial attention network (p = 0.0098) and lower connectivity between anterior and posterior default mode networks (DMN) (p = 0.024), anterior DMN and visual recognition networks (p = 0.026), as well as between visual attention and main dorsal attention networks (p = 0.03), for patients as compared to healthy subjects. The area under the Receiver Operating Characteristics (ROC) curve for the best predictor (partial correlation between sensorimotor and spatial attention networks) was 0.772. These functional alterations were not associated with any gray or white matter structural changes. Our results show higher connectivity between sensorimotor and spatial attention areas in patients that may be related to the reduced movement automaticity in PD. (orig.)

  14. Increased connectivity between sensorimotor and attentional areas in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Onu, Mihaela [Medical Imaging Department, Clinical Hospital ' ' Prof. Dr. Th. Burghele' ' , Bucharest (Romania); Carol Davila University of Medicine and Pharmacy, Biophysics, Bucharest (Romania); Badea, Liviu [National Institute for Research and Development in Informatics, Artificial Intelligence and Bioinformatics Group, Bucharest (Romania); Roceanu, Adina; Bajenaru, Ovidiu [University of Bucharest Emergency Hospital, Neurology Department, Bucharest (Romania); Tivarus, Madalina [University of Rochester Medical Center, Department of Imaging Sciences and Rochester Center for Brain Imaging, Rochester, NY (United States)

    2015-09-15

    Our study is using Independent Component Analysis (ICA) to evaluate functional connectivity changes in Parkinson's disease (PD) in an unbiased manner. Resting-state functional magnetic resonance imaging (rs-fMRI) data was collected for 27 PD patients and 16 healthy subjects. Differences for intra- and inter-network connectivity between healthy subjects and patients were investigated using FMRIB Software Library (FSL) tools (Melodic ICA, dual regression, FSLNets). Twenty-three ICA maps were identified as components of neuronal origin. For intra-network connectivity changes, eight components showed a significant connectivity increase in patients (p < 0.05); these were correlated with clinical scores and were largest for (sensori)motor networks. For inter-network connectivity changes, we found higher connectivity between the sensorimotor network and the spatial attention network (p = 0.0098) and lower connectivity between anterior and posterior default mode networks (DMN) (p = 0.024), anterior DMN and visual recognition networks (p = 0.026), as well as between visual attention and main dorsal attention networks (p = 0.03), for patients as compared to healthy subjects. The area under the Receiver Operating Characteristics (ROC) curve for the best predictor (partial correlation between sensorimotor and spatial attention networks) was 0.772. These functional alterations were not associated with any gray or white matter structural changes. Our results show higher connectivity between sensorimotor and spatial attention areas in patients that may be related to the reduced movement automaticity in PD. (orig.)

  15. Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Anne eHafkemeijer

    2015-09-01

    Full Text Available Alzheimer’s disease (AD and behavioral variant frontotemporal dementia (bvFTD are the most common types of early-onset dementia. Here, we apply resting state functional magnetic resonance imaging (fMRI to study functional brain connectivity differences between AD and bvFTD.We used resting state fMRI data of 31 AD patients, 25 bvFTD patients, and 29 controls. We studied functional connectivity throughout the entire brain, applying two different analysis techniques, studying network-to-region and region-to-region connectivity. A general linear model approach was used to study group differences, while controlling for physiological noise, age, gender, study center, and regional gray matter volume. Given gray matter differences, we observed decreased network-to-region connectivity in bvFTD between a lateral visual cortical network and lateral occipital and cuneal cortex, and b auditory system network and angular gyrus. In AD, we found decreased network-to-region connectivity between the dorsal visual stream network and lateral occipital and parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD between superior temporal gyrus and cuneal, supracalcarine, intracalcarine cortex, and lingual gyrus. We showed that the pathophysiology of functional brain connectivity is different between AD and bvFTD. However, the group differences in functional connectivity are less abundant than has been shown in previous studies.

  16. Secular trends of pregnancies in women with inflammatory connective tissue disease.

    Science.gov (United States)

    Wallenius, Marianne; Salvesen, Kjell Å; Daltveit, Anne K; Skomsvoll, Johan F

    2015-11-01

    This study examined secular trends in reproductive outcome in women with inflammatory connective tissue disease compared with reference deliveries from the general population. Historical cohort study based on data registered in the Medical Birth Register of Norway from 1967 to 2009. The study included singleton births in women recorded with connective tissue disease (n = 851) and reference deliveries from the general population (n = 2 437 110). Births were stratified in four periods, 1967-1979, 1980-1989, 1990-1999 and 2000-2009. Associations between connective tissue disease and maternal and perinatal outcomes by decade were assessed in logistic regression analyses and adjusted for maternal age at delivery and parity. In the 1970s, around 2.7 deliveries/year were registered for women with connective tissue disease (0.004% of all deliveries). This increased to 42 deliveries/year (0.07% of all deliveries) after 2000. Adjusted odds ratios (aOR) for cesarean section were 5.0 (95% CI 2.1-11.9) in the first and 1.8 (95% CI 1.4-2.3) in the last period. For preterm delivery the aOR decreased from 4.9 (95% CI 2.1-11.4) to 3.1 (95% CI 2.3-4.2) and the aOR for birthweight connective tissue disease. Adverse pregnancy outcomes were more common among women with connective tissue disease but risks have decreased over time. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  17. Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.

    Science.gov (United States)

    Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf; Huang, Neng C; Poston, Kathleen L; Bronte-Stewart, Helen M; Schulte, Tilman

    2015-09-01

    Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.

  18. Task-Rest Modulation of Basal Ganglia Connectivity in Mild to Moderate Parkinson’s Disease

    Science.gov (United States)

    Müller-Oehring, Eva M.; Sullivan, Edith V.; Pfefferbaum, Adolf; Huang, Neng C.; Poston, Kathleen L.; Bronte-Stewart, Helen M.; Schulte, Tilman

    2014-01-01

    Parkinson’s disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG–cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen–medial parietal and pallidum–occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate–supramarginal gyrus and pallidum–inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal–cortical connectivity, specifically between caudate–prefrontal, caudate–precuneus, and putamen–motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance. PMID:25280970

  19. Operating a sustainable disease management program for chronic obstructive pulmonary disease.

    Science.gov (United States)

    Endicott, Linda; Corsello, Phillip; Prinzi, Michele; Tinkelman, David G; Schwartz, Abby

    2003-01-01

    Chronic obstructive pulmonary disease (COPD) is one of our nation's most rapidly growing chronic health conditions. It is estimated that over 16 million individuals are diagnosed with COPD (Friedman & Hilleman, 2001). In addition, another 16 million are misdiagnosed as asthma or not diagnosed at all. COPD is a condition that affects the working-age as well as the elderly. Despite the high mortality rate, COPD is a treatable and modifiable condition. Disease management programs (DMPs) for asthma are a common initiative within many health insurance plans and integrated delivery networks. Similar initiatives are not as common for COPD. This article will highlight the National Jewish Medical and Research Center's COPD DMP interventions and outcomes. To outline interventions and operational strategies critical in developing and operating a sustainable and effective disease management program for COPD. Disease Management is an effective model for managing individuals with COPD. Applying a case management model that includes (1) risk-identification and stratification; (2) education and empowerment regarding self-monitoring and management; (3) lifestyle modification; (4) communication and collaboration amongst patients, healthcare providers, and case managers to enhance the treatment plan; (5) providing after-hours support; and (6) monitoring care outcomes is crucial. Applying these interventions in a credible manner will improve the quality of life and quality of care delivered to individuals with mild, moderate, severe, and very severe COPD. Additionally, these interventions can significantly reduce utilization events.

  20. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease

    NARCIS (Netherlands)

    Shah, R.C.; Kamphuis, P.J.; Leurgans, S.; Swinkels, S.H.; Sadowsky, C.H.; Bongers, A.; Rappaport, S.A.; Quinn, J.F.; Wieggers, R.L.; Scheltens, P.; Bennett, D.A.

    2013-01-01

    Introduction. Souvenaid® containing Fortasyn® Connect is a medical food designed to support synapse synthesis in persons with Alzheimer's disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors

  1. Solar hydrogen energy: The European-Maghreb connection. A new way of excellence for a sustainable energy development

    Energy Technology Data Exchange (ETDEWEB)

    Cherigui, Abdel-Nasser [Universite Joseph Fourier Grenoble I, BP 87, 38400 Saint-Martin-D' Heres (France); Mahmah, Bouziane; Harouadi, Farid; Belhamel, Maiouf; Chader, Samira; M' Raoui, Abdelhamid [Renewable Energy Development Centre, CDER, PO Box 62, Route de L' Observatoire, Celeste Valley, Bouzareah, 16340, Algiers (Algeria); Etievant, Claude [Compagnie Europeenne des Technologies de l' Hydrogene - CETH - Innov' Valley Entreprises, 91460 Marcoussis (France)

    2009-06-15

    The global sustainability is a key word of the future energy system for human beings. It should be friendly to our earth. Hydrogen energy is a critical resource to sustainable energy development. Over the coming decades, rapid economic growth will necessitate expanded and diversified energy supplies. This study is proposed to illustrate the attention to the opportunities and possibilities of connecting the energy consumer in North Mediterranean countries, to the reservoir of the Great Sahara of North Africa using hydrogen as a solar energy carrier. It also discusses cooperation between North Africa and north sides of the Mediterranean that has been going on for a long time, in oil and natural gas industry, and why cannot be done in solar hydrogen energy industry, which will reduce pollution and will last forever. Clearly, North Africa is a major bilateral partner with the Europe and the people of the two shares of the Mediterranean will be work together and to built strategic relationships for many decades. In the future, North Africa countries are well-positioned to play a greater role in the Europe clean energy equation. Demographically, interregional migration due to economic concerns will decline. Now, there are good chances to start such cooperation for the benefits of all partners. (author)

  2. Predictors of sustained response to rivastigmine in patients with Alzheimer's disease: a retrospective analysis.

    Science.gov (United States)

    Sadowsky, Carl H; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

    2011-01-01

    The cholinesterase inhibitor rivastigmine is approved for the treatment of mild to moderate Alzheimer's disease. However, it is not possible to predict which individuals will benefit from treatment. This retrospective analysis of an international, 24-week, randomized, double-blind trial aimed to identify the percentage of persons with Alzheimer's disease who have a sustained response with rivastigmine patch, rivastigmine capsules, or placebo; to determine the magnitude of the sustained treatment response; and to investigate baseline patient characteristics predictive of the observed sustained response. Patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) at week 16 and maintained at least the week 16 improvement at week 24 were identified as sustained responders. Treatment differences and baseline predictive factors were assessed in patients demonstrating a 1-, 2-, 3-, 4-, or 5-point sustained improvement. The first patient was screened in November 2003 and the last patient completed the study in January 2006. More persons with Alzheimer's disease had sustained improvements on the ADAS-cog and ADCS-ADL with rivastigmine versus placebo. Sustained improvements of 4 or 5 points on the ADAS-cog or ADCS-ADL were demonstrated in the 9.5-mg/24-h rivastigmine patch (24% and 36% of patients, respectively) and 12-mg/d capsule groups (28% on both outcome measures). Factors predictive of a sustained response to treatment included baseline Mini-Mental State Examination, ADAS-cog, and ADCS-ADL scores and treatment, country of treatment, and time since first symptom was diagnosed by a physician. Understanding factors predictive of sustained cholinesterase inhibitor treatment response should help to optimize Alzheimer's disease management and encourage compliance by allowing more realistic expectations of treatment effects.

  3. Urban Environmental Excursions: Designing field trips to demonstrate sustainable connections between natural and engineered systems in urban environments

    Science.gov (United States)

    Lemke, L. D.

    2012-12-01

    Field trips are a proven and effective instructional tool to connect students with the world around them. In most communities, opportunities abound to allow students to make connections between concepts introduced in classroom or lab activities and the urban environment that surrounds them. Potential destinations include solid and liquid waste disposal sites, brownfield redevelopment sites, hazardous waste sites, industrial complexes, or sites with ongoing environmental restoration efforts. Each of these locations presents opportunities to explore sustainable aspects of anthropogenic activities in relation to the natural systems that they seek to modify or exploit. Early planning is essential, however, because it can sometimes take several months lead time to arrange for a large group tour of industrial or municipal sites. Several practices may be employed to design effective learning experiences for students when visiting such sites. These include: 1) choose local sites to keep trips relevant and practical; 2) balance sites of environmental concern with those where significant progress is being made in environmental restoration or stewardship; 3) connect sites with a pertinent theme (e.g., air quality, water quality, economic development, environmental justice, etc.); 4) develop a sense of location among student participants by providing a map showing the relationship between campus and the field sites; 5) prepare a guidebook containing one-page descriptions of each stop along with a list of questions to stimulate discussion and promote active engagement among all participants; 6) employ expert guides to maximize students' access to authoritative information; 7) tie each field experience to your curriculum; and 8) model active learning by asking genuine questions and engaging in open discussions with experts and student participants. In this presentation, urban field trip design will be illustrated with examples from trips run in conjunction with freshman

  4. Sustainable RC Beam-Column Connections with Headed Bars: A Formula for Shear Strength Evaluation

    Directory of Open Access Journals (Sweden)

    Minh-Tung Tran

    2018-02-01

    Full Text Available Beam-column joints are critical regions for reinforced concrete (RC frames subjected to earthquakes. The steel reinforcement is, in general, highly concentrated in these zones. This is why in many cases, headed bars are used. A headed bar is a longitudinal steel reinforcement whose end has a special button added to reduce the bonding length of the steel rebar. This paper establishes a formula predicting the shear strength of exterior RC beam-column connections where the beam longitudinal reinforcements use headed bars. A database was collected, which contained 30 experimental data about the exterior beam-column joints using headed bars and subjected to quasi-static cyclic loading. First, from the collected database, a statistical study was carried out to identify the most influencing parameters on the shear strength of the beam-column joints tested. The three most important parameters were identified and an empirical modified formula was developed based on the formula existing in the standards. The study showed that the results obtained from the modified formula proposed in the present study were closer to the experimental results than that obtained from the formula existing in the standards. Finally, a numerical study was performed on two T-form RC structures and the numerical results were compared with the prediction calculated from the modified formula proposed. For two investigated cases, the proposed formula provided the results in the safety side and the differences with the numerical results were less than 20%. Thus, the proposed formula can be used for a rapid assessment of the shear strength of RC joints using headed bars.

  5. Resting-state network disruption and APOE genotype in Alzheimer's disease: a lagged functional connectivity study.

    Directory of Open Access Journals (Sweden)

    Leonides Canuet

    Full Text Available BACKGROUND: The apolipoprotein E epsilon 4 (APOE-4 is associated with a genetic vulnerability to Alzheimer's disease (AD and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called "lagged phase synchronization". METHODOLOGY/PRINCIPAL FINDINGS: Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. There was a decreased alpha2 connectivity pattern in AD, involving the left temporal and bilateral parietal cortex. Several brain regions exhibited increased lagged phase synchronization in low frequencies, specifically in the theta band, across and within hemispheres, where temporal lobe connections were particularly compromised. Areas with abnormal theta connectivity correlated with cognitive scores. In patients with early AD, we found an APOE-4-related decrease in interhemispheric alpha connectivity in frontal and parieto-temporal regions. CONCLUSIONS/SIGNIFICANCE: In addition to regional cortical dysfunction, as indicated by abnormal alpha oscillations, there are patterns of functional network disruption affecting theta and alpha bands in AD that associate with the level of cognitive disturbance or with the APOE genotype. These functional patterns of nonlinear connectivity may potentially

  6. Frequency-Dependent Altered Functional Connections of Default Mode Network in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Youjun Li

    2017-08-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder associated with the progressive dysfunction of cognitive ability. Previous research has indicated that the default mode network (DMN is closely related to cognition and is impaired in Alzheimer’s disease. Because recent studies have shown that different frequency bands represent specific physiological functions, DMN functional connectivity studies of the different frequency bands based on resting state fMRI (RS-fMRI data may provide new insight into AD pathophysiology. In this study, we explored the functional connectivity based on well-defined DMN regions of interest (ROIs from the five frequency bands: slow-5 (0.01–0.027 Hz, slow-4 (0.027–0.073 Hz, slow-3 (0.073–0.198 Hz, slow-2 (0.198–0.25 Hzs and standard low-frequency oscillations (LFO (0.01–0.08 Hz. We found that the altered functional connectivity patterns are mainly in the frequency band of slow-5 and slow-4 and that the decreased connections are long distance, but some relatively short connections are increased. In addition, the altered functional connections of the DMN in AD are frequency dependent and differ between the slow-5 and slow-4 bands. Mini-Mental State Examination scores were significantly correlated with the altered functional connectivity patterns in the slow-5 and slow-4 bands. These results indicate that frequency-dependent functional connectivity changes might provide potential biomarkers for AD pathophysiology.

  7. THE UVEITIS – PERIODONTAL DISEASE CONNECTION IN PREGNANCY: CONTROVERSY BETWEEN MYTH AND REALITY

    Directory of Open Access Journals (Sweden)

    Widyawati Sutedjo

    2012-01-01

    Full Text Available Background: Recently, It had been recognized that oral infection, especially periodontal disease are potential contributing factors to a variety of systemic diseases, such as cardiovascular and cerebrovascular diseases, pregnancy problem, diabetes mellitus type 2, etc. However, the adverse effect of periodontal disease toward uveitis still not clearly understood especially if happens during pregnancy. Interestingly, in Indonesia, there is still a myth that pregnant women should not get any dental treatment, therefore, it may deteriorate periodontal disease during pregnancy. Purpose: to explain the possible connection between periodontal disease and uveitis and increase the awareness of these problems during pregnancy that could be understood by doctor and laymen. Reviews: literatures revealed that dental infection can caused uveitis via metastatic spread of toxin and inflammatory mediators. Additionaly, more recent investigation reported that the neural system may also stimulated by oral infection. In the orofacial regions there's trigeminal nerve complex that also related to the orbital region, thus may also involved in the uveitis pathogenesis. The effects of periodonto pathogens toxins toward immunocompetent cell and nerves had also been reported by researcher. Moreover, pregnant women are more susceptible to periodontal disease, therefore maintaining oral hygiene and dental monitoring is a mandatory. Conclusion: in woman who susceptible to uveitis, periodontal disease may exacerbate the symptoms especially in pregnancy. Therefore simple explanation about connection of oral infection-systemic diseases especially in pregnancy should be widespread among Indonesian people.

  8. Communicable disease control programmes and health systems: an analytical approach to sustainability.

    Science.gov (United States)

    Shigayeva, Altynay; Coker, Richard J

    2015-04-01

    There is renewed concern over the sustainability of disease control programmes, and re-emergence of policy recommendations to integrate programmes with general health systems. However, the conceptualization of this issue has remarkably received little critical attention. Additionally, the study of programmatic sustainability presents methodological challenges. In this article, we propose a conceptual framework to support analyses of sustainability of communicable disease programmes. Through this work, we also aim to clarify a link between notions of integration and sustainability. As a part of development of the conceptual framework, we conducted a systematic literature review of peer-reviewed literature on concepts, definitions, analytical approaches and empirical studies on sustainability in health systems. Identified conceptual proposals for analysis of sustainability in health systems lack an explicit conceptualization of what a health system is. Drawing upon theoretical concepts originating in sustainability sciences and our review here, we conceptualize a communicable disease programme as a component of a health system which is viewed as a complex adaptive system. We propose five programmatic characteristics that may explain a potential for sustainability: leadership, capacity, interactions (notions of integration), flexibility/adaptability and performance. Though integration of elements of a programme with other system components is important, its role in sustainability is context specific and difficult to predict. The proposed framework might serve as a basis for further empirical evaluations in understanding complex interplay between programmes and broader health systems in the development of sustainable responses to communicable diseases. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

  9. Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder.

    Science.gov (United States)

    Brinkmann, L; Buff, C; Feldker, K; Tupak, S V; Becker, M P I; Herrmann, M J; Straube, T

    2017-11-01

    Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD. Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations. PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks. We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

  10. Discriminative analysis of Parkinson's disease based on whole-brain functional connectivity.

    Directory of Open Access Journals (Sweden)

    Yongbin Chen

    Full Text Available Recently, there has been an increasing emphasis on applications of pattern recognition and neuroimaging techniques in the effective and accurate diagnosis of psychiatric or neurological disorders. In the present study, we investigated the whole-brain resting-state functional connectivity patterns of Parkinson's disease (PD, which are expected to provide additional information for the clinical diagnosis and treatment of this disease. First, we computed the functional connectivity between each pair of 116 regions of interest derived from a prior atlas. The most discriminative features based on Kendall tau correlation coefficient were then selected. A support vector machine classifier was employed to classify 21 PD patients with 26 demographically matched healthy controls. This method achieved a classification accuracy of 93.62% using leave-one-out cross-validation, with a sensitivity of 90.47% and a specificity of 96.15%. The majority of the most discriminative functional connections were located within or across the default mode, cingulo-opercular and frontal-parietal networks and the cerebellum. These disease-related resting-state network alterations might play important roles in the pathophysiology of this disease. Our results suggest that analyses of whole-brain resting-state functional connectivity patterns have the potential to improve the clinical diagnosis and treatment evaluation of PD.

  11. Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

    International Nuclear Information System (INIS)

    Guit, G.L.; Shaw, P.C.; Ehrlich, J.; Kroon, H.M.; Oudkerk, M.

    1985-01-01

    A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient

  12. Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease.

    Science.gov (United States)

    Rolinski, Michal; Griffanti, Ludovica; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A L; Wilcock, Gordon K; Filippini, Nicola; Zamboni, Giovanna; Hu, Michele T M; Mackay, Clare E

    2015-01-01

    Resting state functional MRI (rs-fMRI) has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD). In order to assess whether changes within the basal ganglia network (BGN) are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD). Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease.

  13. Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Michal Rolinski

    2015-01-01

    Full Text Available Resting state functional MRI (rs-fMRI has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD. In order to assess whether changes within the basal ganglia network (BGN are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD. Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease.

  14. Assessment of the Sustainability Capacity of a Coordinated Approach to Chronic Disease Prevention.

    Science.gov (United States)

    Moreland-Russell, Sarah; Combs, Todd; Polk, LaShaun; Dexter, Sarah

    2017-12-07

    This article outlines some factors that influenced the sustainability capacity of a coordinated approach to chronic disease prevention in state and territory health departments. This study involved a cross-sectional design and mixed-methods approach. Quantitative data were collected using the Program Sustainability Assessment Tool (PSAT), a 40-item multiple-choice instrument that assesses 8 domains of sustainability capacity (environmental support, funding stability, partnerships, organizational capacity, program evaluation, program adaptation, communications, and strategic planning). Qualitative data were collected via phone interviews. The PSAT was administered to staff and stakeholders from public health departments in 50 US states, District of Columbia, and Puerto Rico, who were involved in the implementation of coordinated chronic disease programs. Phone interviews were conducted with program coordinators in each state. Sustainability score patterns and state-level categorical results, as well as strengths and opportunities for improvement across the 8 program sustainability domains, were explored. On average, programs reported the strongest sustainability capacity in the domains of program adaptation, environmental support, and organizational capacity, while funding stability, strategic planning, and communications yielded lowest scores, indicating weakest capacity. Scores varied the most by state in environmental support and strategic planning. The PSAT results highlight the process through which states approached the sustainability of coordinated chronic disease initiatives. This process included an initial focus on program evaluation and partnerships with transfer of priority to long-term strategic planning, communications, and funding stability to further establish coordinated chronic disease efforts. Qualitative interviews provided further context to PSAT results, indicating that leadership, communications, partnerships, funding stability, and policy

  15. Using Tractography to Distinguish SWEDD from Parkinson’s Disease Patients Based on Connectivity

    Directory of Open Access Journals (Sweden)

    Mansu Kim

    2016-01-01

    Full Text Available Background. It is critical to distinguish between Parkinson’s disease (PD and scans without evidence of dopaminergic deficit (SWEDD, because the two groups are different and require different therapeutic approaches. Objective. The aim of this study was to distinguish SWEDD patients from PD patients using connectivity information derived from diffusion tensor imaging tractography. Methods. Diffusion magnetic resonance images of SWEDD (n=37 and PD (n=40 were obtained from a research database. Tractography, the process of obtaining neural fiber information, was performed using custom software. Group-wise differences between PD and SWEDD patients were quantified using the number of connected fibers between two regions, and correlation analyses were performed based on clinical scores. A support vector machine classifier (SVM was applied to distinguish PD and SWEDD based on group-wise differences. Results. Four connections showed significant group-wise differences and correlated with the Unified Parkinson’s Disease Rating Scale sponsored by the Movement Disorder Society. The SVM classifier attained 77.92% accuracy in distinguishing between SWEDD and PD using these identified connections. Conclusions. The connections and regions identified represent candidates for future research investigations.

  16. Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Yu, Lianchun; De Mazancourt, Marine; Hess, Agathe; Ashadi, Fakhrul R; Klein, Isabelle; Mal, Hervé; Courbage, Maurice; Mangin, Laurence

    2016-08-01

    Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736-2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  17. Successful Object Encoding Induces Increased Directed Connectivity in Presymptomatic Early-Onset Alzheimer’s Disease

    Science.gov (United States)

    Ochoa, John Fredy; Alonso, Joan Francesc; Duque, Jon Edinson; Tobón, Carlos Andrés; Mañanas, Miguel Angel; Lopera, Francisco; Hernández, Alher Mauricio

    2016-01-01

    Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD. PMID:27792014

  18. Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions

    Science.gov (United States)

    Krieg, Thomas; Abraham, David; Lafyatis, Robert

    2007-01-01

    Fibrosis, characterized by excessive extracellular matrix accumulation, is a common feature of many connective tissue diseases, notably scleroderma (systemic sclerosis). Experimental studies suggest that a complex network of intercellular interactions involving endothelial cells, epithelial cells, fibroblasts and immune cells, using an array of molecular mediators, drives the pathogenic events that lead to fibrosis. Transforming growth factor-β and endothelin-1, which are part of a cytokine hierarchy with connective tissue growth factor, are key mediators of fibrogenesis and are primarily responsible for the differentiation of fibroblasts toward a myofibroblast phenotype. The tight skin mouse (Tsk-1) model of cutaneous fibrosis suggests that numerous other genes may also be important. PMID:17767742

  19. Flexible modulation of network connectivity related to cognition in Alzheimer’s disease

    Science.gov (United States)

    McLaren, Donald G.; Sperling, Reisa A.; Atria, Alireza

    2014-01-01

    Functional neuroimaging tools, such as fMRI methods, may elucidate the neural correlates of clinical, behavioral, and cognitive performance. Most functional imaging studies focus on regional task-related activity or resting state connectivity rather than how changes in functional connectivity across conditions and tasks are related to cognitive and behavioral performance. To investigate the promise of characterizing context-dependent connectivity-behavior relationships, this study applies the method of generalized psychophysiological interactions (gPPI) to assess the patterns of associative-memory-related fMRI hippocampal functional connectivity in Alzheimer’s disease (AD) associated with performance on memory and other cognitively demanding neuropsychological tests and clinical measures. Twenty-four subjects with mild AD dementia (ages 54–82, nine females) participated in a face-name paired-associate encoding memory study. Generalized PPI analysis was used to estimate the connectivity between the hippocampus and the whole brain during encoding. The difference in hippocampal-whole brain connectivity between encoding novel and repeated face-name pairs was used in multiple-regression analyses as an independent predictor for 10 behavioral, neuropsychological and clinical tests. The analysis revealed connectivity-behavior relationships that were distributed, dynamically overlapping, and task-specific within and across intrinsic networks; hippocampal-whole brain connectivity-behavior relationships were not isolated to single networks, but spanned multiple brain networks. Importantly, these spatially distributed performance patterns were unique for each measure. In general, out-of-network behavioral associations with encoding novel greater than repeated face-name pairs hippocampal-connectivity were observed in the default-mode network, while correlations with encoding repeated greater than novel face-name pairs hippocampal-connectivity were observed in the executive

  20. Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.

    Science.gov (United States)

    Kabasakal, Y; Elvins, D M; Ring, E F; McHugh, N J

    1996-01-01

    OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls. METHODS: A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls. RESULTS: Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%). CONCLUSIONS: There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries. Images PMID:8774177

  1. Designing Sustainable Public Transportation: Integrated Optimization of Bus Speed and Holding Time in a Connected Vehicle Environment

    Directory of Open Access Journals (Sweden)

    Wei Wu

    2016-11-01

    Full Text Available Developing public transportation and giving priority to buses is a feasible solution for improving the level of public transportation service, which facilitates congestion alleviation and prevention, and contributes to urban development and city sustainability. This paper presents a novel bus operation control strategy including both holding control and speed control to improve the level of service of transit systems within a connected vehicle environment. Most previous work focuses on optimization of signal timing to decrease the bus signal delay by assuming that holding control is not applied; the speed of buses is given as a constant input and the acceleration and deceleration processes of buses can be neglected. This paper explores the benefits of a bus operation control strategy to minimize the total cost, which includes bus signal delay, bus holding delay, bus travel delay, acceleration cost due to frequent stops and intense driving. A set of formulations are developed to explicitly capture the interaction between bus holding control and speed control. Experimental analysisand simulation tests have shown that the proposed integrated operational model outperforms the traditional control, speed control only, or holding control only strategies in terms of reducing the total cost of buses. The sensitivity analysis has further demonstrated the potential effectiveness of the proposed approach to be applied in a real-time bus operation control system under different levels of traffic demand, bus stop locations, and speed limits.

  2. Baumol's Cost Disease and the Sustainability of the Welfare State

    DEFF Research Database (Denmark)

    Andersen, Torben M.; Kreiner, Claus T.

    2017-01-01

    If productivity increases more slowly for services than for manufactured goods, then services suffer from Baumol's cost disease and tend to become relatively more costly over time. Since the welfare state in all countries is an important supplier of tax financed services, this translates into a f......If productivity increases more slowly for services than for manufactured goods, then services suffer from Baumol's cost disease and tend to become relatively more costly over time. Since the welfare state in all countries is an important supplier of tax financed services, this translates...

  3. FEATURES OF CLINICAL COURSE OF GASTROESOPHAGEAL REFLUX DISEASE IN NEWLY RECRUITED WITH CONNECTIVE TISSUE UNDIFFERENTIATED DYSPLASIA SYNDROME

    Directory of Open Access Journals (Sweden)

    E.I. Kashkina

    2008-12-01

    Full Text Available The presence of connective tissue undifferentiated dysplasia syndrome against a background of psychological stress at newly recruited can promote the risk of gastroesophageal reflux disease occurrence. To the utmost, correlation between the gastroesophageal reflux disease and such manifestations of connective tissue undifferentiated dysplasia syndrome as asthenic constitution, chest deformation, Gothic palate and hypermobility of joints was found

  4. Multimodal Imaging of Brain Connectivity Using the MIBCA Toolbox: Preliminary Application to Alzheimer's Disease

    Science.gov (United States)

    Ribeiro, André Santos; Lacerda, Luís Miguel; Silva, Nuno André da; Ferreira, Hugo Alexandre

    2015-06-01

    The Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox is a fully automated all-in-one connectivity analysis toolbox that offers both pre-processing, connectivity, and graph theory analysis of multimodal images such as anatomical, diffusion, and functional MRI, and PET. In this work, the MIBCA functionalities were used to study Alzheimer's Disease (AD) in a multimodal MR/PET approach. Materials and Methods: Data from 12 healthy controls, and 36 patients with EMCI, LMCI and AD (12 patients for each group) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu), including T1-weighted (T1-w), Diffusion Tensor Imaging (DTI) data, and 18F-AV-45 (florbetapir) dynamic PET data from 40-60 min post injection (4x5 min). Both MR and PET data were automatically pre-processed for all subjects using MIBCA. T1-w data was parcellated into cortical and subcortical regions-of-interest (ROIs), and the corresponding thicknesses and volumes were calculated. DTI data was used to compute structural connectivity matrices based on fibers connecting pairs of ROIs. Lastly, dynamic PET images were summed, and the relative Standard Uptake Values calculated for each ROI. Results: An overall higher uptake of 18F-AV-45, consistent with an increased deposition of beta-amyloid, was observed for the AD group. Additionally, patients showed significant cortical atrophy (thickness and volume) especially in the entorhinal cortex and temporal areas, and a significant increase in Mean Diffusivity (MD) in the hippocampus, amygdala and temporal areas. Furthermore, patients showed a reduction of fiber connectivity with the progression of the disease, especially for intra-hemispherical connections. Conclusion: This work shows the potential of the MIBCA toolbox for the study of AD, as findings were shown to be in agreement with the literature. Here, only structural changes and beta-amyloid accumulation were considered. Yet, MIBCA is further able to

  5. MEG connectivity analysis in patients with Alzheimer's disease using cross mutual information and spectral coherence.

    Science.gov (United States)

    Alonso, Joan Francesc; Poza, Jesús; Mañanas, Miguel Angel; Romero, Sergio; Fernández, Alberto; Hornero, Roberto

    2011-01-01

    Alzheimer's disease (AD) is an irreversible brain disorder which represents the most common form of dementia in western countries. An early and accurate diagnosis of AD would enable to develop new strategies for managing the disease; however, nowadays there is no single test that can accurately predict the development of AD. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD connectivity patterns. This study compares brain connectivity in terms of linear and nonlinear couplings by means of spectral coherence and cross mutual information function (CMIF), respectively. The variables defined from these functions provide statistically significant differences (p CMIF. The results suggest that AD is characterized by both decreases and increases of functional couplings in different frequency bands as well as by an increase in regularity, that is, more evident statistical deterministic relationships in AD patients' MEG connectivity. The significant differences obtained indicate that AD could disturb brain interactions causing abnormal brain connectivity and operation. Furthermore, the combination of coherence and CMIF features to perform a diagnostic test based on logistic regression improved the tests based on individual variables for its robustness.

  6. Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

    2018-02-07

    Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks

  7. Intrinsic brain connectivity predicts impulse control disorders in patients with Parkinson's disease.

    Science.gov (United States)

    Tessitore, Alessandro; De Micco, Rosa; Giordano, Alfonso; di Nardo, Federica; Caiazzo, Giuseppina; Siciliano, Mattia; De Stefano, Manuela; Russo, Antonio; Esposito, Fabrizio; Tedeschi, Gioacchino

    2017-12-01

    Impulse control disorders can be triggered by dopamine replacement therapies in patients with PD. Using resting-state functional MRI, we investigated the intrinsic brain network connectivity at baseline in a cohort of drug-naive PD patients who successively developed impulse control disorders over a 36-month follow-up period compared with patients who did not. Baseline 3-Tesla MRI images of 30 drug-naive PD patients and 20 matched healthy controls were analyzed. The impulse control disorders' presence and severity at follow-up were assessed by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting-state networks. We also compared internetwork connectivity between patients. Finally, a multivariate Cox regression model was used to investigate baseline predictors of impulse control disorder development. At baseline, decreased connectivity in the default-mode and right central executive networks and increased connectivity in the salience network were detected in PD patients with impulse control disorders at follow-up compared with those without. Increased default-mode/central executive internetwork connectivity was significantly associated with impulse control disorders development (P impulse control disorders while on dopaminergic treatment. We hypothesize that these divergent cognitive and limbic network connectivity changes could represent a potential biomarker and an additional risk factor for the emergence of impulse control disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  8. Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marion Ortner

    2016-09-01

    Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

  9. Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Youngbin Kwak

    2010-09-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

  10. Scleroderma renal crisis in a case of mixed connective tissue disease

    Directory of Open Access Journals (Sweden)

    Mukul Vij

    2014-01-01

    Full Text Available Mixed connective tissue disease (MCTD is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma and polymyositis. Scleroderma renal crisis (SRC is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

  11. Scleroderma renal crisis in a case of mixed connective tissue disease.

    Science.gov (United States)

    Vij, Mukul; Agrawal, Vinita; Jain, Manoj

    2014-07-01

    Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

  12. Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease

    OpenAIRE

    Kobeleva, Xenia; Firbank, Michael; Peraza, Luis; Gallagher, Peter; Thomas, Alan; Burn, David J.; O'Brien, John; Taylor, John-Paul

    2017-01-01

    Attention and executive dysfunction are features of Lewy body dementia (LBD) but their neuroanatomical basis is poorly understood. To investigate underlying dysfunctional attention-executive network (EXEC) interactions, we examined functional connectivity (FC) in 30 patients with LBD, 20 patients with Alzheimer's disease (AD), and 21 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Participants performed a modified Attention Network Test (ANT),...

  13. Changes of intranetwork and internetwork functional connectivity in Alzheimer’s disease and mild cognitive impairment

    Science.gov (United States)

    Zhu, Haoze; Zhou, Peng; Alcauter, Sarael; Chen, Yuanyuan; Cao, Hongbao; Tian, Miao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Zhao, Xin; He, Feng; Ni, Hongyan; Gao, Wei

    2016-08-01

    Objective. Alzheimer’s disease (AD) is a serious neurodegenerative disorder characterized by deficits of working memory, attention, language and many other cognitive functions. Although different stages of the disease are relatively well characterized by clinical criteria, stage-specific pathological changes in the brain remain relatively poorly understood, especially at the level of large-scale functional networks. In this study, we aimed to characterize the potential disruptions of large-scale functional brain networks based on a sample including amnestic mild cognition impairment (aMCI) and AD patients to help delineate the underlying stage-dependent AD pathology. Approach. We sought to identify the neural connectivity mechanisms of aMCI and AD through examination of both intranetwork and internetwork interactions among four of the brain’s key networks, namely dorsal attention network (DAN), default mode network (DMN), executive control network (ECN) and salience network (SAL). We analyzed functional connectivity based on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 Alzheimer’s disease patients, 20 aMCI patients and 35 elderly normal controls (NC). Main results. Intranetwork functional disruptions within the DAN and ECN were detected in both aMCI and AD patients. Disrupted intranetwork connectivity of DMN and anti-correlation between DAN and DMN were observed in AD patients. Moreover, aMCI-specific alterations in the internetwork functional connectivity of SAL were observed. Significance. Our results confirmed previous findings that AD pathology was related to dysconnectivity both within and between resting-state networks but revealed more spatial details. Moreover, the SAL network, reportedly flexibly coupling either with the DAN or DMN networks during different brain states, demonstrated interesting alterations specifically in the early stage of the disease.

  14. Connecting Gaucher and Parkinson Disease: Considerations for Clinical and Research Genetic Counseling Settings.

    Science.gov (United States)

    Cook, Lola; Schulze, Jeanine

    2017-12-01

    There are multiple autosomal recessive disorders in which carriers may be at risk for other diseases. This observation calls into question the previous understanding that carriers of autosomal recessive disorders escape clinical consequences. We also know that childhood genetic conditions may have adult disease counterparts (Zimran et al., The Israel Medical Association Journal: IMAJ, 16(11), 723-724, 2014). Individuals who have Gaucher disease and carriers of the disorder are at increased risk for a seemingly unrelated and complex neurological condition, Parkinson disease. Parkinson disease is, in part, caused by the same mutations in the GBA gene that lead to Gaucher disease, and the two conditions are thought to have shared pathophysiology. Briefly reviewed are how these two diseases historically became linked, where their paths cross, potential problems and considerations in disclosure of the link, and current guidelines and research in this area. Genetic counseling experience with a large Parkinson disease cohort is used as a starting point to question the state of clinical and nonclinical practice in disclosing this unusual connection We conclude that more research and discussion are needed to inform practice regarding the crossroads of Gaucher and Parkinson disease.

  15. Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases

    International Nuclear Information System (INIS)

    Burkhardt, W.C.; Jackson, J.F.; Songcharoen, S.; Meydrech, E.F.

    1980-01-01

    Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P=0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P<0.05). (author)

  16. Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Burkhardt, W C; Jackson, J F; Songcharoen, S; Meydrech, E F [Mississippi Univ., Jackson (USA). Medical Center

    1980-01-01

    Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P=0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P<0.05).

  17. Abnormal ventral tegmental area-anterior cingulate cortex connectivity in Parkinson's disease with depression.

    Science.gov (United States)

    Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong

    2018-07-16

    Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Connecting Gender, Race, Class, and Immigration Status to Disease Management at the Workplace

    Science.gov (United States)

    Rosemberg, Marie-Anne S.; Tsai, Jenny Hsin-Chun

    2016-01-01

    Objective Chronic diseases are the leading causes of death in the United States. Chronic disease management occurs within all aspects of an individual's life, including the workplace. Though the social constructs of gender, race, class, and immigration status within the workplace have been considered, their connection to disease management among workers has been less explicitly explored. Using a sample of immigrant hotel housekeepers, we explored the connections between these four social constructs and hypertension management. Methods This qualitative research study was guided by critical ethnography methodology. Twenty-seven hotel room cleaners and four housemen were recruited (N = 31) and invited to discuss their experiences with hypertension and hypertension management within the context of their work environments. Results Being a woman worker within the hotel industry was perceived to negatively influence participants’ experience with hypertension and hypertension management. In contrast, being a woman played a protective role outside the workplace. Being an immigrant played both a positive and a negative role in hypertension and its management. Being black and from a low socioeconomic class had only adverse influences on participants’ experience with hypertension and its management. Conclusion Being a woman, black, lower class, and an immigrant simultaneously contribute to immigrant hotel housekeepers’ health and their ability to effectively manage their hypertension. The connection between these four constructs (gender, race, class, and immigration status) and disease management must be considered during care provision. Hotel employers and policy stakeholders need to consider those constructs and how they impact workers’ well-being. More studies are needed to identify what mitigates the associations between the intersectionality of these constructs and immigrant workers’ health and disease management within their work environment. PMID:27695659

  19. Connecting Gender, Race, Class, and Immigration Status to Disease Management at the Workplace.

    Science.gov (United States)

    Rosemberg, Marie-Anne S; Tsai, Jenny Hsin-Chun

    2014-01-01

    Chronic diseases are the leading causes of death in the United States. Chronic disease management occurs within all aspects of an individual's life, including the workplace. Though the social constructs of gender, race, class, and immigration status within the workplace have been considered, their connection to disease management among workers has been less explicitly explored. Using a sample of immigrant hotel housekeepers, we explored the connections between these four social constructs and hypertension management. This qualitative research study was guided by critical ethnography methodology. Twenty-seven hotel room cleaners and four housemen were recruited ( N = 31) and invited to discuss their experiences with hypertension and hypertension management within the context of their work environments. Being a woman worker within the hotel industry was perceived to negatively influence participants' experience with hypertension and hypertension management. In contrast, being a woman played a protective role outside the workplace. Being an immigrant played both a positive and a negative role in hypertension and its management. Being black and from a low socioeconomic class had only adverse influences on participants' experience with hypertension and its management. Being a woman, black, lower class, and an immigrant simultaneously contribute to immigrant hotel housekeepers' health and their ability to effectively manage their hypertension. The connection between these four constructs (gender, race, class, and immigration status) and disease management must be considered during care provision. Hotel employers and policy stakeholders need to consider those constructs and how they impact workers' well-being. More studies are needed to identify what mitigates the associations between the intersectionality of these constructs and immigrant workers' health and disease management within their work environment.

  20. Altered Functional Connectivity of Insular Subregions in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Xingyun Liu

    2018-04-01

    Full Text Available Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer’s disease (AD. However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI data including 32 AD patients and 38 healthy controls (HCs. By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1 an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN; (2 a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN; (3 a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN. In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN, suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

  1. Impaired development of cortico-striatal synaptic connectivity in a cell culture model of Huntington's disease.

    Science.gov (United States)

    Buren, Caodu; Parsons, Matthew P; Smith-Dijak, Amy; Raymond, Lynn A

    2016-03-01

    Huntington's disease (HD) is a genetically inherited neurodegenerative disease caused by a mutation in the gene encoding the huntingtin protein. This mutation results in progressive cell death that is particularly striking in the striatum. Recent evidence indicates that early HD is initially a disease of the synapse, in which subtle alterations in synaptic neurotransmission, particularly at the cortico-striatal (C-S) synapse, can be detected well in advance of cell death. Here, we used a cell culture model in which striatal neurons are co-cultured with cortical neurons, and monitored the development of C-S connectivity up to 21days in vitro (DIV) in cells cultured from either the YAC128 mouse model of HD or the background strain, FVB/N (wild-type; WT) mice. Our data demonstrate that while C-S connectivity in WT co-cultures develops rapidly and continuously from DIV 7 to 21, YAC128 C-S connectivity shows no significant growth from DIV 14 onward. Morphological and electrophysiological data suggest that a combination of pre- and postsynaptic mechanisms contribute to this effect, including a reduction in both the postsynaptic dendritic arborization and the size and replenishment rate of the presynaptic readily releasable pool of excitatory vesicles. Moreover, a chimeric culture strategy confirmed that the most robust impairment in C-S connectivity was only observed when mutant huntingtin was expressed both pre- and postsynaptically. In all, our data demonstrate a progressive HD synaptic phenotype in this co-culture system that may be exploited as a platform for identifying promising therapeutic strategies to prevent early HD-associated synaptopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study.

    Science.gov (United States)

    Quattrocchi, Carlo Cosimo; de Pandis, Maria Francesca; Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

    2015-01-01

    The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Clinical Trials.gov NCT01815281.

  3. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

    Science.gov (United States)

    Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

    2015-01-01

    Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

  4. Morphological, clinical and radiological aspects in diagnostics of bronchopulmonary diseases and their complications in children with dysplasia of connective tissue

    Directory of Open Access Journals (Sweden)

    Palchik S.M.

    2016-06-01

    Full Text Available The article provides an overview of the literature devoted to study of radiological, morphological and clinical aspects of diagnostics of respiratory diseases and their complications in children with dysplasia of connective tissue nowadays. We made an analysis of the role of connective tissue disorders in pathogenesis of bronchopulmonary diseases. Theoretically was substantiated the importance of radiological methods in early diagnostics of this disease in children.

  5. Sustained remission of Cushing's disease with mitotane and pituitary irradiation

    International Nuclear Information System (INIS)

    Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.; McKenzie, A.; Victoria, R.; Therrien, B.A.

    1980-01-01

    Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest

  6. Linked Registries: Connecting Rare Diseases Patient Registries through a Semantic Web Layer.

    Science.gov (United States)

    Sernadela, Pedro; González-Castro, Lorena; Carta, Claudio; van der Horst, Eelke; Lopes, Pedro; Kaliyaperumal, Rajaram; Thompson, Mark; Thompson, Rachel; Queralt-Rosinach, Núria; Lopez, Estrella; Wood, Libby; Robertson, Agata; Lamanna, Claudia; Gilling, Mette; Orth, Michael; Merino-Martinez, Roxana; Posada, Manuel; Taruscio, Domenica; Lochmüller, Hanns; Robinson, Peter; Roos, Marco; Oliveira, José Luís

    2017-01-01

    Patient registries are an essential tool to increase current knowledge regarding rare diseases. Understanding these data is a vital step to improve patient treatments and to create the most adequate tools for personalized medicine. However, the growing number of disease-specific patient registries brings also new technical challenges. Usually, these systems are developed as closed data silos, with independent formats and models, lacking comprehensive mechanisms to enable data sharing. To tackle these challenges, we developed a Semantic Web based solution that allows connecting distributed and heterogeneous registries, enabling the federation of knowledge between multiple independent environments. This semantic layer creates a holistic view over a set of anonymised registries, supporting semantic data representation, integrated access, and querying. The implemented system gave us the opportunity to answer challenging questions across disperse rare disease patient registries. The interconnection between those registries using Semantic Web technologies benefits our final solution in a way that we can query single or multiple instances according to our needs. The outcome is a unique semantic layer, connecting miscellaneous registries and delivering a lightweight holistic perspective over the wealth of knowledge stemming from linked rare disease patient registries.

  7. Brain PET substrate of impulse control disorders in Parkinson's disease: A metabolic connectivity study.

    Science.gov (United States)

    Verger, Antoine; Klesse, Elsa; Chawki, Mohammad B; Witjas, Tatiana; Azulay, Jean-Philippe; Eusebio, Alexandre; Guedj, Eric

    2018-04-10

    Impulse control disorders (ICDs) have received increased attention in Parkinson's disease (PD) because of potentially dramatic consequences. Their physiopathology, however, remains incompletely understood. An overstimulation of the mesocorticolimbic system has been reported, while a larger network has recently been suggested. The aim of this study is to specifically describe the metabolic PET substrate and related connectivity changes in PD patients with ICDs. Eighteen PD patients with ICDs and 18 PD patients without ICDs were evaluated using cerebral 18F-fluorodeoxyglucose positron emission tomography. SPM-T maps comparisons were performed between groups and metabolic connectivity was evaluated by interregional correlation analysis (IRCA; p  130) and by graph theory (p < .05). PD patients with ICDs had relative increased metabolism in the right middle and inferior temporal gyri compared to those without ICDs. The connectivity of this area was increased mostly with the mesocorticolimbic system, positively with the orbitofrontal region, and negatively with both the right parahippocampus and the left caudate (IRCA). Moreover, the betweenness centrality of this area with the mesocorticolimbic system was lost in patients with ICDs (graph analysis). ICDs are associated in PD with the dysfunction of a network exceeding the mesocorticolimbic system, and especially the caudate, the parahippocampus, and the orbitofrontal cortex, remotely including the right middle and inferior temporal gyri. This latest area loses its central place with the mesocorticolimbic system through a connectivity dysregulation. © 2018 Wiley Periodicals, Inc.

  8. FLOW-BASED NETWORK MEASURES OF BRAIN CONNECTIVITY IN ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Prasad, Gautam; Joshi, Shantanu H; Nir, Talia M; Toga, Arthur W; Thompson, Paul M

    2013-01-01

    We present a new flow-based method for modeling brain structural connectivity. The method uses a modified maximum-flow algorithm that is robust to noise in the diffusion data and guided by biologically viable pathways and structure of the brain. A flow network is first created using a lattice graph by connecting all lattice points (voxel centers) to all their neighbors by edges. Edge weights are based on the orientation distribution function (ODF) value in the direction of the edge. The maximum-flow is computed based on this flow graph using the flow or the capacity between each region of interest (ROI) pair by following the connected tractography fibers projected onto the flow graph edges. Network measures such as global efficiency, transitivity, path length, mean degree, density, modularity, small world, and assortativity are computed from the flow connectivity matrix. We applied our method to diffusion-weighted images (DWIs) from 110 subjects (28 normal elderly, 56 with early and 11 with late mild cognitive impairment, and 15 with AD) and segmented co-registered anatomical MRIs into cortical regions. Experimental results showed better performance compared to the standard fiber-counting methods when distinguishing Alzheimer's disease from normal aging.

  9. Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

    Science.gov (United States)

    Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

    2014-11-01

    Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

  10. Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

    Science.gov (United States)

    Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

    2018-04-01

    Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

    Directory of Open Access Journals (Sweden)

    Renata Miossi

    2013-01-01

    Full Text Available OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1 virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0 and geometric mean titer (p = 0.83 between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7, seroconversion (68.1% vs. 65.2%, (p = 1.00 and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40 were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20, skin ulcers (p = 0.48, lupus-like cutaneous disease (p = 0.74, secondary Sjogren syndrome (p = 0.78, scleroderma-pattern in the nailfold capillaroscopy (p = 1.0, lymphopenia #1000/mm³ on two or more occasions (p = 1.0, hypergammaglobulinemia $1.6 g/d (p = 0.60, pulmonary hypertension (p = 1.0 and pulmonary fibrosis (p = 0.80 revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94, aldolase (p = 0.73, creatine

  12. Pulmonary MR imaging with ultra-short TEs: Utility for disease severity assessment of connective tissue disease patients

    International Nuclear Information System (INIS)

    Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; Cauteren, Marc van; Sugimura, Kazuro

    2013-01-01

    Purpose: To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2* maps were generated from each MR data set, and mean T2* values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2* values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2* values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Results: Mean T2* values for normal and CTD subjects were significantly different (p = 0.0019) and showed significant correlations with %VC, %DL CO , serum KL-6 and CT-based disease severity of CTD patients (p < 0.05). Conclusion: Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD

  13. Pulmonary MR imaging with ultra-short TEs: Utility for disease severity assessment of connective tissue disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Takenaka, Daisuke [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Hyogo Cancer Center, Akashi, Hyogo (Japan); Takahashi, Masaya [Advanced Imaging Research Center, Department of Radiology, University of Texas Southwestern Medical Center, Houston, TX (United States); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Obara, Makoto; Cauteren, Marc van [Philips Electronics Japan, Tokyo (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

    2013-08-15

    Purpose: To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2* maps were generated from each MR data set, and mean T2* values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2* values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2* values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Results: Mean T2* values for normal and CTD subjects were significantly different (p = 0.0019) and showed significant correlations with %VC, %DL{sub CO}, serum KL-6 and CT-based disease severity of CTD patients (p < 0.05). Conclusion: Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD.

  14. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon.

    Science.gov (United States)

    Wu, Po-Chang; Huang, Min-Nung; Kuo, Yu-Min; Hsieh, Song-Chou; Yu, Chia-Li

    2013-08-01

    Nailfold capillaroscopy is a useful tool to distinguish primary from secondary Raynaud's phenomenon (RP) by examining the morphology of nailfold capillaries but its role in disease diagnosis is not clearly established. The purpose of this study was to evaluate the roles of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases (CTDs) with RP. The data between the year 2005 and 2009 were retrieved from the nailfold capillaroscopic database of National Taiwan University Hospital (NTUH). Only the data from the patients with RP were analyzed. The criteria for interpretation of capillaroscopic findings were predefined. The final diagnoses of the patients were based on the American College of Rheumatology classification criteria for individual diseases, independent of nailfold capillaroscopic findings. The sensitivity and the specificity of each capillaroscopic pattern to the diseases were determined. The data from a total of 67 patients were qualified for the current study. We found the sensitivity and specificity of scleroderma pattern for systemic sclerosis (SSc) were 89.47% and 80%, and the specificity of the early, active, and late scleroderma patterns for SSc reached 87.5%, 97.5%, and 95%, respectively. The sensitivity/specificity of systemic lupus erythematosus (SLE) pattern for SLE and polymyositis/dermatomyositis (PM/DM) pattern for PM/DM were 33.33%/95.45% and 60%/96.3%, respectively. The sensitivity/specificity of mixed connective tissue disease (MCTD) pattern for MCTD were 20%/100%. The nailfold capillaroscopic (NC) patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity. Copyright © 2012. Published by Elsevier B.V.

  15. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    International Nuclear Information System (INIS)

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-01-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results

  16. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-04-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.

  17. A searchable cross-platform gene expression database reveals connections between drug treatments and disease

    Directory of Open Access Journals (Sweden)

    Williams Gareth

    2012-01-01

    Full Text Available Abstract Background Transcriptional data covering multiple platforms and species is collected and processed into a searchable platform independent expression database (SPIED. SPIED consists of over 100,000 expression fold profiles defined independently of control/treatment assignment and mapped to non-redundant gene lists. The database is thus searchable with query profiles defined over genes alone. The motivation behind SPIED is that transcriptional profiles can be quantitatively compared and ranked and thus serve as effective surrogates for comparing the underlying biological states across multiple experiments. Results Drug perturbation, cancer and neurodegenerative disease derived transcriptional profiles are shown to be effective descriptors of the underlying biology as they return related drugs and pathologies from SPIED. In the case of Alzheimer's disease there is high transcriptional overlap with other neurodegenerative conditions and rodent models of neurodegeneration and nerve injury. Combining the query signature with correlating profiles allows for the definition of a tight neurodegeneration signature that successfully highlights many neuroprotective drugs in the Broad connectivity map. Conclusions Quantitative querying of expression data from across the totality of deposited experiments is an effective way of discovering connections between different biological systems and in particular that between drug action and biological disease state. Examples in cancer and neurodegenerative conditions validate the utility of SPIED.

  18. Sustainability of the integrated chronic disease management model at primary care clinics in South Africa

    Science.gov (United States)

    Asmall, Shaidah

    2016-01-01

    Background An integrated chronic disease management (ICDM) model consisting of four components (facility reorganisation, clinical supportive management, assisted self-supportive management and strengthening of support systems and structures outside the facility) has been implemented across 42 primary health care clinics in South Africa with a view to improve the operational efficiency and patient clinical outcomes. Aim The aim of this study was to assess the sustainability of the facility reorganisation and clinical support components 18 months after the initiation. Setting The study was conducted at 37 of the initiating clinics across three districts in three provinces of South Africa. Methods The National Health Service (NHS) Institute for Innovation and Improvement Sustainability Model (SM) self-assessment tool was used to assess sustainability. Results Bushbuckridge had the highest mean sustainability score of 71.79 (95% CI: 63.70–79.89) followed by West Rand Health District (70.25 (95% CI: 63.96–76.53)) and Dr Kenneth Kaunda District (66.50 (95% CI: 55.17–77.83)). Four facilities (11%) had an overall sustainability score of less than 55. Conclusion The less than optimal involvement of clinical leadership (doctors), negative staff behaviour towards the ICDM, adaptability or flexibility of the model to adapt to external factors and infrastructure limitation have the potential to negatively affect the sustainability and scale-up of the model. PMID:28155314

  19. Integration of temporal and spatial properties of dynamic connectivity networks for automatic diagnosis of brain disease.

    Science.gov (United States)

    Jie, Biao; Liu, Mingxia; Shen, Dinggang

    2018-07-01

    Functional connectivity networks (FCNs) using resting-state functional magnetic resonance imaging (rs-fMRI) have been applied to the analysis and diagnosis of brain disease, such as Alzheimer's disease (AD) and its prodrome, i.e., mild cognitive impairment (MCI). Different from conventional studies focusing on static descriptions on functional connectivity (FC) between brain regions in rs-fMRI, recent studies have resorted to dynamic connectivity networks (DCNs) to characterize the dynamic changes of FC, since dynamic changes of FC may indicate changes in macroscopic neural activity patterns in cognitive and behavioral aspects. However, most of the existing studies only investigate the temporal properties of DCNs (e.g., temporal variability of FC between specific brain regions), ignoring the important spatial properties of the network (e.g., spatial variability of FC associated with a specific brain region). Also, emerging evidence on FCNs has suggested that, besides temporal variability, there is significant spatial variability of activity foci over time. Hence, integrating both temporal and spatial properties of DCNs can intuitively promote the performance of connectivity-network-based learning methods. In this paper, we first define a new measure to characterize the spatial variability of DCNs, and then propose a novel learning framework to integrate both temporal and spatial variabilities of DCNs for automatic brain disease diagnosis. Specifically, we first construct DCNs from the rs-fMRI time series at successive non-overlapping time windows. Then, we characterize the spatial variability of a specific brain region by computing the correlation of functional sequences (i.e., the changing profile of FC between a pair of brain regions within all time windows) associated with this region. Furthermore, we extract both temporal variabilities and spatial variabilities from DCNs as features, and integrate them for classification by using manifold regularized multi

  20. Small cell lung cancer presenting as dermatomyositis: mistaken for single connective tissue disease.

    Science.gov (United States)

    Chao, Guanqun; Fang, Lizheng; Lu, Chongrong; Chen, Zhouwen

    2012-06-01

    Dermatomyositis (DM) is well-known to be associated with several types of malignancy. This case emphasizes the importance of a thorough examination for an underlying cancer, in patients with the symptoms of dermatomyositis. We report the case of a 62-year-old Chinese man who presented with a two-month history of edema of face and neck, together with erythema of the eyelids diagnosed of small cell lung cancer. Initially, it was thought to be single connective tissue disease such as DM. This study highlights the importance of a thorough physical examination when visiting a patient.

  1. Trichoderma spp.: a biocontrol agent for sustainable management of plant diseases

    International Nuclear Information System (INIS)

    Naher, L.; Ismail, A.

    2014-01-01

    Trichoderma spp. are mainly asexual fungi that are present in all types of agricultural soils and also in decaying wood. The antagonistic activity of Trichoderma species showed that it is parasitic on many soil-borne and foliage pathogens. The fungus is also a decomposer of cellulosic waste materials. Recent discoveries show that the fungi not only act as biocontrol agents, but also stimulate plant resistance, and plant growth and development resulting in an increase in crop production. The biocontrol activity involving mycoparasitism, antibiotics and competition for nutrients, also induces defence responses or systemic resistance responses in plants. These responses are an important part of Trichoderma in biocontrol program. Currently, Trichoderma spp., is being used to control plant diseases in sustainable diseases management systems. This paper reviews the published information on Trichoderma spp., and its biocontrol activity in sustainable disease management programs. (author)

  2. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

    Directory of Open Access Journals (Sweden)

    Daniel Antunes Silva Pereira

    2015-04-01

    Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

  3. Connecting the dots: could microbial translocation explain commonly reported symptoms in HIV disease?

    Science.gov (United States)

    Wilson, Natalie L; Vance, David E; Moneyham, Linda D; Raper, James L; Mugavero, Michael J; Heath, Sonya L; Kempf, Mirjam-Colette

    2014-01-01

    Microbial translocation within the context of HIV disease has been described as one of the contributing causes of inflammation and disease progression in HIV infection. HIV-associated symptoms have been related to inflammatory markers and sCD14, a surrogate marker for microbial translocation, suggesting a plausible link between microbial translocation and symptom burden in HIV disease. Similar pathophysiological responses and symptoms have been reported in inflammatory bowel disease. We provide a comprehensive review of microbial translocation, HIV-associated symptoms, and symptoms connected with inflammation. We identify studies showing a relationship among inflammatory markers, sCD14, and symptoms reported in HIV disease. A conceptual framework and rationale to investigate the link between microbial translocation and symptoms is presented. The impact of inflammation on symptoms supports recommendations to reduce inflammation as part of HIV symptom management. Research in reducing microbial translocation-induced inflammation is limited, but needed, to further promote positive health outcomes among HIV-infected patients. Published by Elsevier Inc.

  4. Connected health and integrated care: Toward new models for chronic disease management.

    Science.gov (United States)

    Chouvarda, Ioanna G; Goulis, Dimitrios G; Lambrinoudaki, Irene; Maglaveras, Nicos

    2015-09-01

    The increasingly aging population in Europe and worldwide brings up the need for the restructuring of healthcare. Technological advancements in electronic health can be a driving force for new health management models, especially in chronic care. In a patient-centered e-health management model, communication and coordination between patient, healthcare professionals in primary care and hospitals can be facilitated, and medical decisions can be made timely and easily communicated. Bringing the right information to the right person at the right time is what connected health aims at, and this may set the basis for the investigation and deployment of the integrated care models. In this framework, an overview of the main technological axes and challenges around connected health technologies in chronic disease management are presented and discussed. A central concept is personal health system for the patient/citizen and three main application areas are identified. The connected health ecosystem is making progress, already shows benefits in (a) new biosensors, (b) data management, (c) data analytics, integration and feedback. Examples are illustrated in each case, while open issues and challenges for further research and development are pinpointed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Exploratory graphical models of functional and structural connectivity patterns for Alzheimer's Disease diagnosis

    Directory of Open Access Journals (Sweden)

    Andres eOrtiz

    2015-11-01

    Full Text Available Alzheimer’s Disease (AD is the most common neurodegenerative disease in elderly people. Itsdevelopment has been shown to be closely related to changes in the brain connectivity networkand in the brain activation patterns along with structural changes caused by the neurodegenerativeprocess.Methods to infer dependence between brain regions are usually derived from the analysis ofcovariance between activation levels in the different areas. However, these covariance-basedmethods are not able to estimate conditional independence between variables to factor out theinfluence of other regions. Conversely, models based on the inverse covariance, or precisionmatrix, such as Sparse Gaussian Graphical Models allow revealing conditional independencebetween regions by estimating the covariance between two variables given the rest as constant.This paper uses Sparse Inverse Covariance Estimation (SICE methods to learn undirectedgraphs in order to derive functional and structural connectivity patterns from Fludeoxyglucose(18F-FDG Position Emission Tomography (PET data and segmented Magnetic Resonanceimages (MRI, drawn from the ADNI database, for Control, MCI (Mild Cognitive ImpairmentSubjects and AD subjects. Sparse computation fits perfectly here as brain regions usually onlyinteract with a few other areas.The models clearly show different metabolic covariation patters between subject groups, revealingthe loss of strong connections in AD and MCI subjects when compared to Controls. Similarly,the variance between GM (Grey Matter densities of different regions reveals different structuralcovariation patterns between the different groups. Thus, the different connectivity patterns forcontrols and AD are used in this paper to select regions of interest in PET and GM images withdiscriminative power for early AD diagnosis. Finally, functional an structural models are combinedto leverage the classification accuracy.The results obtained in this work show the usefulness

  6. The long noncoding RNA Tug1 connects metabolic changes with kidney disease in podocytes.

    Science.gov (United States)

    Li, Szu Yuan; Susztak, Katalin

    2016-11-01

    An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice. Together, these results highlight an important connection between lncRNA-mediated metabolic alterations in podocytes and kidney disease development.

  7. Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems

    Science.gov (United States)

    Dusi, Veronica; Ghidoni, Alice; Ravera, Alice; De Ferrari, Gaetano M.; Calvillo, Laura

    2016-01-01

    Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a “working-network” in deep linkage with the autonomic nervous system. In this paper we will describe the single chemokines more involved in heart diseases; then we will present a comprehensive perspective of them as a complex network connecting the cardiovascular system to both the immune and the autonomic nervous systems. Finally, some recent evidences indicating chemokines as a possible new tool to predict cardiovascular risk will be described. PMID:27242392

  8. Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Deborah L. Harrington

    2017-06-01

    Full Text Available Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI are common in Parkinson’s disease (PD, but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF and regional homogeneity (ReHo, a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex, sensorimotor cortex (primary motor, pre/post-central gyrus, basal ganglia (putamen, caudate, and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a

  9. Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease.

    Science.gov (United States)

    Rosenberg-Katz, Keren; Maidan, Inbal; Jacob, Yael; Giladi, Nir; Mirelman, Anat; Hausdorff, Jeffrey M

    2016-09-01

    Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI. Specifically, we focused on changes between the groups in task-related functional connectivity using psycho-physiological interaction (PPI) analysis. The anterior cingulate cortex (ACC), which is a brain node previously associated with the Stroop paradigm, was selected as the seed region for this analysis. Patients with PD, as compared to healthy controls, had reduced task-related functional connectivity between the ACC and parietal regions including the precuneus and inferior parietal lobe. This was seen only in the incongruent Stroop condition. A higher level of connectivity between the ACC and precuneus was correlated with a lower error rate in the conflicting, incongruent Stroop condition in the healthy controls, but not in the patients with PD. Furthermore, the patients also had reduced functional connectivity between the ACC and the superior frontal gyrus which was present in both the incongruent and congruent task condition. The present findings shed light on brain mechanisms that are apparently associated with specific cognitive difficulties in patients with PD. Among patients with PD, impaired conflict monitoring processing within the ACC-based fronto-parietal network may contribute to difficulties under increased executive demands. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. HFE gene variants, iron, and lipids: a novel connection in Alzheimer’s disease

    Science.gov (United States)

    Ali-Rahmani, Fatima; Schengrund, Cara-Lynne; Connor, James R.

    2014-01-01

    Iron accumulation and associated oxidative stress in the brain have been consistently found in several neurodegenerative diseases. Multiple genetic studies have been undertaken to try to identify a cause of neurodegenerative diseases but direct connections have been rare. In the iron field, variants in the HFE gene that give rise to a protein involved in cellular iron regulation, are associated with iron accumulation in multiple organs including the brain. There is also substantial epidemiological, genetic, and molecular evidence of disruption of cholesterol homeostasis in several neurodegenerative diseases, in particular Alzheimer’s disease (AD). Despite the efforts that have been made to identify factors that can trigger the pathological events associated with neurodegenerative diseases they remain mostly unknown. Because molecular phenotypes such as oxidative stress, synaptic failure, neuronal loss, and cognitive decline, characteristics associated with AD, have been shown to result from disruption of a number of pathways, one can easily argue that the phenotype seen may not arise from a linear sequence of events. Therefore, a multi-targeted approach is needed to understand a complex disorder like AD. This can be achieved only when knowledge about interactions between the different pathways and the potential influence of environmental factors on them becomes available. Toward this end, this review discusses what is known about the roles and interactions of iron and cholesterol in neurodegenerative diseases. It highlights the effects of gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and how they may contribute to understanding the etiology of complex neurodegenerative diseases. PMID:25071582

  11. HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.

    Science.gov (United States)

    Ali-Rahmani, Fatima; Schengrund, Cara-Lynne; Connor, James R

    2014-01-01

    Iron accumulation and associated oxidative stress in the brain have been consistently found in several neurodegenerative diseases. Multiple genetic studies have been undertaken to try to identify a cause of neurodegenerative diseases but direct connections have been rare. In the iron field, variants in the HFE gene that give rise to a protein involved in cellular iron regulation, are associated with iron accumulation in multiple organs including the brain. There is also substantial epidemiological, genetic, and molecular evidence of disruption of cholesterol homeostasis in several neurodegenerative diseases, in particular Alzheimer's disease (AD). Despite the efforts that have been made to identify factors that can trigger the pathological events associated with neurodegenerative diseases they remain mostly unknown. Because molecular phenotypes such as oxidative stress, synaptic failure, neuronal loss, and cognitive decline, characteristics associated with AD, have been shown to result from disruption of a number of pathways, one can easily argue that the phenotype seen may not arise from a linear sequence of events. Therefore, a multi-targeted approach is needed to understand a complex disorder like AD. This can be achieved only when knowledge about interactions between the different pathways and the potential influence of environmental factors on them becomes available. Toward this end, this review discusses what is known about the roles and interactions of iron and cholesterol in neurodegenerative diseases. It highlights the effects of gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and how they may contribute to understanding the etiology of complex neurodegenerative diseases.

  12. Resting-State Functional Connectivity Predicts Cognitive Impairment Related to Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Qi Lin

    2018-04-01

    Full Text Available Resting-state functional connectivity (rs-FC is a promising neuromarker for cognitive decline in aging population, based on its ability to reveal functional differences associated with cognitive impairment across individuals, and because rs-fMRI may be less taxing for participants than task-based fMRI or neuropsychological tests. Here, we employ an approach that uses rs-FC to predict the Alzheimer's Disease Assessment Scale (11 items; ADAS11 scores, which measure overall cognitive functioning, in novel individuals. We applied this technique, connectome-based predictive modeling, to a heterogeneous sample of 59 subjects from the Alzheimer's Disease Neuroimaging Initiative, including normal aging, mild cognitive impairment, and AD subjects. First, we built linear regression models to predict ADAS11 scores from rs-FC measured with Pearson's r correlation. The positive network model tested with leave-one-out cross validation (LOOCV significantly predicted individual differences in cognitive function from rs-FC. In a second analysis, we considered other functional connectivity features, accordance and discordance, which disentangle the correlation and anticorrelation components of activity timecourses between brain areas. Using partial least square regression and LOOCV, we again built models to successfully predict ADAS11 scores in novel individuals. Our study provides promising evidence that rs-FC can reveal cognitive impairment in an aging population, although more development is needed for clinical application.

  13. Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

    Science.gov (United States)

    Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

    2015-08-06

    Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

  14. Estimating the incidence of connective tissue diseases and vasculitides in a defined population in Northern Savo area in 2010.

    Science.gov (United States)

    Elfving, P; Marjoniemi, O; Niinisalo, H; Kononoff, A; Arstila, L; Savolainen, E; Rutanen, J; Kaipiainen-Seppänen, O

    2016-07-01

    Objective of the study was to evaluate the annual incidence and distribution of autoimmune connective tissue diseases and vasculitides during 2010. All units practicing rheumatology in the Northern Savo area, Finland, participated in the study by collecting data on newly diagnosed adult patients with autoimmune connective tissue disease or vasculitis over 1-year period. Seventy-two cases with autoimmune connective tissue disease were identified. The annual incidence rates were as follows: systemic lupus erythematosus 3.4/100,000 (95 % CI 1.4-7.0), idiopathic inflammatory myopathies 1.9 (0.5-5.0), systemic sclerosis 4.4 (2.0-8.3), mixed connective tissue disease 1.0 (0.1-3.5), Sjögren's syndrome 10.7 (6.7-16.1) and undifferentiated connective tissue disease 13.6 (9.0-19.6). The annual incidence rates among vasculitis category were as follows: antineutrophil cytoplasmic antibody-associated vasculitis 1.5/100,000 (95 % CI 0.3-4.3), central nervous system vasculitis 0.5 (0-2.7) and Henoch-Schönlein purpura 1.5 (0.3-4.3). The annual incidence of giant cell arteritis in the age group of 50 years or older was 7.5/100,000 (95 % CI 3.2-14.8). The longest delay from symptom onset to diagnosis occurred in systemic sclerosis. The incidences of autoimmune connective tissue diseases and vasculitides were comparable with those in published literature. The present study showed female predominance in all connective tissue diseases, excluding idiopathic inflammatory muscle diseases and mean age at onset of disease around 50 years of age. Despite improved diagnostic tools, diagnostic delay is long especially among patients with systemic sclerosis.

  15. Parkinson's disease and pesticides: A meta-analysis of disease connection and genetic alterations.

    Science.gov (United States)

    Ahmed, Hussien; Abushouk, Abdelrahman Ibrahim; Gabr, Mohamed; Negida, Ahmed; Abdel-Daim, Mohamed M

    2017-06-01

    Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant heterogeneity among included studies. Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no statistically significant association between exposure to pesticides and alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI [0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91, 2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta-analysis provides evidence that pesticide exposure is significantly associated with the risk of PD and alterations in genes involved in PD pathogenesis. However, the underlying mechanism of this association and the effect of the duration of exposure or the type of pesticides should be addressed by future research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management

    Directory of Open Access Journals (Sweden)

    Guy Blomme

    2017-07-01

    Full Text Available Bacterial diseases of bananas and enset have not received, until recently, an equal amount of attention compared to other major threats to banana production such as the fungal diseases black leaf streak (Mycosphaerella fijiensis and Fusarium wilt (Fusarium oxysporum f. sp. cubense. However, bacteria cause significant impacts on bananas globally and management practices are not always well known or adopted by farmers. Bacterial diseases in bananas and enset can be divided into three groups: (1 Ralstonia-associated diseases (Moko/Bugtok disease caused by Ralstonia solanacearum and banana blood disease caused by R. syzygii subsp. celebesensis; (2 Xanthomonas wilt of banana and enset, caused by Xanthomonas campestris pv. musacearum and (3 Erwinia-associated diseases (bacterial head rot or tip-over disease Erwinia carotovora ssp. carotovora and E. chrysanthemi, bacterial rhizome and pseudostem wet rot (Dickeya paradisiaca formerly E. chrysanthemi pv. paradisiaca. Other bacterial diseases of less widespread importance include: bacterial wilt of abaca, Javanese vascular wilt and bacterial fingertip rot (probably caused by Ralstonia spp., unconfirmed. This review describes global distribution, symptoms, pathogenic diversity, epidemiology and the state of the art for sustainable disease management of the major bacterial wilts currently affecting banana and enset.

  17. Indissoluble Connection of Russian MC and A System Sustainability with that of the Russian Methodological and Training Center

    International Nuclear Information System (INIS)

    Ryazanov, Boris G.; Goryunov, Victor; Pshakin, Gennady M.; Shapsha, V.; Crawford, Cary E.; Dickman, Deborah A.

    2005-01-01

    During the past 10 years of collaboration under the U.S.-Russian Materials Protection, Control and Accounting (MPC and A) Program great efforts were made to transform and upgrade the Russian Federal Nuclear Materials Control and Accounting (MC and A) System. The efforts were focused not only on MC and A systems for nuclear facilities but also on creating and developing the system infrastructure, including legislation, state inspection and agency monitoring, training of operators and inspectors, instrument and methodological support, and the Federal Information System (FIS). At present the most important and urgent goal is to provide sustainability of MC and A systems at the existing level or at the level that will be achieved in 2007-2008. Since the very beginning of the program, the Russian Methodological and Training Center (RMTC) activities have been focused on intensive training of the personnel as well as the methodological support necessary for transformation and development of the entire system and its elements located at nuclear facilities. Sustainability of the federal MC and A system is impossible without advanced training of personnel and methodological support for upgrading of system elements at nuclear facilities. That is why the RMTC sustainability is one of the key conditions required for the system sustainability as a whole. The paper presents the results of analysis of the conditions for the Russian MC and A system sustainable development in conjunction with the RMTC sustainability

  18. Altered effective connectivity contributes to micrographia in patients with Parkinson's disease and freezing of gait.

    Science.gov (United States)

    Nackaerts, Evelien; Nieuwboer, Alice; Broeder, Sanne; Swinnen, Stephan; Vandenberghe, Wim; Heremans, Elke

    2018-02-01

    Recently, it was shown that patients with Parkinson's disease (PD) and freezing of gait (FOG) can also experience freezing episodes during handwriting and present writing problems outside these episodes. So far, the neural networks underlying increased handwriting problems in subjects with FOG are unclear. This study used dynamic causal modeling of fMRI data to investigate neural network dynamics underlying freezing-related handwriting problems and how these networks changed in response to visual cues. Twenty-seven non-freezers and ten freezers performed a pre-writing task with and without visual cues in the scanner with their right hand. The results showed that freezers and non-freezers were able to recruit networks involved in cued and uncued writing in a similar fashion. Whole group analysis also revealed a trend towards altered visuomotor integration in patients with FOG. Next, we controlled for differences in disease severity between both patient groups using a sensitivity analysis. For this, a subgroup of ten non-freezers matched for disease severity was selected by an independent researcher. This analysis further exposed significantly weaker coupling in mostly left hemispheric visuo-parietal, parietal - supplementary motor area, parietal - premotor, and premotor-M1 pathways in freezers compared to non-freezers, irrespective of cues. Correlation analyses revealed that these impairments in connectivity were related to writing amplitude and quality. Taken together, these findings show that freezers have reduced involvement of the supplementary motor area in the motor network, which explains the impaired writing amplitude regulation in this group. In addition, weaker supportive premotor connectivity may have contributed to micrographia in freezers, a pattern that was independent of cueing.

  19. Does a Board Chairman’s Political Connection Affect Green Investment?—From a Sustainable Perspective

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2018-02-01

    Full Text Available Using a sample consisting of China’s listed manufacturing companies which issue A-shares on the Shenzhen and Shanghai stock exchanges from 2008–2014, this study empirically tests the relationship between board chairman’s political connections and the amount of energy conservation and emission reduction investment. The results show that the existence of politically-connected board chairmen positively affects green investment. In addition, marketization degrees negatively moderate the relationship between political connection and green investment, which supports an institutional logic perspective. The amount of redundant resources also has the same moderating effect, which is consistent with the resource exchange perspective.

  20. Sustained Attention Training Reduces Spatial Bias in Parkinson's Disease: A Pilot Case Series

    OpenAIRE

    DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas; Esterman, Michael; Pistorino, Laura; Cronin-Golomb, Alice

    2015-01-01

    Individuals with Parkinson’s disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD/2 RPD) performed a v...

  1. Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.

    Science.gov (United States)

    Weiler, Marina; de Campos, Brunno Machado; Teixeira, Camila Vieira de Ligo; Casseb, Raphael Fernandes; Carletti-Cassani, Ana Flávia Mac Knight; Vicentini, Jéssica Elias; Magalhães, Thamires Naela Cardoso; Talib, Leda Leme; Forlenza, Orestes Vicente; Balthazar, Marcio Luiz Figueredo

    2017-11-01

    In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

  2. Functional connectivity modeling of consistent cortico-striatal degeneration in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Imis Dogan

    2015-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis we identified core regions of consistent neurodegeneration in premanifest HD in the striatum and middle occipital gyrus (MOG. For early manifest HD convergent evidence of atrophy was most prominent in the striatum, motor cortex (M1 and inferior frontal junction (IFJ. The aim of the present study was to functionally characterize this topography of brain atrophy and to investigate differential connectivity patterns formed by consistent cortico-striatal atrophy regions in HD. Using areas of striatal and cortical atrophy at different disease stages as seeds, we performed task-free resting-state and task-based meta-analytic connectivity modeling (MACM. MACM utilizes the large data source of the BrainMap database and identifies significant areas of above-chance co-activation with the seed-region via the activation-likelihood-estimation approach. In order to delineate functional networks formed by cortical as well as striatal atrophy regions we computed the conjunction between the co-activation profiles of striatal and cortical seeds in the premanifest and manifest stages of HD, respectively. Functional characterization of the seeds was obtained using the behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the premanifest stage of HD showed common co-activation with a rather cognitive network including the striatum, anterior insula, lateral prefrontal, premotor, supplementary motor and parietal regions. A similar but more pronounced co-activation pattern, additionally including the medial prefrontal cortex and thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage. The striatum and M1 were functionally connected mainly to premotor and sensorimotor areas, posterior insula, putamen and thalamus. Behavioral characterization of the seeds confirmed that experiments

  3. Diagnosis of Protein Losing Enteropathy in connective Tissue Diseases with 99mTc-human Serum Albumin(Hsa)

    International Nuclear Information System (INIS)

    Won, Kyoung Sook; Oh, Yeong Seok; Bang, Shin Ho; Park, Won

    1993-01-01

    Anterior abdominal scintigraphy after intravenous injection of 99m Tc-human serum albumin ( 99m Tc-HSA 20 mCi) was done in 16 patients with connective tissue diseases and 15 healthy control patients. Patients with proteinuria or hepatopathy were excluded. 1) 7(44%) patients among 16 connective tissue disease patients without the apparent evidence of external protein loss showed abnormal intestinal accumulation of albumin. 6 patients with positive albumin scintigraphy showed hypoalbuminaemia. 2) There was no false positive scintigraphic finding in control group. 3) The serum albumin level in connective tissue disease patients (3.1 ± 0.6 g/dl, n=16) was lower than control patients(3.9 ± 0.3 g/dl, n=15) (p 99m Tc-HSA scan(2.8 ± 0.6 g/dl, n=7) than the connective tissue disease patients with negative scan(3.3 ± 0.3 g/dl, n=9) (p 99m Tc-HSA scan also must be validated by more extended study and comparison with the quantitative study such as stool α -1 antitrypsin measurement. There must be a reevaluation of PLE in various diseases especially in connective tissue diseases with easy, fast, economical, and noninvasive method.

  4. Air Pollution and Allergic Airway Diseases: Social Determinantsand Sustainability in the Control and Prevention.

    Science.gov (United States)

    Paramesh, H

    2018-04-01

    Air pollution, global warming and climate change are the major contributing factors in causing the increase prevalence of allergic airway diseases like asthma and allergic rhinitis and they will be the defining issues for health system in the twenty-first century. Asthma is an early onset non-communicable environmental disease with global epidemic and contributes a greatest psycho socio economic burden. Nearly 8 million global deaths are from air pollution. Over one billion population are the sufferers during 2015 and will increase to 4 billion by 2050. Air pollution not only triggers the asthma episodes but also changes the genetic pattern in initiating the disease process. Over the years our concept of management of allergic airway disease has changed from control of symptoms to prevention of the disease. To achieve this we need positive development on clean air policies with standard norms, tracking progress, monitoring and evaluation, partnership and conventions with local and global authorities. We do have challenges to overcome like rapid urbanization, lack of multisectorial policy making, lack of finance for research and development and lack of monitoring exposure to health burden from air pollution. We need to prioritize our strategy by sustainable, safe, human settlement, cities, sustainable energy, industrialization, and research. The measures to be adopted are highlighted in this review article. With effective measures by all stake holders we can reduce air pollution and prevent the global warming by 2030, along with 194 countries as adopted by WHO in May 2015.

  5. Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

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    Joanna Świdrowska

    2015-04-01

    Full Text Available Objectives: Connective tissue diseases (CTD are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA. Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient’s clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS, it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods: Data from 24 patients with CTD treated with tumor necrosis factor--blockers (etanercept, adalimumab, golimumab and an interleukin-6 receptor blocker (tocilizumab were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results : Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1% during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions : In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS

  6. Primary Prevention of Asymptomatic Cardiovascular Disease Using Physiological Sensors Connected to an iOS App.

    Science.gov (United States)

    Moreno-Alsasua, Leire; Garcia-Zapirain, Begonya; David Rodrigo-Carbonero, J; Ruiz, Ibon Oleagordia; Hamrioui, Sofiane; de la Torre Díez, Isabel

    2017-10-26

    Cardiovascular disease is the first cause of death and disease and one of the leading causes of disability in developed countries. The prevalence of this disease is expected to increase in coming years although the death rate may be lower due to better treatment. To present the design and development of a technology solution for primary prevention of cardiovascular disease in asymptomatic patients. The system aims to raise the population's awareness of the importance of adopting healthy heart habits by using self-feedback techniques. A series of sensors which makes it possible to detect cardiovascular risk factors in asymptomatic patients were used. These sensors enable evaluation of heart rate, blood pressure, SpO 2 -oxygen saturation in blood- and body temperature. This work has developed a modular solution centred on four parts: iOS app, sensors, server and web. The CoreBluetooth library, which carries out Bluetooth 4.0 communication, was used for the connection between the app and the sensors. The data files are stored on the iPad and the server by using CoreData and SQL mechanisms. The system was validated with 20 healthy volunteers and 10 patients with established structural heart disease. Once the samples had been obtained, a comparison of all the significant data was run, in addition to a statistical analysis. The result of this calculation was a total of 32 cases of first level significance correlations (p < 0.01), for example, the inverse relationship between the daily step count and high blood pressure (p = 0.008) and 24 s level cases (p < 0.05) such as the significant correlation between risk and age (p = 0.013). The system designed in this paper has made it possible to create an application capable of collecting data on cardiovascular risk factors through a sensor system that measures physiological variables and records physical activity and diet.

  7. Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue?

    Science.gov (United States)

    Carrion, Flavio A; Figueroa, Fernando E

    2011-05-11

    Mesenchymal stem cells (MSCs) are now known to display not only adult stem cell multipotency but also robust anti-inflammatory and regenerative properties. After widespread in vitro and in vivo preclinical testing in several autoimmune disease models, allogenic MSCs have been successfully applied in patients with severe treatment-refractory systemic lupus erythematosus. The impressive results of these uncontrolled phase I and II trials - mostly in patients with non-responding renal disease - point to the need to perform controlled multicentric trials. In addition, they suggest that there is much to be learned from the basic and clinical science of MSCs in order to reap the full potential of these multifaceted progenitor cells in the treatment of autoimmune diseases.

  8. Nailfold Capillaroscopy Within and Beyond the Scope of Connective Tissue Diseases.

    Science.gov (United States)

    Lambova, Sevdalina Nikolova; Muller-Ladner, Ulf

    2018-04-20

    Nailfold capillaroscopy is a noninvasive instrumental method for morphological analysis of the nutritive capillaries in the nailfold area. In rheumatology, it is a method of choice among instrumental modalities for differential diagnosis between primary and secondary Raynaud's phenomenon (RP) in systemic rheumatic diseases. RP is a common diagnostic problem in rheumatology. Defining the proper diagnosis is a prerequisite for administration of the appropriate treatment. Thus, nailfold capillaroscopic examination is of crucial importance for the every-day practice of the rheumatologists and is currently gaining increasing attention. The most specific capillaroscopic changes are observed in Systemic Sclerosis (SSc). Due to the high prevalence of the capillaroscopic changes in this clinical entity and their early appearance, they could be used for early and very early diagnosis of the disease. More recently, "scleroderma" type capillaroscopic changes have been defined as diagnostic criterion in the new EULAR/ACR classification criteria for SSc together with the presence of scleroderma-related autoantibodies, RP, telangiectasia and other clinical signs. Capillaroscopic changes in other connective tissue diseases and in different rheumatic-like conditions like those in diabetes mellitus (e.g., diabetic stiff-hand syndrome) and paraneoplastic syndromes associated with microvascular pathology should be interpreted properly in order to obtain precise diagnosis in the shortest possible differential diagnostic process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report

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    João Tadeu Damian Souto Filho

    2011-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

  10. Performance measurement evaluation framework and co-benefit / tradeoff analysis for connected and automated vehicles (CAV) applications : a survey : a research report from the National Center for Sustainable Transportation.

    Science.gov (United States)

    2017-09-01

    A number of Connected and/or Automated Vehicle (CAV) applications have recently been designed to improve the performance of our transportation system. Safety, mobility and environmental sustainability are three cornerstone performance metrics when ev...

  11. Molecular and Genetic Basis of Hereditary Connective-Tissue Diseases Accompanied by Frequent Fractures

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    G. T. Yakhyaeva

    2016-01-01

    Full Text Available Frequent bone fractures in infancy require the elimination of a large number (> 100 of genetic disorders. The modern diagnostic method of hereditary diseases characterized by debilitating course is a new generation sequencing. The article presents the results of molecular-genetic study conducted in 18 patients with clinical symptoms of connective tissue disorders. 10 (56% patients had mutations in the genes encoding type I collagen chains, leading to the development of osteogenesis imperfecta, 5 (28% — mutations in IV and V type collagen genes that are responsible for the development of Ehlers-Danlos syndrome. 3 (17% patients had mutations in the gene encoding fibrillin-1 protein, deficiency of which is manifested by Marfan syndrome. However, the correlation between patient's phenotype and discovered mutations in the investigated gene is established not in all cases.

  12. Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

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    K Gautam

    2015-03-01

    Full Text Available Identification of antinuclear antibodies has been used for the diagnosis of connective tissue diseases for more than fifty years. Indirect immunofluorescence on human epithelial (HEp-2 cells is considered the gold standard screening method for the detection of antinuclear autoantibodies. As the demand of ANA testing increased, the need for automation and standardization has also come forth. A high level of false positive and false negative cases is seen in various populations making it difficult to take clinical decisions. Newer technologies were introduced for the antibody detection to ensure high sensitivity and specificity. This article intends to provide an overview of the concepts on ANA testing, the different diagnostic methods available, the various patterns and clinical utility, the clinical guidelines to be followed, the drawbacks and what lies ahead in the future of ANA testing.Journal of Pathology of Nepal (2015 Vol. 5, 766-773

  13. Are There Any Connections between Language Deficits and Cognitive Slowing in Alzheimer's Disease

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    Michael Schecker

    2014-11-01

    Full Text Available Background: Speech disorders already occur in the early phases of Alzheimer's disease (AD. As a possible cause, problems of executive processes are discussed. Cognitive slowing is also repeatedly addressed. Aims: Are there any connections between cognitive slowing and speech disorders in AD? And is there a relationship between cognitive slowing and executive processes? Methods: The data of 72 healthy controls and 52 AD patients were examined with regard to their language performance and their response times in a computerized Stroop paradigm. Results: The AD patients showed significantly worse results in all language tests as well as much longer reaction times in all Stroop conditions, especially in the interference condition (Stroop 3. Speech errors and response times correlated with severity (MMSE, and the speech errors correlated with the reaction times in Stroop 3 (interference condition, which reflects the processing time of executive processes. Conclusion: The most interesting question now is: How are language processing and executive processing time (Stroop 3 related?

  14. Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases

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    M. Rizzo

    2011-09-01

    Full Text Available Objective: Pulmonary arterial hypertension (PAH is a rare but severe complication of connective tissue diseases (CTD, with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases, SLE (2 cases, mixed connective tissue disease (1 case and polymyositis (1 case attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.

  15. Mediastinal neoplasms in patients with Graves disease: a possible link between sustained hyperthyroidism and thymic neoplasia?

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    Boyd Jonathan D

    2012-07-01

    Full Text Available Abstract Background Anterior mediastinal masses are a rare but well documented finding in Graves disease. The vast majority of these lesions represents benign thymic hypertrophy and regress after treatment of the hyperthyroidism. A small percentage of these cases however represent neoplastic/malignant diseases which require further treatment. Cases 12 year old boy with one year history of refractory Graves disease was found to have an anterior mediastinal mass and underwent curative thyroidectomy for sustained hyperthyroidism. Cervical lymphadenopathy was detected during the procedure and biopsy was obtained. A 23 year old woman who presented with a one month history of hyperthyroid symptoms, was diagnosed with Graves disease and also was found to have an anterior mediastinal mass on imaging. Biopsy of the anterior mediastinal mass was obtained and subsequently the patient underwent robotic thymectomy. Histologic examination and immunophenotyping of the cervical lymph node in a 12 year old boy revealed neoplastic proliferation of T lymphoblasts diagnostic of T lymphoblastic leukemia/lymphoma. Examination of the anterior mediastinal mass biopsy in the 23 year old woman revealed type B1 thymoma which was confirmed after examination of the subsequent robotic thymectomy specimen. Conclusion This is the first reported case of T cell lymphoblastic lymphoma and the third reported case of thymoma associated with sustained hyperthyroidism due to Graves disease. These cases indicate that an anterior mediastinal mass in a patient with active Graves disease may be due to a neoplastic cause, which may require definitive treatment. Caution should be exercised when dismissing a mediastinal mass as benign thymic hyperplasia in patients with active Graves disease.

  16. The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

    Science.gov (United States)

    Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

    2017-12-01

    In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

  17. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease

    OpenAIRE

    Shah, R.C.; Kamphuis, P.J.; Leurgans, S.; Swinkels, S.H.; Sadowsky, C.H.; Bongers, A.; Rappaport, S.A.; Quinn, J.F.; Wieggers, R.L.; Scheltens, P.; Bennett, D.A.

    2013-01-01

    Introduction. Souvenaid® containing Fortasyn® Connect is a medical food designed to support synapse synthesis in persons with Alzheimer's disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal membranes. Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed....

  18. Spatial Disassociation of Disrupted Functional Connectivity for the Default Mode Network in Patients with End-Stage Renal Disease.

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    Xiaofen Ma

    Full Text Available To investigate the aberrant functional connectivity of the default mode network (DMN in patients with end-stage renal disease (ESRD and their clinical relevance.Resting-state functional MRI data were collected from 31 patients with ESRD (24 men, 24-61 years and 31 age- and gender-matched healthy controls (HCs, 21 men, 26-61years. A whole-brain seed-based functional connectivity analysis of these collected R-fMRI data was performed by locating the seeds in the posterior cingulate cortex (PCC and ventromedial prefrontal cortex (vmPFC to investigate the functional connectivity of the posterior and anterior DMN over the whole brain, respectively.Compared to the HCs, the patients exhibited significantly decreased functional connectivity with the PCC in the left middle temporal gyrus, the right anterior cingulate gyrus, and the bilateral medial superior frontal gyrus. For the vmPFC seed, only the right thalamus showed significantly decreased functional connectivity in the patients with ESRD compared to HCs. Interestingly, functional connectivity between the PCC and right medial superior frontal gyrus exhibited a significantly positive correlation with the hemoglobin level in the patients.Our findings suggest a spatially specific disruption of functional connectivity in the DMN in patients with ESRD, thereby providing novel insights into our understanding of the neurophysiology mechanism that underlies the disease.

  19. Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

    Science.gov (United States)

    Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

    2016-01-01

    Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

  20. Longitudinal analysis of quality of life in patients with undifferentiated connective tissue diseases

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    Iudici M

    2017-02-01

    Full Text Available Michele Iudici, Rosaria Irace, Antonella Riccardi, Giovanna Cuomo, Serena Vettori, Gabriele Valentini Rheumatology Section, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Introduction/objectives: To prospectively assess the quality of life (QoL of patients affected by undifferentiated connective tissue diseases (UCTDs and to identify factors associated with changes over time.Patients and methods: A total of 46 consecutive UCTD patients completed the Short-Form 36 (SF-36 questionnaire at presentation and then yearly. At each 6-month visit, all patients underwent a detailed history taking and a laboratory and physical assessment, in order to follow the evolution of the disease over time and to assess the the co-existence of fibromyalgia.Results: At presentation, scores lower than the average of the general population were detected in 34 (74% and 41 (89% patients in the physical and mental domains, respectively. No difference between patients with and without Raynaud’s phenomenon was detected. Fibromyalgia was the only independent variable associated with an impaired physical component summary score (p = 0.0009. No patient feature was found to be associated with the basal mental component summary score. During 24 months of follow-up, a significant improvement (ie, a change ≥5 from baseline in physical component summary and mental component summary scores was observed in 14 (33.3% and 20 (43.4% patients, respectively. Patients who significantly improved in the physical domain more frequently had a history of glucocorticoids intake (p < 0.001, while those who improved in the mental component more frequently had a history of either glucocorticoids (p = 0.043 or immunosuppressors (p = 0.037 intake during follow-up.Conclusion: UCTD patients perceive a worse QoL, regardless of Raynaud’s phenomenon Fibromyalgia is one of the major contributors of physical QoL, whereas no factor influencing

  1. Investing in non-communicable disease prevention and management to advance the Sustainable Development Goals.

    Science.gov (United States)

    Nugent, Rachel; Bertram, Melanie Y; Jan, Stephen; Niessen, Louis W; Sassi, Franco; Jamison, Dean T; Pier, Eduardo González; Beaglehole, Robert

    2018-05-19

    Reduction of the non-communicable disease (NCD) burden is a global development imperative. Sustainable Development Goal (SDG) 3 includes target 3·4 to reduce premature NCD mortality by a third by 2030. Progress on SDG target 3·4 will have a central role in determining the success of at least nine SDGs. A strengthened effort across multiple sectors with effective economic tools, such as price policies and insurance, is necessary. NCDs are heavily clustered in people with low socioeconomic status and are an important cause of medical impoverishment. They thereby exacerbate economic inequities within societies. As such, NCDs are a barrier to achieving SDG 1, SDG 2, SDG 4, SDG 5, and SDG 10. Productivity gains from preventing and managing NCDs will contribute to SDG 8. SDG 11 and SDG 12 offer clear opportunities to reduce the NCD burden and to create sustainable and healthy cities. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Recommendations for obstetric management and principles of cooperation between rheumatologists and obstetricians in systemic connective tissue disease patients

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    Justyna Teliga-Czajkowska

    2014-03-01

    Full Text Available Systemic connective tissue diseases, notably rheumatoid arthritis and systemic lupus erythematosus, frequently affect women of reproductive age. The significant impact of the diseases on the course of pregnancy is well established, and vice versa – the course of systemic connective tissue diseases may be affected by pregnancy. The risk of developing serious pregnancy complications and obstetric failures is markedly higher in the mentioned disease group. The foundation of obstetric success, i.e. giving birth to a healthy child and pregnancy having no effect on the course of a given autoimmune disease, is cooperation between rheumatologists and obstetricians so as to plan procreation at an optimal period and provide accurate pregnancy monitoring. The article delineates recommendations relating to contraception management, obstetric supervision and fetus wellbeing monitoring, from the point of view of the obstetrician.

  3. Pulmonary hypertension not a major feature of early mixed connective tissue disease: A prospective clinicoserological study

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    Haroon N

    2005-01-01

    Full Text Available Background: Mixed connective tissue disease (MCTD has features common to lupus, scleroderma and myositis with high levels of antibodies to U1 ribonucleoprotein (U1 RNP. Identification of a high incidence of pulmonary artery hypertension (PAH has changed its prospect. We report the largest series from India. Settings and Design: Rheumatology unit of a tertiary care centre in India; prospective. Materials and Methods: Patients seen between January 2002 and June 2004, satisfying the Kasukawa criteria were enrolled. All patients had a complete laboratory work-up including pulmonary function test, 2-D echocardiography, and Schirmer′s test, antinuclear antibodies (ANA and antibodies to extractable nuclear antigens. HRCT of chest was done where indicated. All patients were given standard treatment and followed up regularly. Results: Out of 1500 patients, thirteen (one male were diagnosed to have MCTD. The median follow-up period was 18 months [Interquartile range (IQR 12-22]. The median age of onset of symptoms was 36 years (IQR 22-39 and the median duration of disease was three years (IQR 1.75-4. The most common manifestation was polyarthritis followed by puffy fingers. Sjogren′s syndrome, dysphagia and interstitial lung disease, was present in four, three and two patients respectively. Two patients each had myositis and migraine. None had PAH, serositis or renal involvement. Arthritis, puffy fingers and RaynaudÆs phenomenon were the most common manifestations at onset. All patients were positive for ANA and anti U1 RNP. Two patients each had antibodies to Sm and SSA. Response to treatment also was noted. Conclusion: Pulmonary artery hypertension is not common in early MCTD.

  4. Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

    Science.gov (United States)

    Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

    2018-01-01

    Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

  5. Increased brain connectivity and activation after cognitive rehabilitation in Parkinson's disease: a randomized controlled trial.

    Science.gov (United States)

    Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Lucas-Jiménez, Olaia; Gómez-Esteban, Juan Carlos; Gómez-Beldarrain, Maria Ángeles; Ibarretxe-Bilbao, Naroa

    2017-12-01

    Cognitive rehabilitation programs have demonstrated efficacy in improving cognitive functions in Parkinson's disease (PD), but little is known about cerebral changes associated with an integrative cognitive rehabilitation in PD. To assess structural and functional cerebral changes in PD patients, after attending a three-month integrative cognitive rehabilitation program (REHACOP). Forty-four PD patients were randomly divided into REHACOP group (cognitive rehabilitation) and a control group (occupational therapy). T1-weighted, diffusion weighted and functional magnetic resonance images (fMRI) during resting-state and during a memory paradigm (with learning and recognition tasks) were acquired at pre-treatment and post-treatment. Cerebral changes were assessed with repeated measures ANOVA 2 × 2 for group x time interaction. During resting-state fMRI, the REHACOP group showed significantly increased brain connectivity between the left inferior temporal lobe and the bilateral dorsolateral prefrontal cortex compared to the control group. Moreover, during the recognition fMRI task, the REHACOP group showed significantly increased brain activation in the left middle temporal area compared to the control group. During the learning fMRI task, the REHACOP group showed increased brain activation in the left inferior frontal lobe at post-treatment compared to pre-treatment. No significant structural changes were found between pre- and post-treatment. Finally, the REHACOP group showed significant and positive correlations between the brain connectivity and activation and the cognitive performance at post-treatment. This randomized controlled trial suggests that an integrative cognitive rehabilitation program can produce significant functional cerebral changes in PD patients and adds evidence to the efficacy of cognitive rehabilitation programs in the therapeutic approach for PD.

  6. Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease.

    Science.gov (United States)

    Kobeleva, Xenia; Firbank, Michael; Peraza, Luis; Gallagher, Peter; Thomas, Alan; Burn, David J; O'Brien, John; Taylor, John-Paul

    2017-07-01

    Attention and executive dysfunction are features of Lewy body dementia (LBD) but their neuroanatomical basis is poorly understood. To investigate underlying dysfunctional attention-executive network (EXEC) interactions, we examined functional connectivity (FC) in 30 patients with LBD, 20 patients with Alzheimer's disease (AD), and 21 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Participants performed a modified Attention Network Test (ANT), where they were instructed to press a button in response to the majority direction of arrows, which were either all pointing in the same direction or with one pointing in the opposite direction. Network activations during both target conditions and a baseline condition (no target) were derived by (ICA) Independent Component Analysis, and interactions between these networks were examined using the beta series correlations approach. Our study revealed that FC of ventral and dorsal attention networks DAN was reduced in LBD during all conditions, although most prominently during incongruent trials. These alterations in connectivity might be driven by a failure of engagement of ventral attention networks, and consequent over-reliance on the DAN. In contrast, when comparing AD patients with the other groups, we found hyperconnectivity between the posterior part of the default mode network (DMN) and the DAN in all conditions, particularly during incongruent trials. This might be attributable to either a compensatory effect to overcome DMN dysfunction, or be arising as a result of a disturbed transition of the DMN from rest to task. Our results demonstrate that dementia syndromes can be characterized both by hyper- and hypoconnectivity of distinct brain networks, depending on the interplay between task demand and available cognitive resources. However these are dependent upon the underlying pathology, which needs to be taken into account when developing specific cognitive therapies

  7. Altering neuronal excitability to preserve network connectivity in a computational model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Willem de Haan

    2017-09-01

    Full Text Available Neuronal hyperactivity and hyperexcitability of the cerebral cortex and hippocampal region is an increasingly observed phenomenon in preclinical Alzheimer's disease (AD. In later stages, oscillatory slowing and loss of functional connectivity are ubiquitous. Recent evidence suggests that neuronal dynamics have a prominent role in AD pathophysiology, making it a potentially interesting therapeutic target. However, although neuronal activity can be manipulated by various (non-pharmacological means, intervening in a highly integrated system that depends on complex dynamics can produce counterintuitive and adverse effects. Computational dynamic network modeling may serve as a virtual test ground for developing effective interventions. To explore this approach, a previously introduced large-scale neural mass network with human brain topology was used to simulate the temporal evolution of AD-like, activity-dependent network degeneration. In addition, six defense strategies that either enhanced or diminished neuronal excitability were tested against the degeneration process, targeting excitatory and inhibitory neurons combined or separately. Outcome measures described oscillatory, connectivity and topological features of the damaged networks. Over time, the various interventions produced diverse large-scale network effects. Contrary to our hypothesis, the most successful strategy was a selective stimulation of all excitatory neurons in the network; it substantially prolonged the preservation of network integrity. The results of this study imply that functional network damage due to pathological neuronal activity can be opposed by targeted adjustment of neuronal excitability levels. The present approach may help to explore therapeutic effects aimed at preserving or restoring neuronal network integrity and contribute to better-informed intervention choices in future clinical trials in AD.

  8. Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

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    Julian Caspers

    2017-05-01

    Full Text Available Patients suffering from Parkinson's disease (PD often show impairments in executive function (EF like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF and under their regular dopaminergic medication (ON. We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC and left dorsal premotor region (PMd in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part.

  9. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Science.gov (United States)

    Castro-Sánchez, Adelaida María; Moreno-Lorenzo, Carmen; Matarán-Peñarrocha, Guillermo A.; Feriche-Fernández-Castanys, Belen; Granados-Gámez, Genoveva; Quesada-Rubio, José Manuel

    2011-01-01

    The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P < .05) in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg) and left lower limb (lower one-third of thigh and upper and lower one-third of leg). A significant difference (P < .05) was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P < .05) for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD. PMID:19933770

  10. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Adelaida María Castro-Sánchez

    2011-01-01

    Full Text Available The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD (Leriche-Fontaine classification were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P<.05 in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg and left lower limb (lower one-third of thigh and upper and lower one-third of leg. A significant difference (P<.05 was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P<.05 for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD.

  11. Resting-state functional connectivity modulation and sustained changes after real-time functional magnetic resonance imaging neurofeedback training in depression.

    Science.gov (United States)

    Yuan, Han; Young, Kymberly D; Phillips, Raquel; Zotev, Vadim; Misaki, Masaya; Bodurka, Jerzy

    2014-11-01

    Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in

  12. Sustained attention training reduces spatial bias in Parkinson's disease: a pilot case series.

    Science.gov (United States)

    DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas; Esterman, Michael; Pistorino, Laura; Cronin-Golomb, Alice

    2016-01-01

    Individuals with Parkinson's disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention, whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD, 2 RPD) performed a visual search task before and after 1 month of computer training. Before training, all participants showed a significant spatial bias and after training, all participants' spatial bias was eliminated.

  13. Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

    Science.gov (United States)

    Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

    2018-02-01

    Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

  14. Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set

    International Nuclear Information System (INIS)

    Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun; Lee, Jae Hong; Roh, Jee Hoon

    2017-01-01

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease

  15. Genetic Engineering and Sustainable Crop Disease Management: Opportunities for Case-by-Case Decision-Making

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    Paul Vincelli

    2016-05-01

    Full Text Available Genetic engineering (GE offers an expanding array of strategies for enhancing disease resistance of crop plants in sustainable ways, including the potential for reduced pesticide usage. Certain GE applications involve transgenesis, in some cases creating a metabolic pathway novel to the GE crop. In other cases, only cisgenessis is employed. In yet other cases, engineered genetic changes can be so minimal as to be indistinguishable from natural mutations. Thus, GE crops vary substantially and should be evaluated for risks, benefits, and social considerations on a case-by-case basis. Deployment of GE traits should be with an eye towards long-term sustainability; several options are discussed. Selected risks and concerns of GE are also considered, along with genome editing, a technology that greatly expands the capacity of molecular biologists to make more precise and targeted genetic edits. While GE is merely a suite of tools to supplement other breeding techniques, if wisely used, certain GE tools and applications can contribute to sustainability goals.

  16. Decreased functional connectivity of the amygdala in Alzheimer's disease revealed by resting-state fMRI

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Hongxiang [Department of Radiology, Chinese PLA General Hospital, Beijing, 100853 (China); Liu, Yong, E-mail: yliu@nlpr.ia.ac.cn [Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); Zhou, Bo; Zhang, Zengqiang [Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, 100853 (China); An, Ningyu [Department of Radiology, Chinese PLA General Hospital, Beijing, 100853 (China); Wang, Pan; Wang, Luning [Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, 100853 (China); Zhang, Xi, E-mail: zhangxi@301hospital.com.cn [Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, 100853 (China); Jiang, Tianzi [Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190 (China); Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054 (China); The Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072 (Australia)

    2013-09-15

    Alzheimer's disease (AD), the most common cause of dementia, is thought to be a progressive neurodegenerative disease that is clinically characterised by a decline of memory and other cognitive functions. Mild cognitive impairment (MCI) is considered to be the prodromal stage of AD. However, the relationship between AD and MCI and the development process remains unclear. The amygdala is one of the most vulnerable structures in the early stages of AD. To our knowledge, this is the first report on the alteration of the functional connectivity of the amygdala in AD and MCI subjects. We hypothesised that the amygdala-cortical loop is impaired in AD and that these alterations relate to the disease severity. In our study, we used resting-state functional MRIs to investigate the altered amygdala connectivity patterns in 35 AD patients, 27 MCI patients and 27 age- and gender-matched normal controls (NC). Compared with the NC, the decreased functional connectivity found in the AD patients was mainly located between the amygdala and the regions that are included in the default mode, context conditioning and extinction networks. Importantly, the decreased functional connectivity between the amygdala and some of the identified regions was positively correlated with MMSE, which indicated that the cognitive function impairment is related to an altered functional connectivity pattern.

  17. Decreased functional connectivity of the amygdala in Alzheimer's disease revealed by resting-state fMRI

    International Nuclear Information System (INIS)

    Yao, Hongxiang; Liu, Yong; Zhou, Bo; Zhang, Zengqiang; An, Ningyu; Wang, Pan; Wang, Luning; Zhang, Xi; Jiang, Tianzi

    2013-01-01

    Alzheimer's disease (AD), the most common cause of dementia, is thought to be a progressive neurodegenerative disease that is clinically characterised by a decline of memory and other cognitive functions. Mild cognitive impairment (MCI) is considered to be the prodromal stage of AD. However, the relationship between AD and MCI and the development process remains unclear. The amygdala is one of the most vulnerable structures in the early stages of AD. To our knowledge, this is the first report on the alteration of the functional connectivity of the amygdala in AD and MCI subjects. We hypothesised that the amygdala-cortical loop is impaired in AD and that these alterations relate to the disease severity. In our study, we used resting-state functional MRIs to investigate the altered amygdala connectivity patterns in 35 AD patients, 27 MCI patients and 27 age- and gender-matched normal controls (NC). Compared with the NC, the decreased functional connectivity found in the AD patients was mainly located between the amygdala and the regions that are included in the default mode, context conditioning and extinction networks. Importantly, the decreased functional connectivity between the amygdala and some of the identified regions was positively correlated with MMSE, which indicated that the cognitive function impairment is related to an altered functional connectivity pattern

  18. An analysis of the clinical features of lung cancer in patients with connective tissue diseases.

    Science.gov (United States)

    Saijo, Atsuro; Hanibuchi, Masaki; Goto, Hisatsugu; Toyoda, Yuko; Tezuka, Toshifumi; Nishioka, Yasuhiko

    2017-03-01

    Patients with connective tissue diseases (CTDs) are at increased risk for lung cancer (LC); interstitial lung disease (ILD) is a common form of organ dysfunction in cases of CTD. However, the influence of ILD on the treatment and prognosis in LC patients with CTD is unclear. Between January 2010 and December 2014, 27 patients among all patients with CTD at our institution were diagnosed with primary LC. We retrospectively analyzed the clinical features, treatment modalities, and outcomes of these patients, and evaluated the potential prognostic factors. Forty-four LC patients without CTD were also analyzed as a control cohort. LC patients with CTD had a significantly higher incidence of ILD as a complication compared with those without CTD (52% and 14%, respectively). CTD-associated ILD (CTD-ILD) at diagnosis was associated with significantly worse survival in LC patients with CTD. Multivariate analysis demonstrated that the complication of CTD-ILD was an independent poor prognostic factor in LC patients with CTD. The incidence of acute exacerbation (AE) of CTD-ILD was 21% among LC patients with CTD, and all of these patients died despite intensive treatment including high-dose corticosteroids. The restrictions in curative therapy for LC due to the presence of ILD and AE of CTD-ILD were thought to be the major reasons for the poor outcome. LC patients with CTD had a high prevalence of ILD, and the presence of CTD-ILD was significantly associated with poor prognosis. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  19. Sphingolipids and plant defense/disease: the "death" connection and beyond

    Directory of Open Access Journals (Sweden)

    Robert eBerkey

    2012-04-01

    Full Text Available Sphingolipids comprise a major class of structural materials and lipid signaling molecules in all eukaryotic cells. Over the past two decades, there has been a phenomenal growth in the study of sphingolipids (i.e. sphingobiology at an average rate of >1000 research articles per year. Sphingolipid studies in plants, though accounting for only a small fraction (~6% of the total number of publications, have also enjoyed proportionally rapid growth in the past decade. Concomitant with the growth of sphingobiology, there has also been tremendous progress in our understanding of the molecular mechanisms of plant innate immunity. In this review, we (i cross examine and analyze the major findings that establish and strengthen the intimate connections between sphingolipid metabolism and plant programmed cell death (PCD associated with plant defense or disease; (ii highlight and compare key bioactive sphingolipids involved in the regulation of plant PCD and possibly defense; (iii discuss the potential role of sphingolipids in polarized membrane/protein trafficking and formation of lipid rafts as subdomains of cell membranes in relation to plant defense; and (iv where possible, attempt to identify potential parallels for immunity-related mechanisms involving sphingolipids across kingdoms.

  20. Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

    Directory of Open Access Journals (Sweden)

    H.F. Ge

    Full Text Available Invasive pulmonary fungal infection (IPFI is a potentially fatal complication in patients with connective tissue disease (CTD. The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15% CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17% of cases with IPFI. Candida albicans (72.3% accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05. Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI.

  1. Ineffectiveness of rat liver tissues in the screening of connective tissue disease

    International Nuclear Information System (INIS)

    Aziz, Khalil A.

    2004-01-01

    To assess the effectiveness of using rat liver tissue (RLT) for the screening of connective tissue disease (CTD). Results of patient samples submitted to the Clinical Immunology Laboratory, Brimingham Heartlands Hospital, Bordsley Green East, Brimingham, United Kingdom for the investigation of CTD between 2001 and 2002 were analyzed. Positive results for anti-double stranded DNA (dsDNA) antibodies and anti-extractable nuclear antigen (ENA) antibodies were correlated with the results of the corresponding antinuclear antibodies (ANA), obtained by indirect immunofluorescence (IIF) using RLT. In the second part of study samples that were previously tested positive for anti-ENA or anti-dsDNA antibodies were investigated prospectively for ANA using both RLTand human epithelial (Hep-2) cell line. The IIF method employing RLT for screening of CTD, failed to detect ANA patterns from 45% and 25%of patients sample know to contain antibodies to dsDNA and ENA.The anti -dsDNA antibodies that failed to be detected by the RLTwere of low avidity and their clinical significance is unknown. In contrast the antibodies to ENAwere mostly directed against the Ro antigen.In cotrast and like RLT, Hep-2 cell line failed to detect the low avidity anti-dsDNA antibdies.The present study has clearly shown that RLT are ineffective for screening of CTD. It is recommended that laboratories which ars still using these tissues should consider replacing them with the Hep-2 cell line. (author)

  2. Connections between voice ergonomic risk factors and voice symptoms, voice handicap, and respiratory tract diseases.

    Science.gov (United States)

    Rantala, Leena M; Hakala, Suvi J; Holmqvist, Sofia; Sala, Eeva

    2012-11-01

    The aim of the study was to investigate the connections between voice ergonomic risk factors found in classrooms and voice-related problems in teachers. Voice ergonomic assessment was performed in 39 classrooms in 14 elementary schools by means of a Voice Ergonomic Assessment in Work Environment--Handbook and Checklist. The voice ergonomic risk factors assessed included working culture, noise, indoor air quality, working posture, stress, and access to a sound amplifier. Teachers from the above-mentioned classrooms reported their voice symptoms, respiratory tract diseases, and completed a Voice Handicap Index (VHI). The more voice ergonomic risk factors found in the classroom the higher were the teachers' total scores on voice symptoms and VHI. Stress was the factor that correlated most strongly with voice symptoms. Poor indoor air quality increased the occurrence of laryngitis. Voice ergonomics were poor in the classrooms studied and voice ergonomic risk factors affected the voice. It is important to convey information on voice ergonomics to education administrators and those responsible for school planning and taking care of school buildings. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  3. Health activism and the logic of connective action. A case study of rare disease patient organisations.

    Science.gov (United States)

    Vicari, Stefania; Cappai, Franco

    2016-11-01

    This exploratory work investigates the role of digital media in expanding health discourse practices in a way to transform traditional structures of agency in public health. By focusing on a sample of rare disease patient organisations as representative of contemporary health activism, this study investigates the role of digital communication in the development of (1) bottom-up sharing and co-production of health knowledge, (2) health public engagement dynamics and (3) health information pathways. Findings show that digital media affordances for patient organisations go beyond the provision of social support for patient communities; they ease one-way, two-way and crowdsourced processes of health knowledge sharing, exchange and co-production, provide personalised routes to health public engagement and bolster the emergence of varied pathways to health information where experiential knowledge and medical authority are equally valued. These forms of organisationally enabled connective action can help the surfacing of personal narratives that strengthen patient communities, the bottom-up production of health knowledge relevant to a wider public and the development of an informational and eventually cultural context that eases patients' political action.

  4. Altered Functional Connectivity of Cognitive-Related Cerebellar Subregions in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Weimin Zheng

    2017-05-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia. Previous studies have found disrupted resting state functional connectivities (rsFCs in various brain networks in the AD patients. However, few studies have focused on the rsFCs of the cerebellum and its sub-regions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (rs-fMRI data including 32 AD patients and 38 healthy controls (HCs. We selected two cognitive-related subregions of the cerebellum as seed region and mapped the whole-brain rsFCs for each subregion. We identified several distinct rsFC patterns of the two cognitive-related cerebellar subregions: default-mode network (DMN, frontoparietal network (FPN, visual network (VN and sensorimotor network (SMN. Compared with the controls, the AD patients showed disrupted rsFCs in several different networks (DMN, VN and SMN, predicting the impairment of the functional integration in the cerebellum. Notably, these abnormal rsFCs of the two cerebellar subregions were closely associated with cognitive performance. Collectively, we demonstrated the distinct rsFCs patterns of cerebellar sub-regions with various functional networks, which were differentially impaired in the AD patients.

  5. Sustainable management of lakes in connection with mitigation of adverse effects of climate change, agriculture and development of green micro regions based on renewable energy production

    Directory of Open Access Journals (Sweden)

    Sandor Antal Nemethy

    2014-11-01

    Full Text Available Lake management is extremely complex and requires a coordinated effort of research institutions, community groups, individuals, landowners, and government. Lakes constitute an important group of natural resources due to their ecosystem services and often unique cultural environments. Climate change is a growing concern, which particularly strongly affects shallow lakes. The adverse impact of climate change is enhanced by extreme water level fluctuations and human factors such as environmental pollution from waste water discharge, large scale agriculture and shoreline constructions reducing or eliminating valuable wetlands. Since eutrophication is a leading cause of impairment of freshwater ecosystems, specific strategies to address a lake's nutrient enrichment must focus on activities in the watershed and, if needed, in-lake restoration techniques. Analyzing the key factors of sustainable local and regional development in the vicinity of lakes, assessing the environmental risks of pollution, large scale agriculture, waste management and energy production, we propose a complex, stakeholder based management system and holistic regional development in lake areas, which will preserve natural ecosystems without compromising the sustainable use of ecosystem services. There are available technologies to develop ecologically acceptable water level regulations, promote organic agriculture applying grey water irrigation, stop leachate from landfills and control invasive species. Regional and local production and use of renewable energy is essential both for environmental and economical sustainability. Renewable energy production should be well coordinated with agriculture, forestry, waste management and management of water resources of lakes and their watershed areas in a sustainable, holistic way through a participatory approach. This is particularly pronounced in connection with tourism as one of the main uses of lake-ecosystem services, but also an

  6. PPARgamma-2 and ADRB3 polymorphisms in connective tissue diseases and lipid disorders

    Directory of Open Access Journals (Sweden)

    Grygiel-Górniak B

    2018-03-01

    Full Text Available Bogna Grygiel-Górniak,1 Iwona Ziółkowska-Suchanek,2 Elżbieta Kaczmarek,3 Maria Mosor,2 Jerzy Nowak,2 Mariusz Puszczewicz1 1Department of Rheumatology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland; 2Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; 3Department of Bioinformatics and Computational Biology, Poznan University of Medical Sciences, Poznan, Poland Background: The aim of the research genetic study was to investigate the association between variants (C1431T and Pro12Ala of the peroxisome proliferator-activated receptor (PPARgamma-2 gene, Trp64Arg polymorphism of the beta-3-adrenergic receptor gene and lipid profile in Polish population including group of 103 patients with connective tissue disease (CTD and 103 sex- and age-matched controls in context of statin use. Methods: Anthropometric and biochemical parameters were measured by routine methods, followed by genotyping (TagMan® Genotyping Assays, PCR-restriction fragment length polymorphism analysis. Nearly 30% of CTD patients used statins and 10% of the control group. Results: Although there were no differences between alleles and genotypes prevalence between CTD vs control groups, interesting lipid-gene associations were noted in this study. A higher level of triglycerides (TAG and TAG/high-density lipoprotein (HDL ratios was observed in CTD patients compared to controls. Similar differences were noted in CTD and control groups without statin treatment. Atherogenic markers: the atherogenic index of plasma, TAG/HDL and low-density lipoprotein/HDL ratio were low in the analyzed groups. Of the six analyzed polymorphisms, the Pro12Pro or C14131C or Trp64Trp genotypes were related to higher TAG and TAG/HDL ratios in patients with CTD; however, the highest TAG values were observed in the presence of the Trp64Trp genotype. Conclusion: Lipid disorders were present in both groups independent of statin treatment (mixed dyslipidemia and

  7. IMPORTANCE OF MAKING STRATEGIC DECISIONS IN COUNTRIES IN TRANSITION AND CONNECTION WITH THE ENVIRONMENT AND SUSTAINABLE ECONOMY GENERALLY SPEAKING

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    SLOBODAN POPOVIĆ

    2016-04-01

    Full Text Available The accession of a number of transition countries of the EU, such as the Republic of Serbia, essentially means the adoption of strategic decisions at the state level in the context of wider EU decision. The authors based their observations on the EU 2020 strategy, which is essentially defined as: smart, sustainable and inclusive growth. The EU has adopted the basic principles of 2010, with the main objective to economic growth throughout the EU based on knowledge, but with respect for the principles of environmental protection, increasing employment, and increase in other basic principles of economics of the company to the state. You could say that the entire system such observations cohesion productivity growth economies of EU member states and social cohesion and socially responsible behavior. This approach was incurred because there is a need of constant adjustment economies member changes at the global level. Notwithstanding the universal adaptation of all EU member states, however, one part remained reserved for a special adjustment of each member country (it depends on the specific characteristics of each country to adapt in accordance with national goals adopted by any government of a Member State specifically for your country, through national development plans, plans of adjustment and reform plans. The consequences of the Great Depression are highly visible and in early 2016, particularly in terms of rising unemployment, rising unemployment especially of young people in all old EU member states. The responsibility for this state of affairs is not only the governments of member states, but responsibility must be sought from the representatives of big business, trade unions, associations, non-governmental organizations and all other stakeholders who have imposed in the decision-making processes, and in a crisis to minimize its impact, because it does not response. At the end of the aforementioned macro effects should be seen in the

  8. Lung cancer development in patients with connective tissue disease-related interstitial lung disease: A retrospective observational study.

    Science.gov (United States)

    Enomoto, Yasunori; Inui, Naoki; Yoshimura, Katsuhiro; Nishimoto, Koji; Mori, Kazutaka; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Iwashita, Toshihide; Suda, Takafumi

    2016-12-01

    Previous studies have reported that patients with idiopathic pulmonary fibrosis occasionally develop lung cancer (LC). However, in connective tissue disease (CTD)-related interstitial lung disease (ILD), there are few data regarding the LC development. The aim of the present study was to evaluate the clinical significance of LC development in patients with CTD-ILD. A retrospective review of our database of 562 patients with ILD between 2000 and 2014 identified 127 patients diagnosed with CTD-ILD. The overall and cumulative incidences of LC were calculated. In addition, the risk factors and prognostic impact of LC development were evaluated. The median age at the ILD diagnosis was 63 years (range 37-84 years), and 73 patients (57.5%) were female. The median follow-up period from the ILD diagnosis was 67.4 months (range 10.4-322.1 months). During the period, 7 out of the 127 patients developed LC (overall incidence 5.5%). The cumulative incidences at 1, 3, and 5 years were 0.0%, 1.8%, and 2.9%, respectively. The risk of LC development was significantly higher in patients with higher smoking pack-year (odds ratio [OR] 1.028; 95% confidence interval [CI] 1.008-1.049; P = 0.007) and emphysema on chest high-resolution computed tomography (OR 14.667; 95% CI 2.871-74.926; P = 0.001). The median overall survival time after developing LC was 7.0 months (95% CI 4.9-9.1 months), and the most common cause of death was LC, not ILD. According to the Cox proportional hazard model analysis with time-dependent covariates, patients who developed LC showed significantly poorer prognosis than those who did not (hazard ratio 87.86; 95% CI 19.56-394.67; P < 0.001). In CTD-ILD, clinicians should be careful with the risk of LC development in patients with a heavy smoking history and subsequent emphysema. Although not so frequent, the complication could be a poor prognostic determinant.

  9. Algebraic connectivity of brain networks shows patterns of segregation leading to reduced network robustness in Alzheimer's disease

    Science.gov (United States)

    Daianu, Madelaine; Jahanshad, Neda; Nir, Talia M.; Leonardo, Cassandra D.; Jack, Clifford R.; Weiner, Michael W.; Bernstein, Matthew A.; Thompson, Paul M.

    2015-01-01

    Measures of network topology and connectivity aid the understanding of network breakdown as the brain degenerates in Alzheimer's disease (AD). We analyzed 3-Tesla diffusion-weighted images from 202 patients scanned by the Alzheimer's Disease Neuroimaging Initiative – 50 healthy controls, 72 with early- and 38 with late-stage mild cognitive impairment (eMCI/lMCI) and 42 with AD. Using whole-brain tractography, we reconstructed structural connectivity networks representing connections between pairs of cortical regions. We examined, for the first time in this context, the network's Laplacian matrix and its Fiedler value, describing the network's algebraic connectivity, and the Fiedler vector, used to partition a graph. We assessed algebraic connectivity and four additional supporting metrics, revealing a decrease in network robustness and increasing disarray among nodes as dementia progressed. Network components became more disconnected and segregated, and their modularity increased. These measures are sensitive to diagnostic group differences, and may help understand the complex changes in AD. PMID:26640830

  10. Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Noritaka Yoneyama

    Full Text Available Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD, while the underlying functional connectivity (FC and brain volume alterations in PD patients with severe hyposmia (PD-SH are unclear.We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH, and 15 healthy controls (HCs.Decreased gray matter volume (GMV was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH.PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

  11. A randomized trial of heart failure disease management in skilled nursing facilities (SNF Connect): Lessons learned.

    Science.gov (United States)

    Daddato, Andrea; Wald, Heidi L; Horney, Carolyn; Fairclough, Diane L; Leister, Erin C; Coors, Marilyn; Capell, Warren H; Boxer, Rebecca S

    2017-06-01

    Conducting clinical trials in skilled nursing facilities is particularly challenging. This manuscript describes facility and patient recruitment challenges and solutions for clinical research in skilled nursing facilities. Lessons learned from the SNF Connect Trial, a randomized trial of a heart failure disease management versus usual care for patients with heart failure receiving post-acute care in skilled nursing facilities, are discussed. Description of the trial design and barriers to facility and patient recruitment along with regulatory issues are presented. The recruitment of Denver-metro skilled nursing facilities was facilitated by key stakeholders of the skilled nursing facilities community. However, there were still a number of barriers to facility recruitment including leadership turnover, varying policies regarding research, fear of litigation and of an increased workload. Engagement of facilities was facilitated by their strong interest in reducing hospital readmissions, marketing potential to hospitals, and heart failure management education for their staff. Recruitment of patients proved difficult and there were few facilitators. Identified patient recruitment challenges included patients being unaware of their heart failure diagnosis, patients overwhelmed with their illness and care, and frequently there was no available proxy for cognitively impaired patients. Flexibility in changing the recruitment approach and targeting skilled nursing facilities with higher rates of admissions helped to overcome some barriers. Recruitment of skilled nursing facilities and patients in skilled nursing facilities for clinical trials is challenging. Strategies to attract both facilities and patients are warranted. These include aligning study goals with facility incentives and flexible recruitment protocols to work with patients in "transition crisis."

  12. Brain Connectivity Alterations Are Associated with the Development of Dementia in Parkinson's Disease.

    Science.gov (United States)

    Bertrand, Josie-Anne; McIntosh, Anthony R; Postuma, Ronald B; Kovacevic, Natasha; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Gagnon, Jean-François

    2016-04-01

    Dementia affects a high proportion of Parkinson's disease (PD) patients and poses a burden on caregivers and healthcare services. Electroencephalography (EEG) is a common nonevasive and nonexpensive technique that can easily be used in clinical settings to identify brain functional abnormalities. Only few studies had identified EEG abnormalities that can predict PD patients at higher risk for dementia. Brain connectivity EEG measures, such as multiscale entropy (MSE) and phase-locking value (PLV) analyses, may be more informative and sensitive to brain alterations leading to dementia than previously used methods. This study followed 62 dementia-free PD patients for a mean of 3.4 years to identify cerebral alterations that are associated with dementia. Baseline resting state EEG of patients who developed dementia (N = 18) was compared to those of patients who remained dementia-free (N = 44) and of 37 healthy subjects. MSE and PLV analyses were performed. Partial least squares statistical analysis revealed group differences associated with the development of dementia. Patients who developed dementia showed higher signal complexity and lower PLVs in low frequencies (mainly in delta frequency) than patients who remained dementia-free and controls. Conversely, both patient groups showed lower signal variability and higher PLVs in high frequencies (mainly in gamma frequency) compared to controls, with the strongest effect in patients who developed dementia. These findings suggest that specific disruptions of brain communication can be measured before PD patients develop dementia, providing a new potential marker to identify patients at highest risk of developing dementia and who are the best candidates for neuroprotective trials.

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

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    Reverter Antonio

    2008-09-01

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

  14. The potential of positive deviance approach for the sustainable control of neglected tropical diseases.

    Science.gov (United States)

    Ong, Ken Ing Cherng; Araki, Hitomi; Kano, Shigeyuki; Jimba, Masamine

    2016-01-01

    Neglected tropical diseases (NTDs) have gained much attention in recent years due to the support from various agencies. However, the main approach to combat NTDs has been to cure rather than to prevent. As many NTD infections are closely linked with human behaviors such as hygienic practices and tradition, behavior change is also very crucial to prevent relapse or reinfection. Therefore, we would like to suggest a potential new approach-the positive deviance approach-to tackle NTDs by focusing on the preventive phase. What makes this approach unique is that the solution comes from the affected population themselves and not from the expert outsiders. Preventive chemotherapy that relies on outside aid has serious sustainability issues as reinfection is also high after the aid program has ended. Learning from the success story in Vietnam on preventing childhood malnutrition, the positive deviance approach could end the spread of NTDs once and for all by making full use of the available local solutions.

  15. Leaving no one behind: a neglected tropical disease indicator and tracers for the Sustainable Development Goals.

    Science.gov (United States)

    Fitzpatrick, Christopher; Engels, Dirk

    2016-03-01

    The Sustainable Development Goals (SDGs) have emerged as a global pledge to 'leave no one behind'. Under SDG 3, 'Ensure healthy lives and promote wellbeing for all', target 3.3 extends the Millennium Development Goals (MDGs) beyond HIV, TB and malaria to 'end the epidemic' of neglected tropical diseases (NTDs) by 2030. Other targets are also relevant to NTDs, especially 3.8 (Universal Health Coverage), 6.1 (water) and 6.2 (sanitation). This commentary summarises the proposed NTD indicator (3.3) and tracers (3.8 and 6.1/6.2). These will help ensure that the world's poorest and most marginalized people are prioritized at every step on the path towards SDG targets. © The author 2016. The World Health Organization has granted Oxford University Press permission for the reproduction of this article..

  16. Changes in anatomical and functional connectivity of Parkinson's disease patients according to cognitive status

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Boyu, E-mail: cbyzgyk@126.com; Fan, Guo Guang, E-mail: fanguog@sina.com; Liu, Hu, E-mail: liuhu1234567@126.com; Wang, Shanshan, E-mail: jelly_66@126.com

    2015-07-15

    Purpose: This study assesses the patterns of structural and functional connectivity damage in patients with Parkinson's disease dementia (PDD) compared with cognitively unimpaired Parkinson's disease patients (PD-Cu) and healthy controls (HC). Materials and methods: Resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor magnetic resonance imaging (DTI) scans were obtained from 30 PD and 21 sex- and age-matched HC. The between-group difference in posterior cingulate (PCC) functional connectivity (FC) was performed to assess FC dysfunction. Atlas-based spatial statistics of DTI was applied to compare White matter (WM) fibers impairment between groups. Results: (1) Functional connectivity: (1) PD-Cu compared with HC showed a decreased PCC functional connectivity of the right medial temporal lobe (MTL). In addition, PCC-right MTL connectivity strength of PD was significantly correlated with Montreal Cognitive Assessment (MoCA) score. (2) PDD group shows a decreased FC of PCC-right parahippocampa compared with PD-Cu group; while show a widespread decreased PCC FC compared with HC group. (2) Anatomical connectivity: (1) Relative to PD-Cu, significant lower FA values were found in the left hippocampus in PDD. (2) PDD showed higher MD values in a widespread WM regions compared with PD-Cu and HC. (3) Positive correlation was observed between MoCA score and FA value of left inferior longitudinal and hippocampus, and bilateral superior longitudinal fasciculus in PD. Conclusions: Cognitive decline in PD is associated with FC damage of PCC-right MTL and microstructural damage of left hippocampus. Nevertheless, combining fMRI and DTI method may provide markers able to contribute to the prediction of PDD.

  17. Standardized analysis and sharing of genome-phenome data for neuromuscular and rare disease research through the RD-Connect platform

    OpenAIRE

    Thompson, Rachel; Beltran, Sergi; Papakonstantinou, Anastasios; Cañada, Andrés; Fernández, Jose Maria; Thompson, Mark; Kaliyaperumal, Rajaram; Lair, Séverine; Sernadela, Pedro; Girdea, Marta; Brudno, Michael; Blavier, André; Lochmüller, Hanns; Roos, Andreas; Straub, Volker

    2016-01-01

    Abstract: RD-Connect (rd-connect.eu) is an EU-funded project building an integrated platform to narrow the gaps in rare disease research, where patient populations, clinical expertise and research communities are small in number and highly fragmented. Guided by the needs of rare disease researchers and with neuromuscular and neurodegenerative researchers as its original collaborators, the RD-Connect platform securely integrates multiple types of omics data (genomics, proteomics and transcript...

  18. Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease.

    Science.gov (United States)

    Verfaillie, Sander C J; Pichet Binette, Alexa; Vachon-Presseau, Etienne; Tabrizi, Shirin; Savard, Mélissa; Bellec, Pierre; Ossenkoppele, Rik; Scheltens, Philip; van der Flier, Wiesje M; Breitner, John C S; Villeneuve, Sylvia

    2018-05-01

    Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD + ). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values > .05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD + compared with SCD - (all false discovery rate-adjusted p values < .05). When compared with SCD - , SCD + subjects showed increased pDMN-MTMS connectivity (false discovery rate-adjusted p < .05). Higher connectivity between the MTMS and the rest of the brain was associated with better baseline immediate memory, attention, and global cognition, whereas higher MTMS and pDMN-MTMS connectivity were associated with lower immediate memory over time (all false discovery rate-adjusted p values < .05). SCD in cognitively normal individuals is associated with diminished immediate memory practice effects and a brain connectivity pattern that mirrors early AD-related connectivity failure. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease.

    Science.gov (United States)

    Case, Michelle; Zhang, Huishi; Mundahl, John; Datta, Yvonne; Nelson, Stephen; Gupta, Kalpna; He, Bin

    2017-01-01

    Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.

  20. MUSCULOSKELETAL AND CONNECTIVE TISSUE DISEASES: DISABILITY IN THE IRKUTSK REGION IN 2013–2015

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    I. L. Petrunko

    2017-01-01

    Full Text Available Objective: to study the rates of primary disability due to musculoskeletal and connective tissue diseases (MSCTD in the Irkutsk Region in 2013–2015 (in relation to age, gender, and urban or rural residence and its nosological pattern.Material and methods. A continuous method was used to analyze the database on the newly recognized as disabled due to MSCTD in the Irkutsk Region in 2013–2015. The rates were calculated per 10,000 adult population; the pattern was estimated as a percent.Results and discussion. The rates of primary disability due to MSCTD in the Irkutsk Region were higher than those in the Russian Federation as a whole. Its reduction from 10.4 per 10,000 population in 2013 to 10.3 in 2014 and to 5.9 in 2015 was noted in the adults. Osteoarthritis headed the list of the causes of primary disability in the adults (45.5% in 2015 whereas dorsopathies did in the able-bodied (45.9% in 2015, 47.1% in 2014, and 48.2% in 2013. Osteoarthritis ranked first in the retirement-aged (61.5% in 2015, 75.1% in 2014, and 72% in 2013; it occupied the second place in the able-bodied (31.6% in 2015, 36.3% in 2014, and 38.2% in 2013. Rheumatoid arthritis was third among both the able-bodied and the retirement-aged. Higher disability rates were observed in the urban residents over all the years. The women became disabled more frequently than the men. In 2015, the primary disability rates among the men were 5.2, those among the women were 6.4 per 10,000 population; these were 9.2 and 19.4 and 8.4 and 12.1 in 2014 and 2013, respectively. The lower rates of disability due to MSCTD may be attributable to both the greater availability of high-quality and high-tech medical care for patients and the changes in normative documents on disability criteria.

  1. Sustainable rare diseases business and drug access: no time for misconceptions.

    Science.gov (United States)

    Rollet, Pierrick; Lemoine, Adrien; Dunoyer, Marc

    2013-07-23

    Legislative incentives enacted in Europe through the Regulation (EC) No. 141/2000 to incentivize orphan drug development have over the last 12 years constituted a powerful impetus toward R&D directed at the rare diseases population. However, despite therapeutic promises contained in these projects and significant economic impact linked to burgeoning R&D expenditures, the affordability and value of OMPs has become a topic of health policy debate in Europe fueled by the perception that OMPs have high acquisition costs, and by misconceptions around pricing dynamics and rare-diseases business models. In order to maintain sustainable patient access to new and innovative therapies, it is essential to address these misconceptions, and to ensure the successful continuation of a dynamic OMPs R&D within rare-diseases public health policy. Misconceptions abound regarding the pricing of rare diseases drugs and reflect a poor appreciation of the R&D model and the affordability and value of OMPs. Simulation of potential financial returns of small medium sized rare diseases companies focusing on high priced drugs show that their economic returns are likely to be close to their cost of capital. Research in rare diseases is a challenging endeavour characterised by high fixed costs in which companies accrue substantial costs for several years before potentially generating returns from the fruits of their investments. Although heavily dependent upon R&D capabilities of each individual company or R&D organization, continuous flow of R&D financial investment should allow industry to increasingly include efficiencies in research and development in cost considerations to its customers. Industry should also pro-actively work on facilitating development of a specific value based pricing approach to help understanding what constitute value in rare diseases. Policy makers must reward innovation based upon unmet need and patient outcome. Broader understanding by clinicians, the public, and

  2. Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease

    Directory of Open Access Journals (Sweden)

    E.M. McCarthy

    2017-06-01

    The association between circulating MP levels and objective assessment of macro- and microvascular dysfunction within these disease areas suggests that MPs might have a useful role as novel circulating biomarkers of vascular disease within the CTDs.

  3. Effects of bleomycin and x irradiation on the frequency of chromosomal aberrations in selected connective tissue diseases

    International Nuclear Information System (INIS)

    Burkhardt, W.C. Jr.

    1978-01-01

    Whole blood lymphocytes from 28 patients with selected connective tissue disorders (6 progressive systemic sclerosis (PSS), 6 anti-nuclear antibody positive rheumatoid arthritis, 6 anti-nuclear antibody negative rheumatoid arthritis, 6 systemic lupus erythematosus, and 4 mixed connective tissue disease) and 17 controls matched for sex, age, and race were studied to determine the frequency of spontaneous as well as bleomycin and/or x-irradiation induced chromosomal aberrations. The effects of bleomycin on cultured lymphocytes were tested, but differential susceptibilities to this clastogen were not demonstrated among the disease groups and controls investigated. However, the combined effect of bleomycin and x irradiation were found to be additive in control lymphocytes, nearly additive in PSS, RA+, and SLE cultures, but reduced considerably from the expected additive value in Ra- cultures. This study indicated that peripheral blood lymphocytes from patients with connective tissue disease, as a whole, possess greater frequencies of spontaneous chromosomal aberrations than matched controls and that x rays can produce greater frequencies of chromosomal aberrations in whole blood lymphocytes of PSS patients than in suitably matched control individuals

  4. Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

    Science.gov (United States)

    Paradowska-Gorycka, A; Stypińska, B; Olesińska, M; Felis-Giemza, A; Mańczak, M; Czuszynska, Z; Zdrojewski, Z; Wojciechowicz, J; Jurkowska, M

    2016-01-01

    Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. The diagnosis of MR and CT scan for myofascitis of connective tissue disease: comparison with biopsy examination

    International Nuclear Information System (INIS)

    Xu Jianrong; Zhou Yan; Chai Weimin; Yao Qiuying; Li Lei; Li Lan; Li Zhengyang

    2002-01-01

    Objective: To evaluate the utility of MRI, CT and biopsy examinations in detecting myofascitis lesions of connective tissue disease. Methods: The study group consisted of 22 patients proven by clinical features and laboratory examination, including 8 cases of dermatomyositis (DM), 12 cases of polymyositis (PM), and 2 cases of eosinophilic fascitis. All patients received CT scan, SE-T 1 WI, SE-T 2 WI, SPIR, and CT guiding biopsy at the thigh region. Results: Biopsy detected muscular diseases in 17 cases and fascitis in 5 cases. MRI detected muscular diseases in 14 and fascitis in 9. CT detected muscular diseases in 5 and fascitis in 9. Myositis, amyotrophy, and fascitis may be alone or united in one case. Myositis (9 cases) appeared as low signal on T 1 WI and high signal on T 2 WI or SPIR. Amyotrophy (9 cases) presented hyperintensity on both T 1 WI and T 2 WI. SPIR was more sensitive in detecting myositis than CT and T 1 WI, P < 0.05. Myositis was more frequent in cases with DM(6/8) than in cases with PM (3/12), P < 0.05. Also, myositis was more frequently encountered in active phase (7/11) than in quiescent phase (2/11). Conclusion: MRI and CT appear to be valuable in quantitatively and qualitatively estimating myofascitis of connective tissue diseases

  6. [Smoking and other risk factors of cardiovascular diseases, connected with arteriosclerosis among youth].

    Science.gov (United States)

    Chmiel-Połeć, Zdzisława; Cybulska, Idalia

    2008-01-01

    The World Health Organization (WHO) conference on a "second wave" epidemic of cardiovascular diseases connected with arterial sclerosis (AS) foresee that in 2020 cardiovascular diseases will most likely be the leading cause of death in the world. The development of AS begins in youth and progresses with age. It's intensity depends on the risk factors involved, such as: smoking, hypertension, obesity and fat and sugar disorder in a body. Many of these risk factors, manifesting themselves as diseases in adults, can be found during adolescence. The aim of this study was to establish the spread of smoking and other risk factors of cardiovascular diseases, like: hereditary and increasing incidence hypertension and body mass index (BMI), among youth of upper gymnasium school in Podkarpacie. The research was conducted between November 2007 and March 2008, using 193 volunteer students from upper and lower gymnasium schools, aged between 16-20 years. Our research methods included: diagnostic questionnaire, measurement of blood pressure (BP) through the use of sphygmomanometer, as well as anthropometric measurements including high, weight and body mass estimation. BP was established by obtaining an average between two measurements taken under normal conditions. The results were statistically analyzed, in with the in dependent test chi-Parson square, the level of changes a = 0.05--was used. The research showed that 23.31% of respondents smoke, that's 64.44% girls, and 35.56% boys. 12.41% of the girls and 15.09% of boys smoke on regular basis. And 8.57% girls and 15.09% boys smoke from time to time. More than half of young smokers (51.10%) smoked for longer than 2 years, and the initiations of smoking starts at the age of 15 (26.67%) and the age of 16 (26.67%). 10 and more cigarettes a day smoke 26.67% of boys and 13.79% girls. 75.74% of respondents agree that they are victims of passive smoking. Through 17.61% of respondents (mostly boys 64.70%) we found increasing incidence

  7. Imaging of Brain Connectivity in Dementia: Clinical Implications for Diagnosis of its Underlying Diseases

    NARCIS (Netherlands)

    R. Meijboom (Rozanna)

    2017-01-01

    markdownabstractIn this thesis we investigated the use of advanced magnetic resonance imaging (MRI) techniques in identifying subtle brain abnormalities, associating brain abnormalities with disease symptomatology, and improving early (differential) diagnosis in several diseases underlying dementia.

  8. Endovascular Repair of Thoracoabdominal and Arch Aneurysms in Patients with Connective Tissue Disease Using Branched and Fenestrated Devices.

    Science.gov (United States)

    Clough, Rachel E; Martin-Gonzalez, Teresa; Van Calster, Katrien; Hertault, Adrien; Spear, Rafaëlle; Azzaoui, Richard; Sobocinski, Jonathan; Haulon, Stéphan

    2017-10-01

    Prophylactic open surgery is the standard practice in patients with connective tissue and thoracoabdominal aortic aneurysm (TAAA) and aortic arch disease. Branched and fenestrated devices offer a less invasive alternative but there are concerns regarding the durability of the repair and the effect of the stent graft on the fragile aortic wall. The aim of this study is to evaluate mid-term outcomes of fenestrated and/or branched endografting in patients with connective tissue disease. All patients with connective tissue disease who underwent TAAA or arch aneurysm repair using a fenestrated and/or branched endograft in a single, high-volume center between 2004 and 2015 were included. Ruptured aneurysms and acute aortic dissections were excluded from this study, but not chronic aortic dissections. In total, 427 (403 pararenal and TAAAs, and 24 arch aneurysms) endovascular interventions were performed during the study period. Of these, 17 patients (4%) (16 TAAAs, 1 arch) had connective tissue disease. All patients were classified as unfit for open repair. The mean age was 51 ± 8 years. Thirteen patients with TAAA were treated with a fenestrated, 1 with a branched, and 2 with a combined fenestrated/branch device. A double inner branch device was used to treat the arch aneurysm. The technical success rate was 100% with no incidence of early mortality, spinal cord ischemia, stroke, or further dissection. Postoperative deterioration in renal function was seen in 3 patients (18.8%) and no hemodialysis was required. The mean follow-up was 3.4 years (0.3-7.4). Aneurysm sac shrinkage was seen in 35% of patients (6/17) and the sac diameter remained stable in 65% of patients (11/17). No sac or sealing zone enlargement was observed in any of the patients and there were no conversions to open repair. Reintervention was required in 1 patient at 2 years for bilateral renal artery occlusion (successful fibrinolysis). One type II endoleak (lumbar) is under surveillance and 1 type

  9. Chestnut green waste composting for sustainable forest management: Microbiota dynamics and impact on plant disease control.

    Science.gov (United States)

    Ventorino, Valeria; Parillo, Rita; Testa, Antonino; Viscardi, Sharon; Espresso, Francesco; Pepe, Olimpia

    2016-01-15

    Making compost from chestnut lignocellulosic waste is a possible sustainable management strategy for forests that employs a high-quality renewable organic resource. Characterization of the microbiota involved in composting is essential to better understand the entire process as well as the properties of the final product. Therefore, this study investigated the microbial communities involved in the composting of chestnut residues obtained from tree cleaning and pruning. The culture-independent approach taken highlighted the fact that the microbiota varied only slightly during the process, with the exception of those of the starting substrate and mature compost. The statistical analysis indicated that most of the bacterial and fungal species in the chestnut compost persisted during composting. The dominant microbial population detected during the process belonged to genera known to degrade recalcitrant lignocellulosic materials. Specifically, we identified fungal genera, such as Penicillium, Fusarium, Cladosporium, Aspergillus and Mucor, and prokaryotic species affiliated with Bacilli, Actinobacteria, Flavobacteria and γ-Proteobacteria. The suppressive properties of compost supplements for the biocontrol of Sclerotinia minor and Rhizoctonia solani were also investigated. Compared to pure substrate, the addition of compost to the peat-based growth substrates resulted in a significant reduction of disease in tomato plants of up to 70 % or 51 % in the presence of Sclerotinia minor or Rhizoctonia solani, respectively. The obtained results were related to the presence of putative bio-control agents and plant growth-promoting rhizobacteria belonging to the genera Azotobacter, Pseudomonas, Stenotrophomonas, Bacillus, Flavobacterium, Streptomyces and Actinomyces in the chestnut compost. The composting of chestnut waste may represent a sustainable agricultural practice for disposing of lignocellulosic waste by transforming it into green waste compost that can be used to

  10. Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease.

    Science.gov (United States)

    Ara, Toshiaki; Kurata, Kazuyuki; Hirai, Kaname; Uchihashi, Takayuki; Uematsu, Takashi; Imamura, Yasuhiro; Furusawa, Kiyohumi; Kurihara, Saburo; Wang, Pao-Li

    2009-02-01

    A major factor in the pathogenesis of periodontal disease, which is one of the biofilm infectious diseases, is thought to be lipopolysaccharide (LPS), owing to its ability to cause inflammation and promote tissue destruction. Moreover, the elimination of pathogens and their component LPSs is essential for the successful treatment of periodontal disease. Lipopolysaccharide tolerance is a mechanism that prevents excessive and prolonged responses of monocytes and macrophages to LPS. Since persistence of inflammation is necessary for inflammatory cytokine production, cells other than monocytes and macrophages are thought to maintain the production of cytokines in the presence of LPS. In this study, we investigated whether human gingival fibroblasts (HGFs), the most abundant structural cell in periodontal tissue, might be able to maintain inflammatory cytokine production in the presence of LPS bynot displaying LPS tolerance. Human gingival fibroblasts were pretreated with LPS (from Porphyromonas gingivalis and Escherichia coli) and then treated with LPS, and the amounts of interleukin (IL)-6 and IL-8 in the cell culture supernatants were measured. The expression of negative regulators of LPS signalling (suppressor of cytokine signalling-1, interleukin-1 receptor-associated-kinase M and SH2 domain-containing inositol-5-phosphatase-1) was also examined in LPS-treated HGFs. Human gingival fibroblasts did not display LPS tolerance but maintained production of IL-6 and IL-8 when pretreated with LPS, followed by secondary LPS treatment. Lipopolysaccharide-treated HGFs did not express negative regulators. These results demonstrate that HGFs do not show LPS tolerance and suggest that this characteristic of HGFs sustains the inflammatory response in the presence of virulence factors.

  11. Resting-State Connectivity Predicts Levodopa-Induced Dyskinesias in Parkinson's Disease

    DEFF Research Database (Denmark)

    Herz, Damian M.; Haagensen, Brian N.; Nielsen, Silas H.

    2016-01-01

    Background: Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. Objectives: This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico-striatal connect......Background: Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. Objectives: This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico......-striatal connectivity. Methods: Twelve PD patients with peak-of-dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication. All patients received a single dose of fast-acting soluble levodopa and then underwent resting-state functional magnetic resonance imaging before any...... dyskinesias emerged. Levodopa-induced modulation of cortico-striatal resting-state connectivity was assessed between the putamen and the following 3 cortical regions of interest: supplementary motor area, primary sensorimotor cortex, and right inferior frontal gyrus. These functional connectivity measures...

  12. Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease

    NARCIS (Netherlands)

    de-Graft Aikins, Ama; Arhinful, Daniel K.; Pitchforth, Emma; Ogedegbe, Gbenga; Allotey, Pascale; Agyemang, Charles

    2012-01-01

    This paper examines the challenges and opportunities in establishing and sustaining north-south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to

  13. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    Science.gov (United States)

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  14. Bayesian network analysis reveals alterations to default mode network connectivity in individuals at risk for Alzheimer's disease.

    Science.gov (United States)

    Li, Rui; Yu, Jing; Zhang, Shouzi; Bao, Feng; Wang, Pengyun; Huang, Xin; Li, Juan

    2013-01-01

    Alzheimer's disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.

  15. Investigating changes in brain network properties in HIV-associated neurocognitive disease (HAND) using mutual connectivity analysis (MCA)

    Science.gov (United States)

    Abidin, Anas Zainul; D'Souza, Adora M.; Nagarajan, Mahesh B.; Wismüller, Axel

    2016-03-01

    About 50% of subjects infected with HIV present deficits in cognitive domains, which are known collectively as HIV associated neurocognitive disorder (HAND). The underlying synaptodendritic damage can be captured using resting state functional MRI, as has been demonstrated by a few earlier studies. Such damage may induce topological changes of brain connectivity networks. We test this hypothesis by capturing the functional interdependence of 90 brain network nodes using a Mutual Connectivity Analysis (MCA) framework with non-linear time series modeling based on Generalized Radial Basis function (GRBF) neural networks. The network nodes are selected based on the regions defined in the Automated Anatomic Labeling (AAL) atlas. Each node is represented by the average time series of the voxels of that region. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We tested for differences in these properties in network graphs obtained for 10 subjects (6 male and 4 female, 5 HIV+ and 5 HIV-). Global network properties captured some differences between these subject cohorts, though significant differences were seen only with the clustering coefficient measure. Local network properties, such as local efficiency and the degree of connections, captured significant differences in regions of the frontal lobe, precentral and cingulate cortex amongst a few others. These results suggest that our method can be used to effectively capture differences occurring in brain network connectivity properties revealed by resting-state functional MRI in neurological disease states, such as HAND.

  16. Periodontal disease and its connection to systemic biomarkers of cardiovascular disease in young American Indian/Alaskan natives.

    Science.gov (United States)

    Delange, Nicole; Lindsay, Suzanne; Lemus, Hector; Finlayson, Tracy L; Kelley, Scott T; Gottlieb, Roberta A

    2018-02-01

    Periodontal disease has been shown to be associated with cardiovascular disease (CVD). No known studies evaluate the relationship between periodontal disease status and biomarkers of CVD risk in the American Indian/Alaskan Native (AI/AN) population despite their disproportionately high rates of poor oral health and cardiovascular disease-related outcomes. This study compared levels of interleukin (IL)-6 and C-reactive protein (CRP) across increasing severity of periodontal disease status among younger adults between the ages of 21 and 43 years. Plasma levels of IL-6 and CRP were measured in adult participants (ages 21 to 43 years) as part of a study of periodontal disease and CVD risk among an AI/AN population in southern California (n = 59). Periodontal evaluations were performed and disease status was classified into three categories based on highest probing depth (none/mild: disease or active infection were excluded. Severe periodontitis was significantly associated with increased levels of IL-6 compared with those with none or mild periodontitis before controlling for other variables (P = 0.02), but lacked significance after controlling for sex, BMI, smoking status, and high-density lipoprotein (P = 0.09). Moderate periodontal disease was positively associated with IL-6 levels after controlling for potential confounders (P = 0.01). Periodontal status was not associated with CRP, before or after adjusting for covariates. In this otherwise healthy AI/AN adult sample, moderate periodontal disease compared with none or mild periodontal disease was associated with increased levels of IL-6. High levels of CRP found in this population warrant further research. © 2018 American Academy of Periodontology.

  17. Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer's Disease: A Diffusion MRI Study with DTI and HARDI Models.

    Science.gov (United States)

    Wang, Tao; Shi, Feng; Jin, Yan; Yap, Pew-Thian; Wee, Chong-Yaw; Zhang, Jianye; Yang, Cece; Li, Xia; Xiao, Shifu; Shen, Dinggang

    2016-01-01

    Alzheimer's disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.

  18. Ovarian stimulation and embryo banking for fertility preservation in a woman with severe mixed connective tissue disease: Is it safe?

    Science.gov (United States)

    Sioulas, Vasileios D; Gracia, Clarisa R

    2012-03-01

    To report the first case of using assisted reproductive technologies (ART) for fertility preservation in a patient with mixed connective tissue disease (MCTD), secondary pulmonary hypertension (PH) and antiphospholipid syndrome (APS). Case-report and review of the literature. Academic infertility practice and tertiary care center. A 25-year-old woman with MCTD, complicated with PH and APS, who was scheduled for gonadotoxic therapy Controlled ovarian hyperstimulation, egg retrieval, embryo banking. Successful ART cycle leading to embryo banking without worsening her underlying disease. Following successful embryo cryopreservation, the patient experienced respiratory failure and other severe complications, resulting in a prolonged hospital stay. Controlled ovarian hyperstimulation for embryo banking in women with MCTD, PH and APS may pose a risk for potentially catastrophic complications. A multidisciplinary approach to these patients is necessary to optimize the outcomes of such procedures. More data are needed regarding the safety of fertility preservation technologies in patients with complex medical diseases.

  19. Comparison of immunofluorescence investigations and a new anti-DNA-antibody radioimmunoassay for the diagnosis of connective tissue diseases

    International Nuclear Information System (INIS)

    Neumeier, D.; Vogt, W.; Knedel, M.

    1976-01-01

    The procedure of determining the anti-DNA antibody activity is simplified by high-molecular double strand DNA labelled with 125 I. Cases of suspected connective tissue disease should first be examined by immunofluorescence microscopy, since this method can detect a wider spectrum of diseases with similar symptoms. For a differential diagnosis of SLE, the anti-DNA antibody activity is then investigated by a radioimmunoassay. When assessing the antibody activity, the following criteria should be kept in mind: - Findings of less than 10 units/ml serum do not indicate pathological changes, - Higher antibody activities up to 35 units/ml serum may occur in SLE patients but are also possible in other ANA positive diseases with similar symptoms, - Activities over 35 units/ml serum are nearly always a sign of SLE. (orig./GSE) [de

  20. Comparison of immunofluorescence investigations and a new anti-DNA-antibody radioimmunoassay for the diagnosis of connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Neumeier, D; Vogt, W; Knedel, M

    1976-01-01

    The procedure of determining the anti-DNA antibody activity is simplified by high-molecular double strand DNA labelled with /sup 125/I. Cases of suspected connective tissue disease should first be examined by immunofluorescence microscopy, since this method can detect a wider spectrum of diseases with similar symptoms. For a differential diagnosis of SLE, the anti-DNA antibody activity is then investigated by a radioimmunoassay. When assessing the antibody activity, the following criteria should be kept in mind: - Findings of less than 10 units/ml serum do not indicate pathological changes, - Higher antibody activities up to 35 units/ml serum may occur in SLE patients but are also possible in other ANA positive diseases with similar symptoms, - Activities over 35 units/ml serum are nearly always a sign of SLE.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-15

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  3. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

    Science.gov (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry

    2016-08-19

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease

  4. Occupational diseases in uranium and ore miners in connection with radiation exposure in the Czech Republic

    International Nuclear Information System (INIS)

    Mueller, T.

    2003-01-01

    Dozens cases of diseases are submitted to judgement as occupational diseases every year in the Czech Republic. Patients or attending physicians suggest that these cases are caused by occupational ionizing radiation. Only a part of these cases is qualified as occupational disease. The term 'occupational disease' is rather a juridical term which underlies the right to financial compensation. The causal association with exposure to ionizing radiation cannot be indisputably verified by expert medical opinion. Most diseases, which are proposed as occupational disease, are malignant tumors of the lungs. Total majority of judged cases are lung cancers from radioactive agents. In 2002, a total of 33 cases of lung cancer in former uranium or ore miners have been acknowledged as occupational diseases. The decision about occupational disease is derived from probabilistic approach based on estimation of probability of causation of irradiation on disease origin (methodical guideline No. 15 of Ministry of Health Bulletin, part 9, 1998). The presented paper gives a general information about all judged causes of occupational diseases in former uranium and ore miners in the Czech Republic in 2002. A total of 72 cases were submitted to judgement of conditions of disease origin to the National Radiation Protection Institute in 2002. 67 cases were lung cancers, 1 case was chronic myeloid leukemia, acute myeloid leukemia, basaliom, cancer of larynx and cancer of nasal septum. The probability of causation was assessed as prevailing in 32 cases of lung cancer, borderline in 5 cases and low in other 30 cases of lung cancer. The probability of causation was prevailing in both cases of myeloid leukemia. (author)

  5. The Developmental Origins of Health and Disease and Sustainable Development Goals: mapping the way forward.

    Science.gov (United States)

    Kajee, N; Sobngwi, E; Macnab, A; Daar, A S

    2018-02-01

    In this paper, meant to stimulate debate, we argue that there is considerable benefit in approaching together the implementation of two seemingly separate recent developments. First, on the global development agenda, we have the United Nations General Assembly's 2015 finalized list of 17 Sustainable Development Goals (SDGs). Several of the SDGs are related to health. Second, the field of Developmental Origins of Health and Disease (DOHaD) has garnered enough compelling evidence demonstrating that early exposures in life affect not only future health, but that the effects of that exposure can be transmitted across generations - necessitating that we begin to focus on prevention. We argue that implementing the SDGs and DOHaD together will be beneficial in several ways; and will require attending to multiple, complex and multidisciplinary approaches as we reach the point of translating science to policy to impact. Here, we begin by providing the context for our work and making the case for a mutually reinforcing, synergistic approach to implementing SDGs and DOHaD, particularly in Africa. To do this, we initiate discussion via an early mapping of some of the overlapping considerations between SDGs and DOHaD.

  6. Factors in creating sustainable intersectoral community mobilization for prevention of heart and lung disease.

    Science.gov (United States)

    Bourdages, Josée; Sauvageau, Lyne; Lepage, Céline

    2003-06-01

    This paper describes factors facilitating and working against successful community mobilization in the implementation of an integrated prevention programme for cardiovascular disease and lung cancer in four community settings in Québec, Canada. Implementation evaluation data from several sources showed that over the 3-year period, mobilization was partly achieved in all four communities, although the degree of success varied. The data support those of previous studies showing that several factors are key to effective intersectoral community mobilization: (i) involvement of concerned and influential community members with a commitment to shared goals and a visible community focus; (ii) formation of multi-organization systems among appropriate organizations, recognizing their strengths, resources and competencies, and preserving both their autonomy and interdependence with an appreciation of divergent perspectives; (iii) development of decision-making mechanisms through the setting up of formal structural arrangements to facilitate decisions with clear leadership; (iv) clear definition of objectives, tasks, roles and responsibilities; and (v) official support and legitimization from participating agencies, government authorities, and organizations with adequate resources devoted to partnership building. This study also replicated a number of barriers to the creation of sustainable intersectoral community mobilization, notably the potentially destructive role of power conflicts among the key institutional partners.

  7. Sustainable management of root-knot disease of tomato by neem cake and Glomus fasciculatum

    Directory of Open Access Journals (Sweden)

    Rose Rizvi

    2015-12-01

    Full Text Available A pot experiment was conducted during winter season of 2009–2010 in the department of Botany, AMU, Aligarh, India, to determine the nematicidal potential of organic matter, neem cake at third level of dose, and bioagent, Glomus fasciculatum in terms of various growth parameters of tomato, when inoculated individually as well as concomitantly with respect to root-knot development. Neem cake and G. fasciculatum showed potential for sustainable management while providing nutrient sources for proper plant growth. Disease intensity of root-knot nematode decreased while increasing the doses of neem cake along with the G. fasciculatum. Chlorophyll contents have been found to be increased in single and combined application as well. There is a progressive increase in growth parameters raised in soil amended with 10, 20, and 30 g neem cake/kg soil and inoculated with G. fasciculatum. Significant improvement in the plant growth was observed when G. fasciculatum and neem cake were inoculated simultaneously. Neem cake plus G. fasciculatum reduced the nematodes’ multiplication and root-galling, and increased the plant growth of tomato as compared to unamended and Meloidogyne incognita-inoculated plants. Mycorrhyzation and agronomic parameters were increased due to application of G. fasciculatum alone, but enhanced further when inoculated with neem cake.

  8. Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease

    Directory of Open Access Journals (Sweden)

    de-Graft Aikins Ama

    2012-08-01

    Full Text Available Abstract This paper examines the challenges and opportunities in establishing and sustaining north–south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to bring together multidisciplinary chronic disease researchers based in the UK and Africa to collaborate on research, inform policymaking, train and support postgraduates and create a platform for research dissemination. We review the partnership’s achievements and challenges, applying established criteria for developing successful partnerships. During the funded period we achieved major success in creating a platform for research dissemination through international meetings and publications. Other goals, such as engaging in collaborative research and training postgraduates, were not as successfully realised. Enabling factors included trust and respect between core working group members, a shared commitment to achieving partnership goals, and the collective ability to develop creative strategies to overcome funding challenges. Barriers included limited funding, administrative support, and framework for monitoring and evaluating some goals. Chronic disease research partnerships in low-income regions operate within health research, practice, funding and policy environments that prioritise infectious diseases and other pressing public health and developmental challenges. Their long-term sustainability will therefore depend on integrated funding systems that provide a crucial capacity building bridge. Beyond the specific challenges of chronic disease research, we identify social capital, measurable goals, administrative support, creativity and innovation and funding as five key ingredients that are essential for sustaining research partnerships.

  9. Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease

    Science.gov (United States)

    2012-01-01

    This paper examines the challenges and opportunities in establishing and sustaining north–south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to bring together multidisciplinary chronic disease researchers based in the UK and Africa to collaborate on research, inform policymaking, train and support postgraduates and create a platform for research dissemination. We review the partnership’s achievements and challenges, applying established criteria for developing successful partnerships. During the funded period we achieved major success in creating a platform for research dissemination through international meetings and publications. Other goals, such as engaging in collaborative research and training postgraduates, were not as successfully realised. Enabling factors included trust and respect between core working group members, a shared commitment to achieving partnership goals, and the collective ability to develop creative strategies to overcome funding challenges. Barriers included limited funding, administrative support, and framework for monitoring and evaluating some goals. Chronic disease research partnerships in low-income regions operate within health research, practice, funding and policy environments that prioritise infectious diseases and other pressing public health and developmental challenges. Their long-term sustainability will therefore depend on integrated funding systems that provide a crucial capacity building bridge. Beyond the specific challenges of chronic disease research, we identify social capital, measurable goals, administrative support, creativity and innovation and funding as five key ingredients that are essential for sustaining research partnerships. PMID:22897937

  10. Two-stage decompositions for the analysis of functional connectivity for fMRI with application to Alzheimer’s disease risk

    OpenAIRE

    Caffo, Brian S.; Crainiceanu, Ciprian M.; Verduzco, Guillermo; Joel, Suresh; Mostofsky, Stewart H.; Bassett, Susan Spear; Pekar, James J.

    2010-01-01

    Functional connectivity is the study of correlations in measured neurophysiological signals. Altered functional connectivity has been shown to be associated with a variety of cognitive and memory impairments and dysfunction, including Alzheimer’s disease. In this manuscript we use a two-stage application of the singular value decomposition to obtain data driven population-level measures of functional connectivity in functional magnetic resonance imaging (fMRI). The method is computationally s...

  11. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

    Science.gov (United States)

    Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

    2016-03-01

    It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

  12. [Interrelationship between lower limb varicosity, the grade of connective tissue dysplasia and atrial fibrillation in patients with coronary artery disease].

    Science.gov (United States)

    Forster, O V; Tsarev, O A; Shvarts, Iu G

    2006-01-01

    To determine interrelationship between lower limb varicosity, the clinical grade of non-differentiated dysplasia of the connective tissue and atrial fibrillation in patients with coronary artery disease (CAD). Altogether 156 coronary patients were examined. Persistent atrial fibrillation was present in 58 and chronic in 38 patients. The reference group comprised 60 patients without evident rhythm disorders in persons suffering from CAD. Markers of connective tissue dysplasia () were revealed on the part of the skeleton, joints skin and visceral organs. Lower limb varicosity was recorded as well. The number of the stigmas in the study groups was different. So, in the patient group without rhythm disorders, the mean number of the stigmas was equal to 3, which is a variant of normal. In the groups with persistent and constant AF, this indicator was equal to 4.7 and 5.2 respectively (patrial fibrilation there is a direct close correlation between the signs of connective tissue dysplasia and lower limb varicosity. In patients with persistent AF lower limb varicosity occurs more frequently than in CAD patients with normal rhythm.

  13. The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

    Science.gov (United States)

    Liu, Xiaozheng; Chen, Wei; Tu, Yunhai; Hou, Hongtao; Huang, Xiaoyan; Chen, Xingli; Guo, Zhongwei; Bai, Guanghui; Chen, Wei

    2018-01-01

    Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer's disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

  14. Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yuxia Li

    2016-01-01

    Full Text Available Individuals diagnosed with mild cognitive impairment (MCI are at high risk of transition to Alzheimer’s disease (AD. However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD.

  15. Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F.; Bradna, P.; Pospisil, M.; Kubicek, J.; Vizda, J.; Kafka, P.; Palicka, V.; Mazurova, Y.

    1987-02-01

    Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

  16. Bilateral functional connectivity of the basal ganglia in patients with Parkinson's disease and its modulation by dopaminergic treatment.

    Science.gov (United States)

    Little, Simon; Tan, Huiling; Anzak, Anam; Pogosyan, Alek; Kühn, Andrea; Brown, Peter

    2013-01-01

    Parkinson's disease is characterised by excessive subcortical beta oscillations. However, little is known about the functional connectivity of the two basal ganglia across hemispheres and specifically the role beta plays in this. We recorded local field potentials from the subthalamic nucleus bilaterally in 23 subjects with Parkinson's disease at rest, on and off medication. We found suppression of low beta power in response to levodopa (t22 = -4.4, pbasal ganglia networks may have to be approached separately with independent sensing and stimulation during adaptive deep brain stimulation. In addition, our findings highlight the functional distinction between the lower and upper beta frequency ranges and between amplitude co-modulation and phase synchronization across subthalamic nuclei.

  17. Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F; Bradna, P; Pospisil, M; Kubicek, J; Vizda, J; Kafka, P; Palicka, V; Mazurova, Y

    1987-02-01

    Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

  18. Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index.

    Science.gov (United States)

    Lee, Chunsoo; Lee, Kyungsang; Yu, Hyewon; Ryu, Seung-Ho; Moon, Seok Woo; Han, Changsu; Lee, Jun-Young; Lee, Young Min; Kim, Shin-Gyeom; Kim, Ki Woong; Lee, Dong Woo; Kim, Seong Yoon; Lee, Sang-Yeol; Bae, Jae Nam; Jung, Young-Eun; Kim, Jeong Lan; Kim, Byung-Soo; Shin, Il-Seon; Kim, Young Hoon; Kim, Bong Jo; Kang, Hyo Shin; Myung, Woojae; Carroll, Bernard J; Kim, Doh Kwan

    2017-08-01

    Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m). Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002). In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

  19. Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study.

    Directory of Open Access Journals (Sweden)

    Chang Mo Moon

    Full Text Available Diagnostic delay frequently occurs in Crohn's disease (CD patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn's Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that older age at diagnosis (≥40 years (p = 0.014, concomitant upper gastrointestinal (UGI disease (p = 0.012 and penetrating disease behavior at diagnosis (p = 0.001 were positively associated with long diagnostic delay (≥18 months. During the longitudinal follow-up, long diagnostic delay was independently predictive of further development of intestinal stenosis (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07-1.93; p = 0.017, internal fistulas (HR, 1.62; 95% CI, 1.12-2.33; p = 0.011, and perianal fistulas (HR, 1.38; 95% CI, 1.06-1.80; p = 0.016. However, as for the risk of abscess formation, bowel perforation, and CD-related abdominal surgery, no significant association with diagnostic delay was observed. Older age at diagnosis, UGI involvement, and penetrating behavior are associated with long diagnostic delay in Korean CD patients. Moreover, diagnostic delay is associated with an increased risk of CD-related complications such as intestinal stenosis, internal fistulas, and perianal fistulas.

  20. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon

    Directory of Open Access Journals (Sweden)

    Po-Chang Wu

    2013-08-01

    Conclusion: The nailfold capillaroscopic (NC patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity.

  1. Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

    NARCIS (Netherlands)

    Trujillo, J.P.; Gerrits, N.J.H.M.; Vriend, C.; Berendse, H.W.; van den Heuvel, O.A.; van der Werf, Y.D.

    2015-01-01

    Objective: Parkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully

  2. Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease

    NARCIS (Netherlands)

    A. Hafkemeijer (Anne); C. Möller (Christiane); E.G.P. Dopper (Elise); L.C. Jiskoot (Lize); T.M. Schouten (Tijn M.); J.C. van Swieten (John); W.M. van der Flier (Wiesje); H. Vrenken (Hugo); Y. Pijnenburg (Yolande); F. Barkhof (Frederik); P. Scheltens (Philip); J. van der Grond (Jeroen); S.A.R.B. Rombouts (Serge)

    2015-01-01

    textabstractIntroduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. Early differentiation between both types of dementia may be challenging due to heterogeneity and overlap of symptoms. Here, we apply resting

  3. Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study)

    DEFF Research Database (Denmark)

    Buhl, Sine Schnoor; Steenholdt, Casper; Brynskov, Jørn

    2014-01-01

    INTRODUCTION: Infliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance therapy in patients in remission should be considered in order......, biochemical and endoscopic remission (ie, Crohn's Disease Activity Index (CDAI) score therapy. The primary end point...... a patient exhibits sustained remission. Study results will be published in an English language scientific medical journal. The study is approved by the Danish Medicines Agency (EudraCT-number: 2012-002702-51) and the Regional Ethics Committee of Region Hovedstaden Denmark (Approval-number: H-4...

  4. Use of radiations and radioisotopes for investigating problems connected with parasitic diseases of animals in India

    International Nuclear Information System (INIS)

    Tewari, H.C.; Singh, K.S.

    1979-01-01

    The status of the present knowledge regarding the use of isotopes and radiations for studies of animal parasitic diseases in India is reviewed. The concepts in immunology of metazoan parasites with relevance to vaccination have been discussed. A brief review of radiation attenuated vaccines against certain economically important species of helminth parasites and the use of radioisotopes for pathophysiological investigations and for the study of anthelmintic activity is given. (auth.)

  5. Crop diversification can contribute to disease risk control in sustainable biofuels production

    OpenAIRE

    Smith, VH; McBride, RC; Shurin, JB; Bever, JD; Crews, TE; Tilman, GD

    2015-01-01

    © The Ecological Society of America. Global demand for transportation fuels will increase rapidly during the upcoming decades, and concerns about fossil-fuel consumption have stimulated research on renewable biofuels that can be sustainably produced from biological feedstocks. However, if unchecked, pathogens and parasites are likely to infect these cultivated biofuel feedstocks, greatly reducing crop yields and potentially threatening the sustainability of renewable bioenergy production effo...

  6. In-silico analysis of inflammatory bowel disease (IBD GWAS loci to novel connections.

    Directory of Open Access Journals (Sweden)

    Md Mesbah-Uddin

    Full Text Available Genome-wide association studies (GWASs for many complex diseases, including inflammatory bowel disease (IBD, produced hundreds of disease-associated loci-the majority of which are noncoding. The number of GWAS loci is increasing very rapidly, but the process of translating single nucleotide polymorphisms (SNPs from these loci to genomic medicine is lagging. In this study, we investigated 4,734 variants from 152 IBD associated GWAS loci (IBD associated 152 lead noncoding SNPs identified from pooled GWAS results + 4,582 variants in strong linkage-disequilibrium (LD (r2 ≥0.8 for EUR population of 1K Genomes Project using four publicly available bioinformatics tools, e.g. dbPSHP, CADD, GWAVA, and RegulomeDB, to annotate and prioritize putative regulatory variants. Of the 152 lead noncoding SNPs, around 11% are under strong negative selection (GERP++ RS ≥2; and ~30% are under balancing selection (Tajima's D score >2 in CEU population (1K Genomes Project--though these regions are positively selected (GERP++ RS <0 in mammalian evolution. The analysis of 4,734 variants using three integrative annotation tools produced 929 putative functional SNPs, of which 18 SNPs (from 15 GWAS loci are in concordance with all three classifiers. These prioritized noncoding SNPs may contribute to IBD pathogenesis by dysregulating the expression of nearby genes. This study showed the usefulness of integrative annotation for prioritizing fewer functional variants from a large number of GWAS markers.

  7. How is the sustainability of chronic disease health programmes empirically measured in hospital and related healthcare services?—a scoping review

    Science.gov (United States)

    Francis, Linda; Dunt, David; Cadilhac, Dominique A

    2016-01-01

    Objectives Programmes to address chronic disease are a focus of governments worldwide. Despite growth in ‘implementation science’, there is a paucity of knowledge regarding the best means to measure sustainability. The aim of this review was to summarise current practice for measuring sustainability outcomes of chronic disease health programmes, providing guidance for programme planners and future directions for the academic field. Settings A scoping review of the literature spanning 1985–2015 was conducted using MEDLINE, CINAHL, PsychINFO and The Cochrane Library limited to English language and adults. Main search terms included chronic disease, acute care, sustainability, institutionalisation and health planning. A descriptive synthesis was required. Settings included primary care, hospitals, mental health centres and community health. Participants Programmes included preventing or managing chronic conditions including diabetes, heart disease, depression, respiratory disease, cancer, obesity, dental hygiene and multiple chronic diseases. Primary and secondary outcome measures Outcome measures included clarifying a sustainability definition, types of methodologies used, timelines for assessment, criteria levels to determine outcomes and how methodology varies between intervention types. Results Among 153 abstracts retrieved, 87 were retained for full article review and 42 included in the qualitative synthesis. Five definitions for sustainability outcome were identified with ‘maintenance of programme activities’ most frequent. Achieving sustainability was dependent on inter-relationships between various organisational and social contexts supporting a broad scale approach to evaluation. An increasing trend in use of mixed methods designs over multiple time points to determine sustainability outcomes was found. Conclusions Despite the importance and investment in chronic disease programmes, few studies are undertaken to measure sustainability. Methods to

  8. How is the sustainability of chronic disease health programmes empirically measured in hospital and related healthcare services?-a scoping review.

    Science.gov (United States)

    Francis, Linda; Dunt, David; Cadilhac, Dominique A

    2016-05-31

    Programmes to address chronic disease are a focus of governments worldwide. Despite growth in 'implementation science', there is a paucity of knowledge regarding the best means to measure sustainability. The aim of this review was to summarise current practice for measuring sustainability outcomes of chronic disease health programmes, providing guidance for programme planners and future directions for the academic field. A scoping review of the literature spanning 1985-2015 was conducted using MEDLINE, CINAHL, PsychINFO and The Cochrane Library limited to English language and adults. Main search terms included chronic disease, acute care, sustainability, institutionalisation and health planning. A descriptive synthesis was required. Settings included primary care, hospitals, mental health centres and community health. Programmes included preventing or managing chronic conditions including diabetes, heart disease, depression, respiratory disease, cancer, obesity, dental hygiene and multiple chronic diseases. Outcome measures included clarifying a sustainability definition, types of methodologies used, timelines for assessment, criteria levels to determine outcomes and how methodology varies between intervention types. Among 153 abstracts retrieved, 87 were retained for full article review and 42 included in the qualitative synthesis. Five definitions for sustainability outcome were identified with 'maintenance of programme activities' most frequent. Achieving sustainability was dependent on inter-relationships between various organisational and social contexts supporting a broad scale approach to evaluation. An increasing trend in use of mixed methods designs over multiple time points to determine sustainability outcomes was found. Despite the importance and investment in chronic disease programmes, few studies are undertaken to measure sustainability. Methods to evaluate sustainability are diverse with some emerging patterns in measurement found. Use of mixed

  9. Movement analysis of free-grazing domestic ducks in Poyang Lake, China: a disease connection.

    Science.gov (United States)

    Prosser, Diann J; Palm, Eric C; Takekawa, John Y; Zhao, Delong; Xiao, Xiangming; Li, Peng; Liu, Ying; Newman, Scott H

    2016-01-01

    Previous work suggests domestic poultry are important contributors to the emergence and transmission of highly pathogenic avian influenza throughout Asia. In Poyang Lake, China, domestic duck production cycles are synchronized with arrival and departure of thousands of migratory wild birds in the area. During these periods, high densities of juvenile domestic ducks are in close proximity to migratory wild ducks, increasing the potential for the virus to be transmitted and subsequently disseminated via migration. In this paper, we use GPS dataloggers and dynamic Brownian bridge models to describe movements and habitat use of free-grazing domestic ducks in the Poyang Lake basin and identify specific areas that may have the highest risk of H5N1 transmission between domestic and wild birds. Specifically, we determine relative use by free-grazing domestic ducks of natural wetlands, which are the most heavily used areas by migratory wild ducks, and of rice paddies, which provide habitat for resident wild ducks and lower densities of migratory wild ducks. To our knowledge, this is the first movement study on domestic ducks, and our data show potential for free-grazing domestic ducks from farms located near natural wetlands to come in contact with wild waterfowl, thereby increasing the risk for disease transmission. This study provides an example of the importance of movement ecology studies in understanding dynamics such as disease transmission on a complicated landscape.

  10. Movement analysis of free-grazing domestic ducks in Poyang Lake, China: A disease connection

    Science.gov (United States)

    Prosser, Diann J.; Palm, Eric C.; Takekawa, John Y.; Zhao, Delong; Xiao, Xiangming; Li, Peng; Liu, Ying; Newman, Scott H.

    2015-01-01

    Previous work suggests domestic poultry are important contributors to the emergence and transmission of highly pathogenic avian influenza throughout Asia. In Poyang Lake, China, domestic duck production cycles are synchronized with arrival and departure of thousands of migratory wild birds in the area. During these periods, high densities of juvenile domestic ducks are in close proximity to migratory wild ducks, increasing the potential for the virus to be transmitted and subsequently disseminated via migration. In this paper, we use GPS dataloggers and dynamic Brownian bridge models to describe movements and habitat use of free-grazing domestic ducks in the Poyang Lake basin and identify specific areas that may have the highest risk of H5N1 transmission between domestic and wild birds. Specifically, we determine relative use by free-grazing domestic ducks of natural wetlands, which are the most heavily used areas by migratory wild ducks, and of rice paddies, which provide habitat for resident wild ducks and lower densities of migratory wild ducks. To our knowledge, this is the first movement study on domestic ducks, and our data show potential for free-grazing domestic ducks from farms located near natural wetlands to come in contact with wild waterfowl, thereby increasing the risk for disease transmission. This study provides an example of the importance of movement ecology studies in understanding dynamics such as disease transmission on a complicated landscape.

  11. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

    2017-06-15

    Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24

  12. Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

    Science.gov (United States)

    Feder, Stephan; Sundermann, Benedikt; Wersching, Heike; Teuber, Anja; Kugel, Harald; Teismann, Henning; Heindel, Walter; Berger, Klaus; Pfleiderer, Bettina

    2017-11-01

    Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson's disease.

    Science.gov (United States)

    Cagnan, Hayriye; Duff, Eugene Paul; Brown, Peter

    2015-06-01

    Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance

  14. Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

    Science.gov (United States)

    Peguero, Julio G; Arenas, Ivan; Lamas, Gervasio A

    2014-08-01

    Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Similar circuits but different connectivity patterns between the cerebellum, basal ganglia, and supplementary motor area in early Parkinson's disease patients and controls during predictive motor timing.

    Science.gov (United States)

    Husárová, Ivica; Mikl, Michal; Lungu, Ovidiu V; Mareček, Radek; Vaníček, Jiří; Bareš, Martin

    2013-10-01

    The cerebellum, basal ganglia (BG), and other cortical regions, such as supplementary motor area (SMA) have emerged as important structures dealing with various aspects of timing, yet the modulation of functional connectivity between them during motor timing tasks remains unexplored. We used dynamic causal modeling to investigate the differences in effective connectivity (EC) between these regions and its modulation by behavioral outcome during a motor timing prediction task in a group of 16 patients with early Parkinson's disease (PD) and 17 healthy controls. Behavioral events (hits and errors) constituted the driving input connected to the cerebellum, and the modulation in connectivity was assessed relative to the hit condition (successful interception of target). The driving input elicited response in the target area, while modulatory input changed the specific connection strength. The neuroimaging data revealed similar structure of intrinsic connectivity in both groups with unidirectional connections from cerebellum to both sides of the BG, from BG to the SMA, and then from SMA to the cerebellum. However, the type of intrinsic connection was different between two groups. In the PD group, the connection between the SMA and cerebellum was inhibitory in comparison to the HC group, where the connection was activated. Furthermore, the modulation of connectivity by the performance in the task was different between the two groups, with decreased connectivity between the cerebellum and left BG and SMA and a more pronounced symmetry of these connections in controls. In the same time, there was an increased EC between the cerebellum and both sides of BG with more pronounced asymmetry (stronger connection with left BG) in patients. In addition, in the PD group the modulatory input strengthened inhibitory connectivity between the SMA and the cerebellum, while in the HC group the excitatory connection was slightly strengthened. Our findings indicate that although early PD

  16. Automated analysis of connected speech reveals early biomarkers of Parkinson's disease in patients with rapid eye movement sleep behaviour disorder.

    Science.gov (United States)

    Hlavnička, Jan; Čmejla, Roman; Tykalová, Tereza; Šonka, Karel; Růžička, Evžen; Rusz, Jan

    2017-02-02

    For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.

  17. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease.

    Science.gov (United States)

    Shah, Raj C; Kamphuis, Patrick J; Leurgans, Sue; Swinkels, Sophie H; Sadowsky, Carl H; Bongers, Anke; Rappaport, Stephen A; Quinn, Joseph F; Wieggers, Rico L; Scheltens, Philip; Bennett, David A

    2013-01-01

    Souvenaid® containing Fortasyn® Connect is a medical food designed to support synapse synthesis in persons with Alzheimer's disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal membranes. Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed. In a 24-week, double-masked clinical trial at 48 clinical centers, 527 participants taking AD medications [52% women, mean age 76.7 years (Standard Deviation, SD = 8.2), and mean Mini-Mental State Examination score 19.5 (SD = 3.1, range 14-24)] were randomized 1:1 to daily, 125-mL (125 kcal), oral intake of the active product (Souvenaid) or an iso-caloric control. The primary outcome of cognition was assessed by the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Compliance was calculated from daily diary recordings of product intake. Statistical analyses were performed using mixed models for repeated measures. Cognitive performance as assessed by ADAS-cog showed decline over time in both control and active study groups, with no significant difference between study groups (difference =0.37 points, Standard Error, SE = 0.57, p = 0.513). No group differences in adverse event rates were found and no clinically relevant differences in blood safety parameters were noted. Overall compliance was high (94.1% [active] and 94.5% [control]), which was confirmed by significant changes in blood (nutritional) biomarkers. Add-on intake of Souvenaid during 24 weeks did not slow cognitive decline in persons treated for mild-to-moderate AD. Souvenaid was well tolerated in combination with standard care AD medications. DUTCH TRIAL REGISTER NUMBER: NTR1683.

  18. Connection Between Non-Alcoholic Fatty Liver Disease and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Oprea-Călin Gabriela

    2014-06-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the commonest liver condition in the world, accounting for 20-30% of the adult population, and encompasses a spectrum of liver disorders characterized by fat accumulation within the liver, associated or not with varying degrees of hepatic inflammation and liver fibrosis through to cirrhosis. The prevalence of NAFLD increases significantly in the presence of obesity (60-80% and type 2 diabetes (60%. NAFLD is associated with metabolic disorders (type 2 diabetes, obesity and hyperlipidemia grouped together as the metabolic syndrome (MetS. It is now regarded as the hepatic manifestation of this syndrome and is closely linked to insulin resistance (IR.The presence of NAFLD predicts the development of type 2 diabetes independent of established risk factors. NAFLD patients should therefore be screened for diabetes, including by the Oral Glucose Tolerance Test (OGTT if there any abnormalities of fasting blood glucose (FBG and given appropriate lifestyle advice. Early diagnosis with the institution of lifestyle measures could help prevent or retard the onset of these metabolic disorders. Type 2 diabetes causes more severe non-alcoholic steatohepatitis (NASH, and patients with diabetes have an increased risk for cirrhosis and the development of hepatocellular carcinoma (HCC

  19. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts...... that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

  20. Sustainability of the integrated chronic disease management model at primary care clinics in South Africa

    Directory of Open Access Journals (Sweden)

    Ozayr H. Mahomed

    2016-11-01

    Conclusion: The less than optimal involvement of clinical leadership (doctors, negative staff behaviour towards the ICDM, adaptability or flexibility of the model to adapt to external factors and infrastructure limitation have the potential to negatively affect the sustainability and scale-up of the model.

  1. Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease.

    Science.gov (United States)

    Popat, R A; Van Den Eeden, S K; Tanner, C M; Kamel, F; Umbach, D M; Marder, K; Mayeux, R; Ritz, B; Ross, G W; Petrovitch, H; Topol, B; McGuire, V; Costello, S; Manthripragada, A D; Southwick, A; Myers, R M; Nelson, L M

    2011-05-01

    In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04). In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  2. Bilateral Functional Connectivity of the Basal Ganglia in Patients with Parkinson’s Disease and Its Modulation by Dopaminergic Treatment

    Science.gov (United States)

    Little, Simon; Tan, Huiling; Anzak, Anam; Pogosyan, Alek; Kühn, Andrea; Brown, Peter

    2013-01-01

    Parkinson’s disease is characterised by excessive subcortical beta oscillations. However, little is known about the functional connectivity of the two basal ganglia across hemispheres and specifically the role beta plays in this. We recorded local field potentials from the subthalamic nucleus bilaterally in 23 subjects with Parkinson’s disease at rest, on and off medication. We found suppression of low beta power in response to levodopa (t22 = −4.4, psynchronisation in the beta band and found significant amplitude co-modulation and phase locking values in 17 and 16 subjects respectively, off medication. There was a dissociable effect of levodopa on these measures, with a significant suppression only in low beta phase locking value (t22 = −2.8, p = 0.01) and not amplitude co-modulation. The absolute mean values of amplitude co-modulation (0.40±0.03) and phase synchronisation (0.29±0.02) off medication were, however, relatively low, suggesting that the two basal ganglia networks may have to be approached separately with independent sensing and stimulation during adaptive deep brain stimulation. In addition, our findings highlight the functional distinction between the lower and upper beta frequency ranges and between amplitude co-modulation and phase synchronization across subthalamic nuclei. PMID:24376574

  3. Sustaining a Focus on Health Equity at the Centers for Disease Control and Prevention Through Organizational Structures and Functions.

    Science.gov (United States)

    Dean, Hazel D; Roberts, George W; Bouye, Karen E; Green, Yvonne; McDonald, Marian

    2016-01-01

    The public health infrastructure required for achieving health equity is multidimensional and complex. The infrastructure should be responsive to current and emerging priorities and capable of providing the foundation for developing, planning, implementing, and evaluating health initiatives. This article discusses these infrastructure requirements by examining how they are operationalized in the organizational infrastructure for promoting health equity at the Centers for Disease Control and Prevention, utilizing the nation's premier public health agency as a lens. Examples from the history of the Centers for Disease Control and Prevention's work in health equity from its centers, institute, and offices are provided to identify those structures and functions that are critical to achieving health equity. Challenges and facilitators to sustaining a health equity organizational infrastructure, as gleaned from the Centers for Disease Control and Prevention's experience, are noted. Finally, we provide additional considerations for expanding and sustaining a health equity infrastructure, which the authors hope will serve as "food for thought" for practitioners in state, tribal, or local health departments, community-based organizations, or nongovernmental organizations striving to create or maintain an impactful infrastructure to achieve health equity.

  4. Parvovirus B19 infection in an adult presenting with connective tissue disease-like symptoms: a report of the clinical and histological findings.

    Science.gov (United States)

    Liles, J E; Shalin, S C; White, B A; Trigg, L B; Kaley, J R

    2017-06-15

    Parvovirus B19 infections in adults are usually associated with nonspecific and mild symptoms. However, cases presenting with a lupus-like syndrome have been described, leading to the hypothesis that parvovirus infection can induce connective tissue disease. Various histopathologic features of cutaneous manifestations of parvovirus have been reported, including features which overlap with those of connective tissue disease. Herein, we discuss an unusual case of Parvovirus  B19 infection in a middle-aged woman. The biopsy results showed granulomatous vasculitis and were consistent with the previously described superantigen id reaction. This case demonstrates that infectious causes should be considered in the differential diagnosis for granulomatous vasculitis and clinicopathologic correlation is required for accurate diagnosis. We also provide a review of the literature highlighting the possible role of parvovirus in induction of a connective tissue disease-like presentation.

  5. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease

    Science.gov (United States)

    Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher

    2016-01-01

    ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. PMID:26873097

  6. Impaired white matter connections of the limbic system networks associated with impaired emotional memory in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Xiaoshu Li

    2016-10-01

    Full Text Available Background: Discrepancies persist regarding retainment of emotional enhancement of memory (EEM in mild cognitive impairment (MCI and early Alzheimer’s disease (AD patients. In addition, the neural mechanisms are still poorly understood, little is known about emotional memory related changes in white matter (WM.Objective: To observe whether EEM is absent in amnestic MCI (aMCI and AD patients, and to investigate if emotional memory is associated with WM connections and gray matters (GM of the limbic system networks. Methods: Twenty-one AD patients, 20 aMCI patients and 25 normal controls participated in emotional picture recognition tests and MRI scanning. Tract-based spatial statistics (TBSS and voxel-based morphometry (VBM methods were used to determine white and gray matter changes of patients. Fourteen regions of interest (ROI of WM and 20 ROIs of GM were then selected for the correlation analyses with behavioral scores. Results: The EEM effect was lost in AD patients. Both white and gray matter of the limbic system networks were impaired in AD patients. Significant correlations or tendencies between the bilateral uncinate fasciculus, corpus callosum (genu and body, left cingulum bundle, left parahippocampal WM and the recognition sensitivity of emotional valence pictures, and significant correlations or tendencies between the splenium of corpus callosum, left cingulum bundle, left crus of fornix and stria terminalis and the recognition sensitivity of EEM were found. The volume of left amygdala, bilateral insula, medial frontal lobe, anterior and middle cingulum gyrus were positively correlated with the recognition sensitivity of emotional photos, and the right precuneus was positively correlated with the negative EEM effect. However, the affected brain areas of aMCI patients were more localized, and aMCI patients benefited only from positive stimuli. Conclusion: There are impairments of the limbic system networks of AD patients. Damaged WM

  7. The semantic connectivity map: an adapting self-organising knowledge discovery method in data bases. Experience in gastro-oesophageal reflux disease.

    Science.gov (United States)

    Buscema, Massimo; Grossi, Enzo

    2008-01-01

    We describe here a new mapping method able to find out connectivity traces among variables thanks to an artificial adaptive system, the Auto Contractive Map (AutoCM), able to define the strength of the associations of each variable with all the others in a dataset. After the training phase, the weights matrix of the AutoCM represents the map of the main connections between the variables. The example of gastro-oesophageal reflux disease data base is extremely useful to figure out how this new approach can help to re-design the overall structure of factors related to complex and specific diseases description.

  8. A 10-year institutional experience with open branched graft reconstruction of aortic aneurysms in connective tissue disorders versus degenerative disease.

    Science.gov (United States)

    Hicks, Caitlin W; Lue, Jennifer; Glebova, Natalia O; Ehlert, Bryan A; Black, James H

    2017-11-01

    Aortic reconstruction for complex thoracoabdominal aortic aneurysms (TAAAs) can be challenging, especially in patients with connective tissue disorders (CTDs) in whom tissue fragility is a major concern. Branched graft reconstruction is a more complex operation compared with inclusion patch repair of the aorta but is frequently necessary in patients with CTDs or other pathologies because of anatomic reasons. We describe our institutional experience with open branched graft reconstruction of aortic aneurysms and compare outcomes for patients with CTDs vs degenerative pathologies. We retrospectively analyzed all patients undergoing open aortic reconstruction using branched grafts at our institution between July 2006 and December 2015. Postoperative outcomes, including perioperative morbidity and mortality, midterm graft patency, and the development of new aneurysms, were compared for patients with CTD vs degenerative disease. During the 10-year study period, 137 patients (CTD, 29; degenerative, 108) underwent aortic repair with branched graft reconstruction. CTD patients were significantly younger (39 ± 1.9 vs 68 ± 1.0 years; P disease, coronary artery disease; P degenerative disease. Perioperative mortality (CTD: 10% [n = 3] vs degenerative: 6% [n = 6]; P = .40) and any complication (62% vs 55%; P = .47) were similar between groups. At a median follow-up time of 14.5 months (interquartile range: 6.5, 43.9 months), CTD patients were more likely to develop both new aortic (21%) and nonaortic (14%) aneurysms compared with the degenerative group (7% and 4% for aortic and nonaortic aneurysms, respectively; P = .02). Loss of branch graft patency occurred in 0 of 99 grafts (0%) in CTD patients and in 13 of 167 grafts (7.8%) in degenerative disease patients (P = .005). Loss of branch graft patency occurred most commonly in left renal artery bypass grafts (77%) and was clinically asymptomatic (creatinine: 1.77 ± 0.13 mg/dL currently vs 1.41 ± 0

  9. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease.

    Science.gov (United States)

    Bouquet, Jerome; Soloski, Mark J; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher; Aucott, John N; Chiu, Charles Y

    2016-02-12

    Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the "window period" of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. Lyme disease is the most common tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite antibiotic treatment. To better understand the role of the human host response in acute Lyme disease and the

  10. The cross-cutting contribution of the end of neglected tropical diseases to the sustainable development goals.

    Science.gov (United States)

    Bangert, Mathieu; Molyneux, David H; Lindsay, Steve W; Fitzpatrick, Christopher; Engels, Dirk

    2017-04-04

    The Sustainable Development Goals (SDGs) call for an integrated response, the kind that has defined Neglected Tropical Diseases (NTDs) efforts in the past decade.NTD interventions have the greatest relevance for SDG3, the health goal, where the focus on equity, and its commitment to reaching people in need of health services, wherever they may live and whatever their circumstances, is fundamentally aligned with the target of Universal Health Coverage. NTD interventions, however, also affect and are affected by many of the other development areas covered under the 2030 Agenda. Strategies such as mass drug administration or the programmatic integration of NTD and WASH activities (SDG6) are driven by effective global partnerships (SDG17). Intervention against the NTDs can also have an impact on poverty (SDG1) and hunger (SDG2), can improve education (SDG4), work and economic growth (SDG8), thereby reducing inequalities (SDG10). The community-led distribution of donated medicines to more than 1 billion people reinforces women's empowerment (SDG5), logistics infrastructure (SDG9) and non-discrimination against disability (SDG16). Interventions to curb mosquito-borne NTDs contribute to the goals of urban sustainability (SDG11) and resilience to climate change (SDG13), while the safe use of insecticides supports the goal of sustainable ecosystems (SDG15). Although indirectly, interventions to control water- and animal-related NTDs can facilitate the goals of small-scale fishing (SDG14) and sustainable hydroelectricity and biofuels (SDG7).NTDs proliferate in less developed areas in countries across the income spectrum, areas where large numbers of people have little or no access to adequate health care, clean water, sanitation, housing, education, transport and information. This scoping review assesses how in this context, ending the epidemic of the NTDs can impact and improve our prospects of attaining the SDGs.

  11. [Mixed connective tissue disease: prevalence and clinical characteristics in African black, study of 7 cases in Gabon and review of the literature].

    Science.gov (United States)

    Missounga, Landry; Ba, Josaphat Iba; Nseng Nseng Ondo, Ingrid Rosalie; Nziengui Madjinou, Maria Ines Carine; Malekou, Doris; Mouendou Mouloungui, Emeline Gracia; Nzengue, Emmanuel Ecke; Boguikouma, Jean Bruno; Kombila, Moussavou

    2017-01-01

    The literature reports that mixed connective tissue disease seems more frequent in the black population and among Asians. This study aims to determine the prevalence of mixed connective tissue disease (MCTD) among connective tissue disorders and all rheumatologic pathologies in a hospital population in Gabon as well as to describe the clinical features of this disease. We conducted a retrospective study by reviewing the medical records of patients treated for mixed connective tissue disease (Kasukawa criteria) and other entities of connective tissue disorders (ACR criteria) in the Division of Rheumatology at the University Hospital in Libreville between January 2010 and December 2015. For each case of MCTD the parameters studied were articular and extra-articular manifestations, anti-U1RNP antibodies levels, patient's evolution. Over a period of 6 years, data were collected by medical records of 7 patients out of 6050 patients and 67 cases of connective tissue disorders, reflecting a prevalence of 0.11% and 10.44% respectively. the 7 patients were women (100%), with an average age of 39.5 years. Articular manifestations included: polyarthritis, myalgias, chubby fingers and Raynaud's phenomenon in 87.5%, 87.5%, 28.6% and 14% respectively. The 7 patients had high anti-U1RNP antibodies levels, ranging between 5 and 35N (N≤ 7 IU). A case of death due to pulmonary arterial hypertension (PAH) was certified. This is the largest case series of MCTD reported in Black Africa. The disease seems to be rare among the black Africans; the reason could be genetic. The demographic and clinical aspects appear similar to those in Caucasians, Asians and Blacks except for a low frequency of Raynaud?s phenomenon among Blacks.

  12. iConnect CKD - Virtual Medical Consulting: a web-based Chronic Kidney Disease, Hypertension and Diabetes Integrated Care Program.

    Science.gov (United States)

    Katz, Ivor J; Pirabhahar, Saiyini; Williamson, Paula; Raghunath, Vishwas; Brennan, Frank; O'Sullivan, Anthony; Youssef, George; Lane, Cathie; Jacobson, Gary; Feldman, Peter; Kelly, John

    2017-05-04

    Chronic kidney disease (CKD) patients overwhelm specialist services and can potentially be managed in the primary care (PC). Opportunistic screening of high risk (HR) patients and follow-up in PC is the most sustainable model of care. A 'virtual consultation' (VC) model instead of traditional face to face (F2F) consultations was used, aiming to assess efficacy and safety of the model. Seventy patients were recruited from PC sites and hospital clinics, and followed for one year. The HR patients (eGFR 30 mg/mmol/L) were randomised to either VC or F2F. Patients were monitored 6 monthly by a Clinical Nurse Specialist (CNS). The specialist team provided virtual or clinical support and included a Nephrologist, Endocrinologist, Cardiologist and Renal 'Palliative' Supportive Care. Sixty one (87%) patients were virtually tracked or consulted with 14 (23%) being HR. At 12 months there was no difference in outcomes between VC and F2F patients. All patients were successfully monitored. GPs reported high level of satisfaction and supported the model, but found software integration challenging. Patients found the system attractive and felt well managed. Specialist consults occurred within a week and if a second specialist opinion was required it took another two weeks. The program demonstrated safe, expedited and efficient follow up with a clinical and web based program. Support from the GPs and patients was encouraging, despite logistical issues. Ongoing evaluation of VC services will continue and feasibility to larger networks and more chronic diseases remains the long term goal. This article is protected by copyright. All rights reserved.

  13. Towards sustainable partnerships in global health: the case of the CRONICAS Centre of Excellence in Chronic Diseases in Peru.

    Science.gov (United States)

    Miranda, J Jaime; Bernabé-Ortiz, Antonio; Diez-Canseco, Francisco; Málaga, Germán; Cárdenas, María K; Carrillo-Larco, Rodrigo M; Lazo-Porras, María; Moscoso-Porras, Miguel; Pesantes, M Amalia; Ponce, Vilarmina; Araya, Ricardo; Beran, David; Busse, Peter; Boggio, Oscar; Checkley, William; García, Patricia J; Huicho, Luis; León-Velarde, Fabiola; Lescano, Andrés G; Mohr, David C; Pan, William; Peiris, David; Perel, Pablo; Rabadán-Diehl, Cristina; Rivera-Chira, Maria; Sacksteder, Katherine; Smeeth, Liam; Trujillo, Antonio J; Wells, Jonathan C K; Yan, Lijing L; García, Héctor H; Gilman, Robert H

    2016-06-02

    Human capital requires opportunities to develop and capacity to overcome challenges, together with an enabling environment that fosters critical and disruptive innovation. Exploring such features is necessary to establish the foundation of solid long-term partnerships. In this paper we describe the experience of the CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Heredia in Lima, Peru, as a case study for fostering meaningful and sustainable partnerships for international collaborative research. The CRONICAS Centre of Excellence in Chronic Diseases was established in 2009 with the following Mission: "We support the development of young researchers and collaboration with national and international institutions. Our motivation is to improve population's health through high quality research." The Centre's identity is embedded in its core values - generosity, innovation, integrity, and quality- and its trajectory is a result of various interactions between multiple individuals, collaborators, teams, and institutions, which together with the challenges confronted, enables us to make an objective assessment of the partnership we would like to pursue, nurture and support. We do not intend to provide a single example of a successful partnership, but in contrast, to highlight what can be translated into opportunities to be faced by research groups based in low- and middle-income countries, and how these encounters can provide a strong platform for fruitful and sustainable partnerships. In defiant contexts, partnerships require to be nurtured and sustained. Acknowledging that all partnerships are not and should not be the same, we also need to learn from the evolution of such relationships, its key successes, hurdles and failures to contribute to the promotion of a culture of global solidarity where mutual goals, mutual gains, as well as mutual responsibilities are the norm. In so doing, we will all contribute to instil a new culture

  14. Short-Term Effects of Binaural Beats on EEG Power, Functional Connectivity, Cognition, Gait and Anxiety in Parkinson's Disease.

    Science.gov (United States)

    Gálvez, Gerardo; Recuero, Manuel; Canuet, Leonides; Del-Pozo, Francisco

    2018-06-01

    We applied rhythmic binaural sound to Parkinson's Disease (PD) patients to investigate its influence on several symptoms of this disease and on Electrophysiology (Electrocardiography and Electroencephalography (EEG)). We conducted a double-blind, randomized controlled study in which rhythmic binaural beats and control were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design). Patients ([Formula: see text], age [Formula: see text], stage I-III Hoehn & Yahr scale) participated in two sessions of sound stimulation for 10[Formula: see text]min separated by a minimum of 7 days. Data were collected immediately before and after both stimulations with the following results: (1) a decrease in theta activity, (2) a general decrease in Functional Connectivity (FC), and (3) an improvement in working memory performance. However, no significant changes were identified in the gait performance, heart rate or anxiety level of the patients. With regard to the control stimulation, we did not identify significant changes in the variables analyzed. The use of binaural-rhythm stimulation for PD, as designed in this study, seems to be an effective, portable, inexpensive and noninvasive method to modulate brain activity. This influence on brain activity did not induce changes in anxiety or gait parameters; however, it resulted in a normalization of EEG power (altered in PD), normalization of brain FC (also altered in PD) and working memory improvement (a normalizing effect). In summary, we consider that sound, particularly binaural-rhythmic sound, may be a co-assistant tool in the treatment of PD, however more research is needed to consider the use of this type of stimulation as an effective therapy.

  15. Approaches to Sustainable Capacity Building for Cardiovascular Disease Care in Kenya.

    Science.gov (United States)

    Barasa, Felix A; Vedanthan, Rajesh; Pastakia, Sonak D; Crowe, Susie J; Aruasa, Wilson; Sugut, Wilson K; White, Russ; Ogola, Elijah S; Bloomfield, Gerald S; Velazquez, Eric J

    2017-02-01

    Cardiovascular diseases are approaching epidemic levels in Kenya and other low- and middle-income countries without accompanying effective preventive and therapeutic strategies. This is happening in the background of residual and emerging infections and other diseases of poverty, and increasing physical injuries from traffic accidents and noncommunicable diseases. Investments to create a skilled workforce and health care infrastructure are needed. Improving diagnostic capacity, access to high-quality medications, health care, appropriate legislation, and proper coordination are key components to ensuring the reversal of the epidemic and a healthy citizenry. Strong partnerships with the developed countries also crucial. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

    Science.gov (United States)

    Johnson, Bryce G; Ren, Shuyu; Karaca, Gamze; Gomez, Ivan G; Fligny, Cécile; Smith, Benjamin; Ergun, Ayla; Locke, George; Gao, Benbo; Hayes, Sebastian; MacDonnell, Scott; Duffield, Jeremy S

    2017-06-01

    Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ β -catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis. Copyright © 2017 by the American Society of Nephrology.

  17. Asthma disease management-Australian pharmacists' interventions improve patients' asthma knowledge and this is sustained.

    Science.gov (United States)

    Saini, Bandana; LeMay, Kate; Emmerton, Lynne; Krass, Ines; Smith, Lorraine; Bosnic-Anticevich, Sinthia; Stewart, Kay; Burton, Deborah; Armour, Carol

    2011-06-01

    To assess any improvements in knowledge of asthma patients after a tailored education program delivered by pharmacists and measure the sustainability of any improvements. To ascertain patients' perceptions about any changes in their knowledge. Ninety-six specially trained pharmacists recruited patients based on their risk of poor asthma control. A tailored intervention was delivered to patients based on individual needs and goals, and was conducted at three or four time points over six months. Asthma knowledge was assessed at the beginning and end of the service, and six and 12 months after it had ended. Patients' perceptions of the impact of the service on their knowledge were explored qualitatively in interviews. The 96 pharmacists recruited 570 patients, 398 (70%) finished. Asthma knowledge significantly improved as a result of the service (7.65 ± 2.36, n=561, to 8.78 ± 2.14, n=393). This improvement was retained for at least 12 months after the service. Patients reported how the knowledge and skills gained had led to a change in the way they managed their asthma. Improvements in knowledge are achievable and sustainable if pharmacists used targeted educational interventions. Pharmacist educational interventions are an efficient way to improve asthma knowledge in the community. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Externality or sustainability economics?

    International Nuclear Information System (INIS)

    Bergh, Jeroen C.J.M. van den

    2010-01-01

    In an effort to develop 'sustainability economics' Baumgaertner and Quaas (2010) neglect the central concept of environmental economics-'environmental externality'. This note proposes a possible connection between the concepts of environmental externality and sustainability. In addition, attention is asked for other aspects of 'sustainability economics', namely the distinction weak/strong sustainability, spatial sustainability and sustainable trade, distinctive sustainability policy, and the ideas of early 'sustainability economists'. I argue that both sustainability and externalities reflect a systems perspective and propose that effective sustainability solutions require that more attention is given to system feedbacks, notably other-regarding preferences and social interactions, and energy and environmental rebound. The case of climate change and policy is used to illustrate particular statements. As a conclusion, a list of 20 insights and suggestions for research is offered. (author)

  19. Reducing the Risk of Tick-Borne Diseases through Smart, Safe and Sustainable Pest Control

    Science.gov (United States)

    Each year PestWise programs form new partnerships to address ongoing and emerging issues. Reducing the risk from ticks and tick-borne disease is an issue of importance and EPA is contributing to a larger federal effort.

  20. Creating a sustainable collaborative consumer health application for chronic disease self-management.

    Science.gov (United States)

    Johnson, Constance M; McIlwain, Steve; Gray, Oliver; Willson, Bradley; Vorderstrasse, Allison

    2017-07-01

    As the prevalence of chronic diseases increase, there is a need for consumer-centric health informatics applications that assist individuals with disease self-management skills. However, due to the cost of development of these applications, there is also a need to build a disease agnostic architecture so that they could be reused for any chronic disease. This paper describes the architecture of a collaborative virtual environment (VE) platform, LIVE©, that was developed to teach self-management skills and provide social support to those individuals with type 2 diabetes. However, a backend database allows for the application to be easily reused for any chronic disease. We tested its usability in the context of a larger randomized controlled trial of its efficacy. The usability was scored as 'good' by half of the participants in the evaluation. Common errors in the testing and solutions to address initial usability issues are discussed. Overall, LIVE© represents a usable and generalizable platform that will be adapted to other chronic diseases and health needs in future research and applications. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Methodical aspects of radionuclide study of locomotor system in patients with systemic diseases of connective tissue with single photon emission computed tomography

    International Nuclear Information System (INIS)

    Potsibyina, V.V.; Oderyij, Je.A.

    1998-01-01

    The original technique was used to examine 427 patients aged 18-64 with systemic diseases of locomotor system connective tissue and 65 controls. In addition to clinical studies, radionuclide signs of locomotor system lesions was investigated with NUCLETRON APEX SP-6 CT unit using labeled with Tc-99m and osteotropic radiopharmaceuticals

  2. A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Murat Demirtaş

    2017-01-01

    Full Text Available Alzheimer's disease (AD is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC of the subjects with preclinical Alzheimer's disease (PAD, mild cognitive impairment due to AD (MCI and mild dementia due to Alzheimer's disease (AD, the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1−42 total tau (t-tau and phosphorylated tau (p-tau. CSF Aβ1−42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1−42. APOE4 carriership showed no significant correlations with the connectivity measures.

  3. Altered Behavioral and Autonomic Pain Responses in Alzheimer’s Disease Are Associated with Dysfunctional Affective, Self-Reflective and Salience Network Resting-State Connectivity

    Directory of Open Access Journals (Sweden)

    Paul A. Beach

    2017-09-01

    Full Text Available While pain behaviors are increased in Alzheimer’s disease (AD patients compared to healthy seniors (HS across multiple disease stages, autonomic responses are reduced with advancing AD. To better understand the neural mechanisms underlying these phenomena, we undertook a controlled cross-sectional study examining behavioral (Pain Assessment in Advanced Dementia, PAINAD scores and autonomic (heart rate, HR pain responses in 24 HS and 20 AD subjects using acute pressure stimuli. Resting-state fMRI was utilized to investigate how group connectivity differences were related to altered pain responses. Pain behaviors (slope of PAINAD score change and mean PAINAD score were increased in patients vs. controls. Autonomic measures (HR change intercept and mean HR change were reduced in severe vs. mildly affected AD patients. Group functional connectivity differences associated with greater pain behavior reactivity in patients included: connectivity within a temporal limbic network (TLN and between the TLN and ventromedial prefrontal cortex (vmPFC; between default mode network (DMN subcomponents; between the DMN and ventral salience network (vSN. Reduced HR responses within the AD group were associated with connectivity changes within the DMN and vSN—specifically the precuneus and vmPFC. Discriminant classification indicated HR-related connectivity within the vSN to the vmPFC best distinguished AD severity. Thus, altered behavioral and autonomic pain responses in AD reflects dysfunction of networks and structures subserving affective, self-reflective, salience and autonomic regulation.

  4. Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jae Hong; Roh, Jee Hoon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

  5. Cardiovascular Diseases on the Global Agenda: The United Nations High Level Meeting, Sustainable Development Goals, and the Way Forward.

    Science.gov (United States)

    Ralston, Johanna; Reddy, K Srinath; Fuster, Valentin; Narula, Jagat

    2016-12-01

    In 2011, the United Nations (UN) organized the first ever meeting for heads of state to discuss the problem of noncommunicable diseases (NCD), including cardiovascular disease (CVD), cancer, chronic respiratory disease, and diabetes mellitus. Recognizing that these had emerged as leading causes of morbidity and mortality in the world, including in many low- and middle-income countries, advocates from government and civil society had called for increased attention and a UN response. Earlier, NCD including CVD were absent from the global health agenda in part because of their omission from the Millennium Development Goals. The UN meeting and the global advocacy response offered a game-changing opportunity to redress this omission. The World Heart Federation (WHF) played an instrumental role in the UN meeting and follow up, including inclusion of CVD in the Sustainable Development Goals. The next phase of the global CVD movement is expected through national action, including CVD roadmaps and partnering with the World Health Organization. The WHF is heavily committed to these goals and the other nongovernmental organizations invested in the mission must help take this historical mandate forward. Instrumental to this will be the engagement of people affected by or at risk of developing CVD, to draw more attention and resources to NCD and to ensure that successes to date in global policy translate into action at the national level. Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

  6. Abnormal functional connectivity of the posterior cingulate cortex is associated with depressive symptoms in patients with Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Zhang J

    2017-10-01

    Full Text Available Jiangtao Zhang,1,2 Zhongwei Guo,2 Xiaozheng Liu,3 Xize Jia,4 Jiapeng Li,2 Yaoyao Li,1,5 Danmei Lv,1,5 Wei Chen1,5 1Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and the Collaborative Innovation Center for Brain Science, Hangzhou, Zhejiang, China; 2Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China; 3China-USA Neuroimaging Research Institute & Department of Radiology, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; 4Center for Cognitive Brain Disorders & Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou Normal University, Hangzhou, China; 5Key Laboratory of Medical Neurobiology of Chinese Ministry of Health, Hangzhou, Zhejiang, China Background: Depressive symptoms are significant and very common psychiatric complications in patients with Alzheimer’s disease (AD, which can aggravate the decline in social function. However, changes in the functional connectivity (FC of the brain in AD patients with depressive symptoms (D-AD remain unclear.Objective: To investigate whether any differences exist in the FC of the posterior cingulate cortex (PCC between D-AD patients and non-depressed AD patients (nD-AD.Materials and methods: We recruited 15 D-AD patients and 17 age-, sex-, educational level-, and Mini-Mental State Examination (MMSE-matched nD-AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton Depression Rating Scale, and 3.0T resting-state functional magnetic resonance imaging. Bilateral PCC were selected as the regions of interest and between-group differences in the PCC FC network were assessed using Student’s t-test.Results: Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right amygdala, right parahippocampus, right superior temporal pole, right middle temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim correction; P<0.05. In the nD-AD group, MMSE

  7. An Invasive Vector of Zoonotic Disease Sustained by Anthropogenic Resources: The Raccoon Dog in Northern Europe

    OpenAIRE

    Süld, Karmen; Valdmann, Harri; Laurimaa, Leidi; Soe, Egle; Davison, John; Saarma, Urmas

    2014-01-01

    The raccoon dog (Nyctereutes procyonoides) is an introduced species in Europe with a continually expanding range. Since the species is capable of affecting local ecosystems and is a vector for a number of severe zoonotic diseases, it is important to understand its food habits. Raccoon dog diet was studied in Estonia by examining the contents of 223 stomach samples collected during the coldest period of the year, August to March, in 2010-2012. The most frequently consumed food categories were ...

  8. Priority for sustainability. Final report

    International Nuclear Information System (INIS)

    2007-12-01

    The Dutch Minister of Economic Affairs (EZ) has been asked to realize priority in connection to the grid for sustainable production capacity. Currently there are waiting lists for connection of new production capacity to the grid in some areas, due to a shortage in transport capacity. The Dutch connection policy (first come, first serve) may possibly lead to delays in connecting sustainable production capacity, which is not desirable in view of the incentivisation of sustainability. EZ and TenneT have asked Booz Allen to examine the options for giving priority to sustainability (wind and CHP). Priority in connection applies only to new sustainable production capacity, but priority in transport also applies to existing sustainable production capacity. [mk] [nl

  9. Evaluation of computer-based computer tomography stratification against outcome models in connective tissue disease-related interstitial lung disease: a patient outcome study.

    Science.gov (United States)

    Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Brun, Anne Laure; Egashira, Ryoko; Karwoski, Ronald; Kokosi, Maria; Wells, Athol U; Hansell, David M

    2016-11-23

    To evaluate computer-based computer tomography (CT) analysis (CALIPER) against visual CT scoring and pulmonary function tests (PFTs) when predicting mortality in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). To identify outcome differences between distinct CTD-ILD groups derived following automated stratification of CALIPER variables. A total of 203 consecutive patients with assorted CTD-ILDs had CT parenchymal patterns evaluated by CALIPER and visual CT scoring: honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume, emphysema, and traction bronchiectasis. CT scores were evaluated against pulmonary function tests: forced vital capacity, diffusing capacity for carbon monoxide, carbon monoxide transfer coefficient, and composite physiologic index for mortality analysis. Automated stratification of CALIPER-CT variables was evaluated in place of and alongside forced vital capacity and diffusing capacity for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using receiver operating characteristic curve analysis. Cox regression analyses identified four independent predictors of mortality: patient age (P < 0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P = 0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of CALIPER variables identified three morphologically distinct groups which were stronger predictors of mortality than all CT and functional indices. The Stratified-CT model substituted automated stratified groups for functional indices in the ILD-GAP model and maintained model strength (area under curve (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86, respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively

  10. Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease.

    Science.gov (United States)

    Sánchez, Stella M; Abulafia, Carolina; Duarte-Abritta, Barbara; de Guevara, M Soledad Ladrón; Castro, Mariana N; Drucaroff, Lucas; Sevlever, Gustavo; Nemeroff, Charles B; Vigo, Daniel E; Loewenstein, David A; Villarreal, Mirta F; Guinjoan, Salvador M

    2017-01-01

    We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

  11. An invasive vector of zoonotic disease sustained by anthropogenic resources: the raccoon dog in northern Europe.

    Directory of Open Access Journals (Sweden)

    Karmen Süld

    Full Text Available The raccoon dog (Nyctereutes procyonoides is an introduced species in Europe with a continually expanding range. Since the species is capable of affecting local ecosystems and is a vector for a number of severe zoonotic diseases, it is important to understand its food habits. Raccoon dog diet was studied in Estonia by examining the contents of 223 stomach samples collected during the coldest period of the year, August to March, in 2010-2012. The most frequently consumed food categories were anthropogenic plants (e.g. cereals, fruits; FO = 56.1% and carrion (e.g. carcasses of artiodactyls and carnivores; FO = 48.4%. Carrion was also the only food category that was consumed significantly more frequently by raccoon dogs exhibiting symptoms of sarcoptic mange than by uninfected animals. Small mammals, which represent intermediate hosts for the zoonotic tapeworm Echinococcus multilocularis, were more commonly recorded in samples also containing anthropogenic plants than expected by chance. Comparison of raccoon dog and red fox (Vulpes vulpes diet in Estonia revealed higher overlap than found elsewhere in Europe, with 'carrion' and 'anthropogenic plants' making up the bulk of both species' diet; however, raccoon dogs were more omnivorous than red foxes. Our results suggest that while the use of most food categories reflects the phenology of natural food sources, 'anthropogenic plants' and 'carrion' provide an essential resource for raccoon dogs during the coldest period of the year, with the latter resource especially important for individuals infected with sarcoptic mange. Since both of these food categories and small mammals are often found at supplementary feeding sites for wild boar (Sus scrofa, this game management practice may facilitate high densities of mesocarnivores and promote the spread of some severe zoonotic diseases, including alveolar echinococcosis, trichinellosis, rabies and sarcoptic mange.

  12. An invasive vector of zoonotic disease sustained by anthropogenic resources: the raccoon dog in northern Europe.

    Science.gov (United States)

    Süld, Karmen; Valdmann, Harri; Laurimaa, Leidi; Soe, Egle; Davison, John; Saarma, Urmas

    2014-01-01

    The raccoon dog (Nyctereutes procyonoides) is an introduced species in Europe with a continually expanding range. Since the species is capable of affecting local ecosystems and is a vector for a number of severe zoonotic diseases, it is important to understand its food habits. Raccoon dog diet was studied in Estonia by examining the contents of 223 stomach samples collected during the coldest period of the year, August to March, in 2010-2012. The most frequently consumed food categories were anthropogenic plants (e.g. cereals, fruits; FO = 56.1%) and carrion (e.g. carcasses of artiodactyls and carnivores; FO = 48.4%). Carrion was also the only food category that was consumed significantly more frequently by raccoon dogs exhibiting symptoms of sarcoptic mange than by uninfected animals. Small mammals, which represent intermediate hosts for the zoonotic tapeworm Echinococcus multilocularis, were more commonly recorded in samples also containing anthropogenic plants than expected by chance. Comparison of raccoon dog and red fox (Vulpes vulpes) diet in Estonia revealed higher overlap than found elsewhere in Europe, with 'carrion' and 'anthropogenic plants' making up the bulk of both species' diet; however, raccoon dogs were more omnivorous than red foxes. Our results suggest that while the use of most food categories reflects the phenology of natural food sources, 'anthropogenic plants' and 'carrion' provide an essential resource for raccoon dogs during the coldest period of the year, with the latter resource especially important for individuals infected with sarcoptic mange. Since both of these food categories and small mammals are often found at supplementary feeding sites for wild boar (Sus scrofa), this game management practice may facilitate high densities of mesocarnivores and promote the spread of some severe zoonotic diseases, including alveolar echinococcosis, trichinellosis, rabies and sarcoptic mange.

  13. Detection of serum anti-B/B’ UsnRNP antibodies in patients with connective tissue diseases by immunoblotting

    Directory of Open Access Journals (Sweden)

    L. Iaccarino

    2011-09-01

    Full Text Available Objective: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B’ polypeptides of U small nuclear ribonucleoproteins (UsnRNP and to assess the significance of these antibodies in connective tissue disease (CTD patients. Methods: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjogren’s syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD, of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV infection with high titre IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line and Jurkat cells (a human T lymphoid cell line. Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. Results: A high frequency of anti-B/B’ antibodies was found in the sera of CTD patients, confined to SLE (54.4% and overlap CTD with SLE features (55,2%. Anti-B/B’ immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60% anti-B/B’ positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. Conclusions. The Sm B/B’ proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and “lupus-like” overlap CTD. Moreover, anti-B/B’ is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells

  14. Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden.

    OpenAIRE

    Nyrén, O.; Yin, L.; Josefsson, S.; McLaughlin, J. K.; Blot, W. J.; Engqvist, M.; Hakelius, L.; Boice, J. D.; Adami, H. O.

    1998-01-01

    OBJECTIVE: To examine the relation between connective tissue disease and related conditions and breast implants. DESIGN: Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period. SETTING: Sweden. SUBJECTS: 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and ...

  15. Activating Patients for Sustained Chronic Disease Self-Management: Thinking Beyond Clinical Outcomes.

    Science.gov (United States)

    Dye, Cheryl J; Williams, Joel E; Evatt, Janet H

    2016-04-01

    This article describes the impact of an 8-week community program implemented by trained volunteers on the hypertension self-management of 185 patients who were batch randomized to intervention or wait-list control groups. Compared with control group participants, a higher proportion of treatment group participants moved from the cognitive to behavioral stages of motivational readiness for being physically active (P healthy eating habits (P = .001), handling stress well (P = .001), and living an overall healthy lifestyle (P = .003). They also demonstrated a greater average increase in perceived competence for self-management, F(1.134) = 4.957, P = .028, η2 = .036, and a greater increase in mean hypertension-related knowledge, F(1.160) = 16.571, P < .0005, η(2) = .094. Enduring lifestyle changes necessary for chronic disease self-management require that psychosocial determinants of health behavior are instilled, which is typically beyond standard medical practice. We recommend peer-led, community-based programs as a complement to clinical care and support the increasing health system interest in promoting population health beyond clinical walls. © The Author(s) 2016.

  16. [CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

    Science.gov (United States)

    Madiyeva, M; Rymbayeva, T

    2017-11-01

    The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

  17. Altered Amygdala Resting-State Functional Connectivity in Maintenance Hemodialysis End-Stage Renal Disease Patients with Depressive Mood.

    Science.gov (United States)

    Chen, Hui Juan; Wang, Yun Fei; Qi, Rongfeng; Schoepf, U Joseph; Varga-Szemes, Akos; Ball, B Devon; Zhang, Zhe; Kong, Xiang; Wen, Jiqiu; Li, Xue; Lu, Guang Ming; Zhang, Long Jiang

    2017-04-01

    The purpose of this study was to investigate patterns in the amygdala-based emotional processing circuit of hemodialysis patients using resting-state functional MR imaging (rs-fMRI). Fifty hemodialysis patients (25 with depressed mood and 25 without depressed mood) and 26 healthy controls were included. All subjects underwent neuropsychological tests and rs-fMRI, and patients also underwent laboratory tests. Functional connectivity of the bilateral amygdala was compared among the three groups. The relationship between functional connectivity and clinical markers was investigated. Depressed patients showed increased positive functional connectivity of the left amygdala with the left superior temporal gyrus and right parahippocampal gyrus (PHG) but decreased amygdala functional connectivity with the left precuneus, angular gyrus, posterior cingulate cortex (PCC), and left inferior parietal lobule compared with non-depressed patients (P amygdala with bilateral supplementary motor areas and PHG but decreased amygdala functional connectivity with the right superior frontal gyrus, superior parietal lobule, bilateral precuneus, and PCC (P amygdala (P amygdala-prefrontal-PCC-limbic circuits was impaired in depressive hemodialysis patients, with a gradual decrease in ACC between controls, non-depressed, and depressed patients for the right amygdala. This indicates that ACC plays a role in amygdala-based emotional regulatory circuits in these patients.

  18. Measuring the health-related Sustainable Development Goals in 188 countries : A baseline analysis from the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Lim, Stephen S.; Allen, Kate; Bhutta, Zulfiqar A.; Dandona, Lalit; Forouzanfar, Mohammad H.; Fullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Hay, Simon I.; Holmberg, Mollie; Kinfu, Yohannes; Kutz, Michael J.; Larson, Heidi J.; Liang, Xiaofeng; Lopez, Alan D.; Lozano, Rafael; McNellan, Claire R.; Mokdad, Ali H.; Mooney, Meghan D.; Naghavi, Mohsen; Olsen, Helen E.; Pigott, David M.; Salomon, Joshua A.; Vos, Theo; Wang, Haidong; Abajobir, Amanuel Alemu; Abate, Kalkidan Hassen; Abbafati, Cristiana; Abbas, Kaja M.; Abd-Allah, Foad; Abdulle, Abdishakur M.; Abraham, Biju; Abubakar, Ibrahim; Abu-Raddad, Laith J.; Abu-Rmeileh, Niveen M. E.; Abyu, Gebre Yitayih; Achoki, Tom; Adebiyi, Akindele Olupelumi; Adedeji, Isaac Akinkunmi; Afanvi, Kossivi Agbelenko; Afshin, Ashkan; Agarwal, Arnav; Agrawal, Anurag; Kiadaliri, Aliasghar Ahmad; Ahmadieh, Hamid; Ahmed, Kedir Yimam; Amare, Azmeraw T.; Hoek, Hans W.; Singh, Abhishek; Tura, Abera Kenay

    2016-01-01

    Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases,

  19. Congenital portosystemic venous connections and other abdominal venous abnormalities in patients with polysplenia and functionally univentricular heart disease: a case series and literature review.

    Science.gov (United States)

    McElhinney, Doff B; Marx, Gerald R; Newburger, Jane W

    2011-01-01

    Published case reports suggest that congenital portosystemic venous connections (PSVC) and other abdominal venous anomalies may be relatively frequent and potentially important in patients with polysplenia syndrome. Our objective was to investigate the frequency and range of portal and other abdominal systemic venous anomalies in patients with polysplenia and inferior vena cava (IVC) interruption who underwent a cavopulmonary anastomosis procedure at our center, and to review the published literature on this topic and the potential clinical importance of such anomalies. Retrospective cohort study and literature review were used. Among 77 patients with heterotaxy, univentricular heart disease, and IVC interruption who underwent a bidirectional Glenn and/or modified Fontan procedure, pulmonary arteriovenous malformations were diagnosed in 33 (43%). Bilateral superior vena cavas were present in 42 patients (55%). Despite inadequate imaging in many patients, a partial PSVC, dual IVCs, and/or renal vein anomalies were detected in 15 patients (19%). A PSVC formed by a tortuous vessel running from the systemic venous system to the extrahepatic portal vein was found in six patients (8%). Abdominal venous anomalies other than PSVC were documented in 13 patients (16%), including nine (12%) with some form of duplicated IVC system, with a large azygous vein continuing to the superior vena cava and a parallel, contralateral IVC of similar or smaller size, and seven with renal vein anomalies. In patients with a partial PSVC or a duplicate IVC that connected to the atrium, the abnormal connection allowed right-to-left shunting. PSVC and other abdominal venous anomalies may be clinically important but under-recognized in patients with IVC interruption and univentricular heart disease. In such patients, preoperative evaluation of the abdominal systemic venous system may be valuable. More data are necessary to determine whether there is a pathophysiologic connection between the

  20. Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance.

    Science.gov (United States)

    Fragasso, G; Benti, R; Sciammarella, M; Rossetti, E; Savi, A; Gerundini, P; Chierchia, S L

    1991-05-01

    Exercise stress testing is routinely used for the noninvasive assessment of coronary artery disease and is considered a safe procedure. However, the provocation of severe ischemia might potentially cause delayed recovery of myocardial function. To investigate the possibility that maximal exercise testing could induce prolonged impairment of left ventricular function, 15 patients with angiographically proved coronary disease and 9 age-matched control subjects with atypical chest pain and normal coronary arteries were studied. Radionuclide ventriculography was performed at rest, at peak exercise, during recovery and 2 and 7 days after exercise. Ejection fraction, peak filling and peak emptying rates and left ventricular wall motion were analyzed. All control subjects had a normal exercise test at maximal work loads and improved left ventricular function on exercise. Patients developed 1 mm ST depression at 217 +/- 161 s at a work load of 70 +/- 30 W and a rate-pressure product of 18,530 +/- 4,465 mm Hg x beats/min. Although exercise was discontinued when angina or equivalent symptoms occurred, in all patients diagnostic ST depression (greater than or equal to 1 mm) developed much earlier than symptoms. Predictably, at peak exercise patients showed a decrease in ejection fraction and peak emptying and filling rates. Ejection fraction and peak emptying rate normalized within the recovery period, whereas peak filling rate remained depressed throughout recovery (p less than 0.002) and was still reduced 2 days after exercise (p less than 0.02). In conclusion, in patients with severe impairement of coronary flow reserve, maximal exercise may cause sustained impairement of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer’s Disease: A Diffusion MRI Study with DTI and HARDI Models

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2016-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI to detect abnormal topological organization of white matter (WM structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI model and the high angular resolution diffusion imaging (HARDI model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.

  2. Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing’s disease

    Directory of Open Access Journals (Sweden)

    Prachi Bansal

    2017-10-01

    Full Text Available Purpose: Transsphenoidal surgery (TSS is the primary treatment modality for Cushing’s disease (CD. However, the predictors of post-operative remission and recurrence remain debatable. Thus, we studied the post-operative remission and long-term recurrence rates, as well as their respective predictive factors. Methods: A retrospective analysis of case records of 230 CD patients who underwent primary microscopic TSS at our tertiary care referral centre between 1987 and 2015 was undertaken. Demographic features, pre- and post-operative hormonal values, MRI findings, histopathological features and follow-up data were recorded. Remission and recurrence rates as well as their respective predictive factors were studied. Results: Overall, the post-operative remission rate was 65.6% (early remission 46%; delayed remission 19.6%, while the recurrence rate was 41% at mean follow-up of 74 ± 61.1 months (12–270 months. Significantly higher early remission rates were observed in patients with microadenoma vs macroadenoma (51.7% vs 30.6%, P = 0.005 and those with unequivocal vs equivocal MRI for microadenoma (55.8% vs 38.5%, P = 0.007. Patients with invasive macroadenoma had poorer (4.5% vs 45%, P = 0.001 remission rates. Recurrence rates were higher in patients with delayed remission than those with early remission (61.5% vs 30.8%, P = 0.001. Duration of post-operative hypocortisolemia ≥13 months predicted sustained remission with 100% specificity and 46.4% sensitivity. Recurrence could be detected significantly earlier (27.7 vs 69.2 months, P < 0.001 in patients with available serial follow-up biochemistry as compared to those with infrequent follow-up after remission. Conclusion: In our study, remission and recurrence rates were similar to that of reported literature, but proportion of delayed remission was relatively higher. Negative/equivocal MRI findings and presence of macroadenoma, especially those with cavernous sinus invasion were

  3. On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification.

    Science.gov (United States)

    Pläschke, Rachel N; Cieslik, Edna C; Müller, Veronika I; Hoffstaedter, Felix; Plachti, Anna; Varikuti, Deepthi P; Goosses, Mareike; Latz, Anne; Caspers, Svenja; Jockwitz, Christiane; Moebus, Susanne; Gruber, Oliver; Eickhoff, Claudia R; Reetz, Kathrin; Heller, Julia; Südmeyer, Martin; Mathys, Christian; Caspers, Julian; Grefkes, Christian; Kalenscher, Tobias; Langner, Robert; Eickhoff, Simon B

    2017-12-01

    Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc. © 2017

  4. Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

    Directory of Open Access Journals (Sweden)

    Marcelo Cury

    2013-01-01

    Full Text Available There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS, Ehlers-Danlos syndrome (EDS, Loeys-Dietz syndrome (LDS, familial thoracic aortic aneurysms and dissections (TAAD, bicuspid aortic valve disease (BAV, and autosomal dominant polycystic kidney disease (ADPKD. In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

  5. Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Paola Cordiali-Fei

    2013-01-01

    Full Text Available In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc and undifferentiated connective tissue disease (UCTD, we have explored the setting of peripheral T regulatory (T reg cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc or diffuse (dcSSc disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.

  6. Priority for sustainability. Study of the effects on investment climate

    International Nuclear Information System (INIS)

    2007-12-01

    The Dutch cabinet has been asked to make sure that sustainable electricity plants can be connected to the grid with high priority. By request of the Dutch Ministry of Economic Affairs, the effects on the investment climate have been examined (both for sustainable and conventional) if priority (with regard to connection and transport) is given to sustainable generated electricity. Five models for priority for sustainable have been defined, i.e. (1) Sustainable is only given priority on the waiting list for connection; (2) Connect sustainable immediately, but no priority for transport; (3) Connect sustainable immediately and priority granted in transport; (4) Connect sustainable and conventional immediately, no priority for transport; (5) Connect sustainable and conventional immediately and give priority in transport to sustainable. [mk] [nl

  7. Comparison of marginal bone loss between internal- and external-connection dental implants in posterior areas without periodontal or peri-implant disease.

    Science.gov (United States)

    Kim, Dae-Hyun; Kim, Hyun Ju; Kim, Sungtae; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Ku, Young; Rhyu, In-Chul

    2018-04-01

    The purpose of this retrospective study with 4-12 years of follow-up was to compare the marginal bone loss (MBL) between external-connection (EC) and internal-connection (IC) dental implants in posterior areas without periodontal or peri-implant disease on the adjacent teeth or implants. Additional factors influencing MBL were also evaluated. This retrospective study was performed using dental records and radiographic data obtained from patients who had undergone dental implant treatment in the posterior area from March 2006 to March 2007. All the implants that were included had follow-up periods of more than 4 years after loading and satisfied the implant success criteria, without any peri-implant or periodontal disease on the adjacent implants or teeth. They were divided into 2 groups: EC and IC. Subgroup comparisons were conducted according to splinting and the use of cement in the restorations. A statistical analysis was performed using the Mann-Whitney U test for comparisons between 2 groups and the Kruskal-Wallis test for comparisons among more than 2 groups. A total of 355 implants in 170 patients (206 EC and 149 IC) fulfilled the inclusion criteria and were analyzed in this study. The mean MBL was 0.47 mm and 0.15 mm in the EC and IC implants, respectively, which was a statistically significant difference ( P <0.001). Comparisons according to splinting (MBL of single implants: 0.34 mm, MBL of splinted implants: 0.31 mm, P =0.676) and cement use (MBL of cemented implants: 0.27 mm, MBL of non-cemented implants: 0.35 mm, P =0.178) showed no statistically significant differences in MBL, regardless of the implant connection type. IC implants showed a more favorable bone response regarding MBL in posterior areas without peri-implantitis or periodontal disease.

  8. Connecting Grammaticalisation

    DEFF Research Database (Denmark)

    Nørgård-Sørensen, Jens; Heltoft, Lars; Schøsler, Lene

    morphological, topological and constructional paradigms often connect to form complex paradigms. The book introduces the concept of connecting grammaticalisation to describe the formation, restructuring and dismantling of such complex paradigms. Drawing primarily on data from Germanic, Romance and Slavic...

  9. Lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases.

    Science.gov (United States)

    Pascucci, Anabella; Lynch, Peter J; Fazel, Nasim

    2016-05-01

    Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids.

  10. [A case of mixed connective tissue disease positive for proteinase 3 antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1 diabetes mellitus and chronic thyroiditis].

    Science.gov (United States)

    Michitsuji, Tohru; Horai, Yoshiro; Sako, Ayaka; Asano, Taro; Iwanaga, Nozomi; Izumi, Yasumori; Kawakami, Atsushi

    2017-01-01

      A female in her sixties with slowly progressive type 1 diabetes mellitus (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with swelling in her fingers. A prominent atherosclerotic lesion was revealed upon brain magnetic resonance imaging, and she was found to have mixed connective tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

  11. Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Christine Breynaert

    Full Text Available INTRODUCTION: Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS ingestion, to mimic the relapsing nature of the human disease. MATERIALS AND METHODS: C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total. Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. RESULTS: Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn's colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. CONCLUSIONS: Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn's disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of

  12. Chest Abnormalities in Juvenile-Onset Mixed Connective Tissue Disease: Assessment with High-Resolution Computed Tomography and Pulmonary Function Tests

    International Nuclear Information System (INIS)

    Aaloekken, T.M.; Mynarek, G.; Kolbenstvedt, A.; Lilleby, V.; Foerre, Oe.; Soeyseth, V.; Pripp, A.H.; Johansen, B.

    2009-01-01

    Background: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. Purpose: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. Material and Methods: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1-21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. Results: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. Conclusion: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration

  13. A case report of a patient with Ribbing disease underlines the connections between the skeletal and cardiovascular complications

    Directory of Open Access Journals (Sweden)

    Giuseppe Cocco

    2011-06-01

    Full Text Available A 69-year-old woman suffered from Ribbing disease, a hereditary X autosomal dominant disease with multiple sclerosing dysplasias. However, it is less known that the genetic mutation can often induce cardiovascular complications. The patient had a hypertensive cardiopathy and had been treated with percutaneous coronary angioplasty and stenting because of a myocardial infarction. She was seen because of dyspnea and we detected an aneurysm of the ascending thoracic aorta. The patient underwent surgical repair. In Ribbing disease an up-regulation of genes interferes with the production, processing, or formation of collagen type II and XI. These genetic effects are thought to be specific for osteoblasts and are responsible for the skeletal pathology. However, the defective synthesis of collagen can also induce cardiovascular complications which may be similar to those described in patients with type III Ehlers-Danlos syndrome, with type IV Marfan syndrome, and with osteogenesis imperfecta. Rheumatologists who treat patients with Ribbing disease should seek the advice of cardiologists for the occurrence of cardiovascular complications.

  14. A case report of a patient with Ribbing disease underlines the connections between the skeletal and cardiovascular complications

    Directory of Open Access Journals (Sweden)

    Giuseppe Cocco

    2011-07-01

    Full Text Available A 69-year-old woman suffered from Ribbing disease, a hereditary X autosomal dominant disease with multiple sclerosing dysplasias. However, it is less known that the genetic mutation can often induce cardiovascular complications. The patient had a hypertensive cardiopathy and had been treated with percutaneous coronary angioplasty and stenting because of a myocardial infarction. She was seen because of dyspnea and we detected an aneurysm of the ascending thoracic aorta. The patient underwent surgical repair. In Ribbing disease an up-regulation of genes interferes with the production, processing, or formation of collagen type II and XI. These genetic effects are thought to be specific for osteoblasts and are responsible for the skeletal pathology. However, the defective synthesis of collagen can also induce cardiovascular complications which may be similar to those described in patients with type III Ehlers-Danlos syndrome, with type IV Marfan syndrome, and with osteogenesis imperfecta. Rheumatologists who treat patients with Ribbing disease should seek the advice of cardiologists for the occurrence of cardiovascular complications.

  15. Modeling Structural Brain Connectivity

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø

    The human brain consists of a gigantic complex network of interconnected neurons. Together all these connections determine who we are, how we react and how we interpret the world. Knowledge about how the brain is connected can further our understanding of the brain’s structural organization, help...... improve diagnosis, and potentially allow better treatment of a wide range of neurological disorders. Tractography based on diffusion magnetic resonance imaging is a unique tool to estimate this “structural connectivity” of the brain non-invasively and in vivo. During the last decade, brain connectivity...... has increasingly been analyzed using graph theoretic measures adopted from network science and this characterization of the brain’s structural connectivity has been shown to be useful for the classification of populations, such as healthy and diseased subjects. The structural connectivity of the brain...

  16. [The validity of proofs in demonstrating risk and in research into the causal connection of occupational diseases].

    Science.gov (United States)

    Bonetti, Daniela

    2014-01-01

    The verification of the occupational origin of a disease is a forensic medical activity requiring: the confirmation of the existence and of the exact nosographic identification of the disease, as well as the type of work really performed, and the actual exposure to an effective occupational hazard during an adequate time, and finally a reconstruction of the causal relationship based on objective data. Checking the disease is essentially documentary, corroborated by direct survey by medical examination. The assessment of exposure to the occupational hazard must be scrupulous also, not being acceptable the medical history alone: that is, it does require documentary evidence. Finally, the logical process of recognition of causation requires the application of rigorous forensic medical methodology, with references to current scientific knowledge, and the application of legal criteriology from the legal field of law in which you are moving. Indeed, forensic medical methodology is not the same of epidemiological one: probability of occurrence of an event is not a proof, but only a circumstantial element. A forensic medical doctor organizes every evidence and circumstantial evidence in a unique decision-making process, as a result of a logical process, and probabilistic data can be among circumstantial evidence, but they must suit the case in details, in order to reach the so called "logic probability". But this doesn't mean that you have "proven" the occupational origin of a disease. In the "demonstration" of a fact you use the same forensic medical methodology (thus referring to classic criteria: temporality, biological gradient and plausibility, topographical, exclusion, and phenomenal continuity if suitable, too), and also the same general scientific references, nevertheless the law can be different in causality principles admitted (the principles governing the causal link are the same in Criminal Code and Civil law both, but they differ in private insurance), and

  17. Quality of Life Philosophy III. Towards a New Biology: Understanding the Biological Connection between Quality of Life, Disease, and Healing

    Directory of Open Access Journals (Sweden)

    Soren Ventegodt

    2003-01-01

    Full Text Available This paper addresses (in a philosophical way the complex and enigmatic interface between matter, life, and consciousness in modern medical science. The problem today in understanding living matter is not at the molecular level, but at the macro level where all molecular activities in the individual cell are coordinated, and especially at a higher level, where the activities of all the organism’s cells are coordinated. Although we understand very much of the body’s chemistry, we have only just started to get the gist of the tremendous organization of living matter. We are just beginning to acknowledge the enormous flow of information that is needed to make everything function in a healthy organism, including consciousness, where every cell does exactly what it has to do to make the organs function.A concept that seems to be able to bridge the scientifically very different domains of matter, life, and consciousness seems to be “biological information”. If a cell is seen as a liquid crystal in which the cell’s molecules constantly connect in firm mutual relationships only to dissolve again and become fluid and free, whenever the cell needs it, the backbone of the cell seems to be the information that organizes the cell. For example, in cell motion a cell is able to crawl with the help of a skeleton of fibers that can be created guided by biological information, whenever the cell needs the solidity provided by the fibers. The moment it has finished crawling or intends to crawl in another direction, these fibers will dissolve again. The fibers are made of millions of molecules that connect in an arranged pattern, and they dissolve when these molecules again let go of each other. How the cell precisely regulates such processes is today a complete mystery. How cells cocreate consciousness is also an enigma. All we can do is describe the cell and the organisms arising from its cells as filled with energy and information as well as an

  18. Effects of chronic exposure of hydroxychloroquine/ chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Fardet L

    2017-11-01

    Full Text Available L Fardet,1–3 I Nazareth,1 I Petersen1 1Department of Primary Care and Population Health, University College London, UK; 2Department of Dermatology, Henri Mondor Hospital AP-HP, Créteil, France; 3Equipe d’Accueil 7379 EpiDermE, Université Paris Est Créteil, Créteil, France Background: Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases.Methods: The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database.Results: Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6% or chloroquine (1.4% and 24,118 unexposed individuals were included in the study (median age: 56 [45–66] years, women: 76.8%. When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92–1.18], p=0.54, hematological malignancies (adjusted sHR: 1.00 [0.73–1.38], p=0.99, or skin cancers (adjusted sHR: 0.92 [0.78–1.07], p=0.26. The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44–0.95] for the overall population and 0.61 [0.38–1.00] for those diagnosed with incident cancers. The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81–1.00] in the overall population and 0.78 [0.64–0.96] in those diagnosed with incident cancer.Conclusion: Individuals on long-term exposure

  19. Connectivity in river deltas

    Science.gov (United States)

    Passalacqua, P.; Hiatt, M. R.; Sendrowski, A.

    2016-12-01

    Deltas host approximately half a billion people and are rich in ecosystem diversity and economic resources. However, human-induced activities and climatic shifts are significantly impacting deltas around the world; anthropogenic disturbance, natural subsidence, and eustatic sea-level rise are major causes of threat to deltas and in many cases have compromised their safety and sustainability, putting at risk the people that live on them. In this presentation, I will introduce a framework called Delta Connectome for studying connectivity in river deltas based on different representations of a delta as a network. Here connectivity indicates both physical connectivity (how different portions of the system interact with each other) as well as conceptual (pathways of process coupling). I will explore several network representations and show how quantifying connectivity can advance our understanding of system functioning and can be used to inform coastal management and restoration. From connectivity considerations, the delta emerges as a leaky network that evolves over time and is characterized by continuous exchanges of fluxes of matter, energy, and information. I will discuss the implications of connectivity on delta functioning, land growth, and potential for nutrient removal.

  20. Gray matter concentration and effective connectivity changes in Alzheimer's disease: a longitudinal structural MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xingfeng; Coyle, Damien; Maguire, Liam; Watson, David R.; McGinnity, Thomas M. [University of Ulster, Intelligent Systems Research Centre, Magee Campus, Derry, Northern Ireland (United Kingdom)

    2011-10-15

    Understanding disease progression in Alzheimer's disease (AD) awaits the resolution of three fundamental questions: first, can we identify the location of ''seed'' regions where neuropathology is first present? Some studies have suggested the medial temporal lobe while others have suggested the hippocampus. Second, are there similar atrophy rates within affected regions in AD? Third, is there evidence of causality relationships between different affected regions in AD progression ?To address these questions, we conducted a longitudinal MRI study to investigate the gray matter (GM) changes in AD progression. Abnormal brain regions were localized by a standard voxel-based morphometry method, and the absolute atrophy rate in these regions was calculated using a robust regression method. Primary foci of atrophy were identified in the hippocampus and middle temporal gyrus (MTG). A model based upon the Granger causality approach was developed to investigate the cause-effect relationship over time between these regions based on GM concentration. Results show that in the earlier stages of AD, primary pathological foci are in the hippocampus and entorhinal cortex. Subsequently, atrophy appears to subsume the MTG. The causality results show that there is in fact little difference between AD and age-matched healthy control in terms of hippocampus atrophy, but there are larger differences in MTG, suggesting that local pathology in MTG is the predominant progressive abnormality during intermediate stages of AD development. (orig.)

  1. Making Connections

    Science.gov (United States)

    Pien, Cheng Lu; Dongsheng, Zhao

    2011-01-01

    Effective teaching includes enabling learners to make connections within mathematics. It is easy to accord with this statement, but how often is it a reality in the mathematics classroom? This article describes an approach in "connecting equivalent" fractions and whole number operations. The authors illustrate how a teacher can combine a common…

  2. Nonrandom network connectivity comes in pairs

    Directory of Open Access Journals (Sweden)

    Felix Z. Hoffmann

    2017-02-01

    Full Text Available Overrepresentation of bidirectional connections in local cortical networks has been repeatedly reported and is a focus of the ongoing discussion of nonrandom connectivity. Here we show in a brief mathematical analysis that in a network in which connection probabilities are symmetric in pairs, Pij = Pji, the occurrences of bidirectional connections and nonrandom structures are inherently linked; an overabundance of reciprocally connected pairs emerges necessarily when some pairs of neurons are more likely to be connected than others. Our numerical results imply that such overrepresentation can also be sustained when connection probabilities are only approximately symmetric.

  3. Grassland Sustainability

    Science.gov (United States)

    Deborah U. Potter; Paulette L. Ford

    2004-01-01

    In this chapter we discuss grassland sustainability in the Southwest, grassland management for sustainability, national and local criteria and indicators of sustainable grassland ecosystems, and monitoring for sustainability at various scales. Ecological sustainability is defined as: [T]he maintenance or restoration of the composition, structure, and processes of...

  4. A nationwide study of connective tissue disease and other rheumatic conditions among Danish women with long-term cosmetic breast implantation

    DEFF Research Database (Denmark)

    Fryzek, Jon P; Holmich, Lisbet; McLaughlin, Joseph K

    2007-01-01

    PURPOSE: Numerous epidemiologic studies have demonstrated that breast implants are not associated with connective tissue diseases (CTDs). However, many CTDs are rare, and continued follow-up of women with breast implants is warranted. METHODS: We extended by 5 years the follow-up of our earlier...... population-based cohort study of Danish women with cosmetic breast implants (n = 2761) and comparison groups of women with other types of cosmetic surgery (n = 8807). All women were followed from January 1977 through December 2001. Hospitalization and outpatient data for CTD and ill-defined and other...... rheumatic conditions in the implant and comparison groups were compared with those in the general Danish population. Additionally, CTDs and fibromyalgia were confirmed through medical chart review, and direct comparisons of the breast implant cohort with the comparison cohort were performed. RESULTS: When...

  5. Sleep-related modifications of EEG connectivity in the sensory-motor networks in Huntington Disease: An eLORETA study and review of the literature.

    Science.gov (United States)

    Piano, Carla; Imperatori, Claudio; Losurdo, Anna; Bentivoglio, Anna Rita; Cortelli, Pietro; Della Marca, Giacomo

    2017-07-01

    To evaluate EEG functional connectivity in the sensory-motor network, during wake and sleep, in patients with Huntington Disease (HD). 23 patients with HD and 23 age- and sex-matched healthy controls were enrolled. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA). In wake, HD patients showed an increase of delta lagged phase synchronization (T=3.60; p<0.05) among Broadman's Areas (BA) 6-8 bilaterally; right BA 6-8 and right BA 1-2-3; left BA 1-2-3 and left BA 4. In NREM, HD patients showed an increase of delta lagged phase synchronization (T=3.56; p<0.05) among left BA 1-2-3 and right BA 6-8. In REM, HD patients showed an increase of lagged phase synchronization (T=3.60; p<0.05) among the BA 6-8 bilaterally (delta band); left BA 1-2-3 and right BA 1-2-3 (theta); left BA 1-2-3 and right BA 4 (theta); left BA 1-2-3 and right BA 1-2-3 (alpha). Our results may reflect an abnormal function of the motor areas or an effort to counterbalance the pathological motor output. Our results may help to understand the pathophysiology of sleep-related movement disorders in Huntington's Disease, and to define therapeutically strategies. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  6. Effects of chronic exposure of hydroxychloroquine/chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases.

    Science.gov (United States)

    Fardet, L; Nazareth, I; Petersen, I

    2017-01-01

    Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases. The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database. Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6%) or chloroquine (1.4%) and 24,118 unexposed individuals were included in the study (median age: 56 [45-66] years, women: 76.8%). When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92-1.18], p =0.54), hematological malignancies (adjusted sHR: 1.00 [0.73-1.38], p =0.99), or skin cancers (adjusted sHR: 0.92 [0.78-1.07], p =0.26). The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44-0.95] for the overall population and 0.61 [0.38-1.00] for those diagnosed with incident cancers). The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81-1.00] in the overall population and 0.78 [0.64-0.96] in those diagnosed with incident cancer). Individuals on long-term exposure to hydroxychloroquine/chloroquine are not at lower risk of cancer. However, hydroxychloroquine/chloroquine may lower the risk of metastatic cancer and death.

  7. Wicked Challenges in the Anthropocene Age: Supply Chain Implications of Sustainable Enterprise Excellence

    DEFF Research Database (Denmark)

    Edgeman, Rick; Wu, Zhaohui

    , and desertification; food availability and distribution; water pollution, air pollution, and soil contamination; and the connection of these to disease, violence, and terrorism. Wicked challenge traits are discussed in relation to enterprise excellence, sustainability, resilience and robustness (SEER2). The value...

  8. About Connections

    Directory of Open Access Journals (Sweden)

    Kathleen S Rockland

    2015-05-01

    Full Text Available Despite the attention attracted by connectomics, one can lose sight of the very real questions concerning What are connections? In the neuroimaging community, structural connectivity is ground truth and underlying constraint on functional or effective connectivity. It is referenced to underlying anatomy; but, as increasingly remarked, there is a large gap between the wealth of human brain mapping and the relatively scant data on actual anatomical connectivity. Moreover, connections have typically been discussed as pairwise, point x projecting to point y (or: to points y and z, or more recently, in graph theoretical terms, as nodes or regions and the interconnecting edges. This is a convenient shorthand, but tends not to capture the richness and nuance of basic anatomical properties as identified in the classic tradition of tracer studies. The present short review accordingly revisits connectional weights, heterogeneity, reciprocity, topography, and hierarchical organization, drawing on concrete examples. The emphasis is on presynaptic long-distance connections, motivated by the intention to probe current assumptions and promote discussions about further progress and synthesis.

  9. Ureases display biological effects independent of enzymatic activity: Is there a connection to diseases caused by urease-producing bacteria?

    Directory of Open Access Journals (Sweden)

    D. Olivera-Severo

    2006-07-01

    Full Text Available Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.

  10. Internet Connectivity

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Internet Connectivity. BSNL, SIFY, HCL in Guwahati; only BSNL elsewhere in NE (local player in Shillong). Service poor; All vendors lease BW from BSNL.

  11. Mathematics Connection

    African Journals Online (AJOL)

    MATHEMATICS CONNECTION aims at providing a forum topromote the development of Mathematics Education in Ghana. Articles that seekto enhance the teaching and/or learning of mathematics at all levels of theeducational system are welcome.

  12. HR Connect

    Data.gov (United States)

    US Agency for International Development — HR Connect is the USAID HR personnel system which allows HR professionals to process HR actions related to employee's personal and position information. This system...

  13. Why sustain oak forests?

    Science.gov (United States)

    David Wm. Smith

    2006-01-01

    A brief overview and some personal thoughts are offered that deal with the implications of our social and political systems on the long-term sustainability of our forest resources. The connection of the most recent climatic events, in a geologic-time context, to the development of present day oak dominated forests of the Eastern United States is discussed. The impacts...

  14. Poverty-Related Diseases College: a virtual African-European network to build research capacity

    NARCIS (Netherlands)

    Dorlo, Thomas P. C.; Fernández, Carmen; Troye-Blomberg, Marita; de Vries, Peter J.; Boraschi, Diana; Mbacham, Wilfred F.

    2016-01-01

    The Poverty-Related Diseases College was a virtual African-European college and network that connected young African and European biomedical scientists working on poverty-related diseases. The aim of the Poverty-Related Diseases College was to build sustainable scientific capacity and international

  15. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  16. Pulmonary uptake of thallium-201 in patients with congenital heart disease; Comparison between total anomalous pulmonary venous connection and tetralogy of Fallot

    Energy Technology Data Exchange (ETDEWEB)

    Kohata, Tohru; Ono, Yasuo; Iwatani, Hajime; Fukushima, Hideki; Kamiya, Tetsuro; Yagihara, Toshikatsu; Nishimura, Tsunehiko; Takamiya, Makoto (National Cardiovascular Center, Suita, Osaka (Japan))

    1992-01-01

    To evaluate the pulmonary extravascular space in patients with congenital heart disease, lung uptake of Tl-201 was quantitatively studied. Patients' diseases consisted of total anomalous pulmonary venous connection (TAPVC)--supracardiac (I), paracardiac (II) and infracardiac (III) types--, tetralogy of Fallot (T/F), ventricular septal defect (VSD), and patent ductus arteriosus (PDA). Tl-201 imaging was performed before operation and in the early and late stages after operation. Twenty-five other patients with arrhythemias or a history of Kawasaki disease without perfusion defects served as controls. Lung uptake of Tl-201 was analyzed with a computer using the anterior image of the chest, and the averge count ratio of the right lung (P) to the left ventricular wall (LV) was calculated. P/LV values were compared between the patients before and after operation, and differences in anatomical types in TAPVC were also evaluated. In TAPVC, P/LV values decreased gradually after operation, but were significantly higher than those of controls even in the late stage. In the late stage after operation, type I TAPVC had significantly higher P/LV values than those of type-II. In T/F, the P/LV values were significantly higher after operation, even in the late stage, than before operation. In the VSD or PDA group, the P/LV value returned to normal after operation and was significantly lower than that before operation. In conclusion, TAPVC patients was considered to have a larger pulmonary extravascular space even in the late stage after operation, suggesting a sign of pulmonary congestion due to intrapulmonary vascular damage in utero. In T/F, scanty pulmonary vascular beds before operation were perfused with increased pulmonary blood flow after operation. Therefore, postoperative increases in pulmonary blood flow may be responsible for the increased pulmonary extravascular space. (N.K.).

  17. Connections between nutritional status and proton pump inhibitor therapy in patients scheduled for cardiovascular rehabilitation after treatment for ischaemic and valvular heart disease.

    Science.gov (United States)

    Boban, Marko; Persic, Viktor; Petricevic, Mate; Biocina, Bojan; Sipic, Tomislav; Pehar-Pejcnovic, Vesna; Balen, Sanja; Zulj, Marinko; Vcev, Aleksandar

    Multiple and yet uncertain connections exist between cardiovascular diseases and the nutritional status of patients, particularly in relation to cardiovascular treatments. Proton pump inhibitors (PPI) are among the most commonly used group of drugs. To analyse utilisation of PPI in association with nutritional risk of patients scheduled for rehabilitation after treatment for ischaemic and valvular heart disease. Retrospective analyses on a consecutive sample of patients, which included drug utilisation of PPI and nutritional risk screening, using a standardised NRS-2002 tool. The patients (n = 536) were divided into groups based on previous cardiovascular treatments and use of PPI. Nearly half of the patients (244, 46.1%) had PPI in their chronic therapy despite the clinically negligible prevalence of conditions that are their fundamental indications. The odds for using PPI in patients with increased nutritional risk, estimated by logistic regression, were 3.34 (95% confidence intervals [CI] 2.26-4.94), p 3: positive likelihood-ratio (LR) 2.35 (95% CI 2.10-2.60); negative LR 0.46 (95% CI 0.4-0.6); area under the curve (AUC) 0.720; p 6.36% (positive LR 2.22 [95% CI 2.00-2.50]; negative LR 0.41 [95% CI 0.30-0.50]; AUC 0.707; p < 0.001). Utilisation of PPI was found to be of relatively high prevalence and significantly associated with parameters of nutritional risk screening. Furthermore, it was in correlation with the age of patients and the existence of chronic kidney disease, which are well-established predispositions for poor nutritional status. Nutritional risk seems to be additionally negatively challenged by utilisation of PPI due to gastric malabsorption and anaemia.

  18. 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.

  19. Can the sustainable development goals reduce the burden of nutrition-related non-communicable diseases without truly addressing major food system reforms?

    Science.gov (United States)

    Hawkes, Corinna; Popkin, Barry M

    2015-06-16

    While the Millennium Development Goals (MDGs; 2000-2015) focused primarily on poverty reduction, hunger and infectious diseases, the proposed Sustainable Development Goals (SDGs) and targets pay more attention to nutrition and non-communicable diseases (NCDs). One of the 169 proposed targets of the SDGs is to reduce premature deaths from NCDs by one third; another is to end malnutrition in all its forms. Nutrition-related NCDs (NR-NCDs) stand at the intersection between malnutrition and NCDs. Driven in large part by remarkable transformations of food systems, they are rapidly increasing in most low and middle income countries (LMICs). The transformation to modern food systems began in the period following World War II with policies designed to meet a very different set of nutritional and food needs, and continued with globalization in the 1990s onwards. Another type of food systems transformation will be needed to shift towards a healthier and more sustainable diet--as will meeting many of the other SDGs. The process will be complex but is necessary. Communities concerned with NCDs and with malnutrition need to work more closely together to demand food systems change.

  20. Establishing Connectivity

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    Global law settings are characterised by a structural pre-eminence of connectivity norms, a type of norm which differs from coherency or possibility norms. The centrality of connectivity norms emerges from the function of global law, which is to increase the probability of transfers of condensed ...... and human rights can be understood as serving a constitutionalising function aimed at stabilising and facilitating connectivity. This allows for an understanding of colonialism and contemporary global governance as functional, but not as normative, equivalents.......Global law settings are characterised by a structural pre-eminence of connectivity norms, a type of norm which differs from coherency or possibility norms. The centrality of connectivity norms emerges from the function of global law, which is to increase the probability of transfers of condensed...... social components, such as economic capital and products, religious doctrines and scientific knowledge, from one legally structured context to another within world society. This was the case from colonialism and colonial law to contemporary global supply chains and human rights. Both colonial law...

  1. Connected Traveler

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    The Connected Traveler framework seeks to boost the energy efficiency of personal travel and the overall transportation system by maximizing the accuracy of predicted traveler behavior in response to real-time feedback and incentives. It is anticipated that this approach will establish a feedback loop that 'learns' traveler preferences and customizes incentives to meet or exceed energy efficiency targets by empowering individual travelers with information needed to make energy-efficient choices and reducing the complexity required to validate transportation system energy savings. This handout provides an overview of NREL's Connected Traveler project, including graphics, milestones, and contact information.

  2. The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer’s disease

    Science.gov (United States)

    2013-01-01

    Introduction Souvenaid® containing Fortasyn® Connect is a medical food designed to support synapse synthesis in persons with Alzheimer’s disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal membranes. Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed. Methods In a 24-week, double-masked clinical trial at 48 clinical centers, 527 participants taking AD medications [52% women, mean age 76.7 years (Standard Deviation, SD = 8.2), and mean Mini-Mental State Examination score 19.5 (SD = 3.1, range 14–24)] were randomized 1:1 to daily, 125-mL (125 kcal), oral intake of the active product (Souvenaid) or an iso-caloric control. The primary outcome of cognition was assessed by the 11-item Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Compliance was calculated from daily diary recordings of product intake. Statistical analyses were performed using mixed models for repeated measures. Results Cognitive performance as assessed by ADAS-cog showed decline over time in both control and active study groups, with no significant difference between study groups (difference =0.37 points, Standard Error, SE = 0.57, p = 0.513). No group differences in adverse event rates were found and no clinically relevant differences in blood safety parameters were noted. Overall compliance was high (94.1% [active] and 94.5% [control]), which was confirmed by significant changes in blood (nutritional) biomarkers. Conclusions Add-on intake of Souvenaid during 24 weeks did not slow cognitive decline in persons treated for mild-to-moderate AD. Souvenaid was well tolerated in combination with standard care AD medications. Trial registration Dutch Trial Register number: NTR1683. PMID:24280255

  3. The macroecology of sustainability

    Science.gov (United States)

    Burger, Joseph R.; Allen, Craig D.; Brown, James H.; Burnside, William R.; Davidson, Ana D.; Fristoe, Trevor S.; Hamilton, Marcus J.; Mercado-Silva, Norman; Nekola, Jeffrey C.; Okie, Jordan G.; Zuo, Wenyun

    2012-01-01

    The discipline of sustainability science has emerged in response to concerns of natural and social scientists, policymakers, and lay people about whether the Earth can continue to support human population growth and economic prosperity. Yet, sustainability science has developed largely independently from and with little reference to key ecological principles that govern life on Earth. A macroecological perspective highlights three principles that should be integral to sustainability science: 1) physical conservation laws govern the flows of energy and materials between human systems and the environment, 2) smaller systems are connected by these flows to larger systems in which they are embedded, and 3) global constraints ultimately limit flows at smaller scales. Over the past few decades, decreasing per capita rates of consumption of petroleum, phosphate, agricultural land, fresh water, fish, and wood indicate that the growing human population has surpassed the capacity of the Earth to supply enough of these essential resources to sustain even the current population and level of socioeconomic development.

  4. Building a foundation for 'One Health': an education strategy for enhancing and sustaining national and regional capacity in endemic and emerging zoonotic disease management.

    Science.gov (United States)

    Vink, W D; McKenzie, Joanna S; Cogger, Naomi; Borman, Barry; Muellner, Petra

    2013-01-01

    The rapid global spread of diseases such as SARS, H5N1, and H1N1 influenza has emphasized the pressing need for trans-disciplinary collaboration and cross-border action, and has also exposed a serious deficit of capacity and coordination in dealing effectively with emerging disease threats. The need for capacity development is particularly acute in the developing world, which is the least well-equipped to respond adequately. Such capacity development can be achieved through education and the implementation of applied 'One Health' activities. This chapter describes the establishment of a 'One Health' capacity development program in South Asia, consisting of two phases. The first phase provides Masters level training for public health doctors and veterinarians, with a focus on epidemiology, and disease control. The second phase reinforces the postgraduate training by establishing a sustainable framework for the implementation of collaborative 'One Health' activities such as the development of multidisciplinary professional networks, implementation of applied zoonotic disease investigation projects, and support for continuing professional development. The objectives are to provide individual skills required to strengthen capacity; to develop an appreciation of the cross-cutting issues which affect human and animal health, set within an institutional context; and to facilitate the development of regional professional networks which will be instrumental in implementing 'One Health' activities.

  5. Making connections

    NARCIS (Netherlands)

    Marion Duimel

    2007-01-01

    Original title: Verbinding maken; senioren en internet. More and more older people are finding their way to the Internet. Many people aged over 50 who have only recently gone online say that a new world has opened up for them. By connecting to the Internet they have the feeling that they

  6. CMS Connect

    Science.gov (United States)

    Balcas, J.; Bockelman, B.; Gardner, R., Jr.; Hurtado Anampa, K.; Jayatilaka, B.; Aftab Khan, F.; Lannon, K.; Larson, K.; Letts, J.; Marra Da Silva, J.; Mascheroni, M.; Mason, D.; Perez-Calero Yzquierdo, A.; Tiradani, A.

    2017-10-01

    The CMS experiment collects and analyzes large amounts of data coming from high energy particle collisions produced by the Large Hadron Collider (LHC) at CERN. This involves a huge amount of real and simulated data processing that needs to be handled in batch-oriented platforms. The CMS Global Pool of computing resources provide +100K dedicated CPU cores and another 50K to 100K CPU cores from opportunistic resources for these kind of tasks and even though production and event processing analysis workflows are already managed by existing tools, there is still a lack of support to submit final stage condor-like analysis jobs familiar to Tier-3 or local Computing Facilities users into these distributed resources in an integrated (with other CMS services) and friendly way. CMS Connect is a set of computing tools and services designed to augment existing services in the CMS Physics community focusing on these kind of condor analysis jobs. It is based on the CI-Connect platform developed by the Open Science Grid and uses the CMS GlideInWMS infrastructure to transparently plug CMS global grid resources into a virtual pool accessed via a single submission machine. This paper describes the specific developments and deployment of CMS Connect beyond the CI-Connect platform in order to integrate the service with CMS specific needs, including specific Site submission, accounting of jobs and automated reporting to standard CMS monitoring resources in an effortless way to their users.

  7. The risk of cancer in patients with connective tissue diseases but without dermatomyositis or polymyositis: A multicenter cohort study conducted over 15 years in China.

    Science.gov (United States)

    Xu, Wei; Guo, Huan; Liu, Zhi; Chen, Chen; Lei, Cong-Cong

    2016-09-01

    To investigate the relative risk of cancer in Chinese patients with connective tissue diseases (CTD) associated with and without dermatomyositis or polymyositis. A retrospective, multicenter cohort study investigated 32,380 CTD patients (2334 diagnosed with dermatomyositis or polymyositis) without a history of malignancies treated from January 1, 1997, to December 31, 2011. Standardized incidence ratios (SIR) of cancers determined the incidence of malignancies during follow-up. The data was compared with the cancer morbidity of the general population from the Chinese Cancer Registry Annual Report of National Central Cancer Registry. A total of 113 patients (348.98 per 100,000) developed cancer during follow-up, 75 (249.62 per 100,000) were patients with CTD without dermatomyositis or polymyositis. The risk of cancer among patients with CTD was increased (SIR=1.45, 95% confidence interval [CI] 1.22-1.71), and this risk increased with age (60 years SIR=2.34 (95%CI 0.93-2.77]) and the time of follow-up (cancer risk among CTD patients without dermatomyositis or polymyositis was not affected (SIR=0.93, 95%CI 0.75-1.16), regardless of gender, age, or follow-up. The cancer risk for patients with CTD without dermatomyositis or polymyositis was not increased or decreased, but it was increased when patients with dermatomyositis or polymyositis were included. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. High dimensional ICA analysis detects within-network functional connectivity damage of default mode and sensory motor networks in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ottavia eDipasquale

    2015-02-01

    Full Text Available High dimensional independent component analysis (ICA, compared to low dimensional ICA, allows performing a detailed parcellation of the resting state networks. The purpose of this study was to give further insight into functional connectivity (FC in Alzheimer’s disease (AD using high dimensional ICA. For this reason, we performed both low and high dimensional ICA analyses of resting state fMRI (rfMRI data of 20 healthy controls and 21 AD patients, focusing on the primarily altered default mode network (DMN and exploring the sensory motor network (SMN. As expected, results obtained at low dimensionality were in line with previous literature. Moreover, high dimensional results allowed us to observe either the presence of within-network disconnections and FC damage confined to some of the resting state sub-networks. Due to the higher sensitivity of the high dimensional ICA analysis, our results suggest that high-dimensional decomposition in sub-networks is very promising to better localize FC alterations in AD and that FC damage is not confined to the default mode network.

  9. Membranous glomerulonephritis in a patient with anti-u1 ribonucleoprotein (RNP antibody-positive mixed connective tissue disease: A case report

    Directory of Open Access Journals (Sweden)

    Naoya Toriu

    2018-03-01

    Full Text Available We report a 33-year-old Japanese man diagnosed with mixed connective tissue disease (MCTD who developed nephrotic proteinuria. Both speckled antinuclear antibody (ANA and anti-U1 ribonucleoprotein (RNP antibody were positive, but anti-double-stranded DNA (dsDNA antibody and anti-Smith (Sm antibody were negative, while complement levels were normal. Renal biopsy revealed membranous glomerulonephritis (MGN with diffuse thickening of the glomerular basement membrane (GBM plus spike and bubble formation. Immunofluorescence demonstrated granular deposits of IgG and C3 along the GBM. Analysis of IgG subclasses showed predominant deposition of IgG1 and IgG4, unlike typical lupus nephritis in which there is predominant deposition of IgG1, IgG2, IgG3, and C1q. Electron microscopy identified numerous large electron-dense deposits (EDD of various types in the subepithelial region of the GBM, but there were no EDD localized in the mesangium or subendothelium. Based on these findings, MGN was considered to be closely related to MCTD in this patient.

  10. Sustained Effectiveness of Rotavirus Vaccine Against Very Severe Rotavirus Disease Through the Second Year of Life, Bolivia 2013-2014.

    Science.gov (United States)

    Pringle, Kimberly D; Patzi, Maritza; Tate, Jacqueline E; Iniguez Rojas, Volga; Patel, Manish; Inchauste Jordan, Lucia; Montesano, Raul; Zarate, Adolfo; De Oliveira, Lucia; Parashar, Umesh

    2016-05-01

    In Bolivia, monovalent rotavirus vaccine was introduced in 2008 and a previous evaluation reported a vaccine effectiveness (VE) of 77% with 2 doses of vaccine in children aged 5 years after its introduction in Bolivia. Although VE appears to wane in children aged ≥1 year, it still provides significant protection, and does not wane against severe disease. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  11. Sustained high plasma mannose less sensitive to fluctuating blood glucose in glycogen storage disease type Ia children

    NARCIS (Netherlands)

    Nagasaka, Hironori; Yorifuji, Tohru; Bandsma, Robert H. J.; Takatani, Tomozumi; Asano, Hisaki; Mochizuki, Hiroshi; Takuwa, Mayuko; Tsukahara, Hirokazu; Inui, Ayano; Tsunoda, Tomoyuki; Komatsu, Haruki; Hiejima, Eitaro; Fujisawa, Tomoo; Hirano, Ken-ichi; Miida, Takashi; Ohtake, Akira; Taguchi, Tadao; Miwa, Ichitomo

    Plasma mannose is suggested to be largely generated from liver glycogen-oriented glucose-6-phosphate. This study examined plasma mannose in glycogen storage disease type Ia (GSD Ia) lacking conversion of glucose-6-phosphate to glucose in the liver. We initially examined fasting-and postprandial 2

  12. Gendered Connections

    DEFF Research Database (Denmark)

    Jensen, Steffen Bo

    2009-01-01

    This article explores the gendered nature of urban politics in Cape Town by focusing on a group of female, township politicians. Employing the Deleuzian concept of `wild connectivity', it argues that these politically entrepreneurial women were able to negotiate a highly volatile urban landscape...... by drawing on and operationalizing violent, male networks — from struggle activists' networks, to vigilante groups and gangs, to the police. The fact that they were women helped them to tap into and exploit these networks. At the same time, they were restricted by their sex, as their ability to navigate...... space also drew on quite traditional notions of female respectability. Furthermore, the article argues, the form of wild connectivity to an extent was a function of the political transition, which destabilized formal structures of gendered authority. It remains a question whether this form...

  13. In the Name of Sustainability

    DEFF Research Database (Denmark)

    Rasmussen, Louise Mubanda

    2017-01-01

    of ethnographic fieldwork with NGOs supporting ‘orphans and vulnerable children’ in Malawi, this article explores the practices, social relations and contradictory effects that the vision of sustainability engenders. The article illustrates how the commitment to sustainability paradoxically produces practices...... that can only be sustained through continuous flows of donor funding. It argues that the persistence of sustainability as an organising principle is connected both to its self-confirming logic and to the ways in which practices of ‘sustainability’ shape the subjectivities of local brokers and come...

  14. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  15. Tackling socioeconomic inequalities and non-communicable diseases in low-income and middle-income countries under the Sustainable Development agenda.

    Science.gov (United States)

    Niessen, Louis W; Mohan, Diwakar; Akuoku, Jonathan K; Mirelman, Andrew J; Ahmed, Sayem; Koehlmoos, Tracey P; Trujillo, Antonio; Khan, Jahangir; Peters, David H

    2018-05-19

    Five Sustainable Development Goals (SDGs) set targets that relate to the reduction of health inequalities nationally and worldwide. These targets are poverty reduction, health and wellbeing for all, equitable education, gender equality, and reduction of inequalities within and between countries. The interaction between inequalities and health is complex: better economic and educational outcomes for households enhance health, low socioeconomic status leads to chronic ill health, and non-communicable diseases (NCDs) reduce income status of households. NCDs account for most causes of early death and disability worldwide, so it is alarming that strong scientific evidence suggests an increase in the clustering of non-communicable conditions with low socioeconomic status in low-income and middle-income countries since 2000, as previously seen in high-income settings. These conditions include tobacco use, obesity, hypertension, cancer, and diabetes. Strong evidence from 283 studies overwhelmingly supports a positive association between low-income, low socioeconomic status, or low educational status and NCDs. The associations have been differentiated by sex in only four studies. Health is a key driver in the SDGs, and reduction of health inequalities and NCDs should become key in the promotion of the overall SDG agenda. A sustained reduction of general inequalities in income status, education, and gender within and between countries would enhance worldwide equality in health. To end poverty through elimination of its causes, NCD programmes should be included in the development agenda. National programmes should mitigate social and health shocks to protect the poor from events that worsen their frail socioeconomic condition and health status. Programmes related to universal health coverage of NCDs should specifically target susceptible populations, such as elderly people, who are most at risk. Growing inequalities in access to resources for prevention and treatment need to

  16. Personalized game suite: a unified platform to sustain and improve the quality of life of Parkinson's disease patients.

    OpenAIRE

    Sofia B.Dias; Jose .A Diniz.; Stelios K. Hadjidimitriou; Vasileios Charisis; Evdokimos Konstantinidis; Panagiotis Bamidis; Leontios J. Hadjileontiadis

    2016-01-01

    The use of apps/games in healthcare interventions is gaining popularity, but there is still a gap in the understanding on how these types of interventions are used for the management of Parkinson disease (PD). In fact, gamification in healthcare (mHealth) can help people initiate healthier activities in various areas, such as losing weight, sleeping more, making healthier food choices, improving fitness, and monitoring health metrics. In this vein, there are six key elements ...

  17. The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry.

    Science.gov (United States)

    Viviani, Laura; Zolin, Anna; Mehta, Anil; Olesen, Hanne Vebert

    2014-06-07

    Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries. We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results. We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination. We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a shared electronic platform for data

  18. Isolated congenital heart block in undifferentiated connective tissue disease and in primary Sjögren’s syndrome: a clinical study of 81 pregnancies in 41 patients

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: To study the incidence and the features of congenital heart block (CHB in patients with undifferentiated connective tissue disease (UCTD and primary Sjögren’s syndrome (pSS. Methods: We studied 81 pregnancies of 41 women attending the Outpatients’ Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61% were affected with UCTD and 16 (39% with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. Results: CHB was found in 2 out of the 46 (4,3% pregnancies followed by our Staff and in 2 out of the 35 (5,7% included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0,026. Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. Conclusion: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities.

  19. Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.

    Science.gov (United States)

    Somarelli, J A; Mesa, A; Rodriguez, R; Avellan, R; Martinez, L; Zang, Y J; Greidinger, E L; Herrera, R J

    2011-03-01

    Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of 'self ' antigens. Proteins of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) are among the most immunogenic molecules in patients with SLE and MCTD. The recent release of a crystallized U1 snRNP provides a unique opportunity to evaluate the effects of tertiary and quaternary structures on autoantigenicity within the U1 snRNP. In the present study, an epitope map was created using the U1 snRNP crystal structure. A total of 15 peptides were tested in a cohort of 68 patients with SLE, 29 with MCTD and 26 healthy individuals and mapped onto the U1 snRNP structure. Antigenic sites were detected in a variety of structures and appear to include RNA binding domains, but mostly exclude regions necessary for protein-protein interactions. These data suggest that while some autoantibodies may target U1 snRNP proteins as monomers or apoptosis-induced, protease-digested fragments, others may recognize epitopes on assembled protein subcomplexes of the U1 snRNP. Although nearly all of the peptides are strong predictors of autoimmune illness, none were successful at distinguishing between SLE and MCTD. The antigenicity of some peptides significantly correlated with several clinical symptoms. This investigation implicitly highlights the complexities of autoimmune epitopes, and autoimmune illnesses in general, and demonstrates the variability of antigens in patient populations, all of which contribute to difficult clinical diagnoses.

  20. Barriers and facilitators for mental healthcare in pediatric lupus and mixed connective tissue disease: a qualitative study of youth and parent perspectives.

    Science.gov (United States)

    Knight, Andrea M; Vickery, Michelle E; Fiks, Alexander G; Barg, Frances K

    2015-11-24

    Untreated mental health problems may result in poor outcomes for youth with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). We investigated perceptions, barriers and facilitators for mental healthcare of these youth. We conducted 32 semi-structured interviews with 16 outpatient youth with SLE/MCTD, ages 11-22 years, and their parents. We used purposive sampling to deliberately obtain the experiences of youth screened during a previous study for depression and anxiety with the Patient Health Questionnaire 9 and the Screen for Childhood Anxiety and Related Disorders, respectively. We recruited 6 youth with previous positive screens and 10 with negative screens. We assessed interim mental health history, and qualitatively examined perceptions, barriers and facilitators for mental healthcare. Youth with a mental health history increased from 6 (38%) at initial screening to 9 (56%) at interview (mean follow-up = 2.1 years). Youth receiving mental health treatment increased from 33 to 67%. Youth and parents identified rheumatologists as primary physicians and found mental health screening in rheumatology acceptable. Barriers to mental healthcare included: stigma; fear; uncertainty about getting help; parental emotional burden; minimization by doctors; and limited mental healthcare access. Facilitators included: strong clinician relationships; clinician initiative, sincerity and normalization in discussing mental health; and increased patient/family awareness of mental health issues in SLE/MCTD. Youth with SLE/MCTD and their parents perceive pediatric rheumatologists as a preferred source for mental health screening, guidance and referral. Interventions addressing barriers and enhancing facilitators may improve mental healthcare for youth with SLE/MCTD.

  1. Effective artifact removal in resting state fMRI data improves detection of DMN functional connectivity alteration in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ludovica eGriffanti

    2015-08-01

    Full Text Available Artefact removal from resting state fMRI data is an essential step for a better identification of the resting state networks and the evaluation of their functional connectivity (FC, especially in pathological conditions. There is growing interest in the development of cleaning procedures, especially those not requiring external recordings (data-driven, which are able to remove multiple sources of artefacts. It is important that only inter-subject variability due to the artefacts is removed, preserving the between-subject variability of interest - crucial in clinical applications using clinical scanners to discriminate different pathologies and monitor their staging. In Alzheimer’s disease (AD patients, decreased FC is usually observed in the posterior cingulate cortex within the default mode network (DMN, and this is becoming a possible biomarker for AD. The aim of this study was to compare four different data-driven cleaning procedures (regression of motion parameters; regression of motion parameters, mean white matter and cerebrospinal fluid signal; FMRIB's ICA-based X-noiseifier –FIX- cleanup with soft and aggressive options on data acquired at 1.5T. The approaches were compared using data from 20 elderly healthy subjects and 21 AD patients in a mild stage, in terms of their impact on within-group consistency in FC and ability to detect the typical FC alteration of the DMN in AD patients. Despite an increased within-group consistency across subjects after applying any of the cleaning approaches, only after cleaning with FIX the expected DMN FC alteration in AD was detectable. Our study validates the efficacy of artefact removal even in a relatively small clinical population, and supports the importance of cleaning fMRI data for sensitive detection of FC alterations in a clinical environment.

  2. Cosmic Connections

    CERN Document Server

    Ellis, Jonathan Richard

    2003-01-01

    A National Research Council study on connecting quarks with the cosmos has recently posed a number of the more important open questions at the interface between particle physics and cosmology. These questions include the nature of dark matter and dark energy, how the Universe began, modifications to gravity, the effects of neutrinos on the Universe, how cosmic accelerators work, and whether there are new states of matter at high density and pressure. These questions are discussed in the context of the talks presented at this Summer Institute.

  3. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

    Science.gov (United States)

    Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

    2017-07-01

    Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. 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/.

  4. A Biobank for Long-term and Sustainable Research in the Field of Congenital Heart Disease in Germany

    Directory of Open Access Journals (Sweden)

    Thomas Pickardt

    2016-08-01

    Full Text Available Congenital heart disease (CHD is the most frequent birth defect (0.8%–1% of all live births. Due to the advance in prenatal and postnatal early diagnosis and treatment, more than 90% of these patients survive into adulthood today. However, several mid- and long-term morbidities are dominating the follow-up of these patients. Due to the rarity and heterogeneity of the phenotypes of CHD, multicenter registry-based studies are required. The CHD-Biobank was established in 2009 with the aim to collect DNA from patients and their parents (trios or from affected families, as well as cardiovascular tissues from patients undergoing corrective heart surgery for cardiovascular malformations. Clinical/phenotype data are matched to the International Paediatric and Congenital Cardiac Code (IPCCC and the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10. The DNA collection currently comprises samples from approximately 4200 participants with a wide range of CHD phenotypes. The collection covers about 430 trios and 120 families with more than one affected member. The cardiac tissue collection comprises 1143 tissue samples from 556 patients after open heart surgery. The CHD-Biobank provides a comprehensive basis for research in the field of CHD with high standards of data privacy, IT management, and sample logistics.

  5. Sustained pediatric antimicrobial stewardship program with consultation to infectious diseases reduced carbapenem resistance and infection-related mortality.

    Science.gov (United States)

    Horikoshi, Yuho; Suwa, Junichi; Higuchi, Hiroshi; Kaneko, Tetsuji; Furuichi, Mihoko; Aizawa, Yuta; Fukuoka, Kahoru; Okazaki, Kaoru; Ito, Kenta; Shoji, Takayo

    2017-11-01

    The impact of pediatric antimicrobial stewardship programs (ASP) on antimicrobial resistance (AMR) remains largely unknown. This study aimed to evaluate the AMR for carbapenem of Gram-negative bacilli (GNB) and carbapenem use with infectious diseases consultation after the implementation of an ASP. This quasi-experimental study was conducted at Tokyo Metropolitan Children's Medical Center in Japan. The pre- and post-intervention periods were April 2010 to September 2011 and October 2011 to March 2017, respectively. The pre-intervention phase consisted of consultations with the infectious diseases service alone. The ASP was implemented during the post-intervention phase. The carbapenem resistance rates of GNB were calculated. The correlation between carbapenem resistance rates and carbapenem day of therapy (DOT) was examined. The outcome metrics were compared by average length of hospitalization, all-cause mortality, and infection-related mortality. A positive correlation was observed between the carbapenem resistance rate in Pseudomonas aeruginosa and DOT (0.76, p=0.04). The carbapenem resistance rate in P. aeruginosa (pcarbapenem use and resistance in P. aeruginosa, leading to favorable outcomes in terms of length of hospitalization and infection-related mortality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. How Frugal Innovation Promotes Social Sustainability

    OpenAIRE

    Rakhshanda Khan

    2016-01-01

    There is a need to develop an understanding of how frugal innovation promotes social sustainability. The objective of this paper is to find the connections between the two concepts of social sustainability and frugal innovation, by reviewing the existing literature concerning both fields. This paper presents a framework that identifies essential themes of social sustainability and explores them through frugal innovation. The framework builds on the important themes of social sustainability an...

  7. Sustained High Levels of Both Total and High Molecular Weight Adiponectin in Plasma during the Convalescent Phase of Haemorrhagic Fever with Renal Syndrome Are Associated with Disease Severity

    Directory of Open Access Journals (Sweden)

    Kang Tang

    2017-01-01

    Full Text Available Haemorrhagic fever with renal syndrome (HFRS is characterised by an uncontrolled immune response that causes vascular leakage. Adiponectin (APN is an adipocytokine involved in prorevascularisation and immunomodulation. To investigate the possible effects of APN in the pathogenesis of HFRS, total and high molecular weight (HMW APN levels in the plasma of patients with HFRS were quantified using enzyme-linked immunosorbent assay (ELISA. Compared with those in healthy controls, the plasma total and HMW APN levels in patients were elevated to different degrees from the fever onset and remained high at the convalescent phase. Consistent with these results, western blot analysis additionally showed that low molecular weight (LMW, middle molecular weight (MMW, and HMW APN levels were all elevated and contributed to the elevation of the total APN level. Importantly, sustained high levels of total and HMW APN at the convalescent phase were significantly higher in patients with critical disease than those in patients with mild or moderate disease. Moreover, total and HMW APN levels negatively correlated with white blood cell count and positively correlated with platelet count and serum albumin level. These results may provide insights into understanding the roles of total and HMW APN in the pathogenesis of HFRS.

  8. How Frugal Innovation Promotes Social Sustainability

    Directory of Open Access Journals (Sweden)

    Rakhshanda Khan

    2016-10-01

    Full Text Available There is a need to develop an understanding of how frugal innovation promotes social sustainability. The objective of this paper is to find the connections between the two concepts of social sustainability and frugal innovation, by reviewing the existing literature concerning both fields. This paper presents a framework that identifies essential themes of social sustainability and explores them through frugal innovation. The framework builds on the important themes of social sustainability and shows their relevance in practice through frugal innovation. The notion of frugal innovation can be viewed as an approach towards realizing social sustainability and fulfilling the United Nations’ Sustainable Development Goals.

  9. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  10. Places Connected:

    DEFF Research Database (Denmark)

    Hansen, Annette Skovsted

    This paper argues that development assistance contributed to the globalization of the 20th century by financing truly global networks of people. By focusing on the networks financed by development assistance bound by the national histories of Denmark and Japan, I illustrate how the people who...... experiences of place, however, when it is often the same people who experience many different places? Along with many other so-called donors in the 1950s, Denmark and Japan chose to invest in the education of own and other nationals involved in development and thereby financed personal connections between...... individuals throughout the world. Development assistance , where there are two or three links only between a Bangladeshi farmer, a street child in Sao Paolo and the President of the United States, the Queen of Denmark, or a suburban house wife in Japan, who has never left the Osaka area, but mothered a United...

  11. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  12. Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease.

    Science.gov (United States)

    Hourigan, S K; Chen, L A; Grigoryan, Z; Laroche, G; Weidner, M; Sears, C L; Oliva-Hemker, M

    2015-09-01

    Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients. FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity. © 2015 John Wiley & Sons Ltd.

  13. Urban Landscapes and Sustainable Cities

    Directory of Open Access Journals (Sweden)

    Erik Andersson

    2006-06-01

    Full Text Available Ecological research targeting sustainable urban landscapes needs to include findings and methods from many lines of ecological research, such as the link between biodiversity and ecosystem function, the role of humans in ecosystems, landscape connectivity, and resilience. This paper reviews and highlights the importance of these issues for sustainable use of ecosystem services, which is argued to be one aspect of sustainable cities. The paper stresses the need to include social and economic factors when analyzing urban landscapes. Spatially explicit data can be used to assess the roles different green areas have in providing people with ecosystem services, and whether people actually have access to the services. Such data can also be used to assess connectivity and heterogeneity, both argued to be central for continuous, long-term provision of these services, and to determine the role urban form has for sustainability.

  14. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    Declarations on Sustainability in Higher Education (SHE) can be viewed as a piece of international regulation. Over the past 30 years research at universities has produced convincing data to warn about deterioration of the environment, resource scarcity and the need for sustainability. This in turn....... Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...

  15. Investigation of smallholder farmer biosecurity and implications for sustainable foot-and-mouth disease control in Cambodia.

    Science.gov (United States)

    Young, J R; Suon, S; Olmo, L; Bun, C; Hok, C; Ashley, K; Bush, R D; Windsor, P A

    2017-12-01

    In Cambodia, the majority of the population is rural and reliant on subsistence agriculture, with cattle raised by smallholder farmers using traditional practices, resulting in low productivity and vulnerability to foot-and-mouth disease (FMD). As FMD causes deleterious impacts on rural livelihoods, known FMD risk factors were reviewed, using knowledge, attitudes and practice (KAP) surveys of smallholders (n = 240) from four regions. The study aimed to understand current biosecurity threats to smallholder livelihoods and investigate the hypothesis that smallholder farmers practising FMD risk management should be associated with higher incomes from cattle. Descriptive data were examined to demonstrate trends in KAP and a multivariable linear regression model developed to identify cattle income predictors. Results showed that baseline mean knowledge scores were low at 28.4% across all regions and basic biosecurity practices, including quarantine of new cattle, isolation of sick cattle and FMD vaccination, were lacking. As farmers purchase and sell cattle from and to various administration levels (including export), there is high risk of FMD transmission into and from smallholder communities. The final multivariable linear regression model identified significant explanatory parameters for annual cattle income, including region, number of calves born, forage plot size (ha), vaccination of cattle and the number of cattle purchased (F pr. livestock development programmes implement a systems approach to enhance farmer KAP in biosecurity, nutrition, reproduction and marketing of cattle. © 2017 Blackwell Verlag GmbH.

  16. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    /kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study....

  17. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  18. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuil...

  19. Sustainability Labeling

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    Sustainability labeling originated from a need to protect the identity of alternative systems of food production and to increase market transparency. From the 1980s onwards sustainability labeling has changed into a policy instrument replacing direct government regulation of the food market, and a

  20. Afterschool Sustainability

    Directory of Open Access Journals (Sweden)

    Hilary D. Joyce

    2014-12-01

    Full Text Available Youth participation in quality extended learning opportunities (ELOs results in positive academic, physical, mental health, and social/emotional outcomes. Funding is essential to implementing and sustaining quality ELOs; however multiple funding barriers and challenges exist. Understanding the types of funds available for ELOs and the factors that influence sustainability is critical. Through surveys and telephone interviews of ELO providers, this descriptive study identified and examined ELO funding streams, the ways ELO providers use these funding streams, and the barriers and challenges to sustainability. ELO programs often relied on one major funding stream coupled with nutrition supports as well as in-kind resources. Barriers to sustainability included year-to-year funding, transportation costs, reducing community partnerships, and difficulty in diversifying funds. Recommendations to enhance ELO sustainability are offered, particularly in relation to overcoming the challenges to diversification of funding resources and establishing mutually supportive partnerships and collaboration.

  1. Methylphenidate Modulates Functional Network Connectivity to Enhance Attention

    OpenAIRE

    Rosenberg, Monica D.; Zhang, Sheng; Hsu, Wei-Ting; Scheinost, Dustin; Finn, Emily S.; Shen, Xilin; Constable, R. Todd; Li, Chiang-Shan R.; Chun, Marvin M.

    2016-01-01

    Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained...

  2. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  3. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, T.Q.; Tarnow, L.; Jorsal, A.

    2008-01-01

    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic...

  4. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, Tri Q; Tarnow, Lise; Jorsal, Anders

    2008-01-01

    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic pat...

  5. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  6. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  7. Sustainable Futures

    Science.gov (United States)

    Sustainable Futures is a voluntary program that encourages industry to use predictive models to screen new chemicals early in the development process and offers incentives to companies subject to TSCA section 5.

  8. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  9. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt......, that it can be adapted to changing functional needs, and that it has an architectural and cultural value. A specific proposal for a transformation that enhances the architectural qualities and building heritage values of an existing building forms the empirical material, which is discussed using different...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  10. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    The intention of this chapter is to explore the role of consumption and consumers in relation to sustainability transition processes and wider systemic transformations. In contrast to the individualistic focus in much research on sustainable consumption, the embeddedness of consumption activities...... in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...

  11. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  12. Seeking Sustainability

    OpenAIRE

    Clive L. Spash

    2014-01-01

    What does sustainability research do to help the environment? One might well wonder when observing the annual conference season with various academics and professors in sustainability science, ecological economics or environmental ethics driving to the airport to fly off to international meetings to discuss how bad things are getting, what should been done about it, and how time is running out for action. In fact, singling out a few academic groups is highly unfair because the link between pr...

  13. Local Sustainability

    International Nuclear Information System (INIS)

    Carrizosa Umana, Julio

    1998-01-01

    The current polemic about the possibilities of sustainable development has led to a renovated interest for the topic of the sustainability of the communities and the local sustainability. In front of the global sustainability whose conditions have been exposed by systemic ecologists and for macro economists, the sustainability of specific places arises in the planet whose conditions are object of study of the ecology of landscapes, of the ecological economy, of the cultural anthropology, of the environmental sociology and naturally, of the integral environmentalism. In this discussion the Colombian case charges unusual interest to be one of the few countries of Latin America, where a very dense net of municipalities exists, each one with its urban helmet and with a position and some functions defined by the political constitution of the nation. This net of municipalities and of urban helmets it also constitutes net of alternative to the current macro-cephalic situation. As well as Bogota grew, in a hundred years, of less than a hundred thousand inhabitants to six million inhabitants, each one of these municipalities contains a potential of growth that depends on the characteristics of its ecological, social, economic and politic sustainability

  14. Investigation of the possible connection of rock and soil geochemistry to the occurrence of high rates of neurodegenerative diseases on Guam and a hypothesis for the cause of the diseases

    Science.gov (United States)

    Miller, William R.; Sanzolone, Richard F.

    2003-01-01

    High incidences of neurodegenerative diseases, mainly dementia, parkinsonism, and amyotrophic lateral sclerosis, occur on the island of Guam (Koerner, 1952; Kurland and Mulder, 1954). The occurrence and description of the diseases and a summary of the investigations can be found in Perl (1997). The diseases have been more prevalent along the southern coast, particularly the small villages of Umatac, Merizo, and Inarajan (Reed and Brody, 1975; Roman, 1996; and Perl, 1997) (fig. 1), and referred to as the southern villages in this report. Tertiary volcanic rocks underlie most of the southern part of the island, including these villages. The northern part of Guam, with lower incidences of the diseases, consists of carbonate rocks. Epidemiological studies beginning in the early 1950’s failed to show the cause to be genetic etiology (Plato and others, 1986; Zhang and others, 1990). In recent studies, the search for pathogenic mechanisms has shifted to environmental factors. Excesses or deficiencies of various elements from dietary sources including drinking water can have an effect on human health. These deficiencies or excesses can usually be attributed to the geochemical composition of the rocks and derived soils that underlie the area. An example is the high concentration of Se in soil associated with the occurrence of selenosis in adults (Mills, 1996). Yase (1972) suggested that the neurodegenerative diseases on Guam may be related to accumulation of trace elements such as manganese and aluminum, both of which may cause neurodegeneration. It has been suggested that a deficiency in calcium and magnesium in the soil and water along with readily available aluminum could be connected to the occurrence of the diseases (Gajdusek, 1982; Yanagihara and others, 1984; Garruto and others, 1989). Some of the studies investigated metal exposure, particularly aluminum and manganese, and deficiencies in calcium and magnesium (Garruto and others, 1984). Aluminum has been shown to

  15. On the Creation, Utility and Sustaining of Rare Diseases Research Networks: Lessons learned from the Urea Cycle Disorders Consortium, the Japanese Urea Cycle Disorders Consortium and the European Registry and Network for Intoxication Type Metabolic Diseases.

    Science.gov (United States)

    Summar, Marshall L; Endo, Fumio; Kölker, Stefan

    2014-01-01

    The past two decades has seen a rapid expansion in the scientific and public interest in rare diseases and their treatment. One consequence of this has been the formation of registries/longitudinal natural history studies for these disorders. Given the expense and effort needed to develop and maintain such programs, we describe our experience with three linked registries on the same disease group, urea cycle disorders. The Urea Cycle Disorders Consortium (UCDC) was formed in the U.S. in 2003 in response to a request for application from the National Institutes of Health (NIH); the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD) was formed in 2011 in response to a request for applications from the Directorate-General for Health and Consumers (DG SANCO) of the EU; and the Japanese Urea Cycle Disorders Consortium (JUCDC) was founded in 2012 as a sister organization to the UCDC and E-IMD. The functions of these groups are to collect natural history data, educate the professional and lay population, develop and test new treatments, and establish networks of excellence for the care for these disorders. The UCDC and JUCDC focus exclusively on urea cycle disorders while the E-IMD includes patients with urea cycle disorders and organic acidurias. More than 1400 patients have been enrolled in the three consortia, and numerous projects have been developed and joint meetings held including an international UCDC/E-IMD/JUCDC Urea Cycle meeting in Barcelona in 2013. This article summarizes some of the experiences from the three groups regarding formation, funding, and models for sustainability. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  17. Fundamentals of sustainable neighbourhoods

    CERN Document Server

    Friedman, Avi

    2015-01-01

    This book introduces architects, engineers, builders, and urban planners to a range of design principles of sustainable communities and illustrates them with outstanding case studies. Drawing on the author’s experience as well as local and international case studies, Fundamentals of Sustainable Neighbourhoods presents planning concepts that minimize developments' carbon footprint through compact communities, adaptable and expandable dwellings, adaptable landscapes, and smaller-sized yet quality-designed housing. This book also: Examines in-depth global strategies for minimizing the residential carbon footprint, including district heating, passive solar gain, net-zero residences, as well as preserving the communities' natural assets Reconsiders conceptual approaches in building design and urban planning to promote a better connection between communities and nature Demonstrates practical applications of green architecture Focuses on innovative living spaces in urban environments

  18. Mathematics for sustainability

    CERN Document Server

    Roe, John; Jamshidi, Sara

    2018-01-01

    Designed for the 21st century classroom, this textbook poses, refines, and analyzes questions of sustainability in a quantitative environment. Building mathematical knowledge in the context of issues relevant to every global citizen today, this text takes an approach that empowers students of all disciplines to understand and reason with quantitative information. Whatever conclusions may be reached on a given topic, this book will prepare the reader to think critically about their own and other people’s arguments and to support them with careful, mathematical reasoning. Topics are grouped in themes of measurement, flow, connectivity, change, risk, and decision-making. Mathematical thinking is at the fore throughout, as students learn to model sustainability on local, regional, and global scales. Exercises emphasize concepts, while projects build and challenge communication skills. With no prerequisites beyond high school algebra, instructors will find this book a rich resource for engaging all majors in the...

  19. Sustainable practices in hospitality : A research framework

    NARCIS (Netherlands)

    Rheede, van A.; Blomme, R.J.

    2012-01-01

    The hospitality industry is starting to take responsibility for environmental sustainability. A strong focus on energy, waste, and water usage is directly linked with financial benefits in the operation of the hoteliers. Practices connected to the social aspect of sustainability are less developed.

  20. Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

    Science.gov (United States)

    Kattakuzhy, Sarah; Wilson, Eleanor; Sidharthan, Sreetha; Sims, Zayani; McLaughlin, Mary; Price, Angie; Silk, Rachel; Gross, Chloe; Akoth, Elizabeth; McManus, Maryellen; Emmanuel, Benjamin; Shrivastava, Shikha; Tang, Lydia; Nelson, Amy; Teferi, Gebeyehu; Chavez, Jose; Lam, Brian; Mo, Hongmei; Osinusi, Anuoluwapo; Polis, Michael A; Masur, Henry; Kohli, Anita; Kottilil, Shyamasundaran

    2016-02-15

    Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis. Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay. Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen. Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy. CT01805882. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Sustainable Development: Natural and Scientific Principles. Summary

    OpenAIRE

    Kuznetsov Oleg; Bolshakov Boris

    2002-01-01

    The book contains a brief summary of "Sustainable Development: Natural and Scientific Principles" textbook. The connection of sustainable development with the fundamental laws of the nature - society - man system, the logic of the transfer to sustainable development in ecology, economics, finances, politics and education are principally new in the mentioned textbook. A special attention is paid to synthesis and comparison of interconnections and knowledge in the creative process of research a...

  2. Minimum cost connection networks

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Tvede, Mich

    In the present paper we consider the allocation of cost in connection networks. Agents have connection demands in form of pairs of locations they want to be connected. Connections between locations are costly to build. The problem is to allocate costs of networks satisfying all connection demands...

  3. Peculiarities of gastrointestinal disease concomitant to heart connective tissue dysplasia in children born from persons exposed to ionizing radiation in childhood after the ChNPP accident

    International Nuclear Information System (INIS)

    Kondrashova, V.G.; Kolpakov, Yi.Je.; Vdovenko, V.Yu.; And Others

    2014-01-01

    UGITD namely chronic gastroduodenitis with typically concomitant involvement of several parts of digestive tract are most prevalent within all digestive system diseases in remote period upon the Chornobyl disaster in children born from persons exposed to ionizing radiation in a childhood. Presentation of UGITD occurs earlier in children suffering HCTDS with evident systemic pattern of organ and system injury along with an age. Refluxes of various nature and localization are the leading factors for UGITD onset in children suffering HCTDS. Thus a range of multidirectional tools of reflux disease prophylaxis is required for inclusion to the disease management

  4. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity...... and procedures to meet ‘good practice’ in standard setting and management. This is opening space for competing initiatives that are less democratic, quicker, and more aligned with industry interests to establish substantial presence in the market for sustainability certifications. These tend to more easily...

  5. Measuring the health-related Sustainable Development Goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 2015.

    Science.gov (United States)

    2016-10-08

    In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. In 2015, the median health-related SDG index was 59·3 (95% uncertainty interval 56·8-61·8) and varied widely by country, ranging from 85·5 (84·2-86·5) in Iceland to 20·4 (15·4-24·9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r 2 =0·88) and the MDG index (r 2 =0·92), whereas the non-MDG index had a weaker relation with SDI (r 2 =0·79). Between 2000 and 2015, the health-related SDG index improved by a median of 7·9 (IQR 5·0-10·4), and gains on the MDG index (a median change of 10·0 [6·7-13·1]) exceeded that of the non-MDG index (a median change of 5·5 [2·1-8·9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for