Sensitivity and specificity of plain radiographic features of peripheral enthesopathy at major sites in psoriatic arthritis

International Nuclear Information System (INIS)

Helliwell, P.S.; Porter, G.

2007-01-01

It has been proposed that the defining difference between rheumatoid arthritis and spondyloarthropathy (including psoriatic arthritis) is the initial pathological lesion where the emphasis in psoriatic arthritis is on the enthesis and in rheumatoid arthritis on the synovium. Classical radiological descriptions of seronegative spondyloarthropathy include enthesopathy at major entheseal insertions characterised by erosions and exuberant new bone formation. In this study, the plain radiographic features of spondyloarthropathy are compared between psoriatic arthritis, other spondyloarthropathies and rheumatoid arthritis. The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician diagnosed psoriatic arthritis and 525 controls with other inflammatory arthritis, 70% of which had rheumatoid arthritis. Plain radiographs of the pelvis and heels were part of the study protocol, although radiographs of other potential entheseal sites such as the knee, elbow and shoulder, were interpreted if available. All radiographs were read blind by two observers working in tandem. Significant differences in entheseal erosion and entheseal new bone formation were found between psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, rheumatoid arthritis and other diagnoses (entheseal erosion, chi-squared 20.8, p = 0.008; entheseal new bone formation, chi-squared 24.5, p = 0.001). These differences were mainly due to a higher proportion of these features in ankylosing spondylitis. No differences in the plain radiographic features of enthesopathy were found between psoriatic arthritis and rheumatoid arthritis except in the case of entheseal new bone formation at sites of attachment of inguinal ligament, sartorius and rectus femoris muscles to the ilium (OR 3.01, 95% CI 1.13-8.02). Very few subjects with symptomatic heel involvement had radiographic changes and minimal differences were found between those with and without

Hypersensitivity pneumonitis: a complex lung disease.

Science.gov (United States)

Riario Sforza, Gian Galeazzo; Marinou, Androula

2017-01-01

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease.

NARCIS (Netherlands)

Bai, X.; Ovrutsky, A.R.; Kartalija, M.; Chmura, K.; Kamali, A.; Honda, J.R.; Oberley-Deegan, R.E.; Dinarello, C.A.; Crapo, J.D.; Chang, L.Y.; Chan, E.D.

2011-01-01

Lung disease due to Mycobacterium avium complex (MAC) organisms is increasing. A greater understanding of the host immune response to MAC organisms will provide a foundation to develop novel therapies for these recalcitrant infections. IL-32 is a newly described pro-inflammatory cytokine that

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

Directory of Open Access Journals (Sweden)

Paolo Ferrero

2016-11-01

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

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

NARCIS (Netherlands)

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

2012-01-01

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

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

NARCIS (Netherlands)

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

2012-01-01

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

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

Science.gov (United States)

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

2017-08-01

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

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

Science.gov (United States)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

Sato, Kazuhiro; Kourakata, Hiroyo

2004-01-01

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

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Science.gov (United States)

Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

2010-01-01

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

Quantifying the complexity of medical research.

Science.gov (United States)

Rodriguez-Esteban, Raul; Loging, William T

2013-11-15

A crucial phenomenon of our times is the diminishing marginal returns of investments in pharmaceutical research and development. A potential reason is that research into diseases is becoming increasingly complex, and thus more burdensome, for humans to handle. We sought to investigate whether we could measure research complexity by analyzing the published literature. Through the text mining of the publication record of multiple diseases, we have found that the complexity and novelty of disease research has been increasing over the years. Surprisingly, we have also found that research on diseases with higher publication rate does not possess greater complexity or novelty than that on less-studied diseases. We have also shown that the research produced about a disease can be seen as a differentiated area of knowledge within the wider biomedical research. For our analysis, we have conceptualized disease research as a parallel multi-agent search in which each scientific agent (a scientist) follows a search path based on a model of a disease. We have looked at trends in facts published for diseases, measured their diversity and turnover using the entropy measure and found similar patterns across disease areas. raul.rodriguez-esteban@roche.com.

Multivariate Multi-Scale Permutation Entropy for Complexity Analysis of Alzheimer’s Disease EEG

Directory of Open Access Journals (Sweden)

Isabella Palamara

2012-07-01

Full Text Available An original multivariate multi-scale methodology for assessing the complexity of physiological signals is proposed. The technique is able to incorporate the simultaneous analysis of multi-channel data as a unique block within a multi-scale framework. The basic complexity measure is done by using Permutation Entropy, a methodology for time series processing based on ordinal analysis. Permutation Entropy is conceptually simple, structurally robust to noise and artifacts, computationally very fast, which is relevant for designing portable diagnostics. Since time series derived from biological systems show structures on multiple spatial-temporal scales, the proposed technique can be useful for other types of biomedical signal analysis. In this work, the possibility of distinguish among the brain states related to Alzheimer’s disease patients and Mild Cognitive Impaired subjects from normal healthy elderly is checked on a real, although quite limited, experimental database.

Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies.

Science.gov (United States)

Kurbasic, Azra; Poveda, Alaitz; Chen, Yan; Agren, Asa; Engberg, Elisabeth; Hu, Frank B; Johansson, Ingegerd; Barroso, Ines; Brändström, Anders; Hallmans, Göran; Renström, Frida; Franks, Paul W

2014-12-01

Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics.

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

Directory of Open Access Journals (Sweden)

Veturia Ileana Nueleanu

2007-12-01

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

Network biology concepts in complex disease comorbidities

DEFF Research Database (Denmark)

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

2016-01-01

collected electronically, disease co-occurrences are starting to be quantitatively characterized. Linking network dynamics to the real-life, non-ideal patient in whom diseases co-occur and interact provides a valuable basis for generating hypotheses on molecular disease mechanisms, and provides knowledge......The co-occurrence of diseases can inform the underlying network biology of shared and multifunctional genes and pathways. In addition, comorbidities help to elucidate the effects of external exposures, such as diet, lifestyle and patient care. With worldwide health transaction data now often being...

Complex Regional Pain Syndrome: An inflammatory disease

NARCIS (Netherlands)

M. Dirckx (Maaike)

2015-01-01

markdownabstractThe pathophysiology of Complex Regional Pain Syndrome (CRPS) is complex and still not completely understood. In addition to a convincing role of inflammation, there are a number of arguments why an involvement of the immune system has been suggested in the pathophysiology of CRPS.

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

NARCIS (Netherlands)

Iglesias, A.I. (Adriana I.); A. Mishra (Aniket); V. Vitart (Veronique); Y. Bykhovskaya (Yelena); R. Höhn (René); H. Springelkamp (Henriët); G. Cuellar-Partida (Gabriel); P. Gharahkhani (Puya); Bailey, J.N.C. (Jessica N. Cooke); Willoughby, C.E. (Colin E.); X. Li (Xiaohui); S. Yazar (Seyhan); A. Nag (Abhishek); A.P. Khawaja (Anthony); O. Polasek (Ozren); D.S. Siscovick (David); Mitchell, P. (Paul); Y.C. Tham (Yih Chung); J.L. Haines (Jonathan); L.S. Kearns (Lisa S.); C. Hayward (Caroline); Shi, Y. (Yuan); Van Leeuwen, E.M. (Elisabeth M.); K.D. Taylor (Kent); Wang, J.J. (Jie Jin); E. Rochtchina (Elena); J. Attia (John); Scott, R. (Rodney); E.G. Holliday (Elizabeth); P.N. Baird (Paul); Xie, J. (Jing); Inouye, M. (Michael); Viswanathan, A. (Ananth); X. Sim (Xueling); P.W.M. Bonnemaijer (Pieter); J.I. Rotter (Jerome I.); Martin, N.G. (Nicholas G.); T. Zeller (Tanja); R.A. Mills (Richard); S.E. Staffieri (Sandra E.); Jonas, J.B. (Jost B.); Schmidtmann, I. (Irene); T. Boutin (Thibaud); Kang, J.H. (Jae H.); S.E.M. Lucas (Sionne E.M.); Wong, T.Y. (Tien Yin); Beutel, M.E. (Manfred E.); Wilson, J.F. (James F.); R.R. Allingham (R Rand); M.H. Brilliant (Murray H.); D.L. Budenz (Donald L.); W.G. Christen (William G.); J. Fingert (John); D.S. Friedman (David); Gaasterland, D. (Douglas); T. Gaasterland (Terry); M.A. Hauser (Michael); P. Kraft (Peter); Lee, R.K. (Richard K.); P.A. Lichter (Paul A.); Liu, Y. (Yutao); S.J. Loomis (Stephanie J.); S.E. Moroi (Sayoko); M.A. Pericak-Vance (Margaret); A. Realini (Anthony); Richards, J.E. (Julia E.); J.S. Schuman (Joel S.); W.K. Scott (William); K. Singh (Kuldev); A.J. Sit (Arthur J.); D. Vollrath (Douglas); R.N. Weinreb (Robert N.); G. Wollstein (Gadi); D.J. Zack (Donald); K. Zhang (Kang); Donnelly, P. (Peter); I.E. Barroso (Inês); Blackwell, J.M. (Jenefer M.); E. Bramon (Elvira); M.A. Brown (Matthew); J.P. Casas (Juan); A. Corvin (Aiden); Deloukas, P. (Panos); A. Duncanson (Audrey); Jankowski, J. (Janusz); H.S. Markus (Hugh); J. Mathew (Joseph); C.N.A. Palmer (Colin); R. Plomin (Robert); A. Rautanen (Anna); S.J. Sawcer (Stephen); R.C. Trembath (Richard); Wood, N.W. (Nicholas W.); C.C.A. Spencer (Chris C.); G. Band (Gavin); C. Bellenguez (Céline); Freeman, C. (Colin); F.A. Hellenthal; E. Giannoulatou (Eleni); M. Pirinen (Matti); R. Pearson (Ruth); A. Strange (Amy); Z. Su (Zhan); D. Vukcevic (Damjan); Langford, C. (Cordelia); Hunt, S.E. (Sarah E.); T. Edkins (Ted); R. Gwilliam (Rhian); H. Blackburn (Hannah); S. Bumpstead (Suzannah); S. Dronov (Serge); M. Gillman (Matthew); E. Gray (Emma); N. Hammond (Naomi); A. Jayakumar (Alagurevathi); O.T. McCann (Owen); J. Liddle (Jennifer); S.C. Potter (Simon); Ravindrarajah, R. (Radhi); Ricketts, M. (Michelle); P. Waller (Patrick); P. Weston (Paul); S. Widaa (Sara); Whittaker, P. (Pamela); A.G. Uitterlinden (André); E.N. Vithana (Eranga); P.J. Foster (Paul); P.G. Hysi (Pirro); Hewitt, A.W. (Alex W.); C.C. Khor; L.R. Pasquale (Louis); Montgomery, G.W. (Grant W.); C.C.W. Klaver (Caroline); T. Aung (Tin); A.F.H. Pfeiffer (Andreas); D.A. Mackey (David); C.J. Hammond (Christopher); Cheng, C.-Y. (Ching-Yu); J.E. Craig (Jamie); Y.S. Rabinowitz (Yaron); J.L. Wiggs (Janey L.); K.P. Burdon (Kathryn); C.M. van Duijn (Cornelia); MacGregor, S. (Stuart)

2018-01-01

textabstractCentral corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related

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

Directory of Open Access Journals (Sweden)

Min Kyung Sung

2014-12-01

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

Carney complex review: Genetic features.

Science.gov (United States)

Bosco Schamun, María Belén; Correa, Ricardo; Graffigna, Patricia; de Miguel, Valeria; Fainstein Day, Patricia

2018-01-01

Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms. In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex. This review will address the genetic aspects related to Carney complex. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Science.gov (United States)

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

2018-01-01

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

Rare association of anophthalmia, complex congenital heart disease and pulmonary hypertension: case report.

Science.gov (United States)

Ríos-Méndez, Raúl Enrique; Lozano Chinga, Michell Marola

2016-10-07

Clinical congenital anophthalmia is described as the uni- or bilateral absence of the eyeball that might occur in isolation or as part of a syndrome. It has a very low prevalence and its etiology is heterogeneous. Complex congenital cardiac malformations are also rare. The association of congenital anophthalmia and congenital heart disease is rarer still, and the etiology of those associations is not well understood yet. We report the case of a patient who had the very rare association of bilateral anophthalmia, multiple cardiac malformations and severe pulmonary hypertension.

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

International Nuclear Information System (INIS)

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

1979-01-01

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

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

Science.gov (United States)

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

2015-08-01

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

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

Directory of Open Access Journals (Sweden)

Zhi Zhang

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

Low-intensity laser radiation in complex treatment of inflammatory diseases of parodontium

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Sokolova, Irina A.; Erina, Stanislava V.

1995-04-01

The problem of complex treatment of inflammatory disease of parodontium has become very acute and actual at the moment. The diseases of inflammatory nature are considered to be the most vital issues of the day. The state of the local immune system of oral cavity plays the most important role in the complicated mechanism of inflammatory process development in the tissues of parodontium. Recently physical factors have become predominant in the system of complex therapy of parodontitis. The application of low-intense laser radiation (LLR) is considered to be the most important and up-to-date method in the preventive dentistry. There were 60 patients of average damage rate suffering from chronic generalizing parodontitis at the age of 25 up to 55 under observation. The major goal of examination was to get the objective results of the following methods' application: parodontium index (Russel, 1956), hygiene index (Fyodorov, Volodkina, 1971), Bacterioscopy of dental-gingival pockets content, simple and broadened stomatoscopy (Kunin, 1970), SIgA level determination in mixed saliva (Manchini et all, 1965) and R-protein level in gingival blood (Kulberg, 1990). All the patients were split into 2 groups. The first group (30 patients) has undergone the laser therapy course while the second group of 30 patients couldn't get it (LLR). Despite the kind of therapy they have undergone, all the patients have got the local anti-inflammatory medicamental therapy. The results of clinical observations have proved the fact that laser therapy application makes it possible to shorten the course of treatment in 1.5 times. The shifts of oral cavity local resistance take place in case of chronic generalizing parodontitis. The direct immunostimulating effect could be observed as a result of LLR- therapy application. The close connection of both anti-inflammatory medicamental and LLR-therapy has proved the possibility of purposeful local immune status correction in case of parodontitis.

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

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Landreth Gary E

2006-11-01

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

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

Alteration of fecal microbiota profiles in juvenile idiopathic arthritis. Associations with HLA-B27 allele and disease status.

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Monica Di Paola

2016-10-01

Full Text Available Alteration of gut microbiota is involved in several chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, and gut microbial pro-arthritogenic profiles have been hypothesized. Intestinal inflammation may be involved in spondyloarthropathies and in a subset of patients affected by Juvenile Idiopathic Arthritis (JIA, the most common chronic rheumatic disease of childhood. We compared the fecal microbiota composition of JIA patients with healthy subjects (HS, evaluating differences in microbial profiles between sub-categories of JIA, such as enthesitis-related arthritis (JIA-ERA, in which inflammation of entheses occurs, and polyarticular JIA, non-enthesitis related arthritis (JIA-nERA. Through taxon-level analysis, we discovered alteration of fecal microbiota components that could be involved in subclinical gut inflammation, and promotion of joint inflammation. We observed abundance in Ruminococcaceae in both JIA categories, reduction in Clostridiaceae and Peptostreptococcaceae in JIA-ERA, and increase in Veillonellaceae in JIA-nERA, respectively compared with HS. Among the more relevant genera, we found an increase in Clostridium cluster XIVb, involved in colitis and arthritis, in JIA-ERA patients compared with HS, and a trend of decrease in Faecalibacterium, known for anti-inflammatory properties, in JIA-nERA compared with JIA-ERA and HS. Differential abundant taxa identified JIA patients for the HLA-B27 allele, including Bilophila, Clostridium cluster XIVb, Oscillibacter and Parvimonas. Prediction analysis of metabolic functions showed that JIA-ERA metagenome was differentially enriched in bacterial functions related to cell motility and chemotaxis, suggesting selection of potential virulence traits. We also discovered differential microbial profiles and intra-group variability among active disease and remission, suggesting instability of microbial ecosystem in autoimmune diseases with respect to healthy status. Similarly

Integrative analysis for finding genes and networks involved in diabetes and other complex diseases

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Bergholdt, R.; Størling, Zenia, Marian; Hansen, Kasper Lage

2007-01-01

We have developed an integrative analysis method combining genetic interactions, identified using type 1 diabetes genome scan data, and a high-confidence human protein interaction network. Resulting networks were ranked by the significance of the enrichment of proteins from interacting regions. We...... identified a number of new protein network modules and novel candidate genes/proteins for type 1 diabetes. We propose this type of integrative analysis as a general method for the elucidation of genes and networks involved in diabetes and other complex diseases....

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

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

2014-01-01

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

Modified Hemocorrection in the Complex Treatment of Patients with Pyoinflammatory Lung Diseases

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V. V. Gavrikov

2007-01-01

Full Text Available Objective: To evaluate the efficiency of extracorporeal hemocorrection used in the complex therapy in patients with a pyoinflammatory process in the lung.Materials and methods: 62 patients, including 22 patients with lung abscess who underwent routine plasmapheresis and 40 patients with varying pyoinflammatory lung diseases who received modified hemocorrection — plasma exchange combined with laser extracorporeally washed-off cytomass irradiation, were examined and treated. The severity of their general condition was assessed by the SAPS scale and the severity of intoxication was evaluated by the content of low and medium-molecular weight substances (LMMWSs. The hemostatic system was studied by standardized studies.Results. Routine plasmapheresis was established to produce no impact on platelet functional activity within the first 24 hours and, three days later, promoted the progression of disseminated intravascular coagulation. A combination of plasma exchange and laser extracorporeally washed-off cytomass irradiation in patients with pyoinflam-matory lung diseases was attended by a lower blood coagulative activity and plasmin stabilization with attenuated throm-binemia. The plasma and erythrocytic levels of LMMWSs decreased and their urinary concentrations increased, which is indicative of the body’s detoxification block disorders irrespective of the severity of the disease.Conclusion. It is expedient to apply the plasma-exchanging technique in combination with laser extracorporeally washed-off cytomass irradiation to patients with the uncomplicated and complicated course of pulmonary pyoinflammatory processes without the signs of multiple organ dysfunction on admission to a specialized hospital. 

"Bird biting" mosquitoes and human disease: a review of the role of Culex pipiens complex mosquitoes in epidemiology.

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

2011-10-01

The transmission of vector-borne pathogens is greatly influenced by the ecology of their vector, which is in turn shaped by genetic ancestry, the environment, and the hosts that are fed on. One group of vectors, the mosquitoes in the Culex pipiens complex, play key roles in the transmission of a range of pathogens including several viruses such as West Nile and St. Louis encephalitis viruses, avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex includes Culex pipiens pipiens with two forms, pipiens and molestus, Culex pipiens pallens, Culex quinquefasciatus, Culex australicus, and Culex globocoxitus. While several members of the complex have limited geographic distributions, Cx. pipienspipiens and Cx. quinquefasciatus are found in all known urban and sub-urban temperate and tropical regions, respectively, across the world, where they are often principal disease vectors. In addition, hybrids are common in areas of overlap. Although gaps in our knowledge still remain, the advent of genetic tools has greatly enhanced our understanding of the history of speciation, domestication, dispersal, and hybridization. We review the taxonomy, genetics, evolution, behavior, and ecology of members of the Cx. pipiens complex and their role in the transmission of medically important pathogens. The adaptation of Cx. pipiens complex mosquitoes to human-altered environments led to their global distribution through dispersal via humans and, combined with their mixed feeding patterns on birds and mammals (including humans), increased the transmission of several avian pathogens to humans. We highlight several unanswered questions that will increase our ability to control diseases transmitted by these mosquitoes. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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

2015-01-01

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

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

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Wells, Chad R.; Galvani, Alison P.

2015-12-01

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

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

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

2014-01-01

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

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

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

2006-04-21

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

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

International Nuclear Information System (INIS)

Ling Jian; Liu Yuqing

2006-01-01

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

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

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

2017-11-01

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

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

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Parsons-Wingerter, Patricia

2010-01-01

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

Spondyloarthropathy presenting at a young age: case report and review

International Nuclear Information System (INIS)

Hartman, Golda H.; Renaud, Deborah L.; Reed, Ann M.; Sundaram, Murali

2007-01-01

The diagnosis of juvenile spondyloarthritis (JSA) is rarely entertained in young children who present with back and leg pain. We present a case of a 6-year-old male who presented with a 3-year history of severe back and leg pain and a positive Gower's sign, and was given a presumed diagnosis of muscular dystrophy. Presenting serologic evaluation included a mildly elevated sedimentation rate and C-reactive protein (CRP). Computed tomography of the pelvis demonstrated large erosions affecting both sacro-iliac joints. Despite the unusually young age of this patient, ankylosing spondylitis seemed the most plausible diagnosis. Following rheumatological evaluation and treatment for JSA, he showed significant clinical improvement. His disease, however, has not entirely remitted with signs of enthesitis at the Achilles tendon and knees. We present this case to illustrate that JSA could account for symptoms at an early age and not considering it could lead to multiple medical visits and diagnoses. To our knowledge, based on a search of the World literature, this would appear to be the youngest case of JSA reported with demonstrable severe sacroiliitis. (orig.)

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

DEFF Research Database (Denmark)

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

2010-01-01

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

THE VALUE OF THE COMPOUND DRUGS FORMOTEROL AND IPRATROPIUM BROMIDE IN COMPLEX TREATMENT OF CHRONIC NONSPECIFIC LUNG DISEASES IN CHILDREN

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O.I. Simonova

2006-01-01

Full Text Available The complex mechanism of development of bronchoobstructive bronchitis in chronic nonspecific lung diseases in children and its effective therapy with the compound bronchodilator berodual are discussed. Berodual comprises b2-adrenoreceptor agonist — fenoterol and anticholinergic drug — ipatropium bromide, that amplify bronchodilatory action of each other. Indications, contraindication and intake peculiarities are illustrated.Key words: chronic nonspecific lung diseases, bronchoob structive syndrome, bronchodilators, children.

Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

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Nonni Afroditi

2009-11-01

Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

Quantitative disease resistance: to better understand parasite-mediated selection on major histocompatibility complex.

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Westerdahl, Helena; Asghar, Muhammad; Hasselquist, Dennis; Bensch, Staffan

2012-02-07

We outline a descriptive framework of how candidate alleles of the immune system associate with infectious diseases in natural populations of animals. Three kinds of alleles can be separated when both prevalence of infection and infection intensity are measured--qualitative disease resistance, quantitative disease resistance and susceptibility alleles. Our descriptive framework demonstrates why alleles for quantitative resistance and susceptibility cannot be separated based on prevalence data alone, but are distinguishable on infection intensity. We then present a case study to evaluate a previous finding of a positive association between prevalence of a severe avian malaria infection (GRW2, Plasmodium ashfordi) and a major histocompatibility complex (MHC) class I allele (B4b) in great reed warblers Acrocephalus arundinaceus. Using the same dataset, we find that individuals with allele B4b have lower GRW2 infection intensities than individuals without this allele. Therefore, allele B4b provides quantitative resistance rather than increasing susceptibility to infection. This implies that birds carrying B4b can mount an immune response that suppresses the acute-phase GRW2 infection, while birds without this allele cannot and may die. We argue that it is important to determine whether MHC alleles related to infections are advantageous (quantitative and qualitative resistance) or disadvantageous (susceptibility) to obtain a more complete picture of pathogen-mediated balancing selection.

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Effects of natural factors of Niška Banja spa on indexes of mobility of vertebral column in patients with ankylosing spondylitis

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Nedović Jovan

2009-01-01

Full Text Available Introduction. Ankylosing spondilitis (AS is a disease from a group of seronegative spondyloarthropathies with the prevalence of 0.1% affecting mainly young males, which also gives sociomedical significance to the disease. Among all inflammatory arthropathies, AS is the most suitable for balneotherapy. Thermomineral water of the Niška Banja spa is homeothermic, oligomineral, alkaline, low radioactive radon water and also, in conjunction with mineral peloid, is considered to be optimal for this indication. Objective. Our aim was to investigate the effects of natural factors of the Niška Banja spa as a part of complex treatment on the indexes of mobility of the vertebral column in the patients with AS. Methods. The study enrolled 40 patients with the average age of 48.0±14.82 years and the average duration of disease of 16.9±6.42 years. Patients were treated with hydro- and peloid- otherapy during the average of 17.23±2.71 days. At the beginning and at the end of treatment, a number of indexes of spinal mobility were measured. The statistical significance of differences was calculated using the Student's t-test. Results. All of the measured indexes were better after balneotherapy reaching statistically significant differences in regard to the wall-to-occiput distance (p<0.05, the index of sagittal mobility of the cervical (p<0.05 and lumbar (p<0.005 spine. Conclusion. The application of natural factors of the Niška Banja spa during complex treatment of the patients with AS is accompanied with the objective increase of the spine mobility.

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

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Renata Sesti-Costa

2014-10-01

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

Enteropathic Spondyloarthritis: From Diagnosis to Treatment

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Rosario Peluso

2013-01-01

Full Text Available Enteropathic arthritis (EA is a spondyloarthritis (SpA which occurs in patients with inflammatory bowel diseases (IBDs and other gastrointestinal diseases. Diagnosis is generally established on the medical history and physical examination. It was, generally, made according to the European Spondyloarthropathy Study Group (ESSG criteria. Rheumatic manifestations are the most frequent extraintestinal findings of IBD with a prevalence between 17% and 39%, and IBD is associated, less frequently, with other rheumatic disease such as rheumatoid arthritis, Sjogren syndrome, Takayasu arteritis, and fibromyalgia. Although the pathogenesis of EA has not been plainly clarified, the most popular theory supposes that joint inflammation occurs in genetically predisposed subjects with bacterial gut infections, provided an important evidence for a possible relationship between inflammation of the gut mucosa and arthritis. The management of patients with EA requires an active cooperation between the gastroenterologist and rheumatologist.

Caring for people with chronic disease: is 'muddling through' the best way to handle the multiple complexities?

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Sturmberg, Joachim P

2012-12-01

It is stated everywhere that chronic care poses one of the biggest challenges for the future of medicine. Critical analysis however suggests that these statements are oversimplistic and based on limited, and at times, spurious assumptions. This paper highlights some basic realities: epidemiology shows that at any time, 80% of people experience 'good enough health', and that only 0.8% require tertiary medical care; most people with chronic conditions experience a stable illness trajectory; 'true' multi-morbidity is a pattern of advanced age; ageing and the physiological decline of our organ systems is a slow and steady process starting at the age of 30; and, as our health declines in a variety of patterns with disease and ageing, our psycho-socio-semiotic care needs increase dramatically. I argue that managing the complexities associated with chronic disease care successfully requires an equally complex management approach, 'muddling through', defined by Lindblom as making decisions based on successive limited comparisons. Our patients - rightly - expect that we make these decisions in their best interest. Individual health care professionals and health care policy makers firmly need to put the patient at the centre of the health care system. © 2012 Blackwell Publishing Ltd.

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

International Nuclear Information System (INIS)

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

2002-01-01

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

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

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

2010-11-01

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

Factors Influencing Adaptation and Performance at Physical Exercise in Complex Congenital Heart Diseases after Surgical Repair

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P. P. Bassareo

2014-01-01

Full Text Available In the last thirty years, steady progress in the diagnostic tools and care of subjects affected by congenital heart diseases (CHD has resulted in a significant increase in their survival to adulthood, even for those affected by complex CHD. Based on these premises, a number of teenagers and adults affected by corrected (surgically or through interventional techniques CHD ask to be allowed to undertake sporting activities, both at a recreational and competitive level. The purpose of this review is to examine the mechanisms influencing the adaption at physical exercise of patients suffering from complex CHD. The conclusion is that even if there are some modest risks with exercise, they should be seen in perspective, and the life-long benefits of regular exercise on general health, mood, and well-being should be emphasized.

"Are we there yet?": Deciding when one has demonstrated specific genetic causation in complex diseases and quantitative traits.

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Page, Grier P; George, Varghese; Go, Rodney C; Page, Patricia Z; Allison, David B

2003-10-01

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, "Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it." We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what "causation" means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called "causative."

Early-stage reduction of the dendritic complexity in basolateral amygdala of a transgenic mouse model of Alzheimer's disease

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Guo, Congdi; Long, Ben; Hu, Yarong; Yuan, Jing; Gong, Hui; Li, Xiangning

2017-01-01

Alzheimer's disease is a representative age-related neurodegenerative disease that could result in loss of memory and cognitive deficiency. However, the precise onset time of Alzheimer's disease affecting neuronal circuits and the mechanisms underlying the changes are not clearly known. To address the neuroanatomical changes during the early pathologic developing process, we acquired the neuronal morphological characterization of AD in APP/PS1 double-transgenic mice using the Micro-Optical Sectioning Tomography system. We reconstructed the neurons in 3D datasets with a resolution of 0.32 × 0.32 × 1 μm and used the Sholl method to analyze the anatomical characterization of the dendritic branches. The results showed that, similar to the progressive change in amyloid plaques, the number of dendritic branches were significantly decreased in 9-month-old mice. In addition, a distinct reduction of dendritic complexity occurred in third and fourth-order dendritic branches of 9-month-old mice, while no significant changes were identified in these parameters in 6-month-old mice. At the branch-level, the density distribution of dendritic arbors in the radial direction decreased in the range of 40–90 μm from the neuron soma in 6-month-old mice. These changes in the dendritic complexity suggest that these reductions contribute to the progressive cognitive impairment seen in APP/PS1 mice. This work may yield insights into the early changes in dendritic abnormality and its relevance to dysfunctional mechanisms of learning, memory and emotion in Alzheimer's disease. - Highlights: • Neuron-level, reduction of dendritic complexity in BLA of 9-month-old AD mice. • Specific range of branch decrease in density of 6-month-old AD mice. • 3D imaging with high resolution will provide insights into brain aging.

Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

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Brafman-Kennedy Barbara

2011-05-01

Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

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Back, Susan J.; Andronikou, Savvas; Kilborn, Tracy; Kaplan, Bernard S.; Darge, Kassa

2015-01-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

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Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

2015-03-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

PoCos: Population Covering Locus Sets for Risk Assessment in Complex Diseases.

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Marzieh Ayati

2016-11-01

Full Text Available Susceptibility loci identified by GWAS generally account for a limited fraction of heritability. Predictive models based on identified loci also have modest success in risk assessment and therefore are of limited practical use. Many methods have been developed to overcome these limitations by incorporating prior biological knowledge. However, most of the information utilized by these methods is at the level of genes, limiting analyses to variants that are in or proximate to coding regions. We propose a new method that integrates protein protein interaction (PPI as well as expression quantitative trait loci (eQTL data to identify sets of functionally related loci that are collectively associated with a trait of interest. We call such sets of loci "population covering locus sets" (PoCos. The contributions of the proposed approach are three-fold: 1 We consider all possible genotype models for each locus, thereby enabling identification of combinatorial relationships between multiple loci. 2 We develop a framework for the integration of PPI and eQTL into a heterogenous network model, enabling efficient identification of functionally related variants that are associated with the disease. 3 We develop a novel method to integrate the genotypes of multiple loci in a PoCo into a representative genotype to be used in risk assessment. We test the proposed framework in the context of risk assessment for seven complex diseases, type 1 diabetes (T1D, type 2 diabetes (T2D, psoriasis (PS, bipolar disorder (BD, coronary artery disease (CAD, hypertension (HT, and multiple sclerosis (MS. Our results show that the proposed method significantly outperforms individual variant based risk assessment models as well as the state-of-the-art polygenic score. We also show that incorporation of eQTL data improves the performance of identified POCOs in risk assessment. We also assess the biological relevance of PoCos for three diseases that have similar biological mechanisms

The kinesin–tubulin complex: considerations in structural and functional complexity

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Olmsted ZT

2015-02-01

Full Text Available Zachary T Olmsted, Andrew G Colliver, Janet L Paluh State University of New York Polytechnic Institute, Colleges of Nanoscale Science and Engineering, College of Nanoscale Science, Nanobioscience Constellation, Albany, NY, USA Abstract: The ability of cells to respond to external cues by appropriately manipulating their internal environment requires a dynamic microtubule cytoskeleton that is facilitated by associated kinesin motor interactions. The evolutionary adaptations of kinesins and tubulins when merged generate a highly adaptable communication and infrastructure cellular network that is important to understanding specialized cell functions, human disease, and disease therapies. Here, we review the state of the field in the complex relationship of kinesin–tubulin interactions. We propose 12 mechanistic specializations of kinesins. In one category, referred to as sortability, we describe how kinesin interactions with tubulin isoforms, isotypes, or posttranslationally modified tubulins contribute to diverse cellular roles. Fourteen kinesin families have previously been described. Here, we illustrate the great depth of functional complexity that is possible in members within a single kinesin family by mechanistic specialization through discussion of the well-studied Kinesin-14 family. This includes new roles of Kinesin-14 in regulating supramolecular structures such as the microtubule-organizing center γ-tubulin ring complex of centrosomes. We next explore the value of an improved mechanistic understanding of kinesin–tubulin interactions in regard to human development, disease mechanisms, and improving treatments that target kinesin–tubulin complexes. The ability to combine the current kinesin nomenclature along with a more precisely defined kinesin and tubulin molecular toolbox is needed to support more detailed exploration of kinesin–tubulin interaction mechanisms including functional uniqueness, redundancy, or adaptations to new

Three-Year Major Clinical Outcomes of Angiography-Guided Single Stenting Technique in Non-Complex Left Main Coronary Artery Diseases.

Science.gov (United States)

Kim, Yong Hoon; Her, Ae-Young; Rha, Seung-Woon; Choi, Byoung Geol; Shim, Minsuk; Choi, Se Yeon; Byun, Jae Kyeong; Li, Hu; Kim, Woohyeun; Kang, Jun Hyuk; Choi, Jah Yeon; Park, Eun Jin; Park, Sung Hun; Lee, Sunki; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo

2017-10-12

There is limited long-term comparative clinical outcome data concerning angiography- versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in non-complex left main coronary artery (LMCA) disease treated with the single stenting technique in the drug-eluting stent (DES) era.The aim of this study was to investigate whether angiography-guided stenting is comparable to IVUS-guided stenting during 3-year clinical follow-up periods in patients with non-complex LM disease treated with the single stenting technique.A total of 196 patients treated with either angiography-guided (n = 74) or IVUS-guided (n = 122) PCI were included. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-target vessel revascularization (Non-TVR). To adjust for any potential confounders, propensity score (PS) adjusted analysis was performed.During 3-year follow-up, the PS adjusted Cox-proportional hazard ratio (HR) was not significantly different between the two groups for total death, cardiac death, and MI. Also, TLR and the combined rates of TVR and non-TVR were not significantly different. Finally, MACE was not significantly different between the two groups (HR: 0.63, 95% Confidence interval (CI): 0.33-1.17; P = 0.149).Angiography-guided PCI for non-complex LMCA diseases treated with the single stenting technique showed comparable results compared with IVUS-guided PCI in reducing clinical events during 3-year clinical follow-up in the DES era. Although IVUS guided PCI is the ideal strategy, angiography-guided PCI can be an option for LMCA PCI in some selected cases.

Prevalence and clinical patterns of psoriatic arthritis in Indian patients with psoriasis

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Ramesh Kumar

2014-01-01

Full Text Available Background: The prevalence and clinical patterns of psoriatic arthritis (PsA varies in different parts of the world and there is little clinical and epidemiological data from the Indian subcontinent. Aims: Our study was designed to evaluate the prevalence and clinical patterns of PsA in Indian patients. Methods: This was a non-interventional, cross-sectional study, in which 1149 consecutive psoriasis patients seen over 1 year were screened for PsA according to classification of psoriatic arthritis (CASPAR criteria. Demographic and disease parameters were recorded including Psoriasis Area and Severity Index (PASI, Nail Psoriasis Severity Index (NAPSI, and number of swollen and tender joints. Results: Among 1149 patients with psoriasis, 100 (8.7% patients had PsA, of which 83% were newly diagnosed. The most common pattern was symmetrical polyarthritis (58%, followed by spondyloarthropathy 49%, asymmetric oligoarthritis (21%, isolated spondyloarthropathy (5%, predominant distal interphalangeal arthritis (3%, and arthritis mutilans (1%. Enthesitis and dactylitis were present in 67% and 26% of cases, respectively. The mean number of swollen and tender joints were 3.63 ± 3.59 (range, 0-22 and 7.76 ± 6.03 (range, 1-26, respectively. Nail changes were present in 87% of the cases. The median PASI and NAPSI of the subjects with PsA was 3.6 and 20, respectively. There was no significant correlation of number of swollen/tender joints with PASI or NAPSI. Conclusion: There is a relatively low prevalence of PsA among Indian psoriasis patients presenting to dermatologists. No correlation was found between the severity of skin and nail involvement and articular disease.

Incorporating networks in a probabilistic graphical model to find drivers for complex human diseases.

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Mezlini, Aziz M; Goldenberg, Anna

2017-10-01

Discovering genetic mechanisms driving complex diseases is a hard problem. Existing methods often lack power to identify the set of responsible genes. Protein-protein interaction networks have been shown to boost power when detecting gene-disease associations. We introduce a Bayesian framework, Conflux, to find disease associated genes from exome sequencing data using networks as a prior. There are two main advantages to using networks within a probabilistic graphical model. First, networks are noisy and incomplete, a substantial impediment to gene discovery. Incorporating networks into the structure of a probabilistic models for gene inference has less impact on the solution than relying on the noisy network structure directly. Second, using a Bayesian framework we can keep track of the uncertainty of each gene being associated with the phenotype rather than returning a fixed list of genes. We first show that using networks clearly improves gene detection compared to individual gene testing. We then show consistently improved performance of Conflux compared to the state-of-the-art diffusion network-based method Hotnet2 and a variety of other network and variant aggregation methods, using randomly generated and literature-reported gene sets. We test Hotnet2 and Conflux on several network configurations to reveal biases and patterns of false positives and false negatives in each case. Our experiments show that our novel Bayesian framework Conflux incorporates many of the advantages of the current state-of-the-art methods, while offering more flexibility and improved power in many gene-disease association scenarios.

The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.

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Seidel, K; Vinet, J; Dunnen, W F A den; Brunt, E R; Meister, M; Boncoraglio, A; Zijlstra, M P; Boddeke, H W G M; Rüb, U; Kampinga, H H; Carra, S

2012-02-01

HSPB8 is a small heat shock protein that forms a complex with the co-chaperone BAG3. Overexpression of the HSPB8-BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8-BAG3 could thus play a protective role in protein aggregation diseases and might be specifically upregulated in response to aggregate-prone protein-mediated toxicity. Here we analysed HSPB8-BAG3 expression levels in post-mortem human brain tissue from patients suffering of the following protein conformation disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Western blotting and immunohistochemistry techniques were used to analyse HSPB8 and BAG3 expression levels in fibroblasts from SCA3 patients and post-mortem brain tissues, respectively. In all diseases investigated, we observed a strong upregulation of HSPB8 and a moderate upregulation of BAG3 specifically in astrocytes in the cerebral areas affected by neuronal damage and degeneration. Intriguingly, no significant change in the HSPB8-BAG3 expression levels was observed within neurones, irrespective of their localization or of the presence of proteinaceous aggregates. We propose that the upregulation of HSPB8 and BAG3 may enhance the ability of astrocytes to clear aggregated proteins released from neurones and cellular debris, maintain the local tissue homeostasis and/or participate in the cytoskeletal remodelling that astrocytes undergo during astrogliosis. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

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

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

1999-04-01

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

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

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Kaidonis, John; Townsend, Grant

2016-01-01

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

Peer support of complex health behaviors in prevention and disease management with special reference to diabetes: systematic reviews.

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Fisher, Edwin B; Boothroyd, Renée I; Elstad, Emily A; Hays, Laura; Henes, Amy; Maslow, Gary R; Velicer, Clayton

2017-01-01

Examine Peer Support (PS) for complex, sustained health behaviors in prevention or disease management with emphasis on diabetes prevention and management. PS was defined as emotional, motivational and practical assistance provided by nonprofessionals for complex health behaviors. Initial review examined 65 studies drawn from 1442 abstracts identified through PubMed, published 1/1/2000-7/15/2011. From this search, 24 reviews were also identified. Extension of the search in diabetes identified 30 studies published 1/1/2000-12/31/2015. In initial review, 54 of all 65 studies (83.1%) reported significant impacts of PS, 40 (61.5%) reporting between-group differences and another 14 (21.5%) reporting significant within-group changes. Across 19 of 24 reviews providing quantifiable findings, a median of 64.5% of studies reviewed reported significant effects of PS. In extended review of diabetes, 26 of all 30 studies (86.7%) reported significant impacts of PS, 17 (56.7%) reporting between-group differences and another nine (30.0%) reporting significant within-group changes. Among 19 of these 30 reporting HbA1c data, average reduction was 0.76 points. Studies that did not find effects of PS included other sources of support, implementation or methodological problems, lack of acceptance of interventions, poor fit to recipient needs, and possible harm of unmoderated PS. Across diverse settings, including under-resourced countries and health care systems, PS is effective in improving complex health behaviors in disease prevention and management including in diabetes.

The psychological complexity of predictive testing for late onset neurogenetic diseases and hereditary cancers: implications for multidisciplinary counselling and for genetic education.

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Evers-Kiebooms, G; Welkenhuysen, M; Claes, E; Decruyenaere, M; Denayer, L

2000-09-01

Increasing knowledge about the human genome has resulted in the availability of a steadily increasing number of predictive DNA-tests for two major categories of diseases: neurogenetic diseases and hereditary cancers. The psychological complexity of predictive testing for these late onset diseases requires careful consideration. It is the main aim of the present paper to describe this psychological complexity, which necessitates an adequate and systematic multidisciplinary approach, including psychological counselling, as well as ongoing education of professionals and of the general public. Predictive testing for neurogenetic diseases--in an adequate counselling context--so far elicits optimism regarding the short- and mid-term impact of the predictive test result. The psychosocial impact has been most widely studied for Huntington's disease. Longitudinal studies are of the utmost importance in evaluating the long-term impact of predictive testing for neurogenetic diseases on the tested person and his/her family. Given the more recent experience with predictive DNA-testing for hereditary cancers, fewer published scientific data are available. Longitudinal research on the mid- and long-term psychological impact of the predictive test result is essential. Decision making regarding health surveillance or preventive surgery after being detected as a carrier of one of the relevant mutations should receive special attention. Tailoring the professional approach--inside and outside genetic centres--to the families' needs is a continuous challenge. Even if a continuous effort is made, several important questions remain unanswered, last but not least the question regarding the best strategy to guarantee that the availability of predictive genetic testing results in a reduction of suffering caused by genetic disease and in an improvement of the quality of life of families confronted with genetic disease.

Simple deterministic models and applications. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

Science.gov (United States)

Yang, Hyun Mo

2015-12-01

Currently, discrete modellings are largely accepted due to the access to computers with huge storage capacity and high performance processors and easy implementation of algorithms, allowing to develop and simulate increasingly sophisticated models. Wang et al. [7] present a review of dynamics in complex networks, focusing on the interaction between disease dynamics and human behavioral and social dynamics. By doing an extensive review regarding to the human behavior responding to disease dynamics, the authors briefly describe the complex dynamics found in the literature: well-mixed populations networks, where spatial structure can be neglected, and other networks considering heterogeneity on spatially distributed populations. As controlling mechanisms are implemented, such as social distancing due 'social contagion', quarantine, non-pharmaceutical interventions and vaccination, adaptive behavior can occur in human population, which can be easily taken into account in the dynamics formulated by networked populations.

Hidradenitis suppurativa: Inside and out

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Sharmila Patil

2018-01-01

Full Text Available Hidradenitis suppurativa is a chronic, disabling, suppurative disease characterized by deep tender subcutaneous nodules; complicated by fibrosis and extensive sinuses affecting primarily the apocrine gland bearing areas. It affects all races in early 20s with greater prevalence seen in women (3 to 5:1. The estimated disease prevalence is 1 - 4 %. The disease is speculated to be caused by follicular structural abnormalities with associated risk factors as smoking, obesity, positive family history and shaving. Certain co-morbidities can also be seen such as inflammatory bowel disease, spondyloarthropathies, epithelial tumors, pyoderma gangrenosum etc. Treatment modalities include counseling of the patient to lose weight if obese, to wear loose clothes, stop smoking and maintain good hygiene. Topical antibiotics, like 1% clindamycin, have shown to give good results along with benzoyl peroxide wash. Orally cocktail of antibiotics can be given, though biologicals remain the best treatment option. Surgical excision can be done in later stages and in recalcitrant cases.

CD147 is a regulatory subunit of the gamma-secretase complex inAlzheimer's disease amyloid beta-peptide production

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Zhou, Shuxia; Zhou, Hua; Walian, Peter J.; Jap, Bing K.

2005-04-06

{gamma}-secretase is a membrane protein complex that cleaves the {beta}-amyloid precursor protein (APP) within the transmembrane region, following prior processing by {beta}-secretase, producing amyloid {beta}-peptides (A{beta}{sub 40} and A{beta}{sub 42}). Errant production of A{beta}-peptides that substantially increases A{beta}{sub 42} production has been associated with the formation of amyloid plaques in Alzheimer's disease patients. Biophysical and genetic studies indicate that presenilin-1 (Psn-1), which contains the proteolytic active site, and three other membrane proteins, nicastrin (Nct), APH-1, and PEN-2 are required to form the core of the active {gamma}-secretase complex. Here, we report the purification of the native {gamma}-secretase complexes from HeLa cell membranes and the identification of an additional {gamma}-secretase complex subunit, CD147, a transmembrane glycoprotein with two immunoglobulin-like domains. The presence of this subunit as an integral part of the complex itself was confirmed through co-immunoprecipitation studies of the purified protein from HeLa cells and solubilized complexes from other cell lines such as neural cell HCN-1A and HEK293. Depletion of CD147 by RNA interference was found to increase the production of A{beta} peptides without changing the expression level of the other {gamma}-secretase components or APP substrates while CD147 overexpression had no statistically significant effect on amyloid {beta}-peptide production, other {gamma}-secretase components or APP substrates, indicating that the presence of the CD147 subunit within the {gamma}-secretase complex directly down-modulates the production of A{beta}-peptides. {gamma}-secretase was first recognized through its role in the production of the A{beta} peptides that are pathogenic in Alzheimer's disease (AD) (1). {gamma}-secretase is a membrane protein complex with unusual aspartyl protease activity that cleaves a variety of type I membrane proteins

[Neuroimmunological diseases associated with VGKC complex antibodies].

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Watanabe, Osamu

2013-05-01

Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease: The PReVaiL randomized clinical trial.

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Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars; Jakobsen, Janus Christian; Zoffmann, Vibeke; Dideriksen, Kasper; Kruse, Anne; Mikkelsen, Ulla Ramer; Wetterslev, Jørn

2016-10-15

To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. Randomized clinical trial. Denmark. A total of 158 adolescents aged 13-16years with no physical activity restrictions after repaired complex congenital heart disease. PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. The primary outcome was maximal oxygen uptake (VO2 peak) at 52weeks after randomization. The secondary outcome was physical activity. Exploratory outcomes were generic and disease-specific questionnaires. In the intervention group, 58 patients (72%) completed the final test, but of those, only 46 (57%) fulfilled the compliance criteria of using the eHealth application for at least 2 consecutive weeks. In the control group, 61 patients (79%) completed both exercise tests. Adjusted for baseline values, the difference between the intervention group and the control group in mean VO2 peak at 1year was -0.65ml·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. Adding a tailored eHealth intervention to health education and individual counseling did not affect outcomes among adolescents with congenital heart disease. Our results do not support the use of this eHealth intervention in adolescents with complex congenital heart disease. Clinical trials.gov identifier: NCT01189981. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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Burren Oliver S

2004-01-01

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

Porcine respiratory disease complex: Interaction of vaccination and porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, and Mycoplasma hyopneumoniae.

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Chae, Chanhee

2016-06-01

Porcine respiratory disease is a multifactorial and complex disease caused by a combination of infectious pathogens, environmental stressors, differences in production systems, and various management practices; hence the name porcine respiratory disease complex (PRDC) is used. Porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and Mycoplasma hyopneumoniae are considered to be the most important pathogens that cause PRDC. Although interactions among the three major respiratory pathogens are well documented, it is also necessary to understand the interaction between vaccines and the three major respiratory pathogens. PRRSV and M. hyopneumoniae are well known to potentiate PCV2-associated lesions; however, PRRSV and mycoplasmal vaccines can both enhance PCV2 viraemia regardless of the effects of the actual PRRSV or M. hyopneumoniae infection. On the other hand, M. hyopneumoniae potentiates the severity of pneumonia induced by PRRSV, and vaccination against M. hyopneumoniae alone is also able to decrease PRRSV viraemia and PRRSV-induced lung lesions in dually infected pigs. This review focuses on (1) interactions between PCV2, PRRSV, and M. hyopneumoniae; and (2) interactions between vaccines and the three major respiratory pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetics Home Reference: Carney complex

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... cortisol (hypercortisolism) can lead to the development of Cushing syndrome. This syndrome causes weight gain in the face ... Institute of Diabetes and Digestive and Kidney Diseases: Cushing's Syndrome Educational Resources (6 links) Disease InfoSearch: Carney Complex ...

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

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Iglesias, Adriana I; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René; Springelkamp, Henriët; Cuellar-Partida, Gabriel; Gharahkhani, Puya; Bailey, Jessica N Cooke; Willoughby, Colin E; Li, Xiaohui; Yazar, Seyhan; Nag, Abhishek; Khawaja, Anthony P.; Polasek, Ozren

2018-01-01

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. Pathway analyses uncover new, as well as supported the role of connective tissue-related, pathways. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan,...

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

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

2011-01-01

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

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

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Fujiwara, Kiyohiro

2008-01-01

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

[Pulmonary Mycobacterium Avium-Complex (MAC) Disease Differentially Diagnosed from Metastasis of Testicular Cancer : A Case Report].

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Mori, Kohei; Teranishi, Jyn-Ichi; Yoneyama, Shuko; Ishida, Hiroaki; Hattori, Yusuke; Yumura, Yasushi; Miyoshi, Yasuhide; Kondo, Keiichi; Uemura, Hiroji; Noguchi, Kazumi

2017-01-01

A 45 year-old-man was admitted to our hospital because of discomfort in his left scrotum. He had a left testicular tumor. We performed high orchiectomy and pathological findings revealed testicular cancer. He was treated with bleomycin, etoposide and cisplatin. Computed tomography showed a new mass in the left lung after 3 cycles of the chemotherapy. Because of its rapid growth, the tumor was thought to be a metastasis lesion of testicular cancer or pulmonary infection. Transbronchial lung biopsy showed an invasion of multinucleated giant cells and granuloma. The culture and polymerase chain reaction of the bronchial sputum were positive for myobacterium avium-complex (MAC). From these findings, the left lung tumor was diagnosed as pulmonary MAC disease. He received partial resection of the left lung and the lesion was diagnosed as granuloma. There was no recurrence of testicular cancer or pulmonary disease after the surgery.

Infant temperament and parental stress in 3-month-old infants after surgery for complex congenital heart disease.

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Torowicz, Deborah; Irving, Sharon Y; Hanlon, Alexandra L; Sumpter, Danica F; Medoff-Cooper, Barbara

2010-04-01

This study aimed to identify and compare differences in temperament and maternal stress between infants with complex congenital heart disease and healthy controls at 3 months of age. Study sample was drawn from an existing longitudinal study examining growth in infants with congenital heart disease when compared with healthy controls. Infant temperament and parental stress were measured in 129 mother-infant dyads. Inclusion criteria for infants with congenital heart disease were > or = 36-week postmenstrual age, > or = 2500 g at birth, surgery in first 6 weeks of life, and no major congenital anomalies or genetic syndromes. The Early Infancy Temperament Questionnaire and Parent Stress Index were the assessment tools used. Infants with single ventricular (SV) physiology were more negative in mood (F = 7.14, p parenting an irritable infant with SV physiology put these mothers at risk for high levels of stress. Results suggest the need for predischarge anticipatory guidance for parents to better understand and respond to the behavioral style of their infants, in particular, infants with SV physiology.

Fractional flow reserve for the assessment of complex multivessel disease in a patient after hybrid coronary revascularization.

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Corban, Michel T; Eshtehardi, Parham; Samady, Habib

2013-06-01

We present a case of a 43-year-old woman with history of hybrid coronary revascularization [endoscopic atraumatic coronary artery bypass (ACAB)] of left internal mammary artery (LIMA) to the left anterior descending artery (LAD) and stent implantation in right coronary artery (RCA), who presented 6 years later with recurrent atypical angina. Coronary angiography revealed patent LIMA to LAD and RCA stent, with a new lesion in an obtuse marginal artery and significant progression of disease in the proximal/mid LAD proximal to LIMA touchdown. To further evaluate the hemodynamic significance of these new disease segments, the patient underwent fractional flow reserve (FFR) assessment of the left coronary system with subsequent stent implantation in the proximal/mid LAD. This case illustrates (1) the critical value of FFR assessment in determining the ischemia provoking lesions in this post ACAB patient with complex multivessel coronary artery disease; and (2) the accelerated progression of atherosclerosis in bypassed segments as compared to segments proximal to stents. Copyright © 2012 Wiley Periodicals, Inc.

Estimating the total number of susceptibility variants underlying complex diseases from genome-wide association studies.

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Hon-Cheong So

2010-11-01

Full Text Available Recently genome-wide association studies (GWAS have identified numerous susceptibility variants for complex diseases. In this study we proposed several approaches to estimate the total number of variants underlying these diseases. We assume that the variance explained by genetic markers (Vg follow an exponential distribution, which is justified by previous studies on theories of adaptation. Our aim is to fit the observed distribution of Vg from GWAS to its theoretical distribution. The number of variants is obtained by the heritability divided by the estimated mean of the exponential distribution. In practice, due to limited sample sizes, there is insufficient power to detect variants with small effects. Therefore the power was taken into account in fitting. Besides considering the most significant variants, we also tried to relax the significance threshold, allowing more markers to be fitted. The effects of false positive variants were removed by considering the local false discovery rates. In addition, we developed an alternative approach by directly fitting the z-statistics from GWAS to its theoretical distribution. In all cases, the "winner's curse" effect was corrected analytically. Confidence intervals were also derived. Simulations were performed to compare and verify the performance of different estimators (which incorporates various means of winner's curse correction and the coverage of the proposed analytic confidence intervals. Our methodology only requires summary statistics and is able to handle both binary and continuous traits. Finally we applied the methods to a few real disease examples (lipid traits, type 2 diabetes and Crohn's disease and estimated that hundreds to nearly a thousand variants underlie these traits.

Norrie disease as part of a complex syndrome explained by a submicroscopic deletion of the X chromosome.

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Bleeker-Wagemakers, E M; Zweije-Hofman, I; Gal, A

1988-11-01

A 15-year-old male patient with the typical ocular symptoms of Norrie disease is described. Additionally, he presents severe mental retardation, growth disturbances, hypogonadism, and increased susceptibility to infections. This complex syndrome is apparently segregating through three generations: four other male relatives of the patient were blind from birth and died from recurrent infections between the ages of three to 15 months. The DNA sequence of the DXS7 locus (L1.28 probe), known to be closely linked to the Norrie gene, was not found in the patient's DNA. This result suggests that the more complex clinical picture seen is the result of a deletion of the X chromosome spanning DXS7, the Norrie gene, and several neighbouring loci. A detailed clinical description of the patient is given and compared to that of similar cases.

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-07-01

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

The power to detect linkage in complex disease by means of simple LOD-score analyses.

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Greenberg, D A; Abreu, P; Hodge, S E

1998-09-01

Maximum-likelihood analysis (via LOD score) provides the most powerful method for finding linkage when the mode of inheritance (MOI) is known. However, because one must assume an MOI, the application of LOD-score analysis to complex disease has been questioned. Although it is known that one can legitimately maximize the maximum LOD score with respect to genetic parameters, this approach raises three concerns: (1) multiple testing, (2) effect on power to detect linkage, and (3) adequacy of the approximate MOI for the true MOI. We evaluated the power of LOD scores to detect linkage when the true MOI was complex but a LOD score analysis assumed simple models. We simulated data from 14 different genetic models, including dominant and recessive at high (80%) and low (20%) penetrances, intermediate models, and several additive two-locus models. We calculated LOD scores by assuming two simple models, dominant and recessive, each with 50% penetrance, then took the higher of the two LOD scores as the raw test statistic and corrected for multiple tests. We call this test statistic "MMLS-C." We found that the ELODs for MMLS-C are >=80% of the ELOD under the true model when the ELOD for the true model is >=3. Similarly, the power to reach a given LOD score was usually >=80% that of the true model, when the power under the true model was >=60%. These results underscore that a critical factor in LOD-score analysis is the MOI at the linked locus, not that of the disease or trait per se. Thus, a limited set of simple genetic models in LOD-score analysis can work well in testing for linkage.

Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

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Dinov, Ivo D; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W; Price, Nathan D; Van Horn, John D; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M; Dauer, William; Toga, Arthur W

2016-01-01

A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model-based predictive approaches

Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

Directory of Open Access Journals (Sweden)

Ivo D Dinov

Full Text Available A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI. The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data.Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i introduce methods for rebalancing imbalanced cohorts, (ii utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model

A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

Science.gov (United States)

Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

2014-09-24

Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data

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

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Stasia, Marie-José

2007-05-01

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

Using multidetector-row CT in neonates with complex congenital heart disease to replace diagnostic cardiac catheterization for anatomical investigation: initial experiences in technical and clinical feasibility

International Nuclear Information System (INIS)

Lee, Tain; Tsai, I.C.; Chen, Min-Chi; Fu, Yun-Ching; Jan, Sheng-Lin; Wang, Chung-Chi; Chang, Yen

2006-01-01

Echocardiography is the first-line modality for the investigation of neonatal congenital heart disease. Diagnostic cardiac catheterization, which has a small but recognized risk, is usually performed if echocardiography fails to provide a confident evaluation of the lesions. To verify the technical and clinical feasibilities of replacing diagnostic cardiac catheterization with multidetector-row CT (MDCT) in neonatal complex congenital heart disease. Over a 1-year period we prospectively enrolled all neonates with complex congenital heart disease referred for diagnostic cardiac catheterization after initial assessment by echocardiography. MDCT was performed using a 40-detector-row CT scanner with dual syringe injection. A multidisciplinary congenital heart disease team evaluated the MDCT images and decided if further diagnostic cardiac catheterization was necessary. The accuracy of MDCT in detecting separate cardiovascular anomalies and bolus geometry of contrast enhancement were calculated. A total of 14 neonates were included in the study. No further diagnostic cardiac catheterization was needed in any neonate. The accuracy of MDCT in diagnosing separate cardiovascular anomalies was 98% (53/54) with only one atrial septal defect missed in a patient with coarctation syndrome. The average cardiovascular enhancement in evaluated chambers was 471 HU. No obvious beam-hardening artefact was observed. The technical and clinical feasibility of MDCT in complex congenital heart disease in neonates is confirmed. After initial assessment with echocardiography, MDCT could probably replace diagnostic cardiac catheterization for further anatomical clarification in neonates. (orig.)

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

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Yu. G. Romanova

2017-08-01

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

“Are We There Yet?”: Deciding When One Has Demonstrated Specific Genetic Causation in Complex Diseases and Quantitative Traits

Science.gov (United States)

Page, Grier P.; George, Varghese; Go, Rodney C.; Page, Patricia Z.; Allison, David B.

2003-01-01

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, “Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it.” We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what “causation” means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called “causative.” PMID:13680525

Clinical value of MRI on wrists with arthritis

International Nuclear Information System (INIS)

Ma Qiang; Ma Daqing; He Wen; Le Erhu; Ma Xinfa; Wang Jun; Zuo Zhaoyong

2006-01-01

Objective: To study the appearances of various kinds of arthritis on MRI, and to assess and evaluate the role of MRI on diagnosing various kinds of arthritis. Methods: One hundred and fifty-one patients with medical history of wrist pain entered the study. T 1 -weighted spin echo, STIR (short time inversion recovery) of both wrists, gadolinium contrast material-enhanced sequences of dominant wrists were examined in the coronal planes. MRl, plain wrist radiographs, clinical data including swollen joint and patient global assessment (AIMS), and laboratory, examinations including ESR, RF, APF, and AKA were obtained at the same time. Functional disability was assessed using the Health Assessment Questionnaire Disability Score (HAQ). According to 1987 American Rheumatism Association (ARA) revised criteria, in 151 patients, 80 patients were diagnosed as rheumatoid arthritis, 29 patients as undifferentiated spondyloarthropathy, 20 patients as seronegative spondyloarthropathy, and 22 as other kinds of connective tissue diseases. Results: All 80 patients diagnosed with rheumatoid arthritis had bilateral pannus. Among 29 patients diagnosed with undifferentiated spondyloanthropathy, 3 cases had bilateral pannus, 24 had lateral pannus. Among 20 patients diagnosed with seronegative spondyloanthropathy, 4 cases had bilateral pannus, 15 had lateral pannus. Among 22 patients diagnosed with other kinds of connective tissue disease, 21 had lateral pannus. Bilateral pannus on bilateral wrists occured in 87 patients. There were not significant difference in the unilateral pannus among patients with various arthritis (χ 2 =6.157; P>0.05). But there were significant difference in the bilateral pannus among patients with various arthritis (χ 2 =126.882, P 2 =94.192, P 2 =70.354, P 2 =96.174, P<0.001). Conclusion: MRI can show the pathologic changes of wrists with various kinds of arthritis. MRI plays an important role in the differential diagnosis of various kinds of arthritis

Global epidemiology of capsular group W meningococcal disease (1970-2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex.

Science.gov (United States)

Mustapha, Mustapha M; Marsh, Jane W; Harrison, Lee H

2016-03-18

Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

Brenner, Frank; Marwan, Norbert; Hoffmann, Peter

2017-06-01

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

A Rhodium(III) Complex as an Inhibitor of Neural Precursor Cell Expressed, Developmentally Down-Regulated 8-Activating Enzyme with in Vivo Activity against Inflammatory Bowel Disease.

Science.gov (United States)

Zhong, Hai-Jing; Wang, Wanhe; Kang, Tian-Shu; Yan, Hui; Yang, Yali; Xu, Lipeng; Wang, Yuqiang; Ma, Dik-Lung; Leung, Chung-Hang

2017-01-12

We report herein the identification of the rhodium(III) complex [Rh(phq) 2 (MOPIP)] + (1) as a potent and selective ATP-competitive neural precursor cell expressed, developmentally down-regulated 8 (NEDD8)-activating enzyme (NAE) inhibitor. Structure-activity relationship analysis indicated that the overall organometallic design of complex 1 was important for anti-inflammatory activity. Complex 1 showed promising anti-inflammatory activity in vivo for the potential treatment of inflammatory bowel disease.

Asthma in childhood: a complex, heterogeneous disease

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Hai Lee Chung

2011-01-01

Full Text Available Asthma in childhood is a heterogeneous disease with different phenotypes and variable clinical manifestations, which depend on the age, gender, genetic background, and environmental influences of the patients. Several longitudinal studies have been conducted to classify the phenotypes of childhood asthma, on the basis of the symptoms, triggers of wheezing illness, or pathophysiological features of the disease. These studies have provided us with important information about the different wheezing phenotypes in young children and about potential mechanisms and risk factors for the development of chronic asthma. The goal of these studies was to provide a better insight into the causes and natural course of childhood asthma. It is well-known that complicated interactions between genes and environmental factors contribute to the development of asthma. Because childhood is a period of rapid growth in both the lungs and the immune system, developmental factors should be considered in the pathogenesis of childhood asthma. The pulmonary system continues to grow and develop until linear growth is completed. Longitudinal studies have reported significant age-related immune development during postnatal early life. These observations suggest that the phenotypes of childhood asthma vary among children and also in an individual child over time. Improved classification of heterogeneous conditions of the disease will help determine novel strategies for primary and secondary prevention and for the development of individualized treatment for childhood asthma.

Safety and observer variability of cardiac magnetic resonance imaging combined with low-dose dobutamine stress-testing in patients with complex congenital heart disease

NARCIS (Netherlands)

Robbers-Visser, D.; Luijnenburg, S.E.; Berg, J. van den; Roos-Hesselink, J.W.; Strengers, J.L.; Kapusta, L.; Moelker, A.; Helbing, W.A.

2011-01-01

BACKGROUND: In patients with complex congenital heart disease (CHD) abnormal ventricular stress responses have been reported with dobutamine stress cardiovascular magnetic resonance (DCMR). These abnormal stress responses are potential indicators of long-term outcome. However, safety and

Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa

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Clement Nyamunura Mweya

2013-10-01

Full Text Available Background: The East African region has experienced several Rift Valley fever (RVF outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. Methods: Diverse ecological niche modelling techniques have been developed for this purpose: we present a maximum entropy (Maxent approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Results: Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Conclusion: Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa.

Science.gov (United States)

Mweya, Clement Nyamunura; Kimera, Sharadhuli Iddi; Kija, John Bukombe; Mboera, Leonard E G

2013-01-01

The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

Thoracic myelopathy with alkaptonuria.

Science.gov (United States)

Akeda, Koji; Kasai, Yuichi; Kawakita, Eiji; Matsumura, Yoshihiro; Kono, Toshibumi; Murata, Tetsuya; Uchida, Atsumasa

2008-01-15

A case of thoracic myelopathy with alkaptonuria (ochronotic spondyloarthropathy) is presented. To present and review the first reported case of an alkaptonuric patient with concomitant thoracic myelopathy. Alkaptonuria, a rare hereditary metabolic disease, is characterized by accumulation of homogentistic acid, ochronosis, and destruction of connective tissue resulting in degenerative spondylosis and arthritis. Despite the high incidence of intervertebral disc diseases among patients with alkaptonuria, neurologic symptoms caused by spinal disease are rare. Thoracic myelopathy in a patient with alkaptonuria has not been previously reported. The clinical course, radiologic features, pathology, and treatment outcome of an alkaptonuria patient with thoracic myelopathy was documented. Myelopathy of the patient was caused by rupture of a thoracic intervertebral disc. The neurologic symptoms of the patient were markedly improved after surgery. We have reported for the first time, that an alkaptonuria patient showed thoracic myelopathy caused by rupture of a thoracic intervertebral disc. Decompression followed by the instrumented fusion of the thoracic spine was effective for improving the neurologic symptoms.

Magnetic resonance imaging for ankylosing spondylitis; Magnetresonanztomographie bei ankylosierender Spondylitis (Morbus Struempell-Marie-Bechterew)

Energy Technology Data Exchange (ETDEWEB)

Bollow, M. [Augusta-Kranken-Anstalt, Inst. fuer Radiologie, Bochum (Germany)

2002-12-01

Ankylosing spondylitis (AS) is the prototypical form of the spondyloarthropathies, which at a prevalence of 2% is among the most frequent rheumatic diseases. Spondyloarthropathy comprises the following five disorders: AS, reactive arthritis, psoriatic arthritis, enteropathic arthritis in Crohn's disease, and ulcerosing colitis as well as undifferentiated spondyloarthropathy. In 99% of the patients with AS initial abnormal findings affect the sacroiliac joints. The radiographic changes required for diagnosing AS occur as late as 5-9 years after the onset of clinical symptoms. MRI of the sacroiliac joints reliably demonstrates both chronic inflammatory changes (erosions, sclerotic changes, bone bridges) and acute inflammatory changes (synovitis, capsulitis, osteitis) and allows for grading the chronicity and acuity of such changes. Enthesitis of the interosseous ligaments of the retroarticular space is a manifestation of AS. Spondylodiscitis (Andersson 1937) may occur as an inflammatory or non-inflammatory process (transdiscal fatigue fracture). Inflammations of the facet and costospinal joints developing into ankylosis are typical of AS. Changes of the vertebral bodies occur as anterior (Romanus 1952), posterior, and marginal spondylitis. All forms of spondyloarthropathies are furthermore characterized by asymmetrical synovitis of the large joints, particularly of the legs (gonarthritis, coxitis, tarsitis, peripheral oligoarthritis), rheumatic fibroosteitis (pelvic enthesitis, rheumatic calcaneopathy), and peri- and synchrondritis of the public symphisis and sternal synchondrosis. Since early inflammatory changes of the spinal column and of the extravertebral localizations in AS are demonstrated by MRI before they become apparent on radiographs, and thereby the diagnostic gap could be closed, the early use of MRI for diagnostic and follow-up is commendable, when new therapeutical options like the so-called 'biologicals' are employed. (orig.) [German

Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review

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Fabrícia Torres Gonçalves

Full Text Available CONTEXT: Carney complex (CNC, a familial multiple neoplasm syndrome with dominant autosomal transmission, is characterized by tumors of the heart, skin, endocrine and peripheral nervous system, and also cutaneous lentiginosis. This is a rare syndrome and its main endocrine manifestation, primary pigmented nodular adrenal disease (PPNAD, is an uncommon cause of adrenocorticotropic hormone-independent Cushing's syndrome. CASE REPORT: We report the case of a 20-year-old patient with a history of weight gain, hirsutism, acne, secondary amenorrhea and facial lentiginosis. Following the diagnosing of CNC and PPNAD, the patient underwent laparoscopic bilateral adrenalectomy, and she evolved with decreasing hypercortisolism. Screening was also performed for other tumors related to this syndrome. The diagnostic criteria, screening and follow-up for patients and affected family members are discussed.

Applying computation biology and "big data" to develop multiplex diagnostics for complex chronic diseases such as osteoarthritis.

Science.gov (United States)

Ren, Guomin; Krawetz, Roman

2015-01-01

The data explosion in the last decade is revolutionizing diagnostics research and the healthcare industry, offering both opportunities and challenges. These high-throughput "omics" techniques have generated more scientific data in the last few years than in the entire history of mankind. Here we present a brief summary of how "big data" have influenced early diagnosis of complex diseases. We will also review some of the most commonly used "omics" techniques and their applications in diagnostics. Finally, we will discuss the issues brought by these new techniques when translating laboratory discoveries to clinical practice.

Predictive Big Data Analytics: A Study of Parkinson’s Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations

Science.gov (United States)

Dinov, Ivo D.; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W.; Price, Nathan D.; Van Horn, John D.; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M.; Dauer, William; Toga, Arthur W.

2016-01-01

Background A unique archive of Big Data on Parkinson’s Disease is collected, managed and disseminated by the Parkinson’s Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson’s disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data–large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources–all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Methods and Findings Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several

[VGKC-complex antibodies].

Science.gov (United States)

Watanabe, Osamu

2013-04-01

Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

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

Science.gov (United States)

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

2018-01-01

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

Rheumatic Diseases in China

Science.gov (United States)

Zeng, Qing Yu; Chen, Ren; Darmawan, John; Xiao, Zheng Yu; Chen, Su Biao; Wigley, Richard; Le Chen, Shun; Zhang, Nai Zheng

2008-01-01

Introduction Epidemiological studies of rheumatic diseases have been conducted during the past 20 years in China. The aim of this study was to clarify prevalence rates of common rheumatic diseases in China. Methods Relevant reports of population-based surveys conducted from 1980 to 2006 were retrieved. Studies using the World Health Organization-International League of Associations for Rheumatology COPCORD (Community Oriented Program for Control of Rheumatic Diseases) protocol and those that did not employ this protocol but were published in recognized journals were identified and analyzed. Results Thirty-eight surveys including 241,169 adults from 25 provinces/cities were pooled for analysis. The prevalence of rheumatic complaints ranged from 11.6% to 46.4%, varying by locality, study protocol and age of the people surveyed. Prevalence of symptomatic osteoarthritis (OA) varied from 5.1% to 20.8%, with common sites of involvement being the lumbar spine, knee joint and cervical spine. Compared with rates of radiographic and symptomatic knee OA in the USA, elderly men in Beijing exhibited similar prevalence rates and elderly women exhibited a higher prevalence. The prevalence of hip OA and hand OA was much lower in Chinese than in Caucasian populations, but both kinds of OA were more common in coal miners. The prevalence of ankylosing spondylitis ranged from 0.2% to 0.54% among Han ethnic Chinese and were lower among mixed ethnic populations. The prevalence of psoriatic arthritis ranged from 0.01% to 0.1%, and that of reactive arthritis was 0.02%; undifferentiated spondyloarthropathy was identified in 0.64% to 1.2% of the individuals included in the surveys. The prevalence of rheumatoid arthritis (RA) ranged from 0.2% to 0.93%, with the highest rate being reported from a Taiwan urban area. In mainland China there were no significant differences in prevalence of RA between the northern and southern parts of China, or between different ethnic groups. The prevalence of

Complex single step skull reconstruction in Gorham's disease - a technical report and review of the literature.

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Ohla, Victoria; Bayoumi, Ahmed B; Hefty, Markus; Anderson, Matthew; Kasper, Ekkehard M

2015-03-11

Gorham's disease is a rare osteolytic disorder characterized by progressive resorption of bone and replacement of osseous matrix by a proliferative non-neoplastic vascular or lymphatic tissue. A standardized treatment protocol has not yet been defined due to the unpredictable natural history of the disease and variable clinical presentations. No single treatment has proven to be superior in arresting the course of the disease. Trials have included surgery, radiation and medical therapies using drugs such as calcium salts, vitamin D supplements and hormones. We report on our advantageous experience in the management of this osteolyic disorder in a case when it affected only the skull vault. A brief review of pertinent literature about Gorham's disease with skull involvement is provided. A 25-year-old Caucasian male presented with a skull depression over the left fronto-temporal region. He noticed progressive enlargement of the skull defect associated with local pain and mild headache. Physical examination revealed a tender palpable depression of the fronto-temporal convexity. Conventional X-ray of the skull showed widespread loss of bone substance. Subsequent CT scans showed features of patchy erosions indicative of an underlying osteolysis. MRI also revealed marginal enhancement at the site of the defect. The patient was in need of a pathological diagnosis as well as complex reconstruction of the afflicted area. A density graded CT scan was done to determine the variable degrees of osteolysis and a custom made allograft was designed for cranioplasty preoperatively to allow for a single step excisional craniectomy with synchronous skull repair. Gorham's disease was diagnosed based on histopathological examination. No neurological deficit or wound complications were reported postoperatively. Over a two-year follow up period, the patient had no evidence of local recurrence or other systemic involvement. A single step excisional craniectomy and cranioplasty can be an

Oxidative stress caused by blocking of mitochondrial Complex I Hplus pumping as a link in aging/disease vicious cycle

Czech Academy of Sciences Publication Activity Database

Dlasková, Andrea; Hlavatá, Lydie; Ježek, Petr

2008-01-01

Roč. 40, č. 9 (2008), s. 1792-1805 ISSN 1357-2725 R&D Projects: GA MZd(CZ) NR7917; GA AV ČR IAA500110701; GA ČR(CZ) GA301/05/0221; GA ČR GP303/05/P100 Institutional research plan: CEZ:AV0Z50110509 Keywords : aging /oxidative stres related diseases * mitochondrial superoxide production * mitochondrial Complex I Subject RIV: BO - Biophysics Impact factor: 4.178, year: 2008

Complex Nonlinear Autonomic Nervous System Modulation Link Cardiac Autonomic Neuropathy and Peripheral Vascular Disease

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Kinda eKhalaf

2015-03-01

Full Text Available Background: Physiological interactions are abundant within, and between, body systems. These interactions may evolve into discrete states during pathophysiological processes resulting from common mechanisms. An association between arterial stenosis, identified by low ankle-brachial pressure index (ABPI and cardiovascular disease (CVD as been reported. Whether an association between vascular calcification - characterized by high ABPI and a different pathophysiology - is similarly associated with CVD, has not been established. The current study aims to investigate the association between ABPI, and cardiac rhythm, as an indicator of cardiovascular health and functionality, utilising heart rate variability (HRV.Methods and Results: Two hundred and thirty six patients underwent ABPI assessment. Standard time and frequency domain, and non-linear HRV measures were determined from 5-minute electrocardiogram. ABPI data were divided into normal (n=101, low (n=67 and high (n=66 and compared to HRV measures.(DFAα1 and SampEn were significantly different between the low ABPI, high ABPI and control groups (p<0.05.Conclusion: A possible coupling between arterial stenosis and vascular calcification with decreased and increased HRV respectively was observed. Our results suggest a model for interpreting the relationship between vascular pathophysiology and cardiac rhythm. The cardiovascular system may be viewed as a complex system comprising a number of interacting subsystems. These cardiac and vascular subsystems/networks may be coupled and undergo transitions in response to internal or external perturbations. From a clinical perspective, the significantly increased sample entropy compared to the normal ABPI group and the decreased and increased complex correlation properties measured by DFA for the low and high ABPI groups respectively, may be useful indicators that a more holistic treatment approach in line with this more complex clinical picture is required.

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

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Xiaoguang Zhang

2014-01-01

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

Evaluating the impact of a disease management program for chronic complex conditions at two large northeast health plans using a control group methodology.

Science.gov (United States)

Schwerner, Henry; Mellody, Timothy; Goldstein, Allan B; Wansink, Daryl; Sullivan, Virginia; Yelenik, Stephan N; Charlton, Warwick; Lloyd, Kelley; Courtemanche, Ted

2006-02-01

The objective of this study was to observe trends in payer expenditures for plan members with one of 14 chronic, complex conditions comparing one group with a disease management program specific to their condition (the intervention group) and the other with no specific disease management program (the control group) for these conditions. The authors used payer claims and membership data to identify members eligible for the program in a 12-month baseline year (October 2001 to September 2002) and a subsequent 12-month program year (October 2002 to September 2003). Two payers were analyzed: one health plan with members primarily in New Jersey (AmeriHealth New Jersey [AHNJ]), where the disease management program was offered, and one affiliated large plan with members primarily in the metro Philadelphia area, where the program was not offered. The claims payment policy for both plans is identical. Intervention and control groups were analyzed for equivalence. The analysis was conducted in both groups over identical time periods. The intervention group showed statistically significant (p control group. Intervention group members showed a reduction in expenditures of -8%, while control group members showed an increase of +10% over identical time periods. Subsequent analyses controlling for outliers and product lines served to confirm the overall results. The disease management program is likely responsible for the observed difference between the intervention and control group results. A well-designed, targeted disease management program offered by a motivated, supportive health plan can play an important role in cost improvement strategies for members with complex, chronic conditions.

Clinical outcome of Crohn's disease according to the Vienna classification: disease location is a useful predictor of disease course

NARCIS (Netherlands)

Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

2006-01-01

OBJECTIVES: Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

Clinical outcome of Crohn's disease according to the Vienna classification : disease location is a useful predictor of disease course

NARCIS (Netherlands)

Oostenbrug, Liekele E.; van Dullemen, Hendrik M.; te Meerman, Gerard J.; Jansen, Peter L. M.; Kleibeuker, Jan H.

Objectives Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim

Copper(II) complexes of methimazole, an anti Grave's disease drug. Synthesis, characterization and its potential biological behavior as alkaline phosphatase inhibitor.

Science.gov (United States)

Urquiza, Nora M; Manca, Silvia G; Moyano, María A; Dellmans, Raquel Arrieta; Lezama, Luis; Rojo, Teófilo; Naso, Luciana G; Williams, Patricia A M; Ferrer, Evelina G

2010-04-01

Methimazole (MeimzH) is an anti-thyroid drug and the first choice for patients with Grave's disease. Two new copper(II) complexes of this drug: [Cu(MeimzH)(2)(NO(3))(2)]*0.5H(2)O and [Cu(MeimzH)(2)(H(2)O)(2)](NO(3))(2)*H(2)O were synthesized and characterized by elemental analysis, dissolution behavior, thermogravimetric analysis and UV-vis, diffuse reflectance, FTIR and EPR spectroscopies. As it is known that copper(II) cation can act as an inhibitor of alkaline phosphatase (ALP), the inhibitory effect of methimazole and its copper(II) complexes on ALP activity has also been investigated.

Interaction of lifestyle, behaviour or systemic diseases with dental caries and periodontal diseases

DEFF Research Database (Denmark)

Chapple, Iain L C; Bouchard, Philippe; Cagetti, Maria Grazia

2017-01-01

Periodontal diseases and dental caries are the most common diseases of humans and the main cause of tooth loss. Both diseases can lead to nutritional compromise and negative impacts upon self-esteem and quality of life. As complex chronic diseases, they share common risk factors, such as a requir......Periodontal diseases and dental caries are the most common diseases of humans and the main cause of tooth loss. Both diseases can lead to nutritional compromise and negative impacts upon self-esteem and quality of life. As complex chronic diseases, they share common risk factors...... to periodontal diseases and caries susceptibility, with an attributable risk estimated to be up to 50%. The genetics literature for periodontal disease is more substantial than for caries and genes associated with chronic periodontitis are the vitamin D receptor (VDR), Fc gamma receptor IIA (Fc...... or composition, smoking, carbohydrate intake). Identification of these factors is crucial in the prevention of both diseases as well as in their management. AIM: To systematically appraise the scientific literature to identify potential risk factors for caries and periodontal diseases. METHODS: One systematic...

A disease state fingerprint for evaluation of Alzheimer's disease

DEFF Research Database (Denmark)

Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho

2011-01-01

Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization...... interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease...

SYNTAX score based on coronary computed tomography angiography may have a prognostic value in patients with complex coronary artery disease: An observational study from a retrospective cohort.

Science.gov (United States)

Suh, Young Joo; Han, Kyunghwa; Chang, Suyon; Kim, Jin Young; Im, Dong Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Hur, Jin; Kim, Young Jin; Choi, Byoung Wook

2017-09-01

The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score is an invasive coronary angiography (ICA)-based score for quantifying the complexity of coronary artery disease (CAD). Although the SYNTAX score was originally developed based on ICA, recent publications have reported that coronary computed tomography angiography (CCTA) is a feasible modality for the estimation of the SYNTAX score.The aim of our study was to investigate the prognostic value of the SYNTAX score, based on CCTA for the prediction of major adverse cardiac and cerebrovascular events (MACCEs) in patients with complex CAD.The current study was approved by the institutional review board of our institution, and informed consent was waived for this retrospective cohort study. We included 251 patients (173 men, mean age 66.0 ± 9.29 years) who had complex CAD [3-vessel disease or left main (LM) disease] on CCTA. SYNTAX score was obtained on the basis of CCTA. Follow-up clinical outcome data regarding composite MACCEs were also obtained. Cox proportional hazards models were developed to predict the risk of MACCEs based on clinical variables, treatment, and computed tomography (CT)-SYNTAX scores.During the median follow-up period of 1517 days, there were 48 MACCEs. Univariate Cox hazards models demonstrated that MACCEs were associated with advanced age, low body mass index (BMI), and dyslipidemia (P < .2). In patients with LM disease, MACCEs were associated with a higher SYNTAX score. In patients with CT-SYNTAX score ≥23, patients who underwent coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention had significantly lower hazard ratios than patients who were treated with medication alone. In multivariate Cox hazards model, advanced age, low BMI, and higher SYNTAX score showed an increased hazard ratio for MACCE, while treatment with CABG showed a lower hazard ratio (P < .2).On the basis of our results, CT-SYNTAX score

Predictive Big Data Analytics: A Study of Parkinson?s Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations

OpenAIRE

Dinov, Ivo D.; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W.; Price, Nathan D.; Van Horn, John D.; Ames, Joseph

2016-01-01

Background A unique archive of Big Data on Parkinson?s Disease is collected, managed and disseminated by the Parkinson?s Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationsh...

Broncho-pleural fistula with hydropneumothorax at CT: Diagnostic implications in mycobacterium avium complex lung disease with pleural involvement

International Nuclear Information System (INIS)

Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Park, Hye Yun; Koh, Won Jung; Kim, Jung Soo

2016-01-01

To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion

Broncho-pleural fistula with hydropneumothorax at CT: Diagnostic implications in mycobacterium avium complex lung disease with pleural involvement

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Park, Hye Yun; Koh, Won Jung [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jung Soo [Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

2016-04-15

To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion.

Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team.

Science.gov (United States)

Chaisson, R E; Benson, C A; Dube, M P; Heifets, L B; Korvick, J A; Elkin, S; Smith, T; Craft, J C; Sattler, F R

1994-12-15

To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). A randomized, double-blind, dose-ranging study. Outpatient clinics. 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. Median number of colony-forming units of M. avium complex per milliliter of blood. Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem.

Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

Science.gov (United States)

Kim, Ju Han; Ha, Il Soo; Hwang, Chang-Il; Lee, Young-Ju; Kim, Jihoon; Yang, Seung-Hee; Kim, Yon Su; Cao, Yun Anna; Choi, Sangdun; Park, Woong-Yang

2004-11-01

Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.

Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.

Directory of Open Access Journals (Sweden)

Robin G Walters

Full Text Available The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25, we had sufficient statistical power to detect the large majority (80% of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4 (95% confidence interval [9.6×10(-5-3.1×10(-4]; accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10; odds ratio = 25.0 [9.9-60.6]; and results in a mean body mass index (BMI increase of 5.8 kg.m(-2 [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially

Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?

Science.gov (United States)

Macpherson, Eleanor E; Adams, Emily R; Bockarie, Moses J; Hollingsworth, T Deirdre; Kelly-Hope, Louise A; Lehane, Mike; Kovacic, Vanja; Harrison, Robert A; Paine, Mark Ji; Reimer, Lisa J; Torr, Stephen J

2015-01-01

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.

Neurosurgical implications of Carney complex.

Science.gov (United States)

Watson, J C; Stratakis, C A; Bryant-Greenwood, P K; Koch, C A; Kirschner, L S; Nguyen, T; Carney, J A; Oldfield, E H

2000-03-01

The authors present their neurosurgical experience with Carney complex. Carney complex, characterized by spotty skin pigmentation, cardiac myxomas, primary pigmented nodular adrenocortical disease, pituitary tumors, and nerve sheath tumors (NSTs), is a recently described, rare, autosomal-dominant familial syndrome that is relatively unknown to neurosurgeons. Neurosurgery is required to treat pituitary adenomas and a rare NST, the psammomatous melanotic schwannoma (PMS), in patients with Carney complex. Cushing's syndrome, a common component of the complex, is caused by primary pigmented nodular adrenocortical disease and is not secondary to an adrenocorticotropic hormone-secreting pituitary adenoma. The authors reviewed 14 cases of Carney complex, five from the literature and nine from their own experience. Of the 14 pituitary adenomas recognized in association with Carney complex, 12 developed growth hormone (GH) hypersecretion (producing gigantism in two patients and acromegaly in 10), and results of immunohistochemical studies in one of the other two were positive for GH. The association of PMSs with Carney complex was established in 1990. Of the reported tumors, 28% were associated with spinal nerve sheaths. The spinal tumors occurred in adults (mean age 32 years, range 18-49 years) who presented with pain and radiculopathy. These NSTs may be malignant (10%) and, as with the cardiac myxomas, are associated with significant rates of morbidity and mortality. Because of the surgical comorbidity associated with cardiac myxoma and/or Cushing's syndrome, recognition of Carney complex has important implications for perisurgical patient management and family screening. Study of the genetics of Carney complex and of the biological abnormalities associated with the tumors may provide insight into the general pathobiological abnormalities associated with the tumors may provide insight into the general pathobiological features of pituitary adenomas and NSTs.

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

Science.gov (United States)

Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza

2016-11-01

We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Retinal nerve fiber layer and ganglion cell complex thickness assessment in patients with Alzheimer disease and mild cognitive impairment. Preliminary results

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A. S. Tiganov

2014-07-01

Full Text Available Purpose: to investigate the retinal nerve fiber layer (RNFL and the macular ganglion cell complex (GCC in patients with Alzheimer`s disease and mild cognitive impairment.Methods: this study included 10 patients (20 eyes with Alzheimer`s disease, 10 patients with mild cognitive impairment and 10 age- and sex-matched healthy controls that had no history of dementia. All the subjects underwent psychiatric examination, including the Mini-Mental State Examination (MMSE, and complete ophthalmological examination, comprising optical coherence tomography and scanning laser polarimetry.Results: there was a significant decrease in GCC thickness in patients with Alzheimer`s disease compared to the control group, global loss volume of ganglion cells was higher than in control group. there was no significant difference among the groups in terms of RNFL thickness. Weak positive correlation of GCC thickness and MMSE results was observed.Conclusion: Our data confirm the retinal involvement in Alzheimer`s disease, as reflected by loss of ganglion cells. Further studies will clear up the role and contribution of dementia in pathogenesis of optic neuropathy.

Sleeve gastrectomy and gastro-oesophageal reflux disease: a complex relationship.

Science.gov (United States)

Mahawar, Kamal K; Jennings, Neil; Balupuri, Shlok; Small, Peter K

2013-07-01

Sleeve gastrectomy is rapidly becoming popular as a standalone bariatric operation. At the same time, there are valid concerns regarding its long-term durability and postoperative gastro-oesophageal reflux disease. Though gastric bypass remains the gold standard bariatric operation, it is not suitable for all patients. Sleeve gastrectomy is sometimes the only viable option. Patients with inflammatory bowel disease, liver cirrhosis, significant intra-abdominal adhesions involving small bowel and those reluctant to undergo gastric bypass could fall in this category. It is widely recognised that some patients report worsening of their gastro-oesophageal reflux disease after sleeve gastrectomy. Still, others develop de novo reflux. This review examines if it is possible to identify these patients prior to surgery and thus prevent postoperative gastro-oesophageal reflux disease after sleeve gastrectomy.

Complex Interplay of Future Climate Levels of CO₂, Ozone and Temperature on Susceptibility to Fungal Diseases in Barley

DEFF Research Database (Denmark)

Mikkelsen, Bolette Lind

Climate change will modify the environmental growth conditions for plants, and consequently also their physiology and susceptibility to diseases. However, there is a lack of experimental studies on the effect of climate change on plant diseases, which include several climatic factors in order...... to simulate realistic growth conditions. In this PhD thesis, the complex interplay of elevated CO2, temperature and ozone on the susceptibility of barley to the biotrophic powdery mildew fungus (Blumeria graminis f.sp. hordei) and the hemibiotrophic spot blotch fungus (Bipolaris sorokiniana) was revealed....... The underlying mechanisms hereof was examined by studying changes in photosynthesis, accumulation of secondary metabolites and global gene expression after B. graminis attack...

Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

Science.gov (United States)

Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

2015-01-01

Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully

Gut microbiota, immunity and disease: a complex relationship

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Michele M Kosiewicz

2011-09-01

Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

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

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Márcio G. Kiuchi

2017-06-01

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

The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease.

NARCIS (Netherlands)

Nijtmans, L.G.J.; Artal-Sanz, M.; Grivell, L.A.; Coates, P.J.

2002-01-01

Although originally identified as putative negative regulators of the cell cycle, recent studies have demonstrated that the PHB proteins act as a chaperone in the assembly of subunits of mitochondrial respiratory chain complexes. The two PHB proteins, Phblp and Phb2p, are located in the

Complex lipid trafficking in Niemann-Pick disease type C.

Science.gov (United States)

Vanier, Marie T

2015-01-01

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

Comparison of protein profiles of beech bark disease-resistant or beech bark disease-susceptible American beech

Science.gov (United States)

Mary E. Mason; Marek Krasowski; Judy Loo; Jennifer. Koch

2011-01-01

Proteomic analysis of beech bark proteins from trees resistant and susceptible to beech bark disease (BBD) was conducted. Sixteen trees from eight geographically isolated stands, 10 resistant (healthy) and 6 susceptible (diseased/infested) trees, were studied. The genetic complexity of the sample unit, the sampling across a wide geographic area, and the complexity of...

Unmanned Aerial Vehicle (UAV-based remote sensing to monitor grapevine leaf stripe disease within a vineyard affected by esca complex

Directory of Open Access Journals (Sweden)

Salvatore F. DI GENNARO

2016-07-01

Full Text Available Foliar symptoms of grapevine leaf stripe disease (GLSD, a disease within the esca complex are linked to drastic alteration of photosynthetic function and activation of defense responses in affected grapevines several days before the appearance of the first visible symptoms on leaves. The present study suggests a methodology to investigate the relationships between high-resolution multispectral images (0.05 m/pixel acquired using an Unmanned Aerial Vehicle (UAV, and GLSD foliar symptoms monitored by ground surveys. This approach showed high correlation between Normalized Differential Vegetation Index (NDVI acquired by the UAV and GLSD symptoms, and discrimination between symptomatic from asymptomatic plants. High-resolution multispectral images were acquired during June and July of 2012 and 2013, in an experimental vineyard heavily affected by GLSD, located in Tuscany (Italy, where vines had been surveyed and mapped since 2003. Each vine was located with a global positioning system, and classified for appearance of foliar symptoms and disease severity at weekly intervals from the beginning of each season. Remote sensing and ground observation data were analyzed to promptly identify the early stages of disease, even before visual detection. This work suggests an innovative methodology for quantitative and qualitative analysis of spatial distribution of symptomatic plants. The system may also be used for exploring the physiological bases of GLSD, and predicting the onset of this disease. 

DOSim: An R package for similarity between diseases based on Disease Ontology

Science.gov (United States)

2011-01-01

Background The construction of the Disease Ontology (DO) has helped promote the investigation of diseases and disease risk factors. DO enables researchers to analyse disease similarity by adopting semantic similarity measures, and has expanded our understanding of the relationships between different diseases and to classify them. Simultaneously, similarities between genes can also be analysed by their associations with similar diseases. As a result, disease heterogeneity is better understood and insights into the molecular pathogenesis of similar diseases have been gained. However, bioinformatics tools that provide easy and straight forward ways to use DO to study disease and gene similarity simultaneously are required. Results We have developed an R-based software package (DOSim) to compute the similarity between diseases and to measure the similarity between human genes in terms of diseases. DOSim incorporates a DO-based enrichment analysis function that can be used to explore the disease feature of an independent gene set. A multilayered enrichment analysis (GO and KEGG annotation) annotation function that helps users explore the biological meaning implied in a newly detected gene module is also part of the DOSim package. We used the disease similarity application to demonstrate the relationship between 128 different DO cancer terms. The hierarchical clustering of these 128 different cancers showed modular characteristics. In another case study, we used the gene similarity application on 361 obesity-related genes. The results revealed the complex pathogenesis of obesity. In addition, the gene module detection and gene module multilayered annotation functions in DOSim when applied on these 361 obesity-related genes helped extend our understanding of the complex pathogenesis of obesity risk phenotypes and the heterogeneity of obesity-related diseases. Conclusions DOSim can be used to detect disease-driven gene modules, and to annotate the modules for functions and

Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease.

Science.gov (United States)

Gal, A; Wieringa, B; Smeets, D F; Bleeker-Wagemakers, L; Ropers, H H

1986-01-01

Norrie disease (ND), an X-linked recessive disorder, is characterized by congenital blindness followed by bulbar atrophy. We have examined a three-generation family in which ND is part of a complex X-linked syndrome with severe mental retardation, hypogonadism, growth disturbances, and increased susceptibility to infections as additional features. This syndrome is apparently due to an interstitial deletion, as evidenced by the failure of the L1.28 DNA probe (DXS7 locus, Xp11.3) to detect complementary DNA sequences on the defective X chromosome of an affected male and of several obligatory heterozygotes. Attempts to further define this deletion with other DNA probes from the proximal short arm of the X chromosome or by prometaphase chromosome analysis were unsuccessful.

Clearing the complexity: immune complexes and their treatment in lupus nephritis

Directory of Open Access Journals (Sweden)

Catherine Toong

2011-01-01

Full Text Available Catherine Toong1, Stephen Adelstein1, Tri Giang Phan21Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; 2Immunology Program, Garvan Institute of Medical Research and St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaAbstract: Systemic lupus erythematosus (SLE is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.Keywords: immune complex, systemic lupus erythematosus, nephritis, therapy

Role of zinc-protein complexes in the serum of human beings with reference to health and infectious diseases

International Nuclear Information System (INIS)

Bibi, S.; Sajjad, I.; Akram, W.; Viqar, N.; Iqbal, M.S.; Iqbal, M.Z.

1997-01-01

Serum of one hundred thirty normal subjects and 100 patients of different infections were analysed by electrophoresis and atomic absorption flame spectrophotometric technique. It was found that about sixty percent of zinc is bound to albumin and thirty percent is bound to alpha 2-globulins with a variation of 2-5%, beta-globulins and gamma-globulins with a variation of 2-5% in different normal subjects. While the determination of zinc in patients of different infections shows 20-30% decrease in the concentration of albumin bound zinc. The concentration of zinc in alpha 2-globulins remains the same in normal subjects as well as in patients of different infections. The results indicate that in low nourished normal subjects, there is a low concentration of zinc complexes of albumin and a greater chance of different infectious diseases it was further known that albumin works for the transport of zinc and possibly, alpha 2-globulins plays on intermediate role for the attachment of zinc to different body organs. From the above determinations, it is clear that it is the low concentration of zinc in normal subjects which favours the attack of infectious disease. So higher levels of zinc in serum means more resistance towards the attack of infectious diseases. (author)

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

NARCIS (Netherlands)

Eenennaam, Hans van

2002-01-01

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

Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort

NARCIS (Netherlands)

Weersma, R.K.; Stokkers, P.C.F.; van Bodegraven, A.A.; van Hogezand, R.A.; Verspaget, H.W.; de Jong, D.J.; van der Woude, C.J.; Oldenburg, B.; Linskens, R.K.; Festen, E.A.M.; van der Steege, G.; Hommes, D.W.; Crusius, J.B.A.; Wijmenga, C.; Nolte, I.M.; Dijkstra, G.

2009-01-01

Background: Crohn's disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). Methods: We studied 2804 patients (1684

Celiac disease : moving from genetic associations to causal variants

NARCIS (Netherlands)

Hrdlickova, B.; Westra, H-J; Franke, L.; Wijmenga, C.

Genome-wide association studies are providing insight into the genetic basis of common complex diseases: more than 1150 genetic loci [2165 unique single nucleotide polymorphisms (SNPs)] have recently been associated to 159 complex diseases. The hunt for genes contributing to immune-related diseases

Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

2004-01-01

's thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture......B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto...

Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

2004-01-01

B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...

Adult Congenital Heart Disease Patients Experience Similar Symptoms of Disease Activity.

Science.gov (United States)

Cedars, Ari M; Stefanescu Schmidt, Ada; Broberg, Craig; Zaidi, Ali; Opotowsky, Alexander; Grewal, Jasmine; Kay, Joseph; Bhatt, Ami B; Novak, Eric; Spertus, John

2016-03-01

There is a lack of objective data on the symptoms characterizing disease activity among adults with congenital heart disease (ACHD). The purpose of this study was to elicit the most important symptoms from patients across the spectrum of ACHD and to examine whether reported symptoms were similar across the spectrum of ACHD as a foundation for creating a patient-reported outcome measure(s). We constructed a 39-item survey using input from physicians specializing in ACHD to assess the symptoms patients associate with disease activity. Patients (n=124) prospectively completed this survey, and the results were analyzed based on underlying anatomy and disease complexity. A confirmatory cohort of patients (n=40) was then recruited prospectively to confirm the validity of the initial data. When grouped based on underlying anatomy, significant differences in disease-related symptom rankings were found for only 6 of 39 symptoms. Six symptoms were identified which were of particular significance to patients, regardless of underlying anatomy. Patients with anatomy of great complexity experienced greater overall symptom severity than those with anatomy of low or moderate complexity, attributable exclusively to higher ranking of 5 symptoms. The second patient cohort had symptom experiences similar to those of the initial cohort, differing in only 5 of 39 symptoms. This study identified 6 symptoms relevant to patients across the spectrum of ACHD and remarkable homogeneity of patient experience, suggesting that a single disease-specific patient-reported outcome can be created for quality and outcome assessments. © 2016 American Heart Association, Inc.

Dembo polymerase chain reaction technique for detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs.

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Rahpaya, Sayed Samim; Tsuchiaka, Shinobu; Kishimoto, Mai; Oba, Mami; Katayama, Yukie; Nunomura, Yuka; Kokawa, Saki; Kimura, Takashi; Kobayashi, Atsushi; Kirino, Yumi; Okabayashi, Tamaki; Nonaka, Nariaki; Mekata, Hirohisa; Aoki, Hiroshi; Shiokawa, Mai; Umetsu, Moeko; Morita, Tatsushi; Hasebe, Ayako; Otsu, Keiko; Asai, Tetsuo; Yamaguchi, Tomohiro; Makino, Shinji; Murata, Yoshiteru; Abi, Ahmad Jan; Omatsu, Tsutomu; Mizutani, Tetsuya

2018-05-31

Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum ; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.

Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference.

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Krueger, Darcy A; Northrup, Hope

2013-10-01

Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations and progression can be life-threatening with significant impact on cost and quality of life. Current surveillance and management practices are highly variable among region and country, reflective of the fact that last consensus recommendations occurred in 1998 and an updated, comprehensive standard is lacking that incorporates the latest scientific evidence and current best clinical practices. The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 separate subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important clinical management implications and was charged with formulating key clinical questions to address within its focus area, reviewing relevant literature, evaluating the strength of data, and providing a recommendation accordingly. The updated consensus recommendations for clinical surveillance and management in tuberous sclerosis complex are summarized here. The recommendations are relevant to the entire lifespan of the patient, from infancy to adulthood, including both individuals where the diagnosis is newly made as well as individuals where the diagnosis already is established. The 2012 International Tuberous Sclerosis Complex Consensus Recommendations provide an evidence-based, standardized approach for optimal clinical care provided for individuals with tuberous sclerosis complex. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Different Epidemic Models on Complex Networks

International Nuclear Information System (INIS)

Zhang Haifeng; Small, Michael; Fu Xinchu

2009-01-01

Models for diseases spreading are not just limited to SIS or SIR. For instance, for the spreading of AIDS/HIV, the susceptible individuals can be classified into different cases according to their immunity, and similarly, the infected individuals can be sorted into different classes according to their infectivity. Moreover, some diseases may develop through several stages. Many authors have shown that the individuals' relation can be viewed as a complex network. So in this paper, in order to better explain the dynamical behavior of epidemics, we consider different epidemic models on complex networks, and obtain the epidemic threshold for each case. Finally, we present numerical simulations for each case to verify our results.

[Voltage-Gated Potassium Channel-Complex Antibodies Associated Encephalopathy and Related Diseases].

Science.gov (United States)

Watanabe, Osamu

2016-09-01

Voltage-gated potassium channel (VGKC) complex antibodies are auto-antibodies, initially identified in acquired neuromyotonia (aNMT; Isaacs' syndrome), which cause muscle cramps and difficulty in opening the palm of the hands. Subsequently, these antibodies were found in patients presenting with aNMT along with psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) patient with prominent amnesia and frequent seizures. Typical LE cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures (FBDS). The VGKC complex is a group of proteins that are strongly associated in situ and after extraction in the mild detergent digitonin. Recent studies indicated that the VGKC complex antibodies are mainly directed toward associated proteins (for example LGI1, Caspr2) that complex with VGKCs themselves. Patients with aNMT or MoS are most likely to have Caspr2 antibodies, whereas LGI1 antibodies are found characteristically in patients with FBDS and LE. We systematically identified and quantified autoantibodies in patient sera with VGKC-complex antibody associated encephalopathy and showed the relationship between individual antibodies and patient's symptoms. Furthermore, we revealed how autoantibodies disrupt the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, reducing the synaptic AMPA receptors.

A disease state fingerprint for evaluation of Alzheimer's disease

DEFF Research Database (Denmark)

Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho

2011-01-01

Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization...... interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease......'s degree of similarity to previously diagnosed disease population. A summary of patient data and results of the computation are displayed in a succinct Disease State Fingerprint (DSF) visualization. The visualization clearly discloses how patient data contributes to the AD state, facilitating rapid...

Neuropsychological syndromes in patients with Parkinson’s disease after deep electric stimulation of pallidar complex structures

Directory of Open Access Journals (Sweden)

Yu V Mikadze

2013-01-01

Full Text Available The paper provides the results of neuropsychological examinations in 10 patients with Parkinson’s disease who underwent deep electrical stimulation of pallidar complex structures. The general neuropsychological test battery that had been developed by A.R. Luria and allowed the qualitative classification of the cognitive impairment symptoms detectable on examination to be made was used to study cognitive functions. The patients were examined before and just after surgery and in the late period (following 1—2 years. The examinations have shown that the syndromes indicative of dysfunctions in the deep, parietal, and occipital and prefrontal regions of the left hemisphere and in the parietooccipital regions of the right hemisphere are stable components that determine the pattern of cognitive disorders and are preserved throughout all examinations.

GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.

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Yutao Liu

Full Text Available DNA copy number variants (CNVs have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC. This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1. (p = 0.017, fisher's exact test. It was validated with array comparative genomic hybridization (arrayCGH and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio = 3.5, 95% CI -1.1-12.0. Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4. Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

Genetics of simple and complex host-parasite interactions

International Nuclear Information System (INIS)

Sidhu, G.S.; Webster, J.M.

1977-01-01

In nature a host plant can be viewed as a miniature replica of an ecological system where true and incidental parasites share the same habitat. Consequently, they influence each other's presence directly by interspecific interaction, and indirectly by inducing changes in the host's physiology and so form disease complexes. Since all physiological phenomena have their counterpart in the respective genetic systems of interacting organisms, valuable genetic information can be derived from the analysis of complex parasitic systems. Disease complexes may be classified according to the nature of interaction between various parasites on the same host. One parasite may nullify the host's resistance to another (e.g. Tomato - Meloidogyne incognita + Fusarium oxysporum lycopersici system). Conversely, a parasite may invoke resistance in the host against another parasite (e.g. Tomato - Fusarium oxysporum lycopersici + Verticillium albo atrum system). From the study of simple parasitic systems we know that resistance versus susceptibility against a single parasite is normally monogenically controlled. However, when more than one parasite interacts to invoke or nullify each other's responses on the same host plant, the genetic results suggest epistatic ratios. Nevertheless, epistatic ratios have been obtained also from simple parasitic systems owing to gene interaction. The epistatic ratios obtained from complex and simple parasitic systems are contrasted and compared. It is suggested that epistatic ratios obtained from simple parasitic systems may, in fact, be artifacts resulting from complex parasitic associations that often occur in nature. Polygenic inheritance and the longevity of a cultivar is also discussed briefly in relation to complex parasitic associations. Induced mutations can play a significant role in the study of complex parasitic associations, and thus can be very useful in controlling plant diseases

Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease.

Science.gov (United States)

Lundquist, Andrew L; Nigwekar, Sagar U

2016-03-01

The review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and end stage renal disease. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of mineral bone disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Mineral bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders, and with the ability to intervene on more than one pathway, are needed to advance patient care.

Endometriosis research: animal models for the study of a complex disease.

Science.gov (United States)

Tirado-González, Irene; Barrientos, Gabriela; Tariverdian, Nadja; Arck, Petra C; García, Mariana G; Klapp, Burghard F; Blois, Sandra M

2010-11-01

Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence of events involved in disease establishment and progression. Also, because this disease occurs spontaneously only in humans and non-human primates and there are practical problems associated with studying the disease, animal models have been developed for the evaluation of endometriosis. This review describes the animal models for endometriosis that have been used to date, highlighting their importance for the investigation of disease mechanisms that would otherwise be more difficult to elucidate, and proposing new alternatives aimed at overcoming some of these limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Gerstmann-Straüssler-Scheinker disease

Science.gov (United States)

Jones, Matthew; Odunsi, Sola; du Plessis, Daniel; Vincent, Angela; Bishop, Matthew; Head, Mark W.; Ironside, James W.

2014-01-01

Objective: To describe a unique case of Gerstmann-Straüssler-Scheinker (GSS) disease caused by a novel prion protein (PRNP) gene mutation and associated with strongly positive voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Methods: Clinical data were gathered from retrospective review of the case notes. Postmortem neuropathologic examination was performed, and DNA was extracted from frozen brain tissue for full sequence analysis of the PRNP gene. Results: The patient was diagnosed in life with VGKC-complex Ab–associated encephalitis based on strongly positive VGKC-complex Ab titers but no detectable LGI1 or CASPR2 Abs. He died despite 1 year of aggressive immunosuppressive treatment. The neuropathologic diagnosis was GSS disease, and a novel mutation, P84S, in the PRNP gene was found. Conclusion: VGKC-complex Abs are described in an increasingly broad range of clinical syndromes, including progressive encephalopathies, and may be amenable to treatment with immunosuppression. However, the failure to respond to aggressive immunotherapy warns against VGKC-complex Abs being pathogenic, and their presence does not preclude the possibility of prion disease. PMID:24814844

Results of complex treatment of Hodgkin's disease

International Nuclear Information System (INIS)

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

2000-01-01

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

Incidence, risk factors and clinical epidemiology of melioidosis: a complex socio-ecological emerging infectious disease in the Alor Setar region of Kedah, Malaysia

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Vijayalakshmi Natesan

2010-10-01

Full Text Available Abstract Background Melioidosis, a severe and fatal infectious disease caused by Burkholderia pseudomallei, is believed to an emerging global threat. However, data on the natural history, risk factors, and geographic epidemiology of the disease are still limited. Methods We undertook a retrospective analysis of 145 confirmed cases extracted from a hospital-based Melioidosis Registry set up from 2005 in Hospital Sultanah Bahiyah, Alor Setar, Kedah state, Malaysia, in order to provide a first description of the contemporary incidence, risk factors, and clinical epidemiology of the disease in this putatively high risk region of the country. Results The incidence of melioidosis in Alor Setar is remarkably high at 16.35 per 100,000 population per year. The mean age of patients was 50.40 years, with infection varying nonlinearly with age. Males (75.2%; P 2 = 30.57, P Conclusions Melioidosis represents a complex socio-ecological public health problem in Kedah, being strongly related with age, occupation, rainfall and predisposing chronic diseases, such as diabetes mellitus. Among cases, bacteremic patients were associated with significantly high mortality despite provision of the recommended antibacterial therapy. The burden of this disease is likely to grow in this region unless better informed interventions targeted at high-risk groups and associated diseases are urgently implemented.

Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

Science.gov (United States)

Abreu, P C; Greenberg, D A; Hodge, S E

1999-09-01

Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

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

Science.gov (United States)

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

2014-01-01

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

RESULTS OF APPLYING POLYVITAMIN COMPLEX FOR CHILDREN WITH ATOPIC DERMATITIS

Directory of Open Access Journals (Sweden)

N.A. Ivanova

2007-01-01

Full Text Available The article presents findings of applying vitamin-and-mineral complex (VMC for children frequently suffering from diseases and children with atopic dermatitis. It shows that usage of VMC within a complex therapy promotes regression of subnormal vitamin provision symptoms, as well as symptoms of the core disease. This happens against heightened vitamin content in child's organism — which was proven with the test of A and E vitamins content in blood. The research has demonstrated a quite good tolerance of VMC by children suffering from atopic dermatitis.Key words: children frequently suffering from diseases, atopic dermatitis, vitamins, treatment.

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

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Valenza, Gaetano; Citi, Luca; Garcia, Ronald G.; Taylor, Jessica Noggle; Toschi, Nicola; Barbieri, Riccardo

2017-02-01

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.

Commensal intestinal bacterial strains trigger ankylosing enthesopathy of the ankle in inbred B10.BR (H-2k) male mice

Czech Academy of Sciences Publication Activity Database

Šinkorová, Z.; Čapková, Jana; Niederlová, J.; Štěpánková, Renata; Šinkora, Jiří

2008-01-01

Roč. 69, č. 12 (2008), s. 845-850 ISSN 0198-8859 R&D Projects: GA ČR GA305/03/0287 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z5020903 Keywords : Spondyloarthropathies * Ankylosing enthesopathy * Intestinal microflora Subject RIV: EC - Immunology Impact factor: 3.061, year: 2008

Minocycline HCl microspheres reduce red-complex bacteria in periodontal disease therapy.

Science.gov (United States)

Goodson, J Max; Gunsolley, John C; Grossi, Sara G; Bland, Paul S; Otomo-Corgel, Joan; Doherty, Frances; Comiskey, Judy

2007-08-01

The objective of this trial was to measure the antimicrobial effects of a minocycline HCl microsphere (MM) local drug-delivery system when used as an adjunct to scaling and root planing (SRP). DNA probe analysis for 40 bacteria was used to evaluate the oral bacteria of 127 subjects with moderate to advanced chronic periodontitis. Subjects were randomly assigned to either SRP alone (N = 65) or MM + SRP (N = 62). The primary endpoints of this study were changes in numbers and proportions of the red-complex bacteria (RCB) and the sum of Porphyromonas gingivalis, Tannerella forsythia (formally T. forsythensis), and Treponema denticola relative to 40 oral bacteria at each test site from baseline to day 30. Numbers of RCB from the five test sites were averaged to provide a value for each subject. MM + SRP reduced the proportion of RCB by 6.49% and the numbers by 9.4 x 10(5). The reduction in RCB proportions and numbers by SRP alone (5.03% and 5.1 x 10(5), respectively) was significantly less. In addition, MM + SRP reduced probing depth by 1.38 mm (compared to 1.01 mm by SRP alone), bleeding on probing was reduced by 25.2% (compared to 13.8% by SRP alone), and a clinical attachment level gain of 1.16 mm (compared to 0.80 mm by SRP alone) was achieved. These observations support the hypothesis that RCBs are responsible for periodontal disease and that local antimicrobial therapy using MM + SRP effectively reduces numbers of RCBs and their proportions to a greater extent than SRP alone.

Defects in the COG complex and COG-related trafficking regulators affect neuronal Golgi function.

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Leslie K Climer

2015-10-01

Full Text Available The Conserved Oligomeric Golgi (COG complex is an evolutionarily conserved hetero-octameric protein complex that has been proposed to organize vesicle tethering at the Golgi apparatus. Defects in seven of the eight COG subunits are linked to Congenital Disorders of Glycosylation (CDG-type II, a family of rare diseases involving misregulation of protein glycosylation, alterations in Golgi structure, variations in retrograde trafficking through the Golgi and system-wide clinical pathologies. A troublesome aspect of these diseases are the neurological pathologies such as low IQ, microcephaly and cerebellar atrophy. The essential function of the COG complex is dependent upon interactions with other components of trafficking machinery, such as Rab-GTPases and SNAREs. COG-interacting Rabs and SNAREs have been implicated in neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. Defects in Golgi maintenance disrupts trafficking and processing of essential proteins, frequently associated with and contributing to compromised neuron function and human disease. Despite the recent advances in molecular neuroscience, the subcellular bases for most neurodegenerative diseases are poorly understood. This article gives an overview of the potential contributions of the COG complex and its Rab and SNARE partners in the pathogenesis of different neurodegenerative disorders.

Ensemble Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Complex Graph Measures from Diffusion Tensor Images

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Ebadi, Ashkan; Dalboni da Rocha, Josué L.; Nagaraju, Dushyanth B.; Tovar-Moll, Fernanda; Bramati, Ivanei; Coutinho, Gabriel; Sitaram, Ranganatha; Rashidi, Parisa

2017-01-01

The human brain is a complex network of interacting regions. The gray matter regions of brain are interconnected by white matter tracts, together forming one integrative complex network. In this article, we report our investigation about the potential of applying brain connectivity patterns as an aid in diagnosing Alzheimer's disease and Mild Cognitive Impairment (MCI). We performed pattern analysis of graph theoretical measures derived from Diffusion Tensor Imaging (DTI) data representing structural brain networks of 45 subjects, consisting of 15 patients of Alzheimer's disease (AD), 15 patients of MCI, and 15 healthy subjects (CT). We considered pair-wise class combinations of subjects, defining three separate classification tasks, i.e., AD-CT, AD-MCI, and CT-MCI, and used an ensemble classification module to perform the classification tasks. Our ensemble framework with feature selection shows a promising performance with classification accuracy of 83.3% for AD vs. MCI, 80% for AD vs. CT, and 70% for MCI vs. CT. Moreover, our findings suggest that AD can be related to graph measures abnormalities at Brodmann areas in the sensorimotor cortex and piriform cortex. In this way, node redundancy coefficient and load centrality in the primary motor cortex were recognized as good indicators of AD in contrast to MCI. In general, load centrality, betweenness centrality, and closeness centrality were found to be the most relevant network measures, as they were the top identified features at different nodes. The present study can be regarded as a “proof of concept” about a procedure for the classification of MRI markers between AD dementia, MCI, and normal old individuals, due to the small and not well-defined groups of AD and MCI patients. Future studies with larger samples of subjects and more sophisticated patient exclusion criteria are necessary toward the development of a more precise technique for clinical diagnosis. PMID:28293162

COMPLEX FUNCTIONAL ASSESSMENT OF THE HIP JOINT.

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Maya S. Krastanova

2015-09-01

Full Text Available Introduction: In relation to the study reporting the effects of applying phased complex rehabilitation in patients with total hip arthroplasty, it has been concluded that the everyday clinical practice in Bulgaria does not apply complex examination, giving an objective picture about the extent of functional status of patients with trauma and diseases of the hip. Aim: The main goal of this report is to present a test which incorporates all known and routine research and in which the total number of points determines the functional status of patients with trauma and diseases of the hip. Material and Methods: Based on the Hip dysfunction and Osteoarthritis Outcome Score, the Harris Hip Score modified test, scale D’Aubigne and Postel and Iowa’s test for complex functional evaluation of the hip joint, we have developed a test including information about the degree of pain; goniometry and manual muscle testing of the hip; locomotor test – type of gait and adjuvants; test for Daily Activities of Life. The test has been developed on the basis of expert assessment by doctors and physiotherapists of the proposed indicators for evaluation and determination of the weighting factors’ contribution to the general condition of the patient. Conclusion: The developed and tested method of complex functional assessment of the hip joint enables our colleagues, dealing with trauma and diseases of the hip, to use it in various research and scientific projects, as well as in general medical practice.

Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures

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Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; García, María; Fernández, Alberto; Hornero, Roberto

2012-06-01

Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz-Mancini-Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI.

Properties and modeling of GWAS when complex disease risk is due to non-complementing, deleterious mutations in genes of large effect.

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Kevin R Thornton

Full Text Available Current genome-wide association studies (GWAS have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE. This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders, and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated.

Evaluation of obstructive airway lesions in complex congenital heart disease using composite volume-rendered images from multislice CT

International Nuclear Information System (INIS)

Choo, Ki Seok; Kim, Chang Won; Lee, Tae Hong; Kim, Suk; Kim, Kun Il; Lee, Hyoung Doo; Ban, Ji Eun; Sung, Si Chan; Chang, Yun Hee

2006-01-01

Multislice CT (MSCT) allows high-quality volume-rendered (VR) and composite volume-rendered images. To investigate the clinical usefulness of composite VR images in the evaluation of the relationship between cardiovascular structures and the airway in children with complex congenital heart disease (CHD). Four- or 16-slice MSCT scanning was performed consecutively in 77 children (mean age 6.4 months) with CHD and respiratory symptoms, a chest radiographic abnormality, or abnormal course of the pulmonary artery on ECHO. MSCT scanning was performed during breathing or after sedation. Contrast medium (2 ml/kg) was administered through a pedal venous route or arm vein in all patients. The VR technique was used to reconstruct the cardiovascular structures and airway, and then both VR images were composed using the commercial software (VoxelPlus 2 ; Daejeon, Korea). Stenoses were seen in the trachea in 1 patient and in the bronchi in 14 patients (19%). Other patients with complex CHD did not have significant airway stenoses. Composite VR images with MSCT can provide more exact airway images in relationship to the surrounding cardiovascular structures and thus help in optimizing management strategies in treating CHD. (orig.)

Integrated molecular landscape of Parkinson's disease

NARCIS (Netherlands)

Klemann, C.J.H.M.; Martens, G.J.; Sharma, M.; Martens, M.B.; Isacson, O.; Gasser, T.; Visser, J.E.; Poelmans, G.J.V.

2017-01-01

Parkinson's disease is caused by a complex interplay of genetic and environmental factors. Although a number of independent molecular pathways and processes have been associated with familial Parkinson's disease, a common mechanism underlying especially sporadic Parkinson's disease is still largely

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning.

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Witt, Karsten; Daniels, Christine; Daniel, Victoria; Schmitt-Eliassen, Julia; Volkmann, Jens; Deuschl, Günther

2006-01-01

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.

Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

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Scott B Vafai

Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

The adaptation process of mothers raising a child with complex congenital heart disease.

Science.gov (United States)

Ahn, Jeong-Ah; Lee, Sunhee

2018-01-01

Mothers of children with congenital heart disease (CHD) tend to be concerned about their child's normal life. The majority of these mothers tend to experience negative psychological problems. In this study, the adaptation process of mothers raising a child with complex CHD was investigated based on the sociocultural context of Korea. The data collection was conducted by in-depth interviews and theoretical sampling was performed until the data were saturated. The collected data were analyzed using continuous theoretical comparisons. The results of the present study showed that the core category in the mothers' adaptation process was 'anxiety regarding the future', and the mothers' adaptation process consisted of the impact phase, standing against phase, and accepting phase. In the impact phase, the participants emotionally fluctuated between 'feelings of abandonment' and 'entertaining hope'. In the standing against phase, participants tended to dedicate everything to child-rearing while being affected by 'being encouraged by support' and 'being frustrated by tasks beyond their limits'. In the accepting phase, the subjects attempted to 'accept the child as is', 'resist hard feelings', and 'share hope'. Health-care providers need to develop programs that include information regarding CHD, how to care for a child with CHD, and effective child-rearing behaviors.

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

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

2018-02-14

Commercial airplanes fly with an equivalent cabin fraction of inspired oxygen of 0.15, leading to reduced oxygen saturation (SpO 2 ) in passengers. How this affects children with complex congenital heart disease (CHD) is unknown. We conducted Hypoxic Challenge Testing (HCT) to assess need for inflight supplemental oxygen. Children aged heart rate, QT interval corrected for heart rate and partial pressure of carbon dioxide measured transcutaneously (PtcCO 2 ). A test failed when children with (1) normal baseline SpO 2 desaturated to 85%, (2) baseline SpO 2 85%-94% desaturated by 15% of baseline; and (3) baseline SpO 2 75%-84% desaturated to 70%. There were 68 children, mean age 3.3 years (range 10 weeks-14.5 years). Children with normal (n=36) baseline SpO 2 desaturated from median 99% to 91%, Pheart rate and QT interval corrected for heart rate were unaffected by the hypoxic state. This is the first evidence to help guide which children with CHD need a preflight HCT. We suggest all children with an actual or potential R-L shunt should be tested. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia

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Demircioglu, F. Esra; Sosa, Brian A.; Ingram, Jessica; Ploegh, Hidde L.; Schwartz, Thomas U.

2016-08-04

The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.

Flavonoids and Reduction of Cardiovascular Disease (CVD) in Chronic Obstructive Pulmonary Disease (COPD).

Science.gov (United States)

Russo, Patrizia; Prinzi, Giulia; Lamonaca, Palma; Cardaci, Vittorio; Fini, Massimo

2018-05-13

Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CV) often coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it is hypothesizable that treatment of cardiovascular co-morbidities may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight secondary metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point to an important effects on CVD risk prevention. This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk. Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Management of adynamic bone disease in chronic kidney disease: A brief review

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Swathi K. Sista

2016-09-01

Full Text Available The Kidney Disease: Improving Global Outcomes (KDIGO work group released recommendations in 2006 to define the bone-related pathology associated with chronic kidney disease as renal osteodystrophy. In 2009, KDIGO released revised clinical practice guidelines which redefined systemic disorders of bone and mineral metabolism due to chronic kidney disease as chronic kidney disease-mineral and bone disorders. Conditions under this overarching term include osteitis fibrosa cystica, osteomalacia, and adynamic bone disease. We aim to provide a brief review of the histopathology, pathophysiology, epidemiology, and diagnostic features of adynamic bone disease, focusing on current trends in the management of this complex bone disorder.

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

Science.gov (United States)

Bingham, Clifton O.; Moni, Malini

2015-01-01

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

The Molecular Genetics of von Willebrand Disease

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Ergül Berber

2012-12-01

Full Text Available Quantitative and/or qualitative deficiency of von Willebrand factor (vWF is associated with the most common inherited bleeding disease von Willebrand disease (vWD. vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD.

The molecular genetics of von Willebrand disease.

Science.gov (United States)

Berber, Ergül

2012-12-01

Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. None declared.

Sickle cell disease and complex congenital cardiac surgery: a case report and review of the pathophysiology and perioperative management.

Science.gov (United States)

Sanders, D B; Smith, B P; Sowell, S R; Nguyen, D H; Derby, C; Eshun, F; Nigro, J J

2014-03-01

Sickle cell anemia and thalassemia are hemoglobinopathies rarely encountered in the United States. Compounded with congenital heart disease, patients with sickle cell disease (SCD) requiring cardiopulmonary bypass and open-heart surgery represent the proverbial "needle in the haystack". As such, there is some trepidation on the part of clinicians when these patients present for complex cardiac surgery. SCD is an autosomal, recessive condition that results from a single nucleotide polymorphism in the β-globin gene. Hemoglobin SS molecules (HgbSS) with this point mutation can polymerize under the right conditions, stiffening the erythrocyte membrane and distorting the cellular structure to the characteristic sickle shape. This shape change alters cellular transit through the microvasculature. As a result, circumstances such as hypoxia, hypothermia, acidosis or diminished blood flow can lead to aggregation, vascular occlusion and thrombosis. Chronically, SCD can give rise to multiorgan damage secondary to hemolysis and vascular obstruction. This review and case study details an 11-year-old African-American male with known SCD who presented to the cardiothoracic surgical service with congenital heart disease consisting of an anomalous, intramural right coronary artery arising from the left coronary sinus for surgical consultation and subsequent surgical correction. This case report will include a review of the pathophysiology and current literature regarding preoperative, intraoperative and postoperative management of SCD patients.

AIDS dementia complex: a review

NARCIS (Netherlands)

Portegies, P.

1994-01-01

AIDS dementia complex (ADC) is a constellation of cognitive, motor, and behavioral dysfunctions frequently observed in persons with AIDS. Estimates of its prevalence vary. ADC may occur at any stage of AIDS but is usually associated with later stages of disease. Its severity varies among patients

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

NF-κB-Activating Complex Engaged in Response to EGFR Oncogene Inhibition Drives Tumor Cell Survival and Residual Disease in Lung Cancer

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Collin M. Blakely

2015-04-01

Full Text Available Although oncogene-targeted therapy often elicits profound initial tumor responses in patients, responses are generally incomplete because some tumor cells survive initial therapy as residual disease that enables eventual acquired resistance. The mechanisms underlying tumor cell adaptation and survival during initial therapy are incompletely understood. Here, through the study of EGFR mutant lung adenocarcinoma, we show that NF-κB signaling is rapidly engaged upon initial EGFR inhibitor treatment to promote tumor cell survival and residual disease. EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NF-κB-mediated transcriptional survival program. The direct NF-κB inhibitor PBS-1086 suppressed this adaptive survival program and increased the magnitude and duration of initial EGFR inhibitor response in multiple NSCLC models, including a patient-derived xenograft. These findings unveil NF-κB activation as a critical adaptive survival mechanism engaged by EGFR oncogene inhibition and provide rationale for EGFR and NF-κB co-inhibition to eliminate residual disease and enhance patient responses.

Complement Activation in Inflammatory Skin Diseases

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Jenny Giang

2018-04-01

Full Text Available The complement system is a fundamental part of the innate immune system, playing a crucial role in host defense against various pathogens, such as bacteria, viruses, and fungi. Activation of complement results in production of several molecules mediating chemotaxis, opsonization, and mast cell degranulation, which can contribute to the elimination of pathogenic organisms and inflammation. Furthermore, the complement system also has regulating properties in inflammatory and immune responses. Complement activity in diseases is rather complex and may involve both aberrant expression of complement and genetic deficiencies of complement components or regulators. The skin represents an active immune organ with complex interactions between cellular components and various mediators. Complement involvement has been associated with several skin diseases, such as psoriasis, lupus erythematosus, cutaneous vasculitis, urticaria, and bullous dermatoses. Several triggers including auto-antibodies and micro-organisms can activate complement, while on the other hand complement deficiencies can contribute to impaired immune complex clearance, leading to disease. This review provides an overview of the role of complement in inflammatory skin diseases and discusses complement factors as potential new targets for therapeutic intervention.

Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?

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Sujani Yadlapati

2016-01-01

Full Text Available Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA, primary Sjögren’s syndrome (pSS, systemic lupus erythematosus (SLE, dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.

Investigating Mycobacterium chelonae-abscessus Complex

Centers for Disease Control (CDC) Podcasts

2011-11-17

Keith Simmon, scientist at Isentio US discusses research that was done while he was at ARUP laboratories, discusses a new classification of Mycobacterium chelonae-abscessus complex.  Created: 11/17/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/22/2011.

Diseases and partial mortality in Montastraea annularis species complex in reefs with differing environmental conditions (NW Caribbean and Gulf of Mexico).

Science.gov (United States)

Jordán-Dahlgren, Eric; Maldonado, Miguel Angel; Rodríguez-Martínez, Rosa Elisa

2005-01-25

We documented the prevalence of diseases, syndromes and partial mortality in colonies of the Montastraea annularis species complex on 3 reefs, and tested the assumption that a higher prevalence of these parameters occurs when reefs are closer to point-sources of pollution. One reef was isolated from the impact of local factors with the exception of fishing, 1 potentially influenced by local industrial pollutants, and 1 influenced by local urban pollution. Two reefs were surveyed in 1996 and again in 2001 and 1 in 1998 and again in 2001. In 2001, colonies on all reefs had a high prevalence of the yellow-band syndrome and a relatively high degree of recent partial mortality, while the prevalence of black-band and white-plague diseases was low although a new sign, that we named the thin dark line, had relatively high prevalence in all reefs. As no direct relationship was found between disease prevalence and local environmental quality, our results open the possibility that regional and/or global factors may already be playing an important role in the prevalence of coral disease in the Caribbean, and contradict the theory that coral disease prevalence is primarily related to local environmental degradation. Reasons that may partially explain these findings are the high level of potential pathogen connectivity within the Caribbean as a result of its circulation patterns coupled to the large land-derived pollutants and pathogens input into this Mediterranean sea, together with the surface water warming effects which stress corals and enhance pathogen activity.

Dissecting complex phenotypes using the genomics of twins

DEFF Research Database (Denmark)

Tan, Qihua; Ohm Kyvik, Kirsten; Kruse, Torben A

2010-01-01

of human diseases. Besides, twins not only serve as ideal samples for disease gene mapping using conventional genetic markers but also represent an excellent model for associating DNA copy number variations, a structural genetic marker, with human diseases. It is believed that, with the rapid development...... in biotechniques and new advances in bioinformatics, the unique samples of twins will make new contributions to our understanding of the nature and nurture in complex disease development and in human health. This paper aims at summarizing the new uses of twins in current genetic studies and suggesting novel...

The characteristics of patients with pulmonary Mycobacterium avium-intracellulare complex disease diagnosed by bronchial lavage culture compared to those diagnosed by sputum culture.

Science.gov (United States)

Maekawa, Koichi; Naka, Megumi; Shuto, Saki; Harada, Yuka; Ikegami, Yumiko

2017-09-01

The utility of bronchoscopy for the diagnosis of pulmonary Mycobacterium avium-intracellulare complex (MAC) disease has been reported; however, which patients require bronchoscopy remains unclear. Our objective was to identify the characteristics of the patients in whom bronchoscopy is needed for the diagnosis of MAC disease. Fifty-four patients with pulmonary MAC disease were divided into two groups according to established diagnostic criteria: 39 patients were diagnosed by sputum culture and 15 patients were diagnosed by bronchial lavage culture. We analysed the differences in demographic and clinical characteristics as well as microbiological and radiological data between the two groups. There were no significant differences in age, sex, smoking status, MAC species, underlying diseases, or steroid use. Significantly more patients diagnosed by sputum culture than bronchial lavage culture had a positive sputum smear for acid-fast bacilli (79.5% vs. 0.0%, respectively; p disease, bronchiectasis, and cavities. However, more patients diagnosed by sputum culture than bronchial lavage culture had abnormalities in the left upper division (48.7% vs. 13.3%, respectively; p = 0.017) and higher numbers of affected lobes (4.3 ± 1.4 vs. 3.3 ± 1.6, respectively; p = 0.034). If patients suspected of having pulmonary MAC disease have a negative sputum smear, no symptoms, no abnormal findings in the left upper division, or fewer affected lobes on computed tomography, bronchoscopy might be needed for the diagnosis. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Fourier analysis of multi-gated cardiac blood-pool data in patients with congenital heart diseases, (2). Assessment of diseases with complex cardiac anomalies, especially tetralogy of Fallot

Energy Technology Data Exchange (ETDEWEB)

Takeda, Kan; Maeda, Hisato; Yamaguchi, Nobuo; Nakamura, Kazuyoshi; Matsumura, Kaname; Nakagawa, Tsuyoshi; Sakurai, Minoru; Aoki, Kenzo

1985-04-01

The clinical usefulness of Fourier analysis of multi-gated cardiac blood-pool data was evaluated in 18 subjects with normal cardiac functions and 14 patients with complex cardiac anomalies (ten with tetralogy of Fallot, two with tricuspid atresia (TA), one with double-outlet right ventricle (DORV), and one with Ebstein's anomaly (EA)). Using global ventricular time-activity curves, the phase and amplitude at fundamental frequency were calculated, and emptying patterns of the left and right ventricles (LV, RV) were evaluated by phase difference (D(phase)=RV phase minus LV phase) and amplitude ratio of RV to LV (R(amp)). In patients with TOF, mean values of D (phase) and R(amp) were 25.3 +- 10.5 degrees and 13.5 +- 0.49 respectively and significantly larger than those of normal subjects. D (phase) became larger in inverse proportion to the ratio of pulmonary-to-systemic blood flow and there was an inverse linear correlation between these two variables. On visual interpretation of functional images, the dynamic property of hypoplastic ventricles could be easily estimated in patients with TA or DORV. In a case with EA, the atrialized RV was shown clearly as a hypokinetic, atrial phase area. This method is valuable for pathophysiologic investigation of diseases with complex cardiac anomalies. (author).

Protein complexes and cholesterol in the control of late endosomal dynamicsCholesterol and multi-protein complexes in the control of late endosomal dynamics

NARCIS (Netherlands)

Kant, Rik Henricus Nicolaas van der

2013-01-01

Late endosomal transport is disrupted in several diseases such as Niemann-Pick type C, ARC syndrome and Alzheimer’s disease. This thesis describes the regulation of late endosomal dynamics by cholesterol and multi-protein complexes. We find that cholesterol acts as a cellular tomtom that steers the

Physico-Chemical and In-vitro Microbial Studies of Newly Synthesis Organometallic Complexes

Directory of Open Access Journals (Sweden)

Isam Hussain Al-Karkhi

2014-05-01

Full Text Available Drugs normally synthesized to use as medication to treat diseases like cancer and microbial infections, these synthesized drugs were interested more than naturally-derived drugs which have been shows low activity or not as efficient against diseases. A new ligand 3-methylbenzyl (2Z-2-[1-(pyridin-4-ylethylidene]hydrazine carbodithioate (PE3MBC and its Cd(II, Cu(II, Co(II and Zn(II metal complexes. The new ligand and metal complexes were characterized via various physico-chemical and spectroscopic techniques. Cd(II complex show more activity against microbes and against cancer cell line MCF-7, while other complexes does not shows activity like cadmium complex, all the complexes does not shows any activity against MDAMB-231 cell line. The fatal of the cancer and the microbes cell was due to inhibition of DNA synthesis which was probably due to chelating with metals complexes, or could be referred to lipophilicity, presence of hydrophobic moiety in the complex molecule, also could be due to steric effects and electronic effects.

Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata.

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Fernando A Monteiro

Full Text Available BACKGROUND: Triatoma dimidiata is among the main vectors of Chagas disease in Latin America. However, and despite important advances, there is no consensus about the taxonomic status of phenotypically divergent T. dimidiata populations, which in most recent papers are regarded as subspecies. METHODOLOGY AND FINDINGS: A total of 126 cyt b sequences (621 bp long were produced for specimens from across the species range. Forty-seven selected specimens representing the main cyt b clades observed (after a preliminary phylogenetic analysis were also sequenced for an ND4 fragment (554 bp long and concatenated with their respective cyt b sequences to produce a combined data set totalling 1175 bp/individual. Bayesian and Maximum-Likelihood phylogenetic analyses of both data sets (cyt b, and cyt b+ND4 disclosed four strongly divergent (all pairwise Kimura 2-parameter distances >0.08, monophyletic groups: Group I occurs from Southern Mexico through Central America into Colombia, with Ecuadorian specimens resembling Nicaraguan material; Group II includes samples from Western-Southwestern Mexico; Group III comprises specimens from the Yucatán peninsula; and Group IV consists of sylvatic samples from Belize. The closely-related, yet formally recognized species T. hegneri from the island of Cozumel falls within the divergence range of the T. dimidiata populations studied. CONCLUSIONS: We propose that Groups I-IV, as well as T. hegneri, should be regarded as separate species. In the Petén of Guatemala, representatives of Groups I, II, and III occur in sympatry; the absence of haplotypes with intermediate genetic distances, as shown by multimodal mismatch distribution plots, clearly indicates that reproductive barriers actively promote within-group cohesion. Some sylvatic specimens from Belize belong to a different species - likely the basal lineage of the T. dimidiata complex, originated ~8.25 Mya. The evidence presented here strongly supports the proposition

Spinal cord: motor neuron diseases.

Science.gov (United States)

Rezania, Kourosh; Roos, Raymond P

2013-02-01

Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

Integrative Genomic Analysis of Complex traits

DEFF Research Database (Denmark)

Ehsani, Ali Reza

In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... expression, and metabolite abundance of more and more populations in a multitude of invironments. However, a solid model for including all of this complex information in one analysis, to disentangle genetic variation and the underlying genetic architecture of complex traits and diseases, has not yet been...

Regulation of gamma-Secretase in Alzheimer's Disease

Energy Technology Data Exchange (ETDEWEB)

Zhou, Shuxia; Zhou, Hua; Walian, Peter; Jap, Bing

2007-02-07

The {gamma}-secretase complex is an intramembrane aspartyl protease that cleaves its substrates along their transmembrane regions. Sequential proteolytic processing of amyloid precursor protein by {beta}- and {gamma}-secretase produces amyloid {beta}-peptides, which are the major components of amyloid plaques in the brains of Alzheimer's disease patients. The {gamma}-secretase complex is therefore believed to be critical in the pathogenesis of Alzheimer's disease. Here we review the range of factors found to affect the nature and degree of {gamma}-secretase complex activity; these include {gamma}-secretase complex assembly and activation, the integral regulatory subunit CD147, transient or weak binding partners, the levels of cholesterol and sphingolipids in cell membranes, and inflammatory cytokines. Integrated knowledge of the molecular mechanisms supporting the actions of these factors is expected to lead to a comprehensive understanding of the functional regulation of the {gamma}-secretase complex, and this, in turn, should facilitate the development of novel therapeutic strategies for the treatment of Alzheimer's disease.

Mad Cow Disease

Indian Academy of Sciences (India)

Mad Cow Disease, or bovine spongiform encephalopathy (BSE) is one of ... humoral immunity is developed against such infections. ... Most infecti ve agents, ranging from the more complex protozoans to bacteri(! and viruses, contain nucleic.

Presymptomatic detection of Parkinson's disease.

Science.gov (United States)

Jenner, P

1993-01-01

Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.

Getting an Insight into the Complexity of Major Chronic Inflammatory and Degenerative Diseases: A Potential New Systemic Approach to Their Treatment.

Science.gov (United States)

Biava, Pier M; Norbiato, Guido

2015-01-01

As the modern society is troubled by multi-factorial diseases, research has been conducted on complex realities including chronic inflammation, cancer, obesity, HIV infection, metabolic syndrome and its detrimental cardiovascular complications as well as depression and other brain disorders. Deterioration of crucial homeostatic mechanisms in such diseases invariably results in activation of inflammatory mediators, chronic inflammation, loss in immunological function, increased susceptibility to diseases, alteration of metabolism, decrease of energy production and neuro-cognitive decline. Regulation of genes expression by epigenetic code is the dominant mechanism for the transduction of environmental inputs, such as stress and inflammation to lasting physiological changes. Acute and chronic stress determines DNA methylation and histone modifications in brain regions which may contribute to neuro-degenerative disorders. Nuclear glucocorticoids receptor interacts with the epigenoma resulting in a cortisol resistance status associated with a deterioration of the metabolic and immune functions. Gonadal steroids receptors have a similar capacity to produce epigenomic reorganization of chromatine structure. Epigenomic-induced reduction in immune cells telomeres length has been observed in many degenerative diseases, including all types of cancer. The final result of these epigenetic alterations is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In this study, we propose a treatment with stem cells differentiation stage factors taken from zebrafish embryos which are able to regulate the genes expression of normal and pathological stem cells in a different specific way.

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

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Chris Wallace

2015-06-01

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

[Alzheimer's disease cerebro-spinal fluid biomarkers: A clinical research tool sometimes useful in daily clinical practice of memory clinics for the diagnosis of complex cases].

Science.gov (United States)

Magnin, E; Dumurgier, J; Bouaziz-Amar, E; Bombois, S; Wallon, D; Gabelle, A; Lehmann, S; Blanc, F; Bousiges, O; Hannequin, D; Jung, B; Miguet-Alfonsi, C; Quillard, M; Pasquier, F; Peoc'h, K; Laplanche, J-L; Hugon, J; Paquet, C

2017-04-01

The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Hyperparathyroidism in chronic kidney disease: complexities within the commonplace.

Science.gov (United States)

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

2012-08-01

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

Invasive Aspergillus niger complex infections in a Belgian tertiary care hospital.

Science.gov (United States)

Vermeulen, E; Maertens, J; Meersseman, P; Saegeman, V; Dupont, L; Lagrou, K

2014-05-01

The incidence of invasive infections caused by the Aspergillus niger species complex was 0.043 cases/10 000 patient-days in a Belgian university hospital (2005-2011). Molecular typing was performed on six available A. niger complex isolates involved in invasive disease from 2010 to 2011, revealing A. tubingensis, which has higher triazole minimal inhibitory concentrations, in five out of six cases. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Biodiversity and disease: a synthesis of ecological perspectives on Lyme disease transmission.

Science.gov (United States)

Wood, Chelsea L.; Lafferty, Kevin D.

2013-01-01

Recent reviews have argued that disease control is among the ecosystem services yielded by biodiversity. Lyme disease (LD) is commonly cited as the best example of the ‘diluting’ effect of biodiversity on disease transmission, but many studies document the opposite relationship, showing that human LD risk can increase with forestation. Here, we unify these divergent perspectives and find strong evidence for a positive link between biodiversity and LD at broad spatial scales (urban to suburban to rural) and equivocal evidence for a negative link between biodiversity and LD at varying levels of biodiversity within forests. This finding suggests that, across zoonotic disease agents, the biodiversity–disease relationship is scale dependent and complex.

Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension.

OpenAIRE

Smithies, O; Maeda, N

1995-01-01

Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These di...

Polyelectrolyte Complex Optimization for Macrophage Delivery of Redox Enzyme Nanoparticles

Science.gov (United States)

Zhao, Yuling; Haney, Matthew J.; Klyachko, Natalia L.; Li, Shu; Booth, Stephanie L.; Higginbotham, Sheila M.; Jones, Jocelyn; Zimmerman, Matthew C.; Mosley, R. Lee; Kabanov, Alexander V.; Gendelman, Howard E.; Batrakova, Elena V.

2011-01-01

Background We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration induced during Parkinson’s disease. Our prior work demonstrated that macrophages loaded with nanoformulated catalase (“nanozyme”) protect the nigrostriatum in a murine model of Parkinson’s disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymers protects the enzyme degradation in macrophages. Methods We examined relationships between the composition and structure of block ionomer complexes, their physicochemical characteristics, and loadings, release rates, and catalase activity in bone marrow-derived macrophages. Results Formation of block-ionomer complexes resulted in improved aggregation stability. Block ionomer complexes with ε-polylisine, and poly-L-glutamic acid -poly(ethylene glycol) demonstrated the least cytotoxicity and high loading and release rates, however, did not efficiently protect catalase inside macrophages. Conclusion nanozymes with polyethyleneimine- and poly(L-lysine)10-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery. PMID:21182416

Transcription regulation by the Mediator complex.

Science.gov (United States)

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

Physiology and pathogenesis of gastroesophageal reflux disease.

Science.gov (United States)

Mikami, Dean J; Murayama, Kenric M

2015-06-01

Gastroesophageal reflux disease (GERD) is one of the most common problems treated by primary care physicians. Almost 20% of the population in the United States experiences occasional regurgitation, heartburn, or retrosternal pain because of GERD. Reflux disease is complex, and the physiology and pathogenesis are still incompletely understood. However, abnormalities of any one or a combination of the three physiologic processes, namely, esophageal motility, lower esophageal sphincter function, and gastric motility or emptying, can lead to GERD. There are many diagnostic and therapeutic approaches to GERD today, but more studies are needed to better understand this complex disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnosis of Alzheimer’s Disease Using Dual-Tree Complex Wavelet Transform, PCA, and Feed-Forward Neural Network

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Debesh Jha

2017-01-01

Full Text Available Background. Error-free diagnosis of Alzheimer’s disease (AD from healthy control (HC patients at an early stage of the disease is a major concern, because information about the condition’s severity and developmental risks present allows AD sufferer to take precautionary measures before irreversible brain damage occurs. Recently, there has been great interest in computer-aided diagnosis in magnetic resonance image (MRI classification. However, distinguishing between Alzheimer’s brain data and healthy brain data in older adults (age > 60 is challenging because of their highly similar brain patterns and image intensities. Recently, cutting-edge feature extraction technologies have found extensive application in numerous fields, including medical image analysis. Here, we propose a dual-tree complex wavelet transform (DTCWT for extracting features from an image. The dimensionality of feature vector is reduced by using principal component analysis (PCA. The reduced feature vector is sent to feed-forward neural network (FNN to distinguish AD and HC from the input MR images. These proposed and implemented pipelines, which demonstrate improvements in classification output when compared to that of recent studies, resulted in high and reproducible accuracy rates of 90.06 ± 0.01% with a sensitivity of 92.00 ± 0.04%, a specificity of 87.78 ± 0.04%, and a precision of 89.6 ± 0.03% with 10-fold cross-validation.

Learning radiological appearances of diseases: Does comparison help?

NARCIS (Netherlands)

Kok, Ellen M.; de Bruin, Anique B H; Robben, Simon C. F.; van Merrienboer, Jeroen J. G.

Comparison learning is a promising approach for learning complex real-life visual tasks. When medical students study radiological appearances of diseases, comparison of images showing diseases with images showing no abnormalities could help them learn to discriminate relevant, disease-related

A simple method for determining polymeric IgA-containing immune complexes.

Science.gov (United States)

Sancho, J; Egido, J; González, E

1983-06-10

A simplified assay to measure polymeric IgA-immune complexes in biological fluids is described. The assay is based upon the specific binding of a secretory component for polymeric IgA. In the first step, multimeric IgA (monomeric and polymeric) immune complexes are determined by the standard Raji cell assay. Secondly, labeled secretory component added to the assay is bound to polymeric IgA-immune complexes previously fixed to Raji cells, but not to monomeric IgA immune complexes. To avoid false positives due to possible complement-fixing IgM immune complexes, prior IgM immunoadsorption is performed. Using anti-IgM antiserum coupled to CNBr-activated Sepharose 4B this step is not time-consuming. Polymeric IgA has a low affinity constant and binds weakly to Raji cells, as Scatchard analysis of the data shows. Thus, polymeric IgA immune complexes do not bind to Raji cells directly through Fc receptors, but through complement breakdown products, as with IgG-immune complexes. Using this method, we have been successful in detecting specific polymeric-IgA immune complexes in patients with IgA nephropathy (Berger's disease) and alcoholic liver disease, as well as in normal subjects after meals of high protein content. This new, simple, rapid and reproducible assay might help to study the physiopathological role of polymeric IgA immune complexes in humans and animals.

The Microbiota Regulates Immunity and Immunologic Diseases in Dogs and Cats.

Science.gov (United States)

Tizard, Ian R; Jones, Sydney W

2018-03-01

The complex commensal microbiota found on body surfaces controls immune responses and the development of allergic and inflammatory diseases. New genetic technologies permit investigators to determine the composition of the complex microbial populations found on these surfaces. Changes in the microbiota (dysbiosis) as a result of antibiotic use, diet, or other factors thus influence the development of many diseases in the dog and cat. The most important of these include chronic gastrointestinal disease; respiratory allergies, such as asthma; skin diseases, especially atopic dermatitis; and some autoimmune diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System.

Science.gov (United States)

Andres, Daniela S; Darbin, Olivier

2018-01-01

The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

Science.gov (United States)

Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

2014-01-01

Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic

Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

Directory of Open Access Journals (Sweden)

Shripad A

2003-01-01

Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

Lateralisation in Parkinson disease

DEFF Research Database (Denmark)

Riederer, P.; Jellinger, K. A.; Kolber, P.

2018-01-01

Asymmetry of dopaminergic neurodegeneration and subsequent lateralisation of motor symptoms are distinctive features of Parkinson’s disease compared to other forms of neurodegenerative or symptomatic parkinsonism. Even 200 years after the first description of the disease, the underlying causes...... for this striking clinicopathological feature are not yet fully understood. There is increasing evidence that lateralisation of disease is due to a complex interplay of hereditary and environmental factors that are reflected not only in the concept of dominant hemispheres and handedness but also in specific...

Cobalt (III) complexes as novel matrix metalloproteinase-9 inhibitors

International Nuclear Information System (INIS)

Lee, Jiyoun

2012-01-01

We have synthesized a series of novel MMP-9 inhibitors containing cobalt(III) complexes. The synthesized cobalt(III) complexes are effective as enzyme inhibitors and the attachment of a biphenyl group enhanced the efficiency of enzyme inhibition up to 6-fold. When compared to the reported non-hydroxamate MMP inhibitors, the synthesized complexes showed comparable in vitro potency. The enzyme assay showed that the cobalt(III) complex can disrupt the zinc binding active site of MMP-9 and is proposed to work via a ligand exchange mechanism. Since histidine residues are essential for the catalytic activity of a large percentage of enzymes and zinc finger proteins, these cobalt(III) complexes can serve as a prototype inhibitor towards various zinc containing enzymes and proteins. Matrix metalloproteinases (MMPs) are a family of zinc binding endopeptidases that play crucial roles in various physiological processes and diseases such as embryogenic growth, angiogenesis, arthritis, skin ulceration, liver fibrosis and tumor metastasis. Because of their implications in a wide range of diseases, MMPs are considered as intriguing drug targets. The majority of MMP inhibitors are organic small molecules containing a hydroxamate functionality for the zinc binding group. This hydroxamate group binds to a zinc(II) center in a bidentate fashion and creates a distorted trigonal bipyramidal geometry

Cobalt (III) complexes as novel matrix metalloproteinase-9 inhibitors

Energy Technology Data Exchange (ETDEWEB)

Lee, Jiyoun [Sungshin Women' s Univ., Seoul (Korea, Republic of)

2012-04-15

We have synthesized a series of novel MMP-9 inhibitors containing cobalt(III) complexes. The synthesized cobalt(III) complexes are effective as enzyme inhibitors and the attachment of a biphenyl group enhanced the efficiency of enzyme inhibition up to 6-fold. When compared to the reported non-hydroxamate MMP inhibitors, the synthesized complexes showed comparable in vitro potency. The enzyme assay showed that the cobalt(III) complex can disrupt the zinc binding active site of MMP-9 and is proposed to work via a ligand exchange mechanism. Since histidine residues are essential for the catalytic activity of a large percentage of enzymes and zinc finger proteins, these cobalt(III) complexes can serve as a prototype inhibitor towards various zinc containing enzymes and proteins. Matrix metalloproteinases (MMPs) are a family of zinc binding endopeptidases that play crucial roles in various physiological processes and diseases such as embryogenic growth, angiogenesis, arthritis, skin ulceration, liver fibrosis and tumor metastasis. Because of their implications in a wide range of diseases, MMPs are considered as intriguing drug targets. The majority of MMP inhibitors are organic small molecules containing a hydroxamate functionality for the zinc binding group. This hydroxamate group binds to a zinc(II) center in a bidentate fashion and creates a distorted trigonal bipyramidal geometry.

VHL type 2B mutations retain VBC complex form and function.

Directory of Open Access Journals (Sweden)

Kathryn E Hacker

Full Text Available von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1alpha and HIF-2alpha, resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease.This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1alpha.Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.

Complexity and Health Coaching: Synergies in Nursing

Directory of Open Access Journals (Sweden)

Gail J. Mitchell

2013-01-01

Full Text Available Health care professionals are increasingly aware that persons are complex and live in relation with other complex human communities and broader systems. Complex beings and systems are living and evolving in nonlinear ways through a process of mutual influence. Traditional standardized approaches in chronic disease management do not address these non-linear linkages and the meaning and changes that impact day-to-day life and caring for self and family. The RN health coach role described in this paper addresses the complexities and ambiguities for persons living with chronic illness in order to provide person-centered care and support that are unique and responsive to the context of persons’ lives. Informed by complexity thinking and relational inquiry, the RN health coach is an emergent innovation of creative action with community and groups that support persons as they shape their health and patterns of living.

The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

Energy Technology Data Exchange (ETDEWEB)

Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

2007-12-01

The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

Library of molecular associations: curating the complex molecular basis of liver diseases

Directory of Open Access Journals (Sweden)

Maass Thorsten

2010-03-01

Full Text Available Abstract Background Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. Results We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Conclusion Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

Genetics Home Reference: autoimmune Addison disease

Science.gov (United States)

... common in particular ethnic groups? Genetic Changes The cause of autoimmune Addison disease is complex and not completely understood. A combination ... is not caused by an autoimmune reaction. Other causes include infections that ... adrenal glands. Addison disease can also be one of several features of ...

From DNA to RNA to disease and back: The 'central dogma' of regulatory disease variation

Directory of Open Access Journals (Sweden)

Stranger Barbara E

2006-06-01

Full Text Available Abstract Much of the focus of human disease genetics is directed towards identifying nucleotide variants that contribute to disease phenotypes. This is a complex problem, often involving contributions from multiple loci and their interactions, as well as effects due to environmental factors. Although some diseases with a genetic basis are caused by nucleotide changes that alter an amino acid sequence, in other cases, disease risk is associated with altered gene regulation. This paper focuses on how studies of gene expression variation might complement disease studies and provide crucial links between genotype and phenotype.

Caenorhabditis elegans expressing the Saccharomyces cerevisiae NADH alternative dehydrogenase Ndi1p, as a tool to identify new genes involved in complex I related diseases

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Raynald eCossard

2015-06-01

Full Text Available Isolated complex I deficiencies are one of the most commonly observed biochemical features in patients suffering from mitochondrial disorders. In the majority of these clinical cases the molecular bases of the diseases remain unknown suggesting the involvement of unidentified factors that are critical for complex I function.The Saccharomyces cerevisiae NDI1 gene, encoding the mitochondrial internal NADH dehydrogenase was previously shown to complement a complex I deficient strain in Caenorhabitis elegans with notable improvements in reproduction, whole organism respiration. These features indicate that Ndi1p can functionally integrate the respiratory chain, allowing complex I deficiency complementation. Taking into account the Ndi1p ability to bypass complex I, we evaluate the possibility to extend the range of defects/mutations causing complex I deficiencies that can be alleviated by NDI1 expression.We report here that NDI1 expressing animals unexpectedly exhibit a slightly shortened lifespan, a reduction in the progeny and a depletion of the mitochondrial genome. However, Ndi1p is expressed and targeted to the mitochondria as a functional protein that confers rotenone resistance to those animals and without affecting their respiration rate and ATP content.We show that the severe embryonic lethality level caused by the RNAi knockdowns of complex I structural subunit encoding genes (e.g. NDUFV1, NDUFS1, NDUFS6, NDUFS8 or GRIM-19 human orthologs in wild type animals is significantly reduced in the Ndi1p expressing worm.All together these results open up the perspective to identify new genes involved in complex I function, assembly or regulation by screening an RNAi library of genes leading to embryonic lethality that should be rescued by NDI1 expression.

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

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

2017-01-01

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

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

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

Radiodiagnosis of diseases of the small intestine

International Nuclear Information System (INIS)

Anon.

1987-01-01

Roentgenological image of diseases, development anomalies, various diseases of the small intestine is presented. Roentgenological semiotics of chronic enterocolotis, absorption failure syndrome, Crohn's disease, tuberculosis, abdominal actinomycosis, carcenoid, benign tumors, small intestine cancer, is given. To state final correct diagnosis a complex investigation, comprising angiography, computer tomography and ultrasound diagnosis, is necessary

Technology in Parkinson's disease: Challenges and opportunities

NARCIS (Netherlands)

Espay, A.J.; Bonato, P.; Nahab, F.B.; Maetzler, W.; Dean, J.M.; Klucken, J.; Eskofier, B.M.; Merola, A.; Horak, F.; Lang, A.E.; Reilmann, R.; Giuffrida, J.; Nieuwboer, A.; Horne, M.; Little, M.A.; Litvan, I.; Simuni, T.; Dorsey, E.R.; Burack, M.A.; Kubota, K.; Kamondi, A.; Godinho, C.; Daneault, J.F.; Mitsi, G.; Krinke, L.; Hausdorff, J.M.; Bloem, B.R.; Papapetropoulos, S.

2016-01-01

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy

Methylation-regulated decommissioning of multimeric PP2A complexes

Energy Technology Data Exchange (ETDEWEB)

Wu, Cheng-Guo; Zheng, Aiping; Jiang, Li; Rowse, Michael; Stanevich, Vitali; Chen, Hui; Li, Yitong; Satyshur, Kenneth A.; Johnson, Benjamin; Gu, Ting-Jia; Liu, Zuojia; Xing, Yongna

2017-12-01

Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivation of mutant PP2A. Strikingly, TIPRL and the latency chaperone, α4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.

Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells.

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Yang, Chunbo; Al-Aama, Jumana; Stojkovic, Miodrag; Keavney, Bernard; Trafford, Andrew; Lako, Majlinda; Armstrong, Lyle

2015-09-01

Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient-specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC-based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC-derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC-derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC-derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC-based disease modeling. © AlphaMed Press.

Patient-related factors influencing detectability of coronary arteries in 320-row CT angiography in infants with complex congenital heart disease.

Science.gov (United States)

Yamasaki, Yuzo; Kawanami, Satoshi; Kamitani, Takeshi; Sagiyama, Koji; Shin, Seitaro; Hino, Takuya; Nagata, Hazumu; Yabuuchi, Hidetake; Nagao, Michinobu; Honda, Hiroshi

2018-05-05

To investigate the performance of second-generation 320-row computed tomographic (CT) angiography (CTA) in detecting coronary arteries and identify factors influencing visibility of the coronary arteries in infants with complex congenital heart disease (CHD). Data of 60 infants (aged 0-2 years, median 2 months) with complex CHD who underwent examination using 320-row CTA with low-dose prospective electrocardiogram-triggered volume target scanning were reviewed. The coronary arteries of each infant were assessed using a 0-4-point scoring system based on the number of coronary segments with a visible course. Clinical parameters, the CT value in the ascending aorta, image noise, and the radiation dose were subjected to univariate and multivariate analyses. The mean coronary score for all examinations was 2.6 ± 1.5 points. The mean attenuation in the ascending aorta was 306.7 ± 66.2 HU and the mean standard deviation was 21.7 ± 4.4. The mean effective radiation dose was 1.27 ± 0.39 mSv. Multivariate regression analysis showed significant correlations between coronary score and body weight (p < 0.05) and between coronary score and the CT value in the ascending aorta (p < 0.02). Second-generation 320-row CTA with prospective electrocardiogram-triggered volume target scanning and hybrid iterative reconstruction allows good visibility of the coronary arteries in infants with complex CHD. Body weight and the CT value in the ascending aorta are important factors influencing the visibility of the coronary arteries in infants.

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

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

2016-05-13

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

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

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

2016-02-01

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

The reliability and validity of a Venezuelan version of the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

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Rauseo Vera, Mayra; Gutiérrez-González, Luis Arturo; Maldonado, Irama; Al Snih, Soham

2017-09-21

Spondyloarthropathies (SpA) are disabling diseases with a prevalence of 1.9% in the general population. The indices designed for monitoring the disease should be valid, reliable and cross-culturally adapted for decision-making concerning the appropriate treatment. Changing an adjective or pronoun in a self-administered questionnaire could be the big difference in condensing an idea in a few words and transmitting that concept to all those who share the same language. To develop a Venezuelan version of the original English version of the BASDAI/BASFI and to evaluate its reliability and validity in Venezuelan patients with SpA. Certified linguists were needed for the translation of a Venezuelan version of the BASDAI/BASFI. The evaluation of reliability and validity was performed by calculating correlation coefficients in addition to Cronbach's alpha correlation between the BASDAI score and the clinical parameters (for example: erythrocyte sedimentation rate, C-reactive protein, modified Schöber test, occiput-to-wall distance and enthesis count). We studied 40 patients including 31 men (77.5%) and 9 women (22.5%). The mean age was 35.9 years ± standard deviation (SD) 12.01 and the disease duration was 11.5 years (± SD 9.5). The most common diagnoses were undifferentiated spondyloarthritis (45%), ankylosing spondylitis (27.5%) and psoriatic arthritis (20%). The incidences of reactive arthritis, ankylosing spondylitis and juvenile Reiter's syndrome were 2.5% each. The test-retest reliability of the BASDAI and BASFI was high (R = 0.99 and 0.99, respectively; P<.0001). The internal consistency for the BASDAI was high (Cronbach's alpha = 0.88; P=.002) and the intraclass correlation coefficient for internal consistency: 0.9867 (P=.001). Internal consistency for the BASFI: Cronbach's alpha = 0.7985 (P=.002), intraclass correlation coefficient for internal consistency: 0.9055 (P=.001). Construct validity of the BASDAI was high for general well-being of the patient (R = 0

COMPLEX APPROACHES TO TREATMENT OF DYSLIPIDEMIA IN PATIENTS WITH ISHEMIC HEART DISEASE

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M. A. Chichkova

2015-01-01

Full Text Available The risk of coronary heart disease increases significantly with an increase in blood cholesterol and low density lipoprotein (LDL. We know that is not always standard therapy fails to achieve target numbers of blood lipids in patients with coronary artery disease. We examined 100 patients with coronary heart disease (CHD: stable angina II-III functional — study group (60 patients and control group (40 patients. The studies we have obtained evidence that the combination of plasmapheresis, ultraviolet blood irradiation and statins to reduce total cholesterol in patients IIFK 2,7% IIIFK 23,3%, LDL cholesterol in patients IIFK 30,4%, IIIFK 37,3% (r<0,05. Following the combination therapy achieved level of hyperlipidemia can be maintained with lower doses of statins.

Pathogenic Cascades in Lysosomal Disease – Why so Complex?

OpenAIRE

Walkley, Steven U.

2009-01-01

Lysosomal disease represents a large group of more than 50 clinically recognized conditions resulting from inborn errors of metabolism affecting the organelle known as the lysosome.The lysosome is an integral part of the larger endosomal/lysosomal system, and is closely allied with the ubiquitin-proteosomal and autophagosomal systems, which together comprise essential cell machinery for substrate degradation and recycling, homeostatic control, as well as signaling. More than two-thirds of lys...

Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection

DEFF Research Database (Denmark)

Bélard, Erika; Semb, Synne; Ruhwald, Morten

2011-01-01

(TST). METHODS: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44). RESULTS: QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54....../238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had =1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone.......0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P negative effect was found for long...

Marine oils: Complex, confusing, confounded?

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Benjamin B. Albert

2016-09-01

Full Text Available Marine oils gained prominence following the report that Greenland Inuits who consumed a high-fat diet rich in long-chain n-3 polyunsaturated fatty acids (PUFAs also had low rates of cardiovascular disease. Marine n-3 PUFAs have since become a billion dollar industry, which will continue to grow based on current trends. However, recent systematic reviews question the health benefits of marine oil supplements, particularly in the prevention of cardiovascular disease. Marine oils constitute an extremely complex dietary intervention for a number of reasons: i the many chemical compounds they contain; ii the many biological processes affected by n-3 PUFAs; iii their tendency to deteriorate and form potentially toxic primary and secondary oxidation products; and iv inaccuracy in the labelling of consumer products. These complexities may confound the clinical literature, limiting the ability to make substantive conclusions for some key health outcomes. Thus, there is a pressing need for clinical trials using marine oils whose composition has been independently verified and demonstrated to be minimally oxidised. Without such data, it is premature to conclude that n-3 PUFA rich supplements are ineffective.

Multimorbidity Patterns in the Elderly: A New Approach of Disease Clustering Identifies Complex Interrelations between Chronic Conditions

Science.gov (United States)

Schäfer, Ingmar; von Leitner, Eike-Christin; Schön, Gerhard; Koller, Daniela; Hansen, Heike; Kolonko, Tina; Kaduszkiewicz, Hanna; Wegscheider, Karl; Glaeske, Gerd; van den Bussche, Hendrik

2010-01-01

Objective Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients' quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. Methods Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence ≥ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. Results Three multimorbidity patterns were found: 1) cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2) anxiety/depression/somatoform disorders and pain [34%; 22%], and 3) neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively) and the factors explained a large part of the variance (cumulative percent: 78% and 75%, respectively). The patterns were largely age-dependent and overlapped in a sizeable part of the population. Altogether 50% of female and 48% of male persons were assigned to at least one of the three multimorbidity patterns. Conclusion This study shows that statistically significant co-occurrence of chronic diseases can be subsumed in three prevalent multimorbidity patterns if accounting for the fact that different multimorbidity patterns share some diagnosis groups, influence each other and overlap in a large part of the population. In recognizing the full complexity of

Multimorbidity patterns in the elderly: a new approach of disease clustering identifies complex interrelations between chronic conditions.

Directory of Open Access Journals (Sweden)

Ingmar Schäfer

Full Text Available OBJECTIVE: Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients' quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. METHODS: Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence ≥ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. RESULTS: Three multimorbidity patterns were found: 1 cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2 anxiety/depression/somatoform disorders and pain [34%; 22%], and 3 neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively and the factors explained a large part of the variance (cumulative percent: 78% and 75%, respectively. The patterns were largely age-dependent and overlapped in a sizeable part of the population. Altogether 50% of female and 48% of male persons were assigned to at least one of the three multimorbidity patterns. CONCLUSION: This study shows that statistically significant co-occurrence of chronic diseases can be subsumed in three prevalent multimorbidity patterns if accounting for the fact that different multimorbidity patterns share some diagnosis groups, influence each other and overlap in a large part of the population. In recognizing the

[Laser therapy and famotidine in complex restorative treatment of primary chronic gastroduodenitis].

Science.gov (United States)

Filimonov, R M; Musaeva, O M

2003-01-01

Primary chronic gastroduodenitis (PCG) is one of the most frequent diseases of the gastrointestinal tract. Timely and efficient treatment of patients with PCG promotes ulcer prevention. In this connection, an urgent problem of restorative medicine is to develop medical programs with active introduction of pharmacophysiotherapeutic complexes, in particular, laser therapy and anti-secretory preparation (famotidine) that increase therapeutic efficacy of treatment of this disease. To this end, we give results of treatment of 50 patients with primary chronic gastroduodenitis (26 having undergone laser therapy only, and 24 having had a combination of laser therapy and famotidine), which demonstrated that the complex action method has a more adequate effect on pathogenetic components in this disease than monotherapy.

A Complex Interplay: Cognitive Behavioural Therapy for Severe Health Anxiety in Addison's Disease to Reduce Emergency Department Admissions.

Science.gov (United States)

Daniels, Jo; Sheils, Elizabeth

2017-07-01

Addison's disease (AD) is a rare chronic illness caused by adrenocortical insufficiency. Due to the pivotal role of the regulating hormone cortisol in AD, there is a common symptom overlap between the presentation of anxiety and adrenal crisis. Previous literature has identified the prevalence of anxiety in endocrinological disorders, however there is a paucity of research examining the complex interplay between AD and anxiety. This paper describes a single case study of a patient with severe health anxiety and co-morbid AD. The aims of the study were to establish if standard cognitive behavioural therapy for health anxiety in AD can lead to a reduction in psychological distress, and whether this approach is an effective intervention for the reduction of Emergency Department admissions. A single case design was used, with pre- and post-measures of health anxiety, general anxiety and depression. Data on Emergency Department admissions prior to and following treatment were used to assess change in this domain. Reliable and clinically significant reductions were seen across all measures, from severe to sub-clinical levels. There was a complete amelioration of Emergency Department admissions in the 12 months following completion of treatment. This preliminary study provides a sound rationale for further research into AD complicated by anxiety. Findings support the clinical utility of the cognitive behavioural therapy model for complex presentations of AD, offering a potential treatment option where anxiety is elevated and interfering with self-management and leading to high levels of health service use.

Genomics and epigenomics in rheumatic diseases: what do they provide in terms of diagnosis and disease management?

Science.gov (United States)

Castro-Santos, Patricia; Díaz-Peña, Roberto

2017-09-01

Most rheumatic diseases are complex or multifactorial entities with pathogeneses that interact with both multiple genetic factors and a high number of diverse environmental factors. Knowledge of the human genome sequence and its diversity among populations has provided a crucial step forward in our understanding of genetic diseases, identifying many genetic loci or genes associated with diverse phenotypes. In general, susceptibility to autoimmunity is associated with multiple risk factors, but the mechanism of the environmental component influence is poorly understood. Studies in twins have demonstrated that genetics do not explain the totality of the pathogenesis of rheumatic diseases. One method of modulating gene expression through environmental effects is via epigenetic modifications. These techniques open a new field for identifying useful new biomarkers and therapeutic targets. In this context, the development of "-omics" techniques is an opportunity to progress in our knowledge of complex diseases, impacting the discovery of new potential biomarkers suitable for their introduction into clinical practice. In this review, we focus on the recent advances in the fields of genomics and epigenomics in rheumatic diseases and their potential to be useful for the diagnosis, follow-up, and treatment of these diseases. The ultimate aim of genomic studies in any human disease is to understand its pathogenesis, thereby enabling the prediction of the evolution of the disease to establish new treatments and address the development of personalized therapies.

Breast-axillary complex in HIV/AIDS patients.

Science.gov (United States)

Eni, U E; Naaya, H U; Yawe, K D T; Lawan, M A; Bakari, A A

2010-01-01

HIV/AIDS have not only increased the health care burden especially in developing countries, it equally complicates the presentation of many diseases. Some well known disease entities now occur in fulminant complexities not previously described or known as such. The objective of this article is to report an unusual presentation of HIV/AIDS patients to the surgeon with Axillary and ipsilateral breast swelling. This is a report of three cases seen and managed by the authors. Three adult female patients presented with progressively increasing axillary and ipsilateral breast swellings. They also had associated fevers and weight loss. Their main concern had been development of breast cancer. One of the patients was a known retroviral positive on Highly Active Anti-Retroviral Therapy (HAART). Examination revealed axillary abscess and ipsilateral breast oedema in two cases. The patient on HAART had a hard breast-axillary mass complex. Biopsy (FNAB) revealed inflammatory cells and no malignancy in all three cases. HIV screening was positive in all cases. One of the patients had excision of breast-axillary mass complex, and the histology showed features of chronic inflammation, with no malignant cells. The other two had incision and drainage of their axillary abscess. This shows the ubiquitous presentation of HIV/AIDS in our environment and surgeons should be aware of the breast axillary complex in HIV/AIDS. Medical practitioners should be careful to obtain accurate diagnosis before embarking on treatment especially mutilating surgical procedures.

Functional bowel disease

DEFF Research Database (Denmark)

Rumessen, J J; Gudmand-Høyer, E

1988-01-01

Twenty-five patients with functional bowel disease were given fructose, sorbitol, fructose-sorbitol mixtures, and sucrose. The occurrence of malabsorption was evaluated by means of hydrogen breath tests and the gastrointestinal symptoms, if any, were recorded. One patient could not be evaluated...... because of lack of H2 production. Based on a cut-off level of 10 ppm rise of H2 concentration, malabsorption was apparent in 13 patients, in 7 of which the calculated absorption capacities were below 15 g. In contrast, in patients given 50 g of sucrose, malabsorption could not be detected. Ingestion...... with functional bowel disease. The findings may have direct influence on the dietary guidance given to a major group of patients with functional bowel disease and may make it possible to define separate entities in this disease complex....

Selected reaction monitoring as an effective method for reliable quantification of disease-associated proteins in maple syrup urine disease

DEFF Research Database (Denmark)

Fernández-Guerra, Paula; Birkler, Rune I D; Merinero, Begoña

2014-01-01

in mitochondria-enriched samples from cultured fibroblasts from healthy individuals and patients with mutations in branched-chain α-ketoacid dehydrogenase (BCKDH) complex. BCKDH is a mitochondrial multienzyme complex and its defective activity causes maple syrup urine disease (MSUD), a rare but severe inherited...

Binding of properdin to solid-phase immune complexes

DEFF Research Database (Denmark)

Junker, A; Baatrup, G; Svehag, S E

1998-01-01

The capacity of serum to support deposition of C3, properdin and factor B was studied by enzyme-linked immunosorbent assay using solid-phase immune complexes (IC) for activation of complement. Deposition of C3 and properdin occurred in fairly dilute normal human serum (NHS), but factor B uptake...... fixed to IC was the principal ligand for properdin in the assay. The findings could have biological implications relating to complement-mediated modification of immune complexes in disease....

Mutated PET117 causes complex IV deficiency and is associated with neurodevelopmental regression and medulla oblongata lesions.

Science.gov (United States)

Renkema, G H; Visser, G; Baertling, F; Wintjes, L T; Wolters, V M; van Montfrans, J; de Kort, G A P; Nikkels, P G J; van Hasselt, P M; van der Crabben, S N; Rodenburg, R J T

2017-06-01

The genetic basis of the many progressive, multi systemic, mitochondrial diseases that cause a lack of cellular ATP production is heterogeneous, with defects found both in the mitochondrial genome as well as in the nuclear genome. Many different mutations have been found in the genes encoding subunits of the enzyme complexes of the oxidative phosphorylation system. In addition, mutations in genes encoding proteins involved in the assembly of these complexes are known to cause mitochondrial disorders. Here we describe two sisters with a mitochondrial disease characterized by lesions in the medulla oblongata, as demonstrated by brain magnetic resonance imaging, and an isolated complex IV deficiency and reduced levels of individual complex IV subunits. Whole exome sequencing revealed a homozygous nonsense mutation resulting in a premature stop codon in the gene encoding Pet117, a small protein that has previously been predicted to be a complex IV assembly factor. PET117 has not been identified as a mitochondrial disease gene before. Lentiviral complementation of patient fibroblasts with wild-type PET117 restored the complex IV deficiency, proving that the gene defect is responsible for the complex IV deficiency in the patients, and indicating a pivotal role of this protein in the proper functioning of complex IV. Although previous studies had suggested a possible role of this protein in the insertion of copper into complex IV, studies in patient fibroblasts could not confirm this. This case presentation thus implicates mutations in PET117 as a novel cause of mitochondrial disease.

Radiology of congenital heart disease

International Nuclear Information System (INIS)

Amplatz, K.

1986-01-01

This is a text on the radiologic diagnosis of congenital heart disease and its clinical manifestations. The main thrust of the book is the logical approach which allows an understanding of the complex theory of congenital heart disease. The atlas gives a concise overview of the entire field of congenital heart disease. Emphasis is placed on the understanding of the pathophysiology and its clinical and radiological consequences. Surgical treatment is included since it provides a different viewpoint of the anatomy

The emerging paradigm of network medicine in the study of human disease.

Science.gov (United States)

Chan, Stephen Y; Loscalzo, Joseph

2012-07-20

The molecular pathways that govern human disease consist of molecular circuits that coalesce into complex, overlapping networks. These network pathways are presumably regulated in a coordinated fashion, but such regulation has been difficult to decipher using only reductionistic principles. The emerging paradigm of "network medicine" proposes to utilize insights garnered from network topology (eg, the static position of molecules in relation to their neighbors) as well as network dynamics (eg, the unique flux of information through the network) to understand better the pathogenic behavior of complex molecular interconnections that traditional methods fail to recognize. As methodologies evolve, network medicine has the potential to capture the molecular complexity of human disease while offering computational methods to discern how such complexity controls disease manifestations, prognosis, and therapy. This review introduces the fundamental concepts of network medicine and explores the feasibility and potential impact of network-based methods for predicting individual manifestations of human disease and designing rational therapies. Wherever possible, we emphasize the application of these principles to cardiovascular disease.

Diagnostic accuracy of sub-mSv prospective ECG-triggering cardiac CT in young infant with complex congenital heart disease.

Science.gov (United States)

Gao, Wei; Zhong, Yu Min; Sun, Ai Min; Wang, Qian; Ouyang, Rong Zhen; Hu, Li Wei; Qiu, Han Sheng; Wang, Shi Yu; Li, Jian Ying

2016-06-01

To explore the clinical value and evaluate the diagnostic accuracy of sub-mSv low-dose prospective ECG-triggering cardiac CT (CCT) in young infants with complex congenital heart disease (CHD). A total of 102 consecutive infant patients (53 boys and 49 girls with mean age of 2.9 ± 2.4 m and weight less than 5 kg) with complex CHD were prospectively enrolled. Scans were performed on a 64-slice high definition CT scanner with low dose prospective ECG-triggering mode and reconstructed with 80 % adaptive statistical iterative reconstruction algorithm. All studies were performed during free breathing with sedation. The subjective image quality was evaluated by 5-point grading scale and interobserver variability was calculated. The objective image noise (standard deviation, SD) and contrast to noise ratio (CNR) was calculated. The effective radiation dose from the prospective ECG-triggering mode was recorded and compared with the virtual conventional retrospective ECG-gating mode. The detection rate for the origin of coronary artery was calculated. All patients also underwent echocardiography before CCT examination. 81 patients had surgery and their preoperative CCT and echocardiography findings were compared with the surgical results and sensitivity, specificity, positive and negative predictive values and accuracy were calculated for separate cardiovascular anomalies. Heart rates were 70-161 beats per minute (bpm) with mean value of 129.19 ± 14.52 bpm. The effective dose of 0.53 ± 0.15 mSv in the prospective ECG-triggering cardiac CT was lower than the calculated value in a conventional retrospective ECG-gating mode (2.00 ± 0.35 mSv) (p ECG-triggering CCT with sub-mSv effective dose provides excellent imaging quality and high diagnostic accuracy for young infants with complex CHD.

The Effect of Pressure and Temperature on Separation of Free Gadolinium(III) From Gd-DTPA Complex by Nanofiltration-Complexation Method

Science.gov (United States)

Rahayu, Iman; Anggraeni, Anni; Ukun, MSS; Bahti, Husein H.

2017-05-01

Nowdays, the utilization of rare earth elements has been carried out widely in industry and medicine, one of them is gadolinium in Gd-DTPA complex is used as a contrast agent in a magnetic resonance imaging (MRI) diagnostic to increase the visual contrast between normal tissue and diseased. Although the stability of a given complex may be high enough, the complexation step couldnot have been completed, so there is possible to gadolinium(III) in the complex compound. Therefore, the function of that compounds should be dangerous because of the toxicity of gadolinium(III) in human body. So, it is necessarry to separate free gadolinium(III) from Gd-DTPA complex by nanofiltration-complexation. The method of this study is complexing of Gd2O3 with DTPA ligand by reflux and separation of Gd-DTPA complex from gadolinium(III) with a nanofiltration membrane on the variation of pressures(2, 3, 4, 5, 6 bars) and temperature (25, 30, 35, 40 °C) and determined the flux and rejection. The results of this study are the higher of pressures and temperatures, permeation flux are increasing and ion rejections are decreasing and gave the free gadolinium(III) rejection until 86.26%.

Eculizumab for dense deposit disease and C3 glomerulonephritis.

Science.gov (United States)

Bomback, Andrew S; Smith, Richard J; Barile, Gaetano R; Zhang, Yuzhou; Heher, Eliot C; Herlitz, Leal; Stokes, M Barry; Markowitz, Glen S; D'Agati, Vivette D; Canetta, Pietro A; Radhakrishnan, Jai; Appel, Gerald B

2012-05-01

The principle defect in dense deposit disease and C3 glomerulonephritis is hyperactivity of the alternative complement pathway. Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, may prove beneficial. In this open-label, proof of concept efficacy and safety study, six subjects with dense deposit disease or C3 glomerulonephritis were treated with eculizumab every other week for 1 year. All had proteinuria >1 g/d and/or AKI at enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the 1-year mark. The subjects included three patients with dense deposit disease (including one patient with recurrent dense deposit disease in allograft) and three patients with C3 glomerulonephritis (including two patients with recurrent C3 glomerulonephritis in allograft). Genetic and complement function testing revealed a mutation in CFH and MCP in one subject each, C3 nephritic factor in three subjects, and elevated levels of serum membrane attack complex in three subjects. After 12 months, two subjects showed significantly reduced serum creatinine, one subject achieved marked reduction in proteinuria, and one subject had stable laboratory parameters but histopathologic improvements. Elevated serum membrane attack complex levels normalized on therapy and paralleled improvements in creatinine and proteinuria. Clinical and histopathologic data suggest a response to eculizumab in some but not all subjects with dense deposit disease and C3 glomerulonephritis. Elevation of serum membrane attack complex before treatment may predict response. Additional research is needed to define the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom eculizumab therapy can be considered.

Studies on the pathogenesis of Aleutian disease of mink. X. demonstration of immune complexes by the /sup 125/I-C 1 q binding test after experimental infection

Energy Technology Data Exchange (ETDEWEB)

Mueller-Peddinghaus, R [Kali-Chemie Pharma G.m.b.H., Hannover (Germany, F.R.). Abt. fuer Experimentelle Pathologie; Meyer zu Schwabedissen, H [Medizinische Hochschule Hannover (Germany, F.R.). Abt. fuer Klinische Immunologie und Bluttransfusionswesen; Kalden, J R [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. und Poliklinik fuer Klinische Immunologie; Trautwein, G; Ueberschaer, S [Tieraerztliche Hochschule Hannover (Germany, F.R.). Inst. fuer Pathologie

1980-01-01

Aleutian disease (AD) of mink most closely resembles systemic lupus erythematosus (SLE) in man; both are immune complex disease. In experimental AD serum immune complexes are determined by the /sup 125/J-C 1 q-binding test using human C 1 q. Mink (n = 12) infected intraperitoneally with Aleutian disease virus (ADV), grown in fetal mink kidney cells, developed during the course of infection a mean of /sup 125/I-C 1 q serum binding equivalent to 3.62 +- 1.68 mg./ml. aggr. HGG. (aggregated human immunoglobulin). Sera of mink (n = 8) which were infected with ADV grown in L-cells showed a less marked /sup 125/I-C 1 q binding with a mean equivalent to 2.52 +- 1.43 mg./ml. aggr. HGG. In contrast control animals (n = 8) treated with non-ADV-infected mink epidermal fibroblasts or Eagle's minimal essential medium substituted with fetal calf serum only bound /sup 125/I-C 1 q equivalent to 1.02 +- 0.99 mg./ml. aggr. HGG. In mink infected with ADV propagated in fetal mink kidney cells a constant increase in the /sup 125/I-C 1 q serum binding occurred from the 4th to the 7th and 13th week after ADV infection. Mink which were infected with ADV propagated in mouse L-cells exhibited a different pattern of the /sup 125/I-C 1 q serum binding capacity with a sharp increase from the 4th to the 7th week, followed by a decline towards the 13th week post infection. The serum /sup 125/I-C 1 q binding capacity of all experimental animal groups exhibited at different times of the experiment a significant correlation with the presence of hypergammaglobulinaemia and raised ADV-antibody titers. From the data obtained it appears that the /sup 125/I-C 1 q binding test, utilizing human C 1 q, is a suitable method for the detection of circulating serum immune complexes in mink during the course of ADV-infection.

The complexity of evaluating and increasing adherence in inflammatory bowel disease

DEFF Research Database (Denmark)

Weimers, Petra; Burisch, Johan; Munkholm, Pia

2017-01-01

. Nonetheless, adherence remains a common and complex issue in IBD care. Patient characteristics such as young age, male sex and employment has previously been verified as possible predictors of non-adherence. Additionally, evaluating adherence in itself is a challenge since both accurate and easy...

Evaluation of a bovine antibody test for diagnosing Mycobacterium avium complex in patients with cystic fibrosis

DEFF Research Database (Denmark)

Qvist, Tavs; Pressler, Tacjana; Katzenstein, Terese L.

2017-01-01

Introduction: The aim of this study was to test a commercial bovine enzyme-linked immunosorbent assay for investigating antibody activity against Mycobacterium avium complex. Methods: All patients at the Copenhagen Cystic Fibrosis (CF) Center who had culture for nontuberculous mycobacteria...... before and after culture conversion was performed in case patients. Results: Out of 286 included subjects, six had clinical M. avium complex pulmonary disease at the time of sera sampling. These patients presented with higher antibody test values (P-value ... at ruling out pulmonary disease. Screening sera from patients with CF could guide clinicians to focus attention on patients at higher risk of M. avium complex pulmonary disease. Pediatr Pulmonol. 2017;52:34–40....

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

African Journals Online (AJOL)

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have not been fully exploited due to limited breeding efforts and poor ... Flowering ability was low in some cultivars and a few did not flower at all. ... tion with other genes in different genetic backgrounds that can modify flesh ... sweetpotato production and utilisation, thus .... expressed as a percentage of diseased plants.

Mycobacterium abscessus Complex Infections in Humans.

Science.gov (United States)

Lee, Meng-Rui; Sheng, Wang-Huei; Hung, Chien-Ching; Yu, Chong-Jen; Lee, Li-Na; Hsueh, Po-Ren

2015-09-01