Sample records for study identifying disease
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A vector space model approach to identify genetically related diseases.
Sarkar, Indra Neil
2012-01-01
The relationship between diseases and their causative genes can be complex, especially in the case of polygenic diseases. Further exacerbating the challenges in their study is that many genes may be causally related to multiple diseases. This study explored the relationship between diseases through the adaptation of an approach pioneered in the context of information retrieval: vector space models. A vector space model approach was developed that bridges gene disease knowledge inferred across three knowledge bases: Online Mendelian Inheritance in Man, GenBank, and Medline. The approach was then used to identify potentially related diseases for two target diseases: Alzheimer disease and Prader-Willi Syndrome. In the case of both Alzheimer Disease and Prader-Willi Syndrome, a set of plausible diseases were identified that may warrant further exploration. This study furthers seminal work by Swanson, et al. that demonstrated the potential for mining literature for putative correlations. Using a vector space modeling approach, information from both biomedical literature and genomic resources (like GenBank) can be combined towards identification of putative correlations of interest. To this end, the relevance of the predicted diseases of interest in this study using the vector space modeling approach were validated based on supporting literature. The results of this study suggest that a vector space model approach may be a useful means to identify potential relationships between complex diseases, and thereby enable the coordination of gene-based findings across multiple complex diseases.
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Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George
2016-01-01
Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K-means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups. PMID:27330233
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Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George
Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.
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2010-01-01
Background Parkinson's disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson's disease. Identification of gene(s), as part of the etiology of Parkinson's disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria. Since several of the indentified Parkinson's disease genes are expressed in substantia nigra pars compact of the midbrain, expression within the neurons of this area could be a suitable criterion to limit the number of candidates and identify PD genes. Methods In this work we have used the combination of findings from six rodent transcriptome analysis studies on the gene expression profile of midbrain dopaminergic neurons and the PARK loci in OMIM (Online Mendelian Inheritance in Man) database, to identify new candidate genes for Parkinson's disease. Results Merging the two datasets, we identified 20 genes within PARK loci, 7 of which are located in an orphan Parkinson's disease locus and one, which had been identified as a disease gene. In addition to identifying a set of candidates for further genetic association studies, these results show that the criteria of expression in midbrain dopaminergic neurons may be used to narrow down the number of genes in PARK loci for such studies. PMID:20716345
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Innovative research methods for studying treatments for rare diseases: methodological review.
Gagne, Joshua J; Thompson, Lauren; O'Keefe, Kelly; Kesselheim, Aaron S
2014-11-24
To examine methods for generating evidence on health outcomes in patients with rare diseases. Methodological review of existing literature. PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases. We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application. We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified. Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data. © Gagne et al 2014.
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Ng, Victoria; Sargeant, Jan M.
2012-01-01
Background Zoonotic diseases account for over 60% of all communicable diseases causing illness in humans and 75% of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion. Methodology/Principal Findings This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%). Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure. Conclusions/Significance This was the first study to describe a mixed semi-quantitative and qualitative approach to deriving criteria for disease prioritization. This was also the first study to involve the opinion of the general public regarding disease prioritization. The number of criteria identified highlights the difficulty in prioritizing zoonotic diseases. The method presented in this paper has formulated a comprehensive list of criteria that can be used to inform future disease prioritization studies. PMID:22238648
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Histopathological retrospective study of canine renal disease in Korea, 2003~2008
Yhee, Ji-Young; Yu, Chi-Ho; Kim, Jong-Hyuk; Im, Keum-Soon; Chon, Seung-Ki
2010-01-01
Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson's trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations. PMID:21113095
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Rare high-impact disease variants: properties and identifications.
Park, Leeyoung; Kim, Ju Han
2016-03-21
Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of genetic models, the current study provides explanations of the existence of rare variants with high impacts and common variants with low impacts. Disease variants are neither necessary nor sufficient due to gene-gene or gene-environment interactions. A new method was developed based on theoretical aspects to identify both rare and common disease variants by their genotypes. Common disease variants were identified with relatively small odds ratios and relatively small sample sizes, except for specific situations in which the disease variants were in strong LD with a variant with a higher frequency. Rare disease variants with small impacts were difficult to identify without increasing sample sizes; however, the method was reasonably accurate for rare disease variants with high impacts. For rare variants, dominant variants generally showed better Type II error rates than recessive variants; however, the trend was reversed for common variants. Type II error rates increased in gene regions containing more than two disease variants because the more common variant, rather than both disease variants, was usually identified. The proposed method would be useful for identifying common disease variants with small impacts and rare disease variants with large impacts when disease variants have the same effects on disease presentation.
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Zebrafish: An Important Tool for Liver Disease Research
Goessling, Wolfram; Sadler, Kirsten C.
2016-01-01
As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012
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Lessons from rare diseases of cartilage and bone.
Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan
2015-06-01
Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Hendricks, Brian; Mark-Carew, Miguella
2017-02-01
Lyme disease is the most commonly reported vectorborne disease in the United States. The objective of our study was to identify patterns of Lyme disease reporting after multistate inclusion to mitigate potential border effects. County-level human Lyme disease surveillance data were obtained from Kentucky, Maryland, Ohio, Pennsylvania, Virginia, and West Virginia state health departments. Rate smoothing and Local Moran's I was performed to identify clusters of reporting activity and identify spatial outliers. A logistic generalized estimating equation was performed to identify significant associations in disease clustering over time. Resulting analyses identified statistically significant (P=0.05) clusters of high reporting activity and trends over time. High reporting activity aggregated near border counties in high incidence states, while low reporting aggregated near shared county borders in non-high incidence states. Findings highlight the need for exploratory surveillance approaches to describe the extent to which state level reporting affects accurate estimation of Lyme disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Genetic studies of Crohn's disease: Past, present and future
Liu, Jimmy Z.; Anderson, Carl A.
2014-01-01
The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease. PMID:24913378
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Charles-Smith, Lauren E; Reynolds, Tera L; Cameron, Mark A; Conway, Mike; Lau, Eric H Y; Olsen, Jennifer M; Pavlin, Julie A; Shigematsu, Mika; Streichert, Laura C; Suda, Katie J; Corley, Courtney D
2015-01-01
Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals' ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health?Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes?Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n = 15), Infectious Diseases (n = 6), Non-infectious Diseases (n = 4), Medication and Vaccines (n = 3), and Other (n = 5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n = 10), Infectious Diseases (n = 3), Non-infectious Diseases (n = 9), and Other (n = 10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.
Here, research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improvemore » public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.« less
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Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.; Conway, Mike; Lau, Eric H. Y.; Olsen, Jennifer M.; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura C.; Suda, Katie J.; Corley, Courtney D.
2015-01-01
Objective Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n = 15), Infectious Diseases (n = 6), Non-infectious Diseases (n = 4), Medication and Vaccines (n = 3), and Other (n = 5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n = 10), Infectious Diseases (n = 3), Non-infectious Diseases (n = 9), and Other (n = 10). Conclusions The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice. PMID:26437454
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Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.; ...
2015-10-05
Here, research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improvemore » public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.« less
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Schlicksup, Michael D; Van Winkle, Thomas J; Holt, David E
2009-10-01
To determine the prevalence of nonneoplastic middle ear disease among cats undergoing necropsy and the prevalence of clinical abnormalities in cats in which nonneoplastic middle ear disease was identified. Retrospective case series. 59 cats that underwent necropsy between January 1991 and August 2007. Medical records were searched to identify cats in which nonneoplastic middle ear disease was identified at necropsy. For cats included in the study, data that were recorded included signalment, initial complaint, whether the cat had any clinical signs of middle or external ear disease, whether the cat had upper respiratory tract disease, necropsy diagnosis, gross appearance of the bullae, and reason for euthanasia. Signs of middle ear disease that were considered included unilateral peripheral vestibular disease without motor deficits, Horner syndrome, and facial nerve paralysis. Of the 3,442 cats that underwent necropsy during the study period, 59 (1.7%) had nonneoplastic middle ear disease. Six of the 59 (10%) cats, including 1 cat that was affected bilaterally, had clinical signs of middle ear disease. Of these, 5 had signs of unilateral peripheral vestibular disease, and 1 had Horner syndrome. Results suggested that most cats with nonneoplastic middle ear disease did not have associated clinical signs. Findings may be of clinical relevance for cats in which middle ear disease is identified as an incidental finding during computed tomography or magnetic resonance imaging for unrelated diseases.
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Renal diseases in adults with cystic fibrosis: a 40 year single centre experience.
Wilcock, M J; Ruddick, A; Gyi, K M; Hodson, M E
2015-10-01
There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.
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Miller, David S; Weiser, Glen C; Ward, Alton C S; Drew, Mark L; Chapman, Phillip L
2011-06-02
A retrospective study of Pasteurellaceae isolated from domestic sheep (Ovis aries) was conducted. The aim was to identify Pasteurellaceae present in animals that were clinically healthy and others with evidence of respiratory disease. The bacteria had been isolated from samples submitted to the University of Idaho Caine Veterinary Teaching Center as part of disease diagnostic testing. The 844 isolates identified mainly three species of Pasteurellaceae: Mannheimia haemolytica, Pasteurella multocida, and Pasteurella (Bibersteinia) trehalosi. A total of 114 biovariants were identified among these three species. Individual biovariants were identified 1-180 times. Two of those (M. haemolytica 1 and P. (B.) trehalosi 2) constituted 36% of the isolates, and were the only biovariants sufficiently numerous to account for >7% of the total isolates. Samples were primarily submitted from sheep with signs of respiratory disease. Eighty percent of biovariants were identified most often in animals with signs of respiratory disease, but 26% of biovariants were isolated from both sheep with respiratory disease and apparently healthy sheep. P. multocida constituted 4.7% of isolates, and were exclusively associated with animals with respiratory disease. The ability of isolates to produce beta-hemolysis on culture media was not associated with animals with respiratory disease (odds ratio 0.77, 95% CI 0.50-1.19). The inference of this study is limited due to the retrospective study design. However, it is the first study that provides an extensive baseline list of biovariants associated with respiratory disease in domestic sheep. Copyright © 2011 Elsevier B.V. All rights reserved.
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Yang, Jialiang; Qiu, Jing; Wang, Kejing; Zhu, Lijuan; Fan, Jingjing; Zheng, Deyin; Meng, Xiaodi; Yang, Jiasheng; Peng, Lihong; Fu, Yu; Zhang, Dahan; Peng, Shouneng; Huang, Haiyun; Zhang, Yi
2017-01-01
Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease. PMID:29156709
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Zebrafish: an important tool for liver disease research.
Goessling, Wolfram; Sadler, Kirsten C
2015-11-01
As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Network Medicine: A Network-based Approach to Human Disease
Barabási, Albert-László; Gulbahce, Natali; Loscalzo, Joseph
2011-01-01
Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular network. The emerging tools of network medicine offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships between apparently distinct (patho)phenotypes. Advances in this direction are essential to identify new diseases genes, to uncover the biological significance of disease-associated mutations identified by genome-wide association studies and full genome sequencing, and to identify drug targets and biomarkers for complex diseases. PMID:21164525
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Rare variants and cardiovascular disease.
Wain, Louise V
2014-09-01
Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the Western world. Large genome-wide association studies (GWASs) of coronary artery disease, myocardial infarction, stroke and dilated cardiomyopathy have identified a number of common genetic variants with modest effects on disease risk. Similarly, studies of important modifiable risk factors of CVD have identified a large number of predominantly common variant associations, for example, with blood pressure and blood lipid levels. In each case, despite the often large numbers of loci identified, only a small proportion of the phenotypic variance is explained. It has been hypothesised that rare variants with large effects may account for some of the missing variance but large-scale studies of rare variation are in their infancy for cardiovascular traits and have yet to produce fruitful results. Studies of monogenic CVDs, inherited disorders believed to be entirely driven by individual rare mutations, have highlighted genes that play a key role in disease aetiology. In this review, we discuss how findings from studies of rare variants in monogenic disease and GWAS of predominantly common variants are converging to provide further insight into biological disease mechanisms. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Spatial Distribution and Trends of Waterborne Diseases in Tashkent Province
Subramanian, Veluswami Saravanan; Cho, Min Jung; Tan, Siwei Zoe; Fayzieva, Dilorom; Sebaly, Christian
2017-01-01
Introduction: The cumulative effect of limited investment in public water systems, inadequate public health infrastructure, and gaps in infectious disease prevention increased the incidence of waterborne diseases in Uzbekistan. The objectives of this study were: (1) to spatially analyze the distribution of the diseases in Tashkent Province, (2) to identify the intensity of spatial trends in the province, (3) to identify urban-rural characteristics of the disease distribution, and (4) to identify the differences in disease incidence between pediatric and adult populations of the province. Methods: Data on four major waterborne diseases and socio-demographics factors were collected in Tashkent Province from 2011 to 2014. Descriptive epidemiological methods and spatial-temporal methods were used to investigate the distribution and trends, and to identify waterborne diseases hotspots and vulnerable population groups in the province. Results: Hepatitis A and enterobiasis had a high incidence in most of Tashkent Province, with higher incidences in the eastern and western districts. Residents of rural areas, including children, were found to be more vulnerable to the waterborne diseases compared to other populations living in the province. Conclusions: This pilot study calls for more scientific investigations of waterborne diseases and their effect on public health in the region, which could facilitate targeted public health interventions in vulnerable regions of Uzbekistan. PMID:29138738
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Spatial Distribution and Trends of Waterborne Diseases in Tashkent Province.
Subramanian, Veluswami Saravanan; Cho, Min Jung; Tan, Siwei Zoe; Fayzieva, Dilorom; Sebaly, Christian
2017-01-01
The cumulative effect of limited investment in public water systems, inadequate public health infrastructure, and gaps in infectious disease prevention increased the incidence of waterborne diseases in Uzbekistan. The objectives of this study were: (1) to spatially analyze the distribution of the diseases in Tashkent Province, (2) to identify the intensity of spatial trends in the province, (3) to identify urban-rural characteristics of the disease distribution, and (4) to identify the differences in disease incidence between pediatric and adult populations of the province. Data on four major waterborne diseases and socio-demographics factors were collected in Tashkent Province from 2011 to 2014. Descriptive epidemiological methods and spatial-temporal methods were used to investigate the distribution and trends, and to identify waterborne diseases hotspots and vulnerable population groups in the province. Hepatitis A and enterobiasis had a high incidence in most of Tashkent Province, with higher incidences in the eastern and western districts. Residents of rural areas, including children, were found to be more vulnerable to the waterborne diseases compared to other populations living in the province. This pilot study calls for more scientific investigations of waterborne diseases and their effect on public health in the region, which could facilitate targeted public health interventions in vulnerable regions of Uzbekistan.
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Santiago, Jose A; Potashkin, Judith A
2013-01-01
Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that increased expression of APP in blood may modulate the neurodegenerative phenotype in type 2 diabetes patients.
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Raelson, John V; Little, Randall D; Ruether, Andreas; Fournier, Hélène; Paquin, Bruno; Van Eerdewegh, Paul; Bradley, W E C; Croteau, Pascal; Nguyen-Huu, Quynh; Segal, Jonathan; Debrus, Sophie; Allard, René; Rosenstiel, Philip; Franke, Andre; Jacobs, Gunnar; Nikolaus, Susanna; Vidal, Jean-Michel; Szego, Peter; Laplante, Nathalie; Clark, Hilary F; Paulussen, René J; Hooper, John W; Keith, Tim P; Belouchi, Abdelmajid; Schreiber, Stefan
2007-09-11
Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD. A proportion of these were replicated in two independent German Caucasian samples, including the established CD loci NOD2 and IBD5. The recently described IL23R locus was also identified and replicated. For this region, multiple individuals with all major haplotypes in the QFP were sequenced and extensive fine mapping performed to identify risk and protective alleles. Several additional loci, including a region on 3p21 containing several plausible candidate genes, a region near JAKMIP1 on 4p16.1, and two larger regions on chromosome 17 were replicated. Together with previously published loci, the spectrum of CD genes identified to date involves biochemical networks that affect epithelial defense mechanisms, innate and adaptive immune response, and the repair or remodeling of tissue.
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Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.
2017-01-01
Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403
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Matrix factorization-based data fusion for the prediction of lncRNA-disease associations.
Fu, Guangyuan; Wang, Jun; Domeniconi, Carlotta; Yu, Guoxian
2018-05-01
Long non-coding RNAs (lncRNAs) play crucial roles in complex disease diagnosis, prognosis, prevention and treatment, but only a small portion of lncRNA-disease associations have been experimentally verified. Various computational models have been proposed to identify lncRNA-disease associations by integrating heterogeneous data sources. However, existing models generally ignore the intrinsic structure of data sources or treat them as equally relevant, while they may not be. To accurately identify lncRNA-disease associations, we propose a Matrix Factorization based LncRNA-Disease Association prediction model (MFLDA in short). MFLDA decomposes data matrices of heterogeneous data sources into low-rank matrices via matrix tri-factorization to explore and exploit their intrinsic and shared structure. MFLDA can select and integrate the data sources by assigning different weights to them. An iterative solution is further introduced to simultaneously optimize the weights and low-rank matrices. Next, MFLDA uses the optimized low-rank matrices to reconstruct the lncRNA-disease association matrix and thus to identify potential associations. In 5-fold cross validation experiments to identify verified lncRNA-disease associations, MFLDA achieves an area under the receiver operating characteristic curve (AUC) of 0.7408, at least 3% higher than those given by state-of-the-art data fusion based computational models. An empirical study on identifying masked lncRNA-disease associations again shows that MFLDA can identify potential associations more accurately than competing models. A case study on identifying lncRNAs associated with breast, lung and stomach cancers show that 38 out of 45 (84%) associations predicted by MFLDA are supported by recent biomedical literature and further proves the capability of MFLDA in identifying novel lncRNA-disease associations. MFLDA is a general data fusion framework, and as such it can be adopted to predict associations between other biological entities. The source code for MFLDA is available at: http://mlda.swu.edu.cn/codes.php? name = MFLDA. gxyu@swu.edu.cn. Supplementary data are available at Bioinformatics online.
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Should we expect population thresholds for wildlife disease?
Lloyd-Smith, James O.; Cross, P.C.; Briggs, C.J.; Daugherty, M.; Getz, W.M.; Latto, J.; Sanchez, M.; Smith, A.; Swei, A.
2005-01-01
Host population thresholds for invasion or persistence of infectious disease are core concepts of disease ecology, and underlie on-going and controversial disease control policies based on culling and vaccination. Empirical evidence for these thresholds in wildlife populations has been sparse, however, though recent studies have narrowed this gap. Here we review the theoretical bases for population thresholds for disease, revealing why they are difficult to measure and sometimes are not even expected, and identifying important facets of wildlife ecology left out of current theories. We discuss strengths and weaknesses of selected empirical studies that have reported disease thresholds for wildlife, identify recurring obstacles, and discuss implications of our imperfect understanding of wildlife thresholds for disease control policy.
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Evolution, revolution and heresy in the genetics of infectious disease susceptibility
Hill, Adrian V. S.
2012-01-01
Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case–control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference. PMID:22312051
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Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.
Wilbe, Maria; Jokinen, Päivi; Truvé, Katarina; Seppala, Eija H; Karlsson, Elinor K; Biagi, Tara; Hughes, Angela; Bannasch, Danika; Andersson, Göran; Hansson-Hamlin, Helene; Lohi, Hannes; Lindblad-Toh, Kerstin
2010-03-01
The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.
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Jones, Natalie; Schneider, Gary; Kachroo, Sumesh; Rotella, Philip; Avetisyan, Ruzan; Reynolds, Matthew W
2012-01-01
The Food and Drug Administration's Mini-Sentinel pilot program initially aimed to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of pulmonary fibrosis and interstitial lung disease. PubMed and Iowa Drug Information Service Web searches were conducted to identify citations applicable to the pulmonary fibrosis/interstitial lung disease HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify pulmonary fibrosis and interstitial lung disease, including validation estimates of the coding algorithms. Our search revealed a deficiency of literature focusing on pulmonary fibrosis and interstitial lung disease algorithms and validation estimates. Only five studies provided codes; none provided validation estimates. Because interstitial lung disease includes a broad spectrum of diseases, including pulmonary fibrosis, the scope of these studies varied, as did the corresponding diagnostic codes used. Research needs to be conducted on designing validation studies to test pulmonary fibrosis and interstitial lung disease algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.
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Genetics, epidemiology, and cancer disparities: is it black and white?
Rebbeck, Timothy R; Halbert, Chanita Hughes; Sankar, Pamela
2006-05-10
Epidemiologic studies attempt to understand the distribution and determinants of human disease. Epidemiologic research often incorporates information about race, ethnicity, or ancestry, usually as a self-identified race or ethnicity (SIRE) variable. Differences in the distribution and determinants of disease on the basis of SIRE may be identified in these studies. In addition, genetic and other biologic differences according to SIRE are frequently reported. If these differences are real and meaningful, they may have value in identifying disease-causative or -preventive factors, and thus may be beneficial to human health. However, the concepts of race, ethnicity, or ancestry are often poorly considered or crudely applied, particularly in genetic studies of disease etiology or outcome. Consequently, results suggesting genetic differences with respect to disease etiology or outcome across SIRE groups may not be meaningful; in fact, these differences may prove harmful if they propagate stereotypes or spurious differences. Therefore, it is critical to properly consider the meaning, definitions, and use of race, ethnicity, or ancestry in molecular epidemiologic studies.
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Healthy control subjects are poorly defined in case-control studies of irritable bowel syndrome
Ghorbani, Shireen; Nejad, Amir; Law, David; Chua, Kathleen S.; Amichai, Meridythe M.; Pimentel, Mark
2015-01-01
Background Case-control studies are vital for understanding the pathophysiology of gastrointestinal disease. While the definition of disease is clear, the definition of healthy control is not. This is particularly relevant for functional bowel diseases such as irritable bowel syndrome (IBS). In this study, a systematic review formed the basis for a prospective study evaluating the effectiveness of commonly used techniques for defining healthy controls in IBS. Methods A systematic review of the literature was conducted to identify case-control studies involving functional gastrointestinal disorders. “Lack of Rome criteria”, self-description as “healthy” and the bowel disease questionnaire (BDQ) were common methods for identifying healthy controls. These 3 methods were then applied to a cohort of 53 non-patient subjects to determine their validity compared to objective outcome measures (7-day stool diary). Results “Lack of Rome criteria” and “healthy” self-description were the most common methods for identifying healthy control subjects, but many studies failed to describe the methods used. In the prospective study, more subjects were identified as non-healthy using the BDQ than using either lack of Rome criteria (P=0.01) or “healthy” self-description (P=0.026). Furthermore, stool diaries identified several subjects with abnormal stool form and/or frequency which were not identified using lack of Rome criteria or the “healthy” question. Comparisons revealed no agreement (κ) between the different methods for defining healthy controls. Conclusions The definitions of healthy controls in studies of functional bowel diseases such as IBS are inconsistent. Since functional symptoms are common, a strict definition of “normal” is needed in this area of research. PMID:25609236
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Viana, Joana; Hannon, Eilis; Dempster, Emma; Pidsley, Ruth; Macdonald, Ruby; Knox, Olivia; Spiers, Helen; Troakes, Claire; Al-Saraj, Safa; Turecki, Gustavo; Schalkwyk, Leonard C; Mill, Jonathan
2017-01-01
Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular aetiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, which are not enriched in genomic regions identified in genetic studies of schizophrenia and do not reflect direct genetic effects on DNA methylation. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with aetiological variation in complex disease. © The Author 2016. Published by Oxford University Press.
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Kawalec, Paweł
2016-04-01
Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem.
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2016-01-01
Introduction Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. Material and methods The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. Results Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. Conclusions The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem. PMID:27186172
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NASA Astrophysics Data System (ADS)
Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen
2015-03-01
The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.
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Hwang, Jusun; Lee, Kyunglee; Kim, Young-Jun; Sleeman, Jonathan M.; Lee, Hang
2017-01-01
To assess the status of research on wildlife diseases in the Republic of Korea (ROK) and to identify trends, knowledge gaps, and directions for future research, we reviewed epidemiologic publications on wildlife-associated diseases in the ROK. We identified a relatively small but rapidly increasing body of literature. The majority of publications were focused on public or livestock health and relatively few addressed wildlife health. Most studies that focused on human and livestock health were cross-sectional whereas wildlife health studies were mostly case reports. Fifteen diseases notifiable to the World Organisation for Animal Health were identified and 21 diseases were identified as notifiable to either the Korean Ministry of Health, Welfare, and Family Affairs or the Korean Ministry of Agriculture. Two diseases were reported as occurring as epidemics; highly pathogenic avian influenza (HPAI) and virulent Newcastle disease. Six diseases or disease agents were described in the literature as emerging including HPAI, rabies, Babesia microti, avian coronaviruses, scrub typhus, and severe fever thrombocytopenia syndrome virus. The diseases for which there were the largest number of publications were HPAI and rabies. The majority of wildlife-associated zoonotic disease publications focused on food-borne parasitic infections or rodent-associated diseases. Several publications focused on the potential of wildlife as reservoirs of livestock diseases; in particular, water deer (Hydropotes inermis) and wild boar (Sus scrofa). In contrast, there were few publications on diseases of concern for wildlife populations or research to understand the impacts of these diseases for wildlife management. Increased focus on prospective studies would enhance understanding of disease dynamics in wildlife populations. For the high-consequence diseases that impact multiple sectors, a One Health approach, with coordination among the public health, agricultural, and environmental sectors, would be important. This type of review can provide useful information for countries or regions planning or implementing national wildlife health programs.
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Hwang, Jusun; Lee, Kyunglee; Kim, Young-Jun; Sleeman, Jonathan M; Lee, Hang
2017-01-01
To assess the status of research on wildlife diseases in the Republic of Korea (ROK) and to identify trends, knowledge gaps, and directions for future research, we reviewed epidemiologic publications on wildlife-associated diseases in the ROK. We identified a relatively small but rapidly increasing body of literature. The majority of publications were focused on public or livestock health and relatively few addressed wildlife health. Most studies that focused on human and livestock health were cross-sectional whereas wildlife health studies were mostly case reports. Fifteen diseases notifiable to the World Organisation for Animal Health were identified and 21 diseases were identified as notifiable to either the Korea Ministry of Health and Welfare or the Korea Ministry of Agriculture, Food and Rural Affairs. Two diseases were reported as occurring as epidemics; highly pathogenic avian influenza (HPAI) and virulent Newcastle disease. Six diseases or disease agents were described in the literature as emerging including HPAI, rabies, Babesia microti , avian coronaviruses, scrub typhus, and severe fever thrombocytopenia syndrome virus. The diseases for which there were the largest number of publications were HPAI and rabies. The majority of wildlife-associated zoonotic disease publications focused on food-borne parasitic infections or rodent-associated diseases. Several publications focused on the potential of wildlife as reservoirs of livestock diseases; in particular, Korean water deer ( Hydropotes inermis argyropus ) and wild boar ( Sus scrofa ). In contrast, there were few publications on diseases of concern for wildlife populations or research to understand the impacts of these diseases for wildlife management. Increased focus on prospective studies would enhance understanding of disease dynamics in wildlife populations. For the high-consequence diseases that impact multiple sectors, a One Health approach, with coordination among the public health, agricultural, and environmental sectors, would be important. This type of review can provide useful information for countries or regions planning or implementing national wildlife health programs.
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Identifying Local Hotspots of Pediatric Chronic Diseases Using Emergency Department Surveillance
Lee, David C.; Yi, Stella S.; Fong, Hiu-Fai; Athens, Jessica K.; Ravenell, Joseph E.; Sevick, Mary Ann; Wall, Stephen P.; Elbel, Brian
2016-01-01
Objective To use novel geographic methods and large-scale claims data to identify the local distribution of pediatric chronic diseases in New York City. Methods Using a 2009 all-payer emergency claims database, we identified the proportion of unique children aged 0 to 17 with diagnosis codes for specific medical and psychiatric conditions. As a proof of concept, we compared these prevalence estimates to traditional health surveys and registry data using the most geographically granular data available. In addition, we used home addresses to map local variation in pediatric disease burden. Results We identified 549,547 New York City children who visited an emergency department at least once in 2009. Though our sample included more publicly insured and uninsured children, we found moderate to strong correlations of prevalence estimates when compared to health surveys and registry data at pre-specified geographic levels. Strongest correlations were found for asthma and mental health conditions by county among younger children (0.88, p=0.05 and 0.99, p<0.01, respectively). Moderate correlations by neighborhood were identified for obesity and cancer (0.53 and 0.54, p<0.01). Among adolescents, correlations by health districts were strong for obesity (0.95, p=0.05), and depression estimates had a non-significant, but strong negative correlation with suicide attempts (−0.88, p=0.12). Using SaTScan, we also identified local hotspots of pediatric chronic disease. Conclusions For conditions easily identified in claims data, emergency department surveillance may help estimate pediatric chronic disease prevalence with higher geographic resolution. More studies are needed to investigate limitations of these methods and assess reliability of local disease estimates. What’s New This study demonstrated how emergency department surveillance may improve estimates of pediatric disease prevalence with higher geographic resolution. We identified 29% of New York City children with a single year of data and identified local hotspots of pediatric chronic diseases. PMID:28385326
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A Groupwise Association Test for Rare Mutations Using a Weighted Sum Statistic
Madsen, Bo Eskerod; Browning, Sharon R.
2009-01-01
Resequencing is an emerging tool for identification of rare disease-associated mutations. Rare mutations are difficult to tag with SNP genotyping, as genotyping studies are designed to detect common variants. However, studies have shown that genetic heterogeneity is a probable scenario for common diseases, in which multiple rare mutations together explain a large proportion of the genetic basis for the disease. Thus, we propose a weighted-sum method to jointly analyse a group of mutations in order to test for groupwise association with disease status. For example, such a group of mutations may result from resequencing a gene. We compare the proposed weighted-sum method to alternative methods and show that it is powerful for identifying disease-associated genes, both on simulated and Encode data. Using the weighted-sum method, a resequencing study can identify a disease-associated gene with an overall population attributable risk (PAR) of 2%, even when each individual mutation has much lower PAR, using 1,000 to 7,000 affected and unaffected individuals, depending on the underlying genetic model. This study thus demonstrates that resequencing studies can identify important genetic associations, provided that specialised analysis methods, such as the weighted-sum method, are used. PMID:19214210
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Association Studies of Sporadic Parkinson’s Disease in the Genomic Era
Labbé, Catherine; Ross, Owen A
2014-01-01
Parkinson’s disease is a common age-related progressive neurodegenerative disorder. Over the last 10 years, advances have been made in our understanding of the etiology of the disease with the greatest insights perhaps coming from genetic studies, including genome-wide association approaches. These large scale studies allow the identification of genomic regions harboring common variants associated to disease risk. Since the first genome-wide association study on sporadic Parkinson’s disease performed in 2005, improvements in study design, including the advent of meta-analyses, have allowed the identification of ~21 susceptibility loci. The first loci to be nominated were previously associated to familial PD (SNCA, MAPT, LRRK2) and these have been extensively replicated. For other more recently identified loci (SREBF1, SCARB2, RIT2) independent replication is still warranted. Cumulative risk estimates of associated variants suggest that more loci are still to be discovered. Additional association studies combined with deep re-sequencing of known genome-wide association study loci are necessary to identify the functional variants that drive disease risk. As each of these associated genes and variants are identified they will give insight into the biological pathways involved the etiology of Parkinson’s disease. This will ultimately lead to the identification of molecules that can be used as biomarkers for diagnosis and as targets for the development of better, personalized treatment. PMID:24653658
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Ionita-Laza, Iuliana; Ottman, Ruth
2011-11-01
The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.
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Lee, James C; Biasci, Daniele; Roberts, Rebecca; Gearry, Richard B; Mansfield, John C; Ahmad, Tariq; Prescott, Natalie J; Satsangi, Jack; Wilson, David C; Jostins, Luke; Anderson, Carl A; Traherne, James A; Lyons, Paul A; Parkes, Miles; Smith, Kenneth G C
2017-02-01
For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself but instead the course that the disease takes over time (prognosis). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis, but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants. To better characterize how genetic variation influences disease prognosis, we performed a within-cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with disease prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn's disease is largely independent of the contribution to disease susceptibility and point to a biology of prognosis that could provide new therapeutic opportunities.
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How do economic crises affect migrants' risk of infectious disease? A systematic-narrative review.
Kentikelenis, Alexander; Karanikolos, Marina; Williams, Gemma; Mladovsky, Philipa; King, Lawrence; Pharris, Anastasia; Suk, Jonathan E; Hatzakis, Angelos; McKee, Martin; Noori, Teymur; Stuckler, David
2015-12-01
It is not well understood how economic crises affect infectious disease incidence and prevalence, particularly among vulnerable groups. Using a susceptible-infected-recovered framework, we systematically reviewed literature on the impact of the economic crises on infectious disease risks in migrants in Europe, focusing principally on HIV, TB, hepatitis and other STIs. We conducted two searches in PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, websites of key organizations and grey literature to identify how economic changes affect migrant populations and infectious disease. We perform a narrative synthesis in order to map critical pathways and identify hypotheses for subsequent research. The systematic review on links between economic crises and migrant health identified 653 studies through database searching; only seven met the inclusion criteria. Fourteen items were identified through further searches. The systematic review on links between economic crises and infectious disease identified 480 studies through database searching; 19 met the inclusion criteria. Eight items were identified through further searches. The reviews show that migrant populations in Europe appear disproportionately at risk of specific infectious diseases, and that economic crises and subsequent responses have tended to exacerbate such risks. Recessions lead to unemployment, impoverishment and other risk factors that can be linked to the transmissibility of disease among migrants. Austerity measures that lead to cuts in prevention and treatment programmes further exacerbate infectious disease risks among migrants. Non-governmental health service providers occasionally stepped in to cater to specific populations that include migrants. There is evidence that migrants are especially vulnerable to infectious disease during economic crises. Ring-fenced funding of prevention programs, including screening and treatment, is important for addressing this vulnerability. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association.
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How do economic crises affect migrants’ risk of infectious disease? A systematic-narrative review
Karanikolos, Marina; Williams, Gemma; Mladovsky, Philipa; King, Lawrence; Pharris, Anastasia; Suk, Jonathan E.; Hatzakis, Angelos; McKee, Martin; Noori, Teymur; Stuckler, David
2015-01-01
Background: It is not well understood how economic crises affect infectious disease incidence and prevalence, particularly among vulnerable groups. Using a susceptible-infected-recovered framework, we systematically reviewed literature on the impact of the economic crises on infectious disease risks in migrants in Europe, focusing principally on HIV, TB, hepatitis and other STIs. Methods: We conducted two searches in PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, websites of key organizations and grey literature to identify how economic changes affect migrant populations and infectious disease. We perform a narrative synthesis in order to map critical pathways and identify hypotheses for subsequent research. Results: The systematic review on links between economic crises and migrant health identified 653 studies through database searching; only seven met the inclusion criteria. Fourteen items were identified through further searches. The systematic review on links between economic crises and infectious disease identified 480 studies through database searching; 19 met the inclusion criteria. Eight items were identified through further searches. The reviews show that migrant populations in Europe appear disproportionately at risk of specific infectious diseases, and that economic crises and subsequent responses have tended to exacerbate such risks. Recessions lead to unemployment, impoverishment and other risk factors that can be linked to the transmissibility of disease among migrants. Austerity measures that lead to cuts in prevention and treatment programmes further exacerbate infectious disease risks among migrants. Non-governmental health service providers occasionally stepped in to cater to specific populations that include migrants. Conclusions: There is evidence that migrants are especially vulnerable to infectious disease during economic crises. Ring-fenced funding of prevention programs, including screening and treatment, is important for addressing this vulnerability. PMID:26318852
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Hsu, Irving; Chen, Rong; Ramesh, Aditya; Corona, Erik; Kang, Hyunseok Peter; Ruau, David; Butte, Atul J
2013-06-20
Long-term environmental variables are widely understood to play important roles in DNA variation. Previously, clinical studies examining the impacts of these variables on the human genome were localized to a single country, and used preselected DNA variants. Furthermore, clinical studies or surveys are either not available or difficult to carry out for developing countries. A systematic approach utilizing bioinformatics to identify associations among environmental variables, genetic variation, and diseases across various geographical locations is needed but has been lacking. Using a novel Geographic-Wide Association Study (GeoWAS) methodology, we identified Single Nucleotide Polymorphisms (SNPs) in the Human Genome Diversity Project (HGDP) with population allele frequencies associated geographical ultraviolet radiation exposure, and then assessed the diseases known to be assigned with these SNPs. 2,857 radiation SNPs were identified from over 650,000 SNPs in 52 indigenous populations across the world. Using a quantitative disease-SNP database curated from 5,065 human genetic papers, we identified disease associations with those radiation SNPs. The correlation of the rs16891982 SNP in the SLC45A2 gene with melanoma was used as a case study for analysis of disease risk, and the results were consistent with the incidence and mortality rates of melanoma in published scientific literature. Finally, by analyzing the ontology of genes in which the radiation SNPs were significantly enriched, potential associations between SNPs and neurological disorders such as Alzheimer's disease were hypothesized. A systematic approach using GeoWAS has enabled us to identify DNA variation associated with ultraviolet radiation and their connections to diseases such as skin cancers. Our analyses have led to a better understating at the genetic level of why certain diseases are more predominant in specific geographical locations, due to the interactions between environmental variables such as ultraviolet radiation and the population types in those regions. The hypotheses proposed in GeoWAS can lead to future testing and interdisciplinary research.
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Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.
2012-01-01
A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797
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Stressors of School-age Children With Allergic Diseases: A Qualitative Study.
Iio, Misa; Hamaguchi, Mana; Nagata, Mayumi; Yoshida, Koichi
2018-05-08
Most studies of stress in children with chronic diseases have been geared toward parents and caregivers have not considered allergic diseases together. This study aimed to identify the stressors associated with allergic diseases in Japanese school-age children. Stressors associated with allergic diseases of 11 school-age children (seven boys and four girls; age range: 9-12 years) were investigated using semi-structured interviews. In the qualitative thematic analysis of stressors about allergic diseases, two themes: allergic disease-specific stressors and common stressors in chronic diseases, and 12 categories were identified. A thematic map was applied to four domains of stressor: physiological factors, psychological factors, social factors, and environmental factors. The results showed that school-age children with allergic diseases have a variety of stressors. Future studies should aim to develop an allergic disease-specific stress management program with school-age children. In children with allergic diseases, not only is stress management in daily life important, but also stress management for disease-specific matters to control the symptoms and maintain mental health. Stress management should be supported for school-age children with allergic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.
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USDA-ARS?s Scientific Manuscript database
Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonids aquaculture. In previous studies we have identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a high density SNP array and...
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Whole-genome association studies of alcoholism with loci linked to schizophrenia susceptibility.
Namkung, Junghyun; Kim, Youngchul; Park, Taesung
2005-12-30
Alcoholism is a complex disease. There have been many reports on significant comorbidity between alcoholism and schizophrenia. For the genetic study of complex diseases, association analysis has been recommended because of its higher power than that of the linkage analysis for detecting genes with modest effects on disease. To identify alcoholism susceptibility loci, we performed genome-wide single-nucleotide polymorphisms (SNP) association tests, which yielded 489 significant SNPs at the 1% significance level. The association tests showed that tsc0593964 (P-value 0.000013) on chromosome 7 was most significantly associated with alcoholism. From 489 SNPs, 74 genes were identified. Among these genes, GABRA1 is a member of the same gene family with GABRA2 that was recently reported as alcoholism susceptibility gene. By comparing 74 genes to the published results of various linkage studies of schizophrenia, we identified 13 alcoholism associated genes that were located in the regions reported to be linked to schizophrenia. These 13 identified genes can be important candidate genes to study the genetic mechanism of co-occurrence of both diseases.
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Network Medicine: From Cellular Networks to the Human Diseasome
NASA Astrophysics Data System (ADS)
Barabasi, Albert-Laszlo
2014-03-01
Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular network. The tools of network science offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships between apparently distinct (patho)phenotypes. Advances in this direction not only enrich our understanding of complex systems, but are also essential to identify new disease genes, to uncover the biological significance of disease-associated mutations identified by genome-wide association studies and full genome sequencing, and to identify drug targets and biomarkers for complex diseases.
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2013-01-01
Background MicroRNAs (miRNAs) are important post-transcriptional regulators that have been demonstrated to play an important role in human diseases. Elucidating the associations between miRNAs and diseases at the systematic level will deepen our understanding of the molecular mechanisms of diseases. However, miRNA-disease associations identified by previous computational methods are far from completeness and more effort is needed. Results We developed a computational framework to identify miRNA-disease associations by performing random walk analysis, and focused on the functional link between miRNA targets and disease genes in protein-protein interaction (PPI) networks. Furthermore, a bipartite miRNA-disease network was constructed, from which several miRNA-disease co-regulated modules were identified by hierarchical clustering analysis. Our approach achieved satisfactory performance in identifying known cancer-related miRNAs for nine human cancers with an area under the ROC curve (AUC) ranging from 71.3% to 91.3%. By systematically analyzing the global properties of the miRNA-disease network, we found that only a small number of miRNAs regulated genes involved in various diseases, genes associated with neurological diseases were preferentially regulated by miRNAs and some immunological diseases were associated with several specific miRNAs. We also observed that most diseases in the same co-regulated module tended to belong to the same disease category, indicating that these diseases might share similar miRNA regulatory mechanisms. Conclusions In this study, we present a computational framework to identify miRNA-disease associations, and further construct a bipartite miRNA-disease network for systematically analyzing the global properties of miRNA regulation of disease genes. Our findings provide a broad perspective on the relationships between miRNAs and diseases and could potentially aid future research efforts concerning miRNA involvement in disease pathogenesis. PMID:24103777
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Periodontal systemic associations: review of the evidence.
Linden, Gerard J; Lyons, Amy; Scannapieco, Frank A
2013-04-01
To critically appraise recent research into associations between periodontal disease and systemic diseases and conditions specifically respiratory disease, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. A MEDLINE literature search of papers published between 2002 and April 2012 was conducted. Studies that included periodontitis as an exposure were identified. Cross-sectional epidemiological investigations on large samples, prospective studies and systematic reviews formed the basis of the narrative review. A threshold set for the identification of periodontitis was used to identify those studies that contributed to the conclusions of the review. Many of the investigations were cross-sectional secondary analyses of existing data sets in particular the NHANES studies. There were a small number of systematic reviews and prospective studies. There was substantial variability in the definitions of exposure to periodontitis. A small number of studies met the threshold set for periodontitis and supported associations; however, in some of the chronic diseases there were no such studies. There was strong evidence from randomized controlled trials that interventions, which improve oral hygiene have positive effects on the prevention of nosocomial pneumonias. There was substantial heterogeneity in the definitions used to identify periodontitis and very few studies met a stringent threshold for periodontitis. Published evidence supports modest associations between periodontitis and some, although not all, of the diseases and conditions reviewed. There is a need to reach a consensus on what constitutes periodontitis for future studies of putative associations with systemic diseases.
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Periodontal systemic associations: review of the evidence.
Linden, Gerard J; Lyons, Amy; Scannapieco, Frank A
2013-04-01
To critically appraise recent research into associations between periodontal disease and systemic diseases and conditions specifically respiratory disease, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. A MEDLINE literature search of papers published between 2002 and April 2012 was conducted. Studies that included periodontitis as an exposure were identified. Cross-sectional epidemiological investigations on large samples, prospective studies and systematic reviews formed the basis of the narrative review. A threshold set for the identification of periodontitis was used to identify those studies that contributed to the conclusions of the review. Many of the investigations were cross-sectional secondary analyses of existing data sets in particular the NHANES studies. There were a small number of systematic reviews and prospective studies. There was substantial variability in the definitions of exposure to periodontitis. A small number of studies met the threshold set for periodontitis and supported associations; however, in some of the chronic diseases there were no such studies. There was strong evidence from randomized controlled trials that interventions, which improve oral hygiene have positive effects on the prevention of nosocomial pneumonias. There was substantial heterogeneity in the definitions used to identify periodontitis and very few studies met a stringent threshold for periodontitis. Published evidence supports modest associations between periodontitis and some, although not all, of the diseases and conditions reviewed. There is a need to reach a consensus on what constitutes periodontitis for future studies of putative associations with systemic diseases. © 2013 European Federation of Periodontology and American Academy of Periodontology.
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Blood biomarker for Parkinson disease: peptoids
Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C
2016-01-01
Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535
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Lee, Theresa M; Tu, Karen; Wing, Laura L; Gershon, Andrea S
2017-05-15
Little is known about using electronic medical records to identify patients with chronic obstructive pulmonary disease to improve quality of care. Our objective was to develop electronic medical record algorithms that can accurately identify patients with obstructive pulmonary disease. A retrospective chart abstraction study was conducted on data from the Electronic Medical Record Administrative data Linked Database (EMRALD ® ) housed at the Institute for Clinical Evaluative Sciences. Abstracted charts provided the reference standard based on available physician-diagnoses, chronic obstructive pulmonary disease-specific medications, smoking history and pulmonary function testing. Chronic obstructive pulmonary disease electronic medical record algorithms using combinations of terminology in the cumulative patient profile (CPP; problem list/past medical history), physician billing codes (chronic bronchitis/emphysema/other chronic obstructive pulmonary disease), and prescriptions, were tested against the reference standard. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) were calculated. There were 364 patients with chronic obstructive pulmonary disease identified in a 5889 randomly sampled cohort aged ≥ 35 years (prevalence = 6.2%). The electronic medical record algorithm consisting of ≥ 3 physician billing codes for chronic obstructive pulmonary disease per year; documentation in the CPP; tiotropium prescription; or ipratropium (or its formulations) prescription and a chronic obstructive pulmonary disease billing code had sensitivity of 76.9% (95% CI:72.2-81.2), specificity of 99.7% (99.5-99.8), PPV of 93.6% (90.3-96.1), and NPV of 98.5% (98.1-98.8). Electronic medical record algorithms can accurately identify patients with chronic obstructive pulmonary disease in primary care records. They can be used to enable further studies in practice patterns and chronic obstructive pulmonary disease management in primary care. NOVEL ALGORITHM SEARCH TECHNIQUE: Researchers develop an algorithm that can accurately search through electronic health records to find patients with chronic lung disease. Mining population-wide data for information on patients diagnosed and treated with chronic obstructive pulmonary disease (COPD) in primary care could help inform future healthcare and spending practices. Theresa Lee at the University of Toronto, Canada, and colleagues used an algorithm to search electronic medical records and identify patients with COPD from doctors' notes, prescriptions and symptom histories. They carefully adjusted the algorithm to improve sensitivity and predictive value by adding details such as specific medications, physician codes related to COPD, and different combinations of terminology in doctors' notes. The team accurately identified 364 patients with COPD in a randomly-selected cohort of 5889 people. Their results suggest opportunities for broader, informative studies of COPD in wider populations.
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Lee, James C.; Biasci, Daniele; Roberts, Rebecca; Gearry, Richard B.; Mansfield, John C.; Ahmad, Tariq; Prescott, Natalie J.; Satsangi, Jack; Wilson, David C.; Jostins, Luke; Anderson, Carl A.; Traherne, James A.; Lyons, Paul A.; Parkes, Miles; Smith, Kenneth G.C.
2017-01-01
For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself, but the course the disease takes over time (prognosis)1–3. This varies substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis4–6, but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants7–13. To better characterise how genetic variation influences disease prognosis, we performed a within-cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn’s disease is largely independent from the contribution to disease susceptibility, and point to a biology of prognosis that could provide new therapeutic opportunities. PMID:28067912
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Brand, Oliver J; Gough, Stephen C L
2011-12-01
The autoimmune thyroid diseases (AITD) include Graves' disease (GD) and Hashimoto's thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology.
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Brand, Oliver J; Gough, Stephen C.L
2011-01-01
The autoimmune thyroid diseases (AITD) include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology. PMID:22654554
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RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.
Kobayashi, Hatasu; Brozman, Miroslav; Kyselová, Kateřina; Viszlayová, Daša; Morimoto, Takaaki; Roubec, Martin; Školoudík, David; Petrovičová, Andrea; Juskanič, Dominik; Strauss, Jozef; Halaj, Marián; Kurray, Peter; Hranai, Marián; Harada, Kouji H; Inoue, Sumiko; Yoshida, Yukako; Habu, Toshiyuki; Herzig, Roman; Youssefian, Shohab; Koizumi, Akio
2016-01-01
RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients.
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RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients
Kyselová, Kateřina; Viszlayová, Daša; Morimoto, Takaaki; Roubec, Martin; Školoudík, David; Petrovičová, Andrea; Juskanič, Dominik; Strauss, Jozef; Halaj, Marián; Kurray, Peter; Hranai, Marián; Harada, Kouji H.; Inoue, Sumiko; Yoshida, Yukako; Habu, Toshiyuki; Herzig, Roman; Youssefian, Shohab; Koizumi, Akio
2016-01-01
RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients. PMID:27736983
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Reported gum disease as a cardiovascular risk factor in adults with intellectual disabilities.
Hsieh, K; Murthy, S; Heller, T; Rimmer, J H; Yen, G
2018-03-01
Several risk factors for cardiovascular disease (CVD) have been identified among adults with intellectual disabilities (ID). Periodontitis has been reported to increase the risk of developing a CVD in the general population. Given that individuals with ID have been reported to have a higher prevalence of poor oral health than the general population, the purpose of this study was to determine whether adults with ID with informant reported gum disease present greater reported CVD than those who do not have reported gum disease and whether gum disease can be considered a risk factor for CVD. Using baseline data from the Longitudinal Health and Intellectual Disability Study from which informant survey data were collected, 128 participants with reported gum disease and 1252 subjects without reported gum disease were identified. A series of univariate logistic regressions was conducted to identify potential confounding factors for a multiple logistic regression. The series of univariate logistic regressions identified age, Down syndrome, hypercholesterolemia, hypertension, reported gum disease, daily consumption of fruits and vegetables and the addition of table salt as significant risk factors for reported CVD. When the significant factors from the univariate logistic regression were included in the multiple logistic analysis, reported gum disease remained as an independent risk factor for reported CVD after adjusting for the remaining risk factors. Compared with the adults with ID without reported gum disease, adults in the gum disease group demonstrated a significantly higher prevalence of reported CVD (19.5% vs. 9.7%; P = .001). After controlling for other risk factors, reported gum disease among adults with ID may be associated with a higher risk of CVD. However, further research that also includes clinical indices of periodontal disease and CVD for this population is needed to determine if there is a causal relationship between gum disease and CVD. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.
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A retrospective study of diseases in Ambystoma mexicanum: a report of 97 cases
TAKAMI, Yoshinori; UNE, Yumi
2017-01-01
Ambystoma mexicanum kept as pets are affected by a variety of diseases. However, no reports regarding the incidence of specific diseases are available. This study aimed to identify the diseases that occur frequently in this species by surveying the incidence of conditions in pet A. mexicanum specimens brought to a veterinary hospital. The sample comprised 97 pet A. mexicanum individuals brought to the authors’ hospital during the 82-month period, i.e., from January 2008 to October 2014. In total, 116 diseases were identified. The most common disease was hydrocoelom (32 cases; 27.5% of all cases). Elucidating the pathogenesis of hydrocoelom, which has a high prevalence rate, is vital to maintaining the long-term health of A. mexicanum pets. PMID:28529268
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A retrospective study of diseases in Ambystoma mexicanum: a report of 97 cases.
Takami, Yoshinori; Une, Yumi
2017-06-16
Ambystoma mexicanum kept as pets are affected by a variety of diseases. However, no reports regarding the incidence of specific diseases are available. This study aimed to identify the diseases that occur frequently in this species by surveying the incidence of conditions in pet A. mexicanum specimens brought to a veterinary hospital. The sample comprised 97 pet A. mexicanum individuals brought to the authors' hospital during the 82-month period, i.e., from January 2008 to October 2014. In total, 116 diseases were identified. The most common disease was hydrocoelom (32 cases; 27.5% of all cases). Elucidating the pathogenesis of hydrocoelom, which has a high prevalence rate, is vital to maintaining the long-term health of A. mexicanum pets.
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Steidl, Eduardo; Ribeiro, Carla Simone; Gonçalves, Bruna Franciele; Fernandes, Natália; Antunes, Vívian; Mancopes, Renata
2014-01-01
Introduction The literature presents studies correlating chronic obstructive pulmonary disease to dysphagia and suggesting that the aspiration laryngeal phenomenon related to changes in the pharyngeal phase contributes significantly to the exacerbation of symptoms of lung disease. Objectives This study aimed to conduct a literature review to identify the relation between dysphagia and exacerbations of chronic obstructive pulmonary disease. Data Synthesis We found 21 studies and included 19 in this review. The few studies that related to the subject agreed that the presence of dysphagia, due to lack of coordination between swallowing and breathing, may be one of the triggering factors of chronic obstructive pulmonary disease exacerbation. Conclusions The review noted that there is a relationship between dysphagia and exacerbations of chronic obstructive pulmonary disease, identified by studies demonstrating that the difficulties associated with swallowing may lead to exacerbation of the disease. There was difficulty in comparing studies by their methodological differences. More research is needed to clarify the relationship between dysphagia and exacerbations of chronic obstructive pulmonary disease, making it possible to develop multiprofessional treatment strategies for these patients, catered to specific needs due to the systemic manifestations of the disease. PMID:25992155
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Head, Michael G; Fitchett, Joseph R; Cooke, Mary K; Wurie, Fatima B; Hayward, Andrew C; Lipman, Marc C; Atun, Rifat
2014-01-01
Objectives Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. Setting The UK. Participants Institutions that host and carry out infectious disease research. Primary and secondary outcome measures The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. Results We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. Conclusions The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats. PMID:24670431
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Head, Michael G; Fitchett, Joseph R; Cooke, Mary K; Wurie, Fatima B; Hayward, Andrew C; Lipman, Marc C; Atun, Rifat
2014-03-26
Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. The UK. Institutions that host and carry out infectious disease research. The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I-IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.
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Lebo, Roger V; Tonk, Vijay S
2015-01-21
Our genomewide studies support targeted testing the most frequent genetic diseases by patient category: (1) pregnant patients, (2) at-risk conceptuses, (3) affected children, and (4) abnormal adults. This approach not only identifies most reported disease causing sequences accurately, but also minimizes incorrectly identified additional disease causing loci. Diseases were grouped in descending order of occurrence from four data sets: (1) GeneTests 534 listed population prevalences, (2) 4129 high risk prenatal karyotypes, (3) 1265 affected patient microarrays, and (4) reanalysis of 25,452 asymptomatic patient results screened prenatally for 108 genetic diseases. These most frequent diseases are categorized by transmission: (A) autosomal recessive, (B) X-linked, (C) autosomal dominant, (D) microscopic chromosome rearrangements, (E) submicroscopic copy number changes, and (F) frequent ethnic diseases. Among affected and carrier patients worldwide, most reported mutant genes would be identified correctly according to one of four patient categories from at-risk couples with <64 tested genes to affected adults with 314 tested loci. Three clinically reported patient series confirmed this approach. First, only 54 targeted chromosomal sites would have detected all 938 microscopically visible unbalanced karyotypes among 4129 karyotyped POC, CVS, and amniocentesis samples. Second, 37 of 48 reported aneuploid regions were found among our 1265 clinical microarrays confirming the locations of 8 schizophrenia loci and 20 aneuploidies altering intellectual ability, while also identifying 9 of the most frequent deletion syndromes. Third, testing 15 frequent genes would have identified 124 couples with a 1 in 4 risk of a fetus with a recessive disease compared to the 127 couples identified by testing all 108 genes, while testing all mutations in 15 genes could have identified more couples. Testing the most frequent disease causing abnormalities in 1 of 8 reported disease loci [~1 of 84 total genes] will identify ~ 7 of 8 reported abnormal Caucasian newborn genotypes. This would eliminate ~8 to 10 of ~10 Caucasian newborn gene sequences selected as abnormal that are actually normal variants identified when testing all ~2500 diseases looking for the remaining 1 of 8 disease causing genes. This approach enables more accurate testing within available laboratory and reimbursement resources.
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Noppert, Grace A; Kubale, John T; Wilson, Mark L
2017-01-01
Background Infectious disease epidemiologists have long recognised the importance of social variables as drivers of epidemics and disease risk, yet few apply analytic approaches from social epidemiology. We quantified and evaluated the extent to which recent infectious disease research is employing the perspectives and methods of social epidemiology by replicating the methodology used by Cohen et al in a 2007 study. Methods 2 search strategies were used to identify and review articles published from 1 January 2005 to 31 December 2013. First, we performed a keyword search of ‘social epidemiology’ in the title/abstract/text of published studies identified in PubMed, PsychInfo and ISI Web of Science, and classified each study as pertaining to infectious, non-infectious or other outcomes. A second PubMed search identified articles that were cross-referenced under non-infectious or infectious, and search terms relating to social variables. The abstracts of all articles were read, classified and examined to identify patterns over time. Results Findings suggest that infectious disease research publications that explicitly or implicitly incorporate social epidemiological approaches have stagnated in recent years. While the number of publications that were explicitly self-classified as ‘social epidemiology’ has risen, the proportion that investigated infectious disease outcomes has declined. Furthermore, infectious diseases accounted for the smallest proportion of articles that were cross-referenced with Medical Subject Headings (MeSH) terms related to social factors, and most of these involved sexually transmitted diseases. Conclusions The current landscape of infectious disease epidemiology could benefit from new approaches to understanding how the social and biophysical environment sustains transmission and exacerbates disparities. The framework of social epidemiology provides infectious disease researchers with such a perspective and research opportunity. PMID:27799618
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Garrow, Adam P; Yorke, Janelle; Khan, Naimat; Vestbo, Jørgen; Singh, Dave; Tyson, Sarah
2015-01-01
Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies. The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified. One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD. The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD.
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... NINDS scientists are studying the mechanisms by which lipids accumulating in these storage diseases causes harm to the body. Additional research studies hope to identify biomarkers (signs that may ...
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Braun, Joseph M; Gray, Kimberly
2017-12-01
Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision.
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Pooled genome wide association detects association upstream of FCRL3 with Graves' disease.
Khong, Jwu Jin; Burdon, Kathryn P; Lu, Yi; Laurie, Kate; Leonardos, Lefta; Baird, Paul N; Sahebjada, Srujana; Walsh, John P; Gajdatsy, Adam; Ebeling, Peter R; Hamblin, Peter Shane; Wong, Rosemary; Forehan, Simon P; Fourlanos, Spiros; Roberts, Anthony P; Doogue, Matthew; Selva, Dinesh; Montgomery, Grant W; Macgregor, Stuart; Craig, Jamie E
2016-11-18
Graves' disease is an autoimmune thyroid disease of complex inheritance. Multiple genetic susceptibility loci are thought to be involved in Graves' disease and it is therefore likely that these can be identified by genome wide association studies. This study aimed to determine if a genome wide association study, using a pooling methodology, could detect genomic loci associated with Graves' disease. Nineteen of the top ranking single nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056 reaching genome wide significance (p = 5 × 10 -8 ). Technical validation of top ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with individual genotyping in the discovery cohort revealed four single nucleotide polymorphisms with p ≤ 10 -4 . Rs17676303 on chromosome 1q23.1, located upstream of FCRL3, showed evidence of association with Graves' disease across the discovery, replication and combined cohorts. A second single nucleotide polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association supported by finding in the replication cohort that warrants further study. Pooled genome wide association study identified a genetic variant upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to those identified in the Major Histo-compatibility Complex. A second locus downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease that requires further confirmation.
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Clinical Utility of Serologic Testing for Celiac Disease in Asymptomatic Patients
2011-01-01
Executive Summary Objective The objective of this evidence-based analysis was to evaluate the clinical utility of serologic testing for celiac disease in asymptomatic individuals presenting with one of the non-gastrointestinal conditions evaluated in this report. The clinical utility was based on the effects of a gluten-free diet (GFD) on outcomes specific to each of these conditions. The prevalence of celiac disease in asymptomatic individuals and one of these non-gastrointestinal conditions was also evaluated. Clinical Need and Target Population Celiac Disease Celiac disease is an autoimmune disease characterized by a chronic inflammatory state of the proximal small bowel mucosa accompanied by structural and functional changes. Technology Under Evaluation Serologic Tests for Celiac Disease There are a number of serologic tests for celiac disease available. Serologic tests are automated with the exception of the anti-endomysial antibody test, which is more time-consuming and operator-dependent than the other tests. Research Questions What is the prevalence of asymptomatic celiac disease in patients presenting with one of the non-gastrointestinal conditions evaluated? What is the effect of the gluten-free diet on condition-specific outcomes in patients with asymptomatic celiac disease presenting with one of the non-gastrointestinal conditions evaluated? What is the clinical utility of serologic testing for celiac disease in asymptomatic patients presenting with one of the non-gastrointestinal conditions evaluated? The clinical utility was defined as the impact of the GFD on disease specific outcomes. What is the risk of all-cause mortality and lymphoma in individuals with asymptomatic celiac disease? What is the budget impact of serologic testing for celiac disease in asymptomatic subjects presenting with one of the non-gastrointestinal conditions evaluated? Research Methods Study Population The study population consisted of individuals with newly diagnosed celiac disease without any symptoms consistent with the disease presenting with one of the non-gastrointestinal conditions evaluated. When evaluating the risk of lymphoma and all-cause mortality, the study population consisted of asymptomatic individuals with a positive celiac disease serologic test and/or small bowel biopsy. Literature Search Search Strategy Literature searches were performed for each disease/condition evaluated between December 2010 and March 2011 using OVID MEDLINE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA). No restrictions for start date of search were used. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. Inclusion Criteria Studies, systematic reviews, and meta-analyses that assessed the effects of a GFD in patients with newly diagnosed asymptomatic celiac disease presenting with one of the non-gastrointestinal conditions evaluated. If symptoms were not reported in the study but subjects were identified through screening for celiac disease the study was included. Studies, systematic reviews, and meta-analyses that assessed the prevalence of newly diagnosed asymptomatic celiac disease in patients with one of the non-gastrointestinal conditions evaluated. If symptoms were not reported in the study but subjects were identified through screening for celiac disease the study was included. Studies, systematic reviews, and meta-analyses that evaluated the risk of all-cause mortality or lymphoma in individuals with asymptomatic celiac disease. Sample size ≥ 10. Publications in English. Exclusion Criteria Studies that retrospectively assessed the prevalence of asymptomatic celiac disease. Studies that reported the prevalence of one of the non-gastrointestinal conditions evaluated in subjects already diagnosed with celiac disease. Studies in individuals with one of the non-gastrointestinal conditions evaluated if the condition could be explained by other causes. Studies in subjects with celiac disease and symptoms consistent with the disease. If the study included individuals with and without symptoms consistent with celiac disease and their results were analysed separately, the results in individuals without symptoms were included in the analysis. Studies in which individuals did not report any symptoms consistent with celiac disease at study start but that either retrospectively reported the presence of such symptoms after following a GFD, or that previously presented with symptoms consistent with celiac disease. Study results published in letters to the editor or comments about other studies. Studies with a sample size ≥ 10, however, in which less than 10 patients were included in the analysis. Outcomes of Interest The effects of a GFD on disease-specific outcomes for each condition evaluated in patients with asymptomatic celiac disease was assessed. The prevalence of asymptomatic celiac disease in patients presenting with one of the conditions evaluated was also assessed. Results of Evidence-Based Analysis Three eligible observational studies evaluated the effects of GFD on growth parameters in subjects with asymptomatic celiac disease and idiopathic short stature. Four eligible observational studies evaluated the effects of GFD on metabolic control in subjects with asymptomatic celiac disease and type 1 diabetes. Five eligible observational studies evaluated the risk of all-cause mortality and five eligible observational studies evaluated the risk of lymphoma in subjects with asymptomatic celiac disease. No eligible studies on the effects of the GFD for the other conditions evaluated were identified. Twenty-three eligible studies measured the prevalence of asymptomatic celiac disease in subjects presenting with one of the conditions evaluated. Prevalence of Celiac Disease in Asymptomatic Patients The prevalence of celiac disease in asymptomatic patients presenting with one of the conditions evaluated was analysed. Most studies also included a control group that generally consisted of individuals randomly selected from the general population. Although there was a trend to a higher prevalence of asymptomatic celiac disease in individuals with the conditions evaluated compared to the controls, it only reached statistical significance in type 1 diabetes. No eligible prevalence studies were identified in patients with amenorrhea, delayed puberty, alopecia, and depression. The Effects of a Gluten-Free Diet on Disease-Specific Outcomes in Patients with Asymptomatic Celiac Disease The effects of GFD on metabolic control in patients with asymptomatic celiac disease and Type 1 Diabetes The effects of a GFD on metabolic control (HbA1c, number of hypoglycemic episodes, and changes in insulin dosage) in subjects with asymptomatic celiac disease and type 1 diabetes were evaluated. One prospective case-control study reported an increase in HbA1c levels in cases with type 1 diabetes and asymptomatic celiac disease after the introduction of a GFD, however, the clinical significance of this change is unclear. Only one eligible retrospective case-control study evaluated the effects of a GFD on hypoglycemia episodes and since there were inadequate details in the study about both the ascertainment and severity of hypoglycemia episodes in both cases and controls, it is not possible to draw conclusions regarding the effects of a GFD on hypoglycemia episodes based on this study. One prospective case-control study did not show a statistically significant change in insulin dosage between cases with type 1 diabetes and asymptomatic celiac disease and controls with type 1 diabetes either before or after the introduction of a GFD. No eligible studies that evaluated the effects of a GFD on the long-term outcomes of type 1 diabetes such as cardiovascular or renal events in patients with asymptomatic celiac disease were identified. The effects of a Gluten-Free Diet in Patients with Idiopathic Short Stature and Asymptomatic Celiac Disease A total of 3 eligible studies were identified. All studies consisted of case series that compared growth parameters in subjects with asymptomatic celiac disease and idiopathic short stature before and after the celiac disease was diagnosed and the GFD was instituted. Most subjects included in the studies demonstrated an improvement in growth parameters. Compliance with the GFD was not reported in the studies. The results of the studies suggest an increase in growth velocity in pediatric patients with asymptomatic celiac disease and idiopathic short stature once a GFD is introduced. Risk of lymphoma in patients with asymptomatic celiac disease One retrospective cohort study evaluated the risk of lymphoma in patients with asymptomatic celiac disease. The authors concluded that the number of events identified was low during the long follow-up period and that the risk of overall malignancies was not increased among patients with asymptomatic celiac disease. Risk of Asymptomatic Celiac Disease in Patients with Lymphoma Four case-control studies, one of which retrospective, evaluated the risk of asymptomatic celiac disease in patients newly diagnosed with lymphoma. One retrospective cohort study did not show an increase in the risk of lymphoma among subjects with asymptomatic celiac disease. Three prospective case-control studies did not find a statistically significant risk of asymptomatic celiac disease in patients with newly diagnosed lymphoma. Risk of All-Cause Mortality in Patients with Asymptomatic Celiac Disease A total of 5 studies that evaluated the risk of all-cause mortality in asymptomatic patients with celiac disease were identified. There were 5 cohort studies, 2 prospective and 3 retrospective. The two prospective studies did not show an increased risk of all-cause mortality in subjects with asymptomatic celiac disease. Grading of Evidence The quality of the evidence for each serologic tests evaluated based on the GRADE Working Group criteria. Overall, the quality of the evidence ranged from low to very low depending on the outcome evaluated. The Clinical Utility of Serologic Testing for Celiac Disease in Asymptomatic Subjects Eligible studies that evaluated the effects of a GFD on disease-specific outcomes were only identified for two of the conditions evaluated, type 1 diabetes and idiopathic short stature. The clinical utility of serologic testing for celiac disease in patients with type 1 diabetes without symptoms consistent with celiac disease was not demonstrated since the studies identified did not provide evidence of the impact of the GFD on either metabolic control or long-term outcomes in these patients. The clinical utility of serologic testing for celiac disease in patients with idiopathic short stature without symptoms consistent with celiac disease was demonstrated since the studies identified showed an acceleration in growth once the diagnosis of celiac disease was made and a GFD was introduced. The Budget Impact of Serologic Testing for Celiac Disease in Asymptomatic Patients The budget impact of serologic testing for celiac disease in asymptomatic patients was calculated for the conditions for which clinical utility for serologic testing was demonstrated. The budget impact in patients with idiopathic short stature without symptoms consistent with celiac disease was estimated as C$552,000 as calculated by multiplying the number of individuals in Ontario with idiopathic short stature that may be eligible for the test by the cost of the serologic test for celiac disease. Conclusions Based on a review of the literature, there is an increased risk of asymptomatic celiac disease in patients with type 1 diabetes. Based on low quality evidence, in patients with idiopathic short stature and asymptomatic celiac disease there is an acceleration in growth once a gluten-free diet is introduced. With the exception of idiopathic short stature, there was no published evidence of clinical utility of celiac disease testing in asymptomatic patients with respect to a gluten-free diet intervention in the other conditions evaluated. Based on low to very low quality evidence, asymptomatic celiac disease does not confer an increased risk of lymphoma or mortality. Similarly, in patients with lymphoma there is no increased risk of asymptomatic celiac disease. PMID:23074415
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Boucher, Gabrielle; Lo, Ken Sin; Rivas, Manuel A.; Stevens, Christine; Alikashani, Azadeh; Ladouceur, Martin; Ellinghaus, David; Törkvist, Leif; Goel, Gautam; Lagacé, Caroline; Annese, Vito; Bitton, Alain; Begun, Jakob; Brant, Steve R.; Bresso, Francesca; Cho, Judy H.; Duerr, Richard H.; Halfvarson, Jonas; McGovern, Dermot P. B.; Radford-Smith, Graham; Schreiber, Stefan; Schumm, Philip L.; Sharma, Yashoda; Silverberg, Mark S.; Weersma, Rinse K.; D'Amato, Mauro; Vermeire, Severine; Franke, Andre; Lettre, Guillaume; Xavier, Ramnik J.; Daly, Mark J.; Rioux, John D.
2013-01-01
Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (∼14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. PMID:24068945
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Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.
2013-01-01
The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results. PMID:24324827
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Siebert, Uwe; Wurm, Johannes; Gothe, Raffaella Matteucci; Arvandi, Marjan; Vavricka, Stephan R; von Känel, Roland; Begré, Stefan; Sulz, Michael C; Meyenberger, Christa; Sagmeister, Markus
2013-01-01
Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability.
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López-Isac, Elena; Martín, Jose-Ezequiel; Assassi, Shervin; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M; González-Gay, Miguel A; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg HW; Riekemasten, Gabriella; van der Helm-van Mil, Annete H; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E; Vonk, Madelon C; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby PC; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy RDJ; Worthington, Jane; Mayes, Maureen D; Martín, Javier
2017-01-01
Objectives Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc-RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposing-direction allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 × 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 × 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci. PMID:27111665
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Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I
2017-01-01
Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz - neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach's coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses.
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Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I
2017-01-01
Purpose Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Methods Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Results Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz – neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach’s coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. Discussion The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses. PMID:28919803
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Factors in Patient Empowerment: A Survey of an Online Patient Research Network.
Chiauzzi, Emil; DasMahapatra, Pronabesh; Cochin, Elisenda; Bunce, Mikele; Khoury, Raya; Dave, Purav
2016-12-01
Providers and healthcare organizations have begun recognizing the importance of patient empowerment as a driver of patient-centered care. Unfortunately, most studies have investigated empowerment with single diseases. Identifying factors of empowerment across conditions and populations would enable a greater understanding of this construct. The purpose of this study was to understand empowerment in relation to health information-seeking, interactions with providers and peers, and healthcare access in chronic disease patients. This study also sought to identify key empowerment factors and their association with patient characteristics. Participants were recruited through PatientsLikeMe, an online research platform where patients share their personal and medical history data. Patients completed an online survey that assessed self-reported health behavior (e.g. knowledge-seeking, experiences with healthcare providers, and peer interactions) and healthcare access. An exploratory factor analysis identified key empowerment domains. Domain level sum scores and sum of all domains (total score) were compared across patient characteristics and diseases. Overall, 3988 participants were included in the study, with the majority actively involved in their healthcare, but many cited difficulties with matching their treatment goals with those of their physician (34 %) and spending sufficient time with the physician (36 %). Factor analysis identified two domains-Positive Patient-Provider Interaction, and Knowledge and Personal Control-that explained >60 % of the overall variance in the observed variables. Mean total empowerment scores for patients with a primary complaint of Parkinson's disease (61.8) and multiple sclerosis (60.3) were significantly greater than fibromyalgia (55.3) and chronic fatigue syndrome (54.8). Patients who were older, male, more educated, and insured also reported significantly greater levels of empowerment. The two domains of empowerment identified in this study are consistent with previous studies, but the differences in empowerment levels across diseases suggest a need for further studies on disease-related attributes of empowerment. Future research should examine the pathways for empowerment, as well as the relationship between empowerment domains and clinical outcomes.
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Complement Factor B Mutations in Atypical Hemolytic Uremic Syndrome—Disease-Relevant or Benign?
Marinozzi, Maria Chiara; Vergoz, Laura; Rybkine, Tania; Ngo, Stephanie; Bettoni, Serena; Pashov, Anastas; Cayla, Mathieu; Tabarin, Fanny; Jablonski, Mathieu; Hue, Christophe; Smith, Richard J.; Noris, Marina; Halbwachs-Mecarelli, Lise; Donadelli, Roberta; Fremeaux-Bacchi, Veronique
2014-01-01
Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association. PMID:24652797
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Becker, Kerstin; Siegert, Sabine; Toliat, Mohammad Reza; Du, Juanjiangmeng; Casper, Ramona; Dolmans, Guido H.; Werker, Paul M.; Tinschert, Sigrid; Franke, Andre; Gieger, Christian; Strauch, Konstantin; Nothnagel, Michael; Nürnberg, Peter; Hennies, Hans Christian
2016-01-01
Dupuytren´s disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins. In spite of this striking first insight into the genetic factors in Dupuytren´s disease, much of the inherited risk in Dupuytren´s disease still needs to be discovered. The already identified loci jointly explain ~1% of the heritability in this disease. To further elucidate the genetic basis of Dupuytren´s disease, we performed a genome-wide meta-analysis combining three genome-wide association study (GWAS) data sets, comprising 1,580 cases and 4,480 controls. We corroborated all nine previously identified loci, six of these with genome-wide significance (p-value < 5x10-8). In addition, we identified 14 new suggestive loci (p-value < 10−5). Intriguingly, several of these new loci contain genes associated with Wnt signalling and therefore represent excellent candidates for replication. Next, we compared whole-transcriptome data between patient- and control-derived tissue samples and found the Wnt/β-catenin pathway to be the top deregulated pathway in patient samples. We then conducted network and pathway analyses in order to identify protein networks that are enriched for genes highlighted in the GWAS meta-analysis and expression data sets. We found further evidence that the Wnt signalling pathways in conjunction with other pathways may play a critical role in Dupuytren´s disease. PMID:27467239
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The relationship between postmenopausal osteoporosis and periodontal disease.
Dodd, Diane Z; Rowe, Dorothy J
2013-12-01
The purpose of this literature review is to summarize the scientific evidence, examining the relationship between postmenopausal osteoporosis and periodontal disease, and to determine if the relationship is causal or casual. A total of 8 electronic databases were searched to identify studies that included the following keywords: osteoporosis, periodontal disease, alveolar bone loss, estrogen deficiency, tooth loss and postmenopausal. Relevant abstracts were retrieved and critically evaluated. Based on the inclusion criteria of dentate postmenopausal women, selected articles were identified to read for more thorough examination. Of the 5 longitudinal studies reviewed, 4 (80%) showed an association between osteoporosis and periodontal disease. A relationship between the 2 diseases was demonstrated in 20 (80%) of the 25 cross-sectional studies. All 3 of the case-control studies showed an association. These data suggest a positive association between osteoporosis and periodontal disease. Determining whether this relationship is causal will require more longitudinal studies. Based on these findings, it is recommended that medical and dental professionals enhance their collaborative actions for prevention, evaluation and treatment of oral diseases and osteoporosis, in order to improve the health of these postmenopausal women.
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Sweet, M. J.; Croquer, A.; Bythell, J. C.
2014-01-01
Coral diseases have been increasingly reported over the past few decades and are a major contributor to coral decline worldwide. The Caribbean, in particular, has been noted as a hotspot for coral disease, and the aptly named white syndromes have caused the decline of the dominant reef building corals throughout their range. White band disease (WBD) has been implicated in the dramatic loss of Acropora cervicornis and Acropora palmata since the 1970s, resulting in both species being listed as critically endangered on the International Union for Conservation of Nature Red list. The causal agent of WBD remains unknown, although recent studies based on challenge experiments with filtrate from infected hosts concluded that the disease is probably caused by bacteria. Here, we report an experiment using four different antibiotic treatments, targeting different members of the disease-associated microbial community. Two antibiotics, ampicillin and paromomycin, arrested the disease completely, and by comparing with community shifts brought about by treatments that did not arrest the disease, we have identified the likely candidate causal agent or agents of WBD. Our interpretation of the experimental treatments is that one or a combination of up to three specific bacterial types, detected consistently in diseased corals but not detectable in healthy corals, are likely causal agents of WBD. In addition, a histophagous ciliate (Philaster lucinda) identical to that found consistently in association with white syndrome in Indo-Pacific acroporas was also consistently detected in all WBD samples and absent in healthy coral. Treatment with metronidazole reduced it to below detection limits, but did not arrest the disease. However, the microscopic disease signs changed, suggesting a secondary role in disease causation for this ciliate. In future studies to identify a causal agent of WBD via tests of Henle–Koch's postulates, it will be vital to experimentally control for populations of the other potential pathogens identified in this study. PMID:24943374
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Sweet, M J; Croquer, A; Bythell, J C
2014-08-07
Coral diseases have been increasingly reported over the past few decades and are a major contributor to coral decline worldwide. The Caribbean, in particular, has been noted as a hotspot for coral disease, and the aptly named white syndromes have caused the decline of the dominant reef building corals throughout their range. White band disease (WBD) has been implicated in the dramatic loss of Acropora cervicornis and Acropora palmata since the 1970s, resulting in both species being listed as critically endangered on the International Union for Conservation of Nature Red list. The causal agent of WBD remains unknown, although recent studies based on challenge experiments with filtrate from infected hosts concluded that the disease is probably caused by bacteria. Here, we report an experiment using four different antibiotic treatments, targeting different members of the disease-associated microbial community. Two antibiotics, ampicillin and paromomycin, arrested the disease completely, and by comparing with community shifts brought about by treatments that did not arrest the disease, we have identified the likely candidate causal agent or agents of WBD. Our interpretation of the experimental treatments is that one or a combination of up to three specific bacterial types, detected consistently in diseased corals but not detectable in healthy corals, are likely causal agents of WBD. In addition, a histophagous ciliate (Philaster lucinda) identical to that found consistently in association with white syndrome in Indo-Pacific acroporas was also consistently detected in all WBD samples and absent in healthy coral. Treatment with metronidazole reduced it to below detection limits, but did not arrest the disease. However, the microscopic disease signs changed, suggesting a secondary role in disease causation for this ciliate. In future studies to identify a causal agent of WBD via tests of Henle-Koch's postulates, it will be vital to experimentally control for populations of the other potential pathogens identified in this study.
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The Search for Autism Disease Genes
ERIC Educational Resources Information Center
Wassink, Thomas H.; Brzustowicz, Linda M.; Bartlett, Christopher W.; Szatmari, Peter
2004-01-01
Autism is a heritable disorder characterized by phenotypic and genetic complexity. This review begins by surveying current linkage, gene association, and cytogenetic studies performed with the goal of identifying autism disease susceptibility variants. Though numerous linkages and associations have been identified, they tend to diminish upon…
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Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases
Wang, Lan; Wu, Long-Fei; Lu, Xin; Mo, Xing-Bo; Tang, Zai-Xiang; Lei, Shu-Feng; Deng, Fei-Yan
2015-01-01
Objective Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. Methods We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. Results We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. Conclusion The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases. PMID:26352601
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Lim, Sunghoon; Tucker, Conrad S; Kumara, Soundar
2017-02-01
The authors of this work propose an unsupervised machine learning model that has the ability to identify real-world latent infectious diseases by mining social media data. In this study, a latent infectious disease is defined as a communicable disease that has not yet been formalized by national public health institutes and explicitly communicated to the general public. Most existing approaches to modeling infectious-disease-related knowledge discovery through social media networks are top-down approaches that are based on already known information, such as the names of diseases and their symptoms. In existing top-down approaches, necessary but unknown information, such as disease names and symptoms, is mostly unidentified in social media data until national public health institutes have formalized that disease. Most of the formalizing processes for latent infectious diseases are time consuming. Therefore, this study presents a bottom-up approach for latent infectious disease discovery in a given location without prior information, such as disease names and related symptoms. Social media messages with user and temporal information are extracted during the data preprocessing stage. An unsupervised sentiment analysis model is then presented. Users' expressions about symptoms, body parts, and pain locations are also identified from social media data. Then, symptom weighting vectors for each individual and time period are created, based on their sentiment and social media expressions. Finally, latent-infectious-disease-related information is retrieved from individuals' symptom weighting vectors. Twitter data from August 2012 to May 2013 are used to validate this study. Real electronic medical records for 104 individuals, who were diagnosed with influenza in the same period, are used to serve as ground truth validation. The results are promising, with the highest precision, recall, and F 1 score values of 0.773, 0.680, and 0.724, respectively. This work uses individuals' social media messages to identify latent infectious diseases, without prior information, quicker than when the disease(s) is formalized by national public health institutes. In particular, the unsupervised machine learning model using user, textual, and temporal information in social media data, along with sentiment analysis, identifies latent infectious diseases in a given location. Copyright © 2016 Elsevier Inc. All rights reserved.
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Castillo-Garit, Juan Alberto; Abad, Concepción; Rodríguez-Borges, J Enrique; Marrero-Ponce, Yovani; Torrens, Francisco
2012-01-01
The neglected tropical diseases (NTDs) affect more than one billion people (one-sixth of the world's population) and occur primarily in undeveloped countries in sub-Saharan Africa, Asia, and Latin America. Available drugs for these diseases are decades old and present an important number of limitations, especially high toxicity and, more recently, the emergence of drug resistance. In the last decade several Quantitative Structure-Activity Relationship (QSAR) studies have been developed in order to identify new organic compounds with activity against the parasites responsible for these diseases, which are reviewed in this paper. The topics summarized in this work are: 1) QSAR studies to identify new organic compounds actives against Chaga's disease; 2) Development of QSAR studies to discover new antileishmanial drusg; 3) Computational studies to identify new drug-like compounds against human African trypanosomiasis. Each topic include the general characteristics, epidemiology and chemotherapy of the disease as well as the main QSAR approaches to discovery/identification of new actives compounds for the corresponding neglected disease. The last section is devoted to a new approach know as multi-target QSAR models developed for antiparasitic drugs specifically those actives against trypanosomatid parasites. At present, as a result of these QSAR studies several promising compounds, active against these parasites, are been indentify. However, more efforts will be required in the future to develop more selective (specific) useful drugs.
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Landscape genetics and the spatial distribution of chronic wasting disease
Blanchong, Julie A.; Samuel, M.D.; Scribner, K.T.; Weckworth, B.V.; Langenberg, J.A.; Filcek, K.B.
2008-01-01
Predicting the spread of wildlife disease is critical for identifying populations at risk, targeting surveillance and designing proactive management programmes. We used a landscape genetics approach to identify landscape features that influenced gene flow and the distribution of chronic wasting disease (CWD) in Wisconsin white-tailed deer. CWD prevalence was negatively correlated with genetic differentiation of study area deer from deer in the area of disease origin (core-area). Genetic differentiation was greatest, and CWD prevalence lowest, in areas separated from the core-area by the Wisconsin River, indicating that this river reduced deer gene flow and probably disease spread. Features of the landscape that influence host dispersal and spatial patterns of disease can be identified based on host spatial genetic structure. Landscape genetics may be used to predict high-risk populations based on their genetic connection to infected populations and to target disease surveillance, control and preventative activities. ?? 2007 The Royal Society.
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Hirschsprung's disease in twins: a systematic review and meta-analysis.
Henderson, D; Zimmer, J; Nakamura, H; Puri, Prem
2017-08-01
Hirschsprung's disease (HSCR) is known to occur in families. The reported overall incidence of familial cases is 7.6%, with a higher incidence of 15-21% in total colonic aganglionosis and 50% in the rare total intestinal aganglionosis. HSCR is extremely rare in twins. The aim of this study was to systematically analyse the patterns of HSCR in twins published in the literature. Electronic databases Pubmed and Medline were screened for relevant articles using the keywords "Hirschsprung's disease", "aganglionosis", "twins", "monozygotic", and "dizygotic". Examining reference lists identified further relevant papers. Twelve studies with a total of 18 twin pairs were included in this analysis. 67% twins were discordant. HSCR was found in 24 out of 36 twin subjects (67%), of which 83% affected were male. Rectosigmoid type was reported in 71% of patients, long-segment disease in 21, and 8% presented with a total aganglionosis. Three twin pairs had at least one family member affected with HSCR. HSCR was found in two-thirds of twin subjects with a male predominance. Rectosigmoid aganglionosis was the most common variant. Disease discordance was identified, where environmental insults were postulated to be predisposing factors to disease expression. Future studies investigating the disease-associated mutations in the already identified HSCR genes should provide insights into the genetic basis of HSCR in twins.
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The limitations of opportunistic epidemiology, pseudopod epidemiology.
Kuller, Lewis H
2016-10-01
Epidemiology has been remarkably successful in the past in identifying the important agents of disease, the impact of the environment, both physical and social, and interrelationship with host susceptibility (genomics). Many of the advances in improving the health of individuals and populations have been the result of epidemiology studies that have identified the specific "agents" of disease and application of public health and preventive medicine. In recent years, large longitudinal studies have dominated epidemiology research, especially long incubation period chronic diseases. The initial hypotheses in these studies have been expanded by vertical extension studies using newer technologies to measure independent variables, vertical pseudopods, and additional studies of other diseases, horizontal pseudopods, of the original longitudinal study. Host susceptibility, i.e. genomics, has also become a prominent component of these longitudinal studies. The critical question addressed in this paper is whether these "pseudopod" epidemiology approaches have enhanced public health or generated a large number of studies of little impact.
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Teleosts Genomics: Progress and Prospects in Disease Prevention and Control.
Munang'andu, Hetron Mweemba; Galindo-Villegas, Jorge; David, Lior
2018-04-04
Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs) as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL) mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.
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The Oral Microbiota in Health and Disease: An Overview of Molecular Findings.
Siqueira, José F; Rôças, Isabela N
2017-01-01
Culture-independent nucleic acid technologies have been extensively applied to the analysis of oral bacterial communities associated with healthy and diseased conditions. These methods have confirmed and substantially expanded the findings from culture studies to reveal the oral microbial inhabitants and candidate pathogens associated with the major oral diseases. Over 1000 bacterial distinct species-level taxa have been identified in the oral cavity and studies using next-generation DNA sequencing approaches indicate that the breadth of bacterial diversity may be even much larger. Nucleic acid technologies have also been helpful in profiling bacterial communities and identifying disease-related patterns. This chapter provides an overview of the diversity and taxonomy of oral bacteria associated with health and disease.
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Human susceptibility to legionnaires' disease.
Berrington, William R; Hawn, Thomas R
2013-01-01
Legionella pneumophila is a facultative intracellular pathogen that is an important cause of pneumonia. Although host factors that may predispose to acquisition of Legionnaire's Disease (LD) include comorbid illnesses (e.g., diabetes, chronic lung disease), age, male sex, and smoking, many individuals have no identifiable risk factors. Some studies suggest that genetic factors may enhance susceptibility to LD. In this chapter we discuss current techniques and scientific methods to identify genetic susceptibility factors. These genetic studies provide insight into the human immune response to intracellular pathogens and may improve strategies for treatment and vaccine development.
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The incidence of Crohn's disease in Cardiff over the last 75 years: an update for 1996-2005.
Gunesh, S; Thomas, G A O; Williams, G T; Roberts, A; Hawthorne, A B
2008-02-01
The incidence of Crohn's disease rose rapidly in industralized countries over the past 50 years, but it is unclear whether the incidence is still rising or has reached a plateau. To update the long-term incidence study of Crohn's disease in Cardiff for 1996-2005, to investigate whether incidence is still rising and to study changes in disease characteristics over time. Crohn's cases identified by retrospective analysis of hospital records as in previous studies in Cardiff. Two hundred and twelve cases were identified. Corrected incidence for this decade was 66 x 10(6) per year (95% confidence interval: 58-76), showing a continuing rise compared to previous decades. The proportion with colonic disease at presentation continues to rise (43%) with a corresponding fall in those with terminal ileal disease. There remains a strong female preponderance (F:M 1.6:1) as in previous studies. The incidence in children under age 16 continues to rise, and the median age at diagnosis has fallen slightly. Crohn's disease incidence continues to rise slowly in Cardiff with a continuing increase in those presenting with colonic disease, which is now the commonest disease pattern.
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[Genome-wide association study for adolescent idiopathic scoliosis].
Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro
2016-04-01
Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS.
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Patel, Chirag J
2017-01-01
Mixtures, or combinations and interactions between multiple environmental exposures, are hypothesized to be causally linked with disease and health-related phenotypes. Established and emerging molecular measurement technologies to assay the exposome , the comprehensive battery of exposures encountered from birth to death, promise a new way of identifying mixtures in disease in the epidemiological setting. In this opinion, we describe the analytic complexity and challenges in identifying mixtures associated with phenotype and disease. Existing and emerging machine-learning methods and data analytic approaches (e.g., "environment-wide association studies" [EWASs]), as well as large cohorts may enhance possibilities to identify mixtures of correlated exposures associated with phenotypes; however, the analytic complexity of identifying mixtures is immense. If the exposome concept is realized, new analytical methods and large sample sizes will be required to ascertain how mixtures are associated with disease. The author recommends documenting prevalent correlated exposures and replicated main effects prior to identifying mixtures.
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A past Haff disease outbreak associated with eating freshwater pomfret in South China
2013-01-01
Background Haff disease is unexplained rhabdomyolysis caused by consumption of fishery products in the previous 24 h. It was first identified in Europe in 1924 but the condition is extremely rare in China. Here we describe a past outbreak of acute food borne muscle poisoning that occurred in Guangdong Province (South China) in 2009. Methods The first full outbreak of Haff disease reported in Jiangsu Province (East China) in 2010, indicated that the incidence of the disease may be increasing in China. We, therefore first retrospectively reviewed epidemiologic, trace-back, environmental studies, and laboratory analyses, including oral toxicity testing to ascertain risk and chemical analysis to identify toxin(s), from the 2009 Guangdong outbreak. Then we compared data from the 2009 outbreak with data from all other Haff disease outbreaks that were available. Results Clinical symptoms and laboratory findings indicated that the 2009 Guangdong outbreak disease was consistent with rhabdomyolysis. Epidemiologic, trace-back, environmental studies and laboratory analyses implied that the disease was caused by freshwater Pomfrets consumed prior to the onset of symptoms. We also identified common factors between the 2009 Guangdong outbreak and previous Haff disease outbreaks reported around the world, while as with other similar outbreaks, the exact etiological factor(s) of the disease remains unknown. Conclusions The 2009 Guangdong outbreak of ‘muscle poisoning’ was retrospectively identified as an outbreak of Haff disease. This comprised the highest number of cases reported in China thus far. Food borne diseases emerging in this unusual form and the irregular pattern of outbreaks present an ongoing public health risk, highlighting the need for improved surveillance and diagnostic methodology. PMID:23642345
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Tick-Borne Pathogen – Reversed and Conventional Discovery of Disease
Tijsse-Klasen, Ellen; Koopmans, Marion P. G.; Sprong, Hein
2014-01-01
Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a “reversed way,” detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, reverse order discovery presents researchers with new challenges. Estimating public health risks of such agents is especially challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, and epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in the future. PMID:25072045
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Herrmann, Wolfram J; Weikert, Cornelia; Bergmann, Manuela; Boeing, Heiner; Katzke, Verena A; Kaaks, Rudolf; Tiller, Daniel; Greiser, Karin Halina; Heier, Margit; Meisinger, Christa; Schmidt, Carsten Oliver; Neuhauser, Hannelore; Heidemann, Christin; Jünger, Claus; Wild, Philipp S; Schramm, Sara Helena; Jöckel, Karl-Heinz; Dörr, Marcus; Pischon, Tobias
2018-04-01
Cardiovascular and metabolic diseases are a major cause of mortality and loss of quality of life in Germany. Research into risk factors of these diseases requires large population-based cohort studies. Complete and accurate assessment of the incidence of cardiovascular and metabolic diseases is a key element for valid interpretation of the results from such studies. Our aim was to identify population-based cohort studies with incidence of cardiovascular and metabolic diseases in Germany and to summarize their methods for assessment and classification of disease endpoints, including myocardial infarction, type 2 diabetes, stroke, heart failure, and arterial hypertension. Within the framework of a workshop, representatives of the ascertained population-based cohort studies in Germany with incidence of cardiovascular or metabolic diseases were invited to present and to systematically provide information on their methods of endpoint identification. We identified eight studies from different regions in Germany with a total of 100,571 participants, aged 18-83 years at baseline. Self-reporting by study participants is the major source for further inquiries to assess disease endpoints in these studies. Most studies use additional data sources to verify the incidence of diseases, such as documents provided by the treating physician or hospital. Our results highlight the central role of self-reporting and the efforts associated with identification and verification of disease endpoints in cohort studies. They also provide a basis for future population-based studies that aim for standardized assessment of the incidence of cardiovascular and metabolic diseases.
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Munang’andu, Hetron M.
2016-01-01
Studies on the epidemiology of viral diseases in aquaculture have for a long time depended on isolation of viruses from infected aquatic organisms. The role of aquatic environments in the epidemiology of viral diseases in aquaculture has not been extensively expounded mainly because of the lack of appropriate tools for environmental studies on aquatic viruses. However, the upcoming of metagenomics analyses opens great avenues in which environmental samples can be used to study the epidemiology of viral diseases outside their host species. Hence, in this review I have shown that epidemiological factors that influence the composition of viruses in different aquatic environments include ecological factors, anthropogenic activities and stocking densities of cultured organisms based on environmental metagenomics studies carried out this far. Ballast water transportation and global trade of aquatic organisms are the most common virus dispersal process identified this far. In terms of disease control for outdoor aquaculture systems, baseline data on viruses found in different environments intended for aquaculture use can be obtained to enable the design of effective disease control strategies. And as such, high-risk areas having a high specter of pathogenic viruses can be identified as an early warning system. As for the control of viral diseases for indoor recirculation aquaculture systems (RAS), the most effective disinfection methods able to eliminate pathogenic viruses from water used in RAS can be identified. Overall, the synopsis I have put forth in this review shows that environmental samples can be used to study the epidemiology of viral diseases in aquaculture using viral metagenomics analysis as an overture for the design of rational disease control strategies. PMID:28018317
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Garcia-Etxebarria, Koldo; Jauregi-Miguel, Amaia; Romero-Garmendia, Irati; Plaza-Izurieta, Leticia; Legarda, Maria; Irastorza, Iñaki; Bilbao, Jose Ramon
2016-12-01
To identify candidate genes in celiac disease (CD), we reanalyzed the whole Immunochip CD cohort using a different approach that clusters individuals based on immunoancestry prior to disease association analysis, rather than by geographical origin. We detected 636 new associated SNPs (P<7.02 × 10 -07 ) and identified 5 novel genomic regions, extended 8 others previously identified and also detected 18 isolated signals defined by one or very few significant SNPs. To test whether we could identify putative candidate genes, we performed expression analyses of several genes from the top novel region (chr2:134533564-136169524), from a previously identified locus that is now extended, and a gene marked by an isolated SNP, in duodenum biopsies of active and treated CD patients, and non-celiac controls. In the largest novel region, CCNT2 and R3HDM1 were constitutively underexpressed in disease, even after gluten removal. Moreover, several genes within this region were coexpressed in patients, but not in controls. Other novel genes like KIF21B, REL and SORD also showed altered expression in active disease. Apart from the identification of novel CD loci, these results suggest that ancestry-based stratified analysis is an efficient strategy for association studies in complex diseases.
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Jabbarian, Lea J; Zwakman, Marieke; van der Heide, Agnes; Kars, Marijke C; Janssen, Daisy J A; van Delden, Johannes J; Rietjens, Judith A C; Korfage, Ida J
2018-03-01
Advance care planning (ACP) supports patients in identifying and documenting their preferences and timely discussing them with their relatives and healthcare professionals (HCPs). Since the British Thoracic Society encourages ACP in chronic respiratory disease, the objective was to systematically review ACP practice in chronic respiratory disease, attitudes of patients and HCPs and barriers and facilitators related to engagement in ACP. We systematically searched 12 electronic databases for empirical studies on ACP in adults with chronic respiratory diseases. Identified studies underwent full review and data extraction. Of 2509 studies, 21 were eligible: 10 were quantitative studies. Although a majority of patients was interested in engaging in ACP, ACP was rarely carried out. Many HCPs acknowledged the importance of ACP but were hesitant to initiate it. Barriers to engagement in ACP were the complex disease course of patients with chronic respiratory diseases, HCPs' concern of taking away patients' hopes and lack of continuity of care. The identification of trigger points and training of HCPs on how to communicate sensitive topics were identified as facilitators to engagement in ACP. In conclusion, ACP is surprisingly uncommon in chronic respiratory disease, possibly due to the complex disease course of chronic respiratory diseases and ambivalence of both patients and HCPs to engage in ACP. Providing patients with information about their disease can help meeting their needs. Additionally, support of HCPs through identification of trigger points, training and system-related changes can facilitate engagement in ACP. CRD42016039787. © 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.
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Szabo, Eva; Croxton, Thomas L.; Shapiro, Steven D.; Dubinett, Steven M.
2009-01-01
Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI. PMID:19351920
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Epidemiological Trends of Dengue Disease in Colombia (2000-2011): A Systematic Review
Villar, Luis Angel; Rojas, Diana Patricia; Besada-Lombana, Sandra; Sarti, Elsa
2015-01-01
A systematic literature review was conducted to describe the epidemiology of dengue disease in Colombia. Searches of published literature in epidemiological studies of dengue disease encompassing the terms “dengue”, “epidemiology,” and “Colombia” were conducted. Studies in English or Spanish published between 1 January 2000 and 23 February 2012 were included. The searches identified 225 relevant citations, 30 of which fulfilled the inclusion criteria defined in the review protocol. The epidemiology of dengue disease in Colombia was characterized by a stable “baseline” annual number of dengue fever cases, with major outbreaks in 2001–2003 and 2010. The geographical spread of dengue disease cases showed a steady increase, with most of the country affected by the 2010 outbreak. The majority of dengue disease recorded during the review period was among those <15 years of age. Gaps identified in epidemiological knowledge regarding dengue disease in Colombia may provide several avenues for future research, namely studies of asymptomatic dengue virus infection, primary versus secondary infections, and under-reporting of the disease. Improved understanding of the factors that determine disease expression and enable improvement in disease control and management is also important. PMID:25790245
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The practice of physical activity and cryotherapy in rheumatoid arthritis: systematic review.
Peres, Daniele; Sagawa, Yoshimasa; Dugué, Benoit; Domenech, Susana C; Tordi, Nicolas; Prati, Clement
2017-10-01
Rheumatoid arthritis (RA) is an autoimmune, chronic and inflammatory disease, which the affected patients present a higher cardiovascular mortality rate. Physical activities have been identified as the most important strategy to prevent cardiovascular diseases. However, the articular damage and the chronic pain caused by RA challenges its regular practice. Moreover, persons with RA tend to avoid PA due to the fear of exacerbating the inflammatory potential and pain. One alternative to avoid the collateral effects of the PA could be the cryotherapy. Therefore, this study aimed to review studies focused on the use of both PA and cryotherapy in RA patients and to identify evidences that both therapies could be combined in order to optimize the symptomatic treatment. Four databases (MEDLINE, CINAHL, Elsevier and PEDro) were searched to identify publications regarding RA patients, PA and cryotherapy intervention by the terms and operators (rheumatoid arthritis AND exercise OR physical activity OR activity OR training OR reconditioning OR cryotherapy OR cold OR immersion). The selected studies should at least present one measure of the aerobic capacity, disease activity or pain relief. Among 19 studies with RA patients identified, only 4 studies used PA combined with cryotherapy. The other 13 studies used physical activities and 2 studies used cryotherapy intervention. The results of the physical activities combined with cryotherapy studies showed an improvement in the disease activity and pain relief, however without details of the physical activities intervention and an aerobic capacity. Among the physical activities studies, evidence was found suggesting that aerobic exercises and multiactivity exercises with high intensity are the more effective for improve the aerobic capacity. Even if few studies on cryotherapy were found, there are enough evidences in the literature that demonstrate the benefits of this intervention on pain relief and disease activity. In summary, neither study found associated physical activities to improve aerobic capacity with cryotherapy to improve disease activity and pain relief. This may be an innovative therapeutic strategy to improve the aerobic capacity in arthritis patients and consequently reduce their cardiovascular risk while minimizing pain and disease activity.
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Identifying critical transitions and their leading biomolecular networks in complex diseases.
Liu, Rui; Li, Meiyi; Liu, Zhi-Ping; Wu, Jiarui; Chen, Luonan; Aihara, Kazuyuki
2012-01-01
Identifying a critical transition and its leading biomolecular network during the initiation and progression of a complex disease is a challenging task, but holds the key to early diagnosis and further elucidation of the essential mechanisms of disease deterioration at the network level. In this study, we developed a novel computational method for identifying early-warning signals of the critical transition and its leading network during a disease progression, based on high-throughput data using a small number of samples. The leading network makes the first move from the normal state toward the disease state during a transition, and thus is causally related with disease-driving genes or networks. Specifically, we first define a state-transition-based local network entropy (SNE), and prove that SNE can serve as a general early-warning indicator of any imminent transitions, regardless of specific differences among systems. The effectiveness of this method was validated by functional analysis and experimental data.
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Anderson, Carl A; Boucher, Gabrielle; Lees, Charlie W; Franke, Andre; D'Amato, Mauro; Taylor, Kent D; Lee, James C; Goyette, Philippe; Imielinski, Marcin; Latiano, Anna; Lagacé, Caroline; Scott, Regan; Amininejad, Leila; Bumpstead, Suzannah; Baidoo, Leonard; Baldassano, Robert N; Barclay, Murray; Bayless, Theodore M; Brand, Stephan; Büning, Carsten; Colombel, Jean-Frédéric; Denson, Lee A; De Vos, Martine; Dubinsky, Marla; Edwards, Cathryn; Ellinghaus, David; Fehrmann, Rudolf S N; Floyd, James A B; Florin, Timothy; Franchimont, Denis; Franke, Lude; Georges, Michel; Glas, Jürgen; Glazer, Nicole L; Guthery, Stephen L; Haritunians, Talin; Hayward, Nicholas K; Hugot, Jean-Pierre; Jobin, Gilles; Laukens, Debby; Lawrance, Ian; Lémann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; McGovern, Dermot P; Milla, Monica; Montgomery, Grant W; Morley, Katherine I; Mowat, Craig; Ng, Aylwin; Newman, William; Ophoff, Roel A; Papi, Laura; Palmieri, Orazio; Peyrin-Biroulet, Laurent; Panés, Julián; Phillips, Anne; Prescott, Natalie J; Proctor, Deborah D; Roberts, Rebecca; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Schumm, Philip; Seibold, Frank; Sharma, Yashoda; Simms, Lisa A; Seielstad, Mark; Steinhart, A Hillary; Targan, Stephan R; van den Berg, Leonard H; Vatn, Morten; Verspaget, Hein; Walters, Thomas; Wijmenga, Cisca; Wilson, David C; Westra, Harm-Jan; Xavier, Ramnik J; Zhao, Zhen Z; Ponsioen, Cyriel Y; Andersen, Vibeke; Torkvist, Leif; Gazouli, Maria; Anagnou, Nicholas P; Karlsen, Tom H; Kupcinskas, Limas; Sventoraityte, Jurgita; Mansfield, John C; Kugathasan, Subra; Silverberg, Mark S; Halfvarson, Jonas; Rotter, Jerome I; Mathew, Christopher G; Griffiths, Anne M; Gearry, Richard; Ahmad, Tariq; Brant, Steven R; Chamaillard, Mathias; Satsangi, Jack; Cho, Judy H; Schreiber, Stefan; Daly, Mark J; Barrett, Jeffrey C; Parkes, Miles; Annese, Vito; Hakonarson, Hakon; Radford-Smith, Graham; Duerr, Richard H; Vermeire, Séverine; Weersma, Rinse K; Rioux, John D
2011-03-01
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
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Noppert, Grace A; Kubale, John T; Wilson, Mark L
2017-04-01
Infectious disease epidemiologists have long recognised the importance of social variables as drivers of epidemics and disease risk, yet few apply analytic approaches from social epidemiology. We quantified and evaluated the extent to which recent infectious disease research is employing the perspectives and methods of social epidemiology by replicating the methodology used by Cohen et al in a 2007 study. 2 search strategies were used to identify and review articles published from 1 January 2005 to 31 December 2013. First, we performed a keyword search of 'social epidemiology' in the title/abstract/text of published studies identified in PubMed, PsychInfo and ISI Web of Science, and classified each study as pertaining to infectious, non-infectious or other outcomes. A second PubMed search identified articles that were cross-referenced under non-infectious or infectious, and search terms relating to social variables. The abstracts of all articles were read, classified and examined to identify patterns over time. Findings suggest that infectious disease research publications that explicitly or implicitly incorporate social epidemiological approaches have stagnated in recent years. While the number of publications that were explicitly self-classified as 'social epidemiology' has risen, the proportion that investigated infectious disease outcomes has declined. Furthermore, infectious diseases accounted for the smallest proportion of articles that were cross-referenced with Medical Subject Headings (MeSH) terms related to social factors, and most of these involved sexually transmitted diseases. The current landscape of infectious disease epidemiology could benefit from new approaches to understanding how the social and biophysical environment sustains transmission and exacerbates disparities. The framework of social epidemiology provides infectious disease researchers with such a perspective and research opportunity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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Etiology and clinical outcome in dogs with aspiration pneumonia: 88 cases (2004-2006).
Kogan, David A; Johnson, Lynelle R; Sturges, Beverly K; Jandrey, Karl E; Pollard, Rachel E
2008-12-01
To evaluate the number and types of underlying disorders detected in dogs with aspiration pneumonia and determine the survival rate among affected dogs. Retrospective case series. Animals-88 dogs with aspiration pneumonia. Medical records were reviewed to identify disease processes that could result in aspiration pneumonia. To assess outcome (ie, survival to discharge from the hospital or nonsurvival), dogs were grouped by the type and number of underlying disease processes. Duration of hospitalization and radiographic severity of disease were evaluated with regard to case outcome. As the cause of aspiration pneumonia, a single underlying disorder was identified in 60 of the 88 dogs; 2 or more diseases were identified in the remaining dogs. Esophageal disease (n = 35), vomiting (34), neurologic disorders (24), laryngeal disease (16), and postanesthetic aspiration (12) were identified most commonly. Overall, 68 dogs survived to discharge from the hospital (survival rate, 77%). Survival rates were comparable among dogs regardless of the underlying cause of aspiration pneumonia. Radiographic severity of disease and duration of hospitalization did not influence survival. Among these study dogs, aspiration pneumonia was associated with a high survival rate. The presence of more than 1 underlying disease associated with aspiration pneumonia did not adversely impact survival rate. Interestingly, radiographic severity of disease and duration of hospitalization were not associated with overall survival rate.
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Complex disease and phenotype mapping in the domestic dog
Hayward, Jessica J.; Castelhano, Marta G.; Oliveira, Kyle C.; Corey, Elizabeth; Balkman, Cheryl; Baxter, Tara L.; Casal, Margret L.; Center, Sharon A.; Fang, Meiying; Garrison, Susan J.; Kalla, Sara E.; Korniliev, Pavel; Kotlikoff, Michael I.; Moise, N. S.; Shannon, Laura M.; Simpson, Kenneth W.; Sutter, Nathan B.; Todhunter, Rory J.; Boyko, Adam R.
2016-01-01
The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies. PMID:26795439
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Identification of Genes Expressed in Premalignant Breast Disease by Microscopy-Directed Cloning
NASA Astrophysics Data System (ADS)
Jensen, Roy A.; Page, David L.; Holt, Jeffrey T.
1994-09-01
Histopathologic study of human breast biopsy samples has identified specific lesions which are associated with a high risk of development of invasive breast cancer. Presumably, these lesions (collectively termed premalignant breast disease) represent the earliest recognizable morphologic expression of fundamental molecular events that lead to the development of invasive breast cancer. To study molecular events underlying premalignant breast disease, we have developed a method for isolating RNA from histologically identified lesions from frozen human breast tissue. This method specifically obtains mRNA from breast epithelial cells and has identified three genes which are differentially expressed in premalignant breast epithelial lesions. One gene identified by this method is overexpressed in four of five noncomedo ductal carcinoma in situ lesions and appears to be the human homologue of the gene encoding the M2 subunit of ribonucleotide reductase, an enzyme involved in DNA synthesis.
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Next Generation Analytic Tools for Large Scale Genetic Epidemiology Studies of Complex Diseases
Mechanic, Leah E.; Chen, Huann-Sheng; Amos, Christopher I.; Chatterjee, Nilanjan; Cox, Nancy J.; Divi, Rao L.; Fan, Ruzong; Harris, Emily L.; Jacobs, Kevin; Kraft, Peter; Leal, Suzanne M.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Province, Michael A.; Ramos, Erin M.; Ritchie, Marylyn D.; Roeder, Kathryn; Schaid, Daniel J.; Stephens, Matthew; Thomas, Duncan C.; Weinberg, Clarice R.; Witte, John S.; Zhang, Shunpu; Zöllner, Sebastian; Feuer, Eric J.; Gillanders, Elizabeth M.
2012-01-01
Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled “Next Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases” on September 15–16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large-scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene-gene and gene-environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized. PMID:22147673
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NASA Astrophysics Data System (ADS)
Lee, J.
2017-12-01
As of April 2017, California is the third most prevalent state on the United States for Zika Infection and Southern California has an ever growing population of Aedes mosquitos. Zika is a disease which poses a significant risk to humans and other mammals due to its effects on pregnancy. This emerging disease is highly contagious due to its spread of infection primarily by Aedes aegypti mosquitos. Aedes mosquitos are able to breed in small rain collecting containers which allow the species to persevere in urban and semi urban environments. We hope to identify potential areas with risk of human infection within Los Angeles and its surrounding areas. This study integrates remote sensing, GIS, statistical, and environmental techniques to study favorable habitats for this particular species of mosquitos and their larvae. The study of the geographic and landscape factors which promote the larvae development allow for the disease spread to be analyzed and modeled. There are several goals in the development of this study. These include the coordination of statistical data with local epidemiology departments, identify workflows to improve efficiency, create models which can be utilized for disease prevention, and identify geographic risk factors for the spread of Zika.
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The role of epigenetics in genetic and environmental epidemiology.
Ladd-Acosta, Christine; Fallin, M Daniele
2016-02-01
Epidemiology is the branch of science that investigates the causes and distribution of disease in populations in order to provide preventative measures and promote human health. The fields of genetic and environmental epidemiology primarily seek to identify genetic and environmental risk factors for disease, respectively. Epigenetics is emerging as an important piece of molecular data to include in these studies because it can provide mechanistic insights into genetic and environmental risk factors for disease, identify potential intervention targets, provide biomarkers of exposure, illuminate gene-environment interactions and help localize disease-relevant genomic regions. Here, we describe the importance of including epigenetics in genetic and environmental epidemiology studies, provide a conceptual framework when considering epigenetic data in population-based studies and touch upon the many challenges that lie ahead.
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NASA Astrophysics Data System (ADS)
Catry, Thibault; Li, Zhichao; Roux, Emmanuel; Herreteau, Vincent; Revillion, Christophe; Dessay, Nadine
2016-08-01
Vector-borne diseases like malaria represent a major public health issue worldwide. Other mosquito-borne diseases affect more and more countries and people, with effects on health which are not all identified yet. Recent developments in the field of remote-sensing allow to consider overriding the existing limits of studying such diseases in tropical regions, where cloud and vegetation cover often prevent to identify and characterize environmental features.We highlight the potential of SAR-optical fusion for the mapping of land cover, the identification of wetlands, and the monitoring of environmental changes in different habitats related to vector-borne diseases in the French Guiana - Brazil cross-border area. This study is the foundation of a landscape-based model of malaria transmission risk. Environmental factors, together with epidemiological, socio-economic, behavioral, demographics, and entomological ones, contribute to assess risks related to such pathologies and support disease control and decision-making by local public health actors.
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Sterling, N W; Lewis, M M; Du, G; Huang, X
2016-05-27
Parkinson's disease (PD) is a progressive age-related neurodegenerative disorder. Although the pathological hallmark of PD is dopaminergic cell death in the substantia nigra pars compacta, widespread neurodegenerative changes occur throughout the brain as disease progresses. Postmortem studies, for example, have demonstrated the presence of Lewy pathology, apoptosis, and loss of neurotransmitters and interneurons in both cortical and subcortical regions of PD patients. Many in vivo structural imaging studies have attempted to gauge PD-related pathology, particularly in gray matter, with the hope of identifying an imaging biomarker. Reports of brain atrophy in PD, however, have been inconsistent, most likely due to differences in the studied populations (i.e. different disease stages and/or clinical subtypes), experimental designs (i.e. cross-sectional vs. longitudinal), and image analysis methodologies (i.e. automatic vs. manual segmentation). This review attempts to summarize the current state of gray matter structural imaging research in PD in relationship to disease progression, reconciling some of the differences in reported results, and to identify challenges and future avenues.
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Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease: Utility and Limitations
Zhao, Xiao; Paterson, Andrew D.; Zahirieh, Alireza; He, Ning; Wang, Kairong; Pei, York
2008-01-01
Background and objectives: Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting. Design, setting, participants, & measurements: Using a molecular diagnostic service, genomic DNA of one affected individual from each study family was screened for pathologic PKD1 and PKD2 mutations. Bidirectional sequencing was performed to identify sequence variants in all exons and splice junctions of both genes and to confirm the specific mutations in other family members. In two multiplex families, microsatellite markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint linkage analysis was performed. Results: Three of five probands studied were referred for assessment of renal cystic disease without a family history of autosomal dominant polycystic kidney disease, and two others were younger at-risk members of families with autosomal dominant polycystic kidney disease being evaluated as living-related kidney donors. Gene-based mutation screening identified pathogenic mutations that provided confirmation or exclusion of disease in three probands, but in the other two, only unclassified variants were identified. In one proband in which mutation screening was indeterminate, DNA linkage studies provided strong evidence for disease exclusion. Conclusions: Gene-based mutation screening or DNA linkage analysis should be considered in individuals in whom the diagnosis of autosomal dominant polycystic kidney disease is uncertain because of a lack of family history or equivocal imaging results and in younger at-risk individuals who are being evaluated as living-related kidney donors. PMID:18077784
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Wu, Bechien U.; Batech, Michael; Quezada, Michael; Lew, Daniel; Fujikawa, Kelly; Kung, Jonathan; Jamil, Laith H.; Chen, Wansu; Afghani, Elham; Reicher, Sonya; Buxbaum, James; Pandol, Stephen J.
2017-01-01
OBJECTIVES Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis. METHODS We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity. RESULTS From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure. CONCLUSIONS We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis. PMID:28462914
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Wu, Bechien U; Batech, Michael; Quezada, Michael; Lew, Daniel; Fujikawa, Kelly; Kung, Jonathan; Jamil, Laith H; Chen, Wansu; Afghani, Elham; Reicher, Sonya; Buxbaum, James; Pandol, Stephen J
2017-07-01
Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis. We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity. From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure. We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis.
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Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A
2016-11-01
Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.
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Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A; Spritz, Richard A
2016-01-01
Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment. PMID:27723757
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Identifying gene networks underlying the neurobiology of ethanol and alcoholism.
Wolen, Aaron R; Miles, Michael F
2012-01-01
For complex disorders such as alcoholism, identifying the genes linked to these diseases and their specific roles is difficult. Traditional genetic approaches, such as genetic association studies (including genome-wide association studies) and analyses of quantitative trait loci (QTLs) in both humans and laboratory animals already have helped identify some candidate genes. However, because of technical obstacles, such as the small impact of any individual gene, these approaches only have limited effectiveness in identifying specific genes that contribute to complex diseases. The emerging field of systems biology, which allows for analyses of entire gene networks, may help researchers better elucidate the genetic basis of alcoholism, both in humans and in animal models. Such networks can be identified using approaches such as high-throughput molecular profiling (e.g., through microarray-based gene expression analyses) or strategies referred to as genetical genomics, such as the mapping of expression QTLs (eQTLs). Characterization of gene networks can shed light on the biological pathways underlying complex traits and provide the functional context for identifying those genes that contribute to disease development.
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Investigation of In vitro Mineral forming bacterial isolates from supragingival calculus.
Baris, O; Demir, T; Gulluce, M
2017-12-01
Although it is known that bacterial mechanisms are involved in dental calculus formation, which is a predisposing factor in periodontal diseases, there have been few studies of such associations, and therefore, information available is limited. The purpose of this study was to isolate and identify aerobic bacteria responsible for direct calcification from supragingival calculus samples. The study was conducted using supragingival calculus samples from patients with periodontal disease, which was required as part of conventional treatment. Isolations were performed by sampling the supragingival calculus with buffer and inoculating the samples on media on which crystallization could be observed. The 16S recombinant DNA of the obtained pure cultures was then amplified and sequenced. A few bacterial species that have not previously been associated with mineralization or identified on bacterial plaque or calculus were detected. The bacteria that caused mineralization an aerobic environment are identified as Neisseria flava, Aggregatibacter segnis, Streptococcus tigurinus, and Morococcus cerebrosus. These findings proved that bacteria potentially play a role in the etiopathology of supragingival calculus. The association between the effects of the identified bacteria on periodontal diseases and calculus formation requires further studies.
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Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.
Tomas, Cara; Newton, Julia
2018-04-17
Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease. There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease. This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5'-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here. Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas. The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets. Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease
Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Choi, Seung-Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George-Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez-Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O’Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li-san; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe
2013-01-01
Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease. PMID:24162737
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The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA
Yarwood, Annie; Huizinga, Tom W. J.
2016-01-01
There is now a general consensus that RA has a spectrum of disease stages that can begin many years before the onset of clinical symptoms. It is widely thought that understanding the complex interplay between genetics and environment, and their role in pathogenesis, is essential in gaining further insight into the mechanisms that drive disease development and progression. More than 100 genetic susceptibility loci have now been identified for RA through studies that have focused on patients with established RA compared with healthy controls. Studying the early preclinical phases of disease will provide valuable insights into the biological events that precede disease and could potentially identify biomarkers to predict disease onset and future therapeutic targets. In this review we will cover recent advances in the knowledge of genetic and environmental risk factors and speculate on how these factors may influence the transition from one stage of disease to another. PMID:25239882
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On the use of haplotype phylogeny to detect disease susceptibility loci
Bardel, Claire; Danjean, Vincent; Hugot, Jean-Pierre; Darlu, Pierre; Génin, Emmanuelle
2005-01-01
Background The cladistic approach proposed by Templeton has been presented as promising for the study of the genetic factors involved in common diseases. This approach allows the joint study of multiple markers within a gene by considering haplotypes and grouping them in nested clades. The idea is to search for clades with an excess of cases as compared to the whole sample and to identify the mutations defining these clades as potential candidate disease susceptibility sites. However, the performance of this approach for the study of the genetic factors involved in complex diseases has never been studied. Results In this paper, we propose a new method to perform such a cladistic analysis and we estimate its power through simulations. We show that under models where the susceptibility to the disease is caused by a single genetic variant, the cladistic test is neither really more powerful to detect an association nor really more efficient to localize the susceptibility site than an individual SNP testing. However, when two interacting sites are responsible for the disease, the cladistic analysis greatly improves the probability to find the two susceptibility sites. The impact of the linkage disequilibrium and of the tree characteristics on the efficiency of the cladistic analysis are also discussed. An application on a real data set concerning the CARD15 gene and Crohn disease shows that the method can successfully identify the three variant sites that are involved in the disease susceptibility. Conclusion The use of phylogenies to group haplotypes is especially interesting to pinpoint the sites that are likely to be involved in disease susceptibility among the different markers identified within a gene. PMID:15904492
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Ofman, Joshua J; Badamgarav, Enkhe; Henning, James M; Knight, Kevin; Gano, Anacleto D; Levan, Rebecka K; Gur-Arie, Shoval; Richards, Margaret S; Hasselblad, Vic; Weingarten, Scott R
2004-08-01
To assess the clinical and economic effects of disease management in patients with chronic diseases. Electronic databases were searched for English-language articles from 1987 to 2001. Articles were included if they used a systematic approach to care and evaluated patients with chronic disease, reported objective measurements of the processes or outcomes of care, and employed acceptable experimental or quasi-experimental study designs as defined by the Cochrane Effective Practice and Organization of Care Group. Two reviewers evaluated 16,917 titles and identified 102 studies that met the inclusion criteria. Identified studies represented 11 chronic conditions: depression, diabetes, rheumatoid arthritis, chronic pain, coronary artery disease, asthma, heart failure, back pain, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia. Disease management programs for patients with depression had the highest percentage of comparisons (48% [41/86]) showing substantial improvements in patient care, whereas programs for patients with chronic obstructive pulmonary disease (9% [2/22]) or chronic pain (8% [1/12]) appeared to be the least effective. Of the outcomes more frequently studied, disease management appeared to improve patient satisfaction (71% [12/17]), patient adherence (47% [17/36]), and disease control (45% [33/74]) most commonly and cost-related outcomes least frequently (11% to 16%). Disease management programs were associated with marked improvements in many different processes and outcomes of care. Few studies demonstrated a notable reduction in costs. Further research is needed to understand how disease management can most effectively improve the quality and cost of care for patients with chronic diseases.
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Helicobacter pylori infection in Canadian and related Arctic Aboriginal populations
Goodman, Karen J; Jacobson, Kevan; van Zanten, Sander Veldhuyzen
2008-01-01
In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities. PMID:18354758
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Meditation Interventions for Chronic Disease Populations: A Systematic Review.
Chan, Roxane Raffin; Larson, Janet L
2015-12-01
The rapidly growing body of research regarding the use of meditation interventions in chronic disease presents an opportunity to compare outcomes based on intervention content. For this review, meditation interventions were described as those interventions delivered to persons with chronic disease where sitting meditation was the main or only content of the intervention with or without the addition of mindful movement. This systematic review identified 45 individual research studies that examined meditations effect on levels of anxiety, depression, and chronic disease symptoms in persons with chronic disease. Individual studies were assessed based on interventional content, the consistency with which interventions were applied, and the research quality. This study identified seven categories of meditation interventions based on the meditation skills and mindful movement practices that were included in the intervention. Overall, half of the interventions had clearly defined and specific meditation interventions (25/45) and half of the studies were conducted using randomized control trials (24/45). © The Author(s) 2015.
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Unorthodox Alternative Therapies Marketed to Treat Lyme Disease
Lantos, Paul M.; Shapiro, Eugene D.; Auwaerter, Paul G.; Baker, Phillip J.; Halperin, John J.; McSweegan, Edward; Wormser, Gary P.
2015-01-01
Background. Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Methods. Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. Results. More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Conclusions. Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful. PMID:25852124
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Reprogramming the metabolome rescues retinal degeneration.
Park, Karen Sophia; Xu, Christine L; Cui, Xuan; Tsang, Stephen H
2018-05-01
Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes-including but not limited to glucose and oxygen metabolism-that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages.
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Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype
Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio
2015-01-01
Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662
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Goldstein, J A; Norris, S A; Aronoff, D M
2017-06-01
The prenatal environment is now recognized as a key driver of non-communicable disease risk later in life. Within the developmental origins of health and disease (DOHaD) paradigm, studies are increasingly identifying links between maternal morbidity during pregnancy and disease later in life for offspring. Nutrient restriction, metabolic disorders during gestation, such as diabetes or obesity, and maternal immune activation provoked by infection have been linked to adverse health outcomes for offspring later in life. These factors frequently co-occur, but the potential for compounding effects of multiple morbidities on DOHaD-related outcomes has not received adequate attention. This is of particular importance in low- or middle-income countries (LMICs), which have ongoing high rates of infectious diseases and are now experiencing transitions from undernutrition to excess adiposity. The purpose of this scoping review is to summarize studies examining the effect and interaction of co-occurring metabolic or nutritional stressors and infectious diseases during gestation on DOHaD-related health outcomes. We identified nine studies in humans - four performed in the United States and five in LMICs. The most common outcome, also in seven of nine studies, was premature birth or low birth weight. We identified nine animal studies, six in mice, two in rats and one in sheep. The interaction between metabolic/nutritional exposures and infectious exposures had varying effects including synergism, inhibition and independent actions. No human studies were specifically designed to assess the interaction of metabolic/nutritional exposures and infectious diseases. Future studies of neonatal outcomes should measure these exposures and explicitly examine their concerted effect.
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ERIC Educational Resources Information Center
Hopp, Joyce W.; And Others
This study demonstrated the feasibility of joint parent-child education to change the behaviors known to be associated with increased risk of coronary heart disease. Earlier studies have shown that parents who are at increased risk of coronary heart disease can be identified by studying certain factors in the children. Utilizing a combined risk…
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Coventry, Peter A; Grande, Gunn E; Richards, David A; Todd, Chris J
2005-05-01
most people in contemporary western society die of the chronic diseases of old age. Whilst palliative care is appropriate for elderly patients with chronic, non-malignant disease, few of these patients access such care compared with cancer patients. Objective referral criteria based on accurate estimation of survival may facilitate more timely referral of non-cancer patients most appropriate for specialist palliative care. to identify tools and predictor variables that might aid clinicians estimate survival and assess palliative status in non-cancer patients aged 65 years and older. systematic review and quality assessment using criteria modified from the literature. 11 studies that evaluated prognoses in hospitalised and community-based older adults with non-malignant disease were identified. Key generic predictors of survival were increased dependency of activities of daily living, presence of comorbidities, poor nutritional status and weight loss, and abnormal vital signs and laboratory values. Disease-specific predictors of survival were identified for dementia, chronic obstructive pulmonary disorder and congestive heart failure. No study evaluated the relationship between survival and palliative status. prognostic models that attempt to estimate survival of < or = 6 months in non-cancer patients have generally poor discrimination, reflecting the unpredictable nature of most non-malignant disease. However, a number of generic and disease-specific predictor variables were identified that may help clinicians identify older, non-cancer patients with poor prognoses and palliative care needs. Simple, well-validated prognostic models that provide clinicians with objective measures of palliative status in non-cancer patients are needed. Additionally, research that evaluates the effect of general and specialist palliative care on psychosocial outcomes in non-cancer patients and their carers is needed.
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Unorthodox alternative therapies marketed to treat Lyme disease.
Lantos, Paul M; Shapiro, Eugene D; Auwaerter, Paul G; Baker, Phillip J; Halperin, John J; McSweegan, Edward; Wormser, Gary P
2015-06-15
Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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A Systematic Review Regarding Tonometry and the Transmission of Infectious Diseases.
Atkins, Nicole; Hodge, William; Li, Bruce
2018-03-01
Tonometry has been identified as a common method for measuring the intraocular pressure in patients. The direct contact between the tonometer and the eye may contribute to the risk of cross infection, especially of viral particles, from one patient to another. A systematic review was undertaken to address the likelihood of human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and prion diseases transmission through the use of tonometers. Additionally, a comparison of the current tonometer disinfection methods is provided to assist with identifying which technique effectively reduces the risk of disease transmission. An electronic literature search was conducted using the following databases: Web of Science, EMBASE, CINAHL, SCOPUS, Biosis Previews, Cochrane Library, PubMed, and Google Scholar. Dissertation indexes were also searched, and these included: Dissertations and Abstracts, and Dissertations and Abstracts - UK/Ireland. Additionally, the Clinicaltrials.gov trial registry was searched to identify any other relevant literature. Two independent reviewers critically appraised the articles retrieved through the literature search. In total, 11 unique studies were deemed relevant for this systematic review. The available evidence demonstrated that the use of tonometers contributes to the transmission of these infectious diseases in vitro . The results also demonstrated variability in determining the most effective tonometer sterilization technique against these infectious diseases in vitro . There was limited evidence available regarding the transmission of HIV, hepatitis B, hepatitis C, and prion diseases through the use of tonometers. Additionally, due to the variability regarding the most effective sterilization techniques, it is difficult to identify which sterilization technique is most effective or adequately effective against these infectious diseases. Future research studies regarding infectious disease transmission through tonometry and sterilization techniques should be completed to more adequately inform infectious disease control guidelines.
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Molecular diagnosis of putative Stargardt disease probands by exome sequencing
2012-01-01
Background The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD) caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. Methods We performed whole exome sequencing (WES) of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. Results Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. Conclusions Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques. PMID:22863181
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A global systematic review of Chagas disease prevalence among migrants.
Conners, Erin E; Vinetz, Joseph M; Weeks, John R; Brouwer, Kimberly C
2016-04-01
Human migration has been identified as a potential factor for increased Chagas disease risk and has transformed the disease from a Latin American problem to a global one. We conducted a systematic review of the scientific literature between 2004-2014 in order to: summarize recent seroprevalence estimates of Chagas disease among Latin American migrants, in both endemic and non-endemic settings; compare seroprevalence estimates in migrants to countrywide prevalence estimates; and identify risk factors for Chagas disease among migrants. A total of 320 studies were screened and 23 studies were included. We found evidence that the prevalence of Chagas disease is higher than expected in some migrant groups and that reliance on blood donor screening prevalence estimates underestimates the burden of disease. Overall there is a dearth of high quality epidemiologic studies on the prevalence of Chagas disease in migrants, especially among intra-regional migrants within Latin America. Given that this zoonotic disease cannot likely be eradicated, improved surveillance and reporting is vital to continuing control efforts. More accurate health surveillance of both Latin American migrants and the Chagas disease burden will help countries appropriately scale up their response to this chronic disease. Overall, improved estimates of Chagas disease among migrants would likely serve to highlight the real need for better screening, diagnostics, and treatment of individuals living with the disease. Copyright © 2016 Elsevier B.V. All rights reserved.
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Suratanee, Apichat; Plaimas, Kitiporn
2017-01-01
The associations between proteins and diseases are crucial information for investigating pathological mechanisms. However, the number of known and reliable protein-disease associations is quite small. In this study, an analysis framework to infer associations between proteins and diseases was developed based on a large data set of a human protein-protein interaction network integrating an effective network search, namely, the reverse k -nearest neighbor (R k NN) search. The R k NN search was used to identify an impact of a protein on other proteins. Then, associations between proteins and diseases were inferred statistically. The method using the R k NN search yielded a much higher precision than a random selection, standard nearest neighbor search, or when applying the method to a random protein-protein interaction network. All protein-disease pair candidates were verified by a literature search. Supporting evidence for 596 pairs was identified. In addition, cluster analysis of these candidates revealed 10 promising groups of diseases to be further investigated experimentally. This method can be used to identify novel associations to better understand complex relationships between proteins and diseases.
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Therapeutic approaches for celiac disease
Plugis, Nicholas M.; Khosla, Chaitan
2015-01-01
Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114
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[Scrining workers employed at the weapons and military technology recycling and disposal facilitie].
2012-01-01
A screening study was performed to identify factors of the raised risk of cardiovascular and bronchopulmonary diseases among workers involved in weapons and military technology recycling and disposal. A high prevalence of risk factors such as smoking, excess body mass, adiposis, disorders of the carbohydrate, lipid and purine metabolism was found for workers aged 35 years and older. Circulatory, musculoskeletal, and eye diseases prevailed in the structure of first diagnosed diseases. Taking into account an unfavorable profile of risk factors, groups with the raised risk of cardiovascular and bronchopulmonary diseases were identified. An expansion of the standard scope of examination in the framework of regular medical monitoring in compliance with the applicable regulatory documents by inclusion of screening studies would provide additional opportunities for the early diagnosing and prevention of the above diseases.
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The lung may play a role in the pathogenesis of rheumatoid arthritis
Demoruelle, M Kristen; Solomon, Joshua J; Fischer, Aryeh; Deane, Kevin D
2015-01-01
Multiple studies have identified strong associations between the lung and rheumatoid arthritis (RA). Such studies identify a high prevalence of lung disease, both airways and parenchymal disease, in subjects with clinically classifiable RA. It has been suggested that lung disease in RA results from targeting of the lung from circulating autoimmunity or other factors such as medications. However, findings that lung disease, specifically inflammatory airways disease, and lung generation of autoimmunity can be present before the onset of joint symptoms suggest that immune reactions in the lung may be involved in the initial development of RA-related autoimmunity. Herein we review these issues in detail, as well as outline a potential research agenda to understand the natural history of lung involvement in RA and its relation to the overall pathogenesis of RA. PMID:26089988
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Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases.
Fung, Isaac Chun-Hai; Hao, Yi; Cai, Jingxian; Ying, Yuchen; Schaible, Braydon James; Yu, Cynthia Mengxi; Tse, Zion Tsz Ho; Fu, King-Wa
2015-01-01
This study aimed to identify what information triggered social media users' responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education/information; alternative health information/Traditional Chinese Medicine; commercial advertisement/entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.
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Hellyer, Nicole Elizabeth; Haddock-Fraser, Janet
2011-02-01
This study identifies (i) the extent to which newsprint media communicate to their readers the lifestyle factors associated with the development of cardiovascular disease and Type 2 diabetes and (ii) newspaper portrayal of social determinants affecting onset of disease. A content analysis of five leading UK national newspapers and their Sunday equivalents was conducted over a 3-month period between January and March 2008. This study shows that cardiovascular disease had much higher press interest than Type 2 diabetes. 'Middle-market' and 'Quality' papers had higher levels of reporting than the 'Popular' press, but the patterns were more complex when the comprehensiveness of reporting was measured within each article. Social determinants affecting disease onset were poorly reported by newspapers, supporting similar research conducted in other countries. This research identifies that there is potential for newspapers to improve their reporting of lifestyle diseases, by including individual and social determinants of disease onset. Lower social classes who read the popular press receive the lowest frequency of reporting and could benefit most from this information. While the research identifies that newspapers are missing the potential to actively communicate and reinforce government health policy, it recognises that the commercial context of the print media may counter such behaviour.
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Rijks, J M; Cito, F; Cunningham, A A; Rantsios, A T; Giovannini, A
2016-07-01
Prioritization of companion animal transmissible diseases was performed by the Companion Animals multisectoriaL interprofessionaL Interdisciplinary Strategic Think tank On zoonoses (CALLISTO) project. The project considered diseases occurring in domesticated species commonly kept as pets, such as dogs and cats, but also included diseases occurring in captive wild animals and production animal species. The prioritization process led to the selection of 15 diseases of prime public health relevance, agricultural economic importance, or both. An analysis was made of the current knowledge on the risk of occurrence and transmission of these diseases among companion animals, and from companion animals to man (zoonoses) or to livestock. The literature was scanned for risk assessments for these diseases. Studies were classified as import risk assessments (IRAs) or risk factor analyses (RFAs) in endemic areas. For those pathogens that are absent from Europe, only IRAs were considered; for pathogens present throughout Europe, only RFAs were considered. IRAs were identified for seven of the eight diseases totally or partially absent from Europe. IRAs for classical rabies and alveolar echinococcosis found an increased risk for introduction of the pathogen into officially disease-free areas as a consequence of abandoning national rules and adopting the harmonized EU rules for pet travel. IRAs for leishmaniosis focused on risk associated with the presence of persistently infected dogs in new geographical areas, taking into consideration the risk of disease establishment should a competent vector arise. IRAs for Crimean-Congo haemorrhagic fever and West Nile fever indicated that the likelihood of introduction via companion animals was low. IRAs for bluetongue paid no attention to the risk of introduction via companion animals, which was also the case for IRAs for foot-and-mouth disease, the only disease considered to be absent from Europe. RFAs dealing with the risk factors for companion animals to become infected were identified for eight of the 14 diseases found in Europe or parts of it. RFAs for leptospirosis were most numerous (four studies). The host related risk factor 'age' was identified as significant for dogs in at least two RFAs for cystic echinococcosis and giardiasis. Among husbandry and healthcare related factors, 'eating (uncooked) offal', 'being free roaming' and 'poor deworming practice' were associated with risk for dogs in at least two RFAs for cystic echinococcosis, while 'having received recent veterinary treatment' was identified as a risk factor in at least two studies on infection with extended spectrum beta lactamase-producing bacteria, one in horses and the other in dogs and cats. Finally, although the environmental factors 'season' and 'hydrological density' were identified as significant risk factors for dogs in at least two RFAs for leptospirosis, the inconsistent case definitions used in those studies made comparison of study results problematic. RFAs considering the risk of people becoming infected from companion animals were identified for eight of the 14 diseases found in Europe or parts of it. RFAs for human campylobacteriosis were the most numerous (n = 6). Most studies made an assessment as to whether keeping a pet per se, or keeping a pet with supposed or known risk factors, was a risk factor for people relative to other risks. This allowed some studies to report the population attributable risk or population attributable fraction of the incidence of human disease due to companion animals (for campylobacteriosis, salmonellosis and toxoplasmosis), which is a measure that is easy to perceive for laymen and policy makers. No RFAs were found that dealt with the risk to food animals from companion animals for any of the 15 pathogens investigated. Few risk method-based studies were identified that provided information on risk factors for companion animals and on their role as a source of these 15 selected diseases, indicating a clear knowledge gap. There were not enough assessments for any of the 15 diseases to allow meta-analyses, whether these assessments dealt with companion animal disease risk or companion animal-associated human disease risk. Important method and technology gaps were the lack of harmonization in the case definitions used for a given disease and the lack of good diagnostics allowing pathogen identification to taxonomic levels that are meaningful for risk analysis. Molecular epidemiology studies on zoonotic pathogens, which included companion animals among the potential human risk factors, were not found, although such studies would provide good preliminary insights without requiring any tracing of people or any interviews. In addition to performing further risk studies that take into account these issues, there is a need for responsible pet ownership and continued education of professionals in companion animal zoonoses. Additional risk assessment studies should allow more targeted actions to reduce the risk of zoonotic diseases transferred via companion animals and provide information that will promote risk-awareness in healthy human-animal relationships. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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de Silva, Andrea M; Martin-Kerry, Jacqueline M; McKee, Katherine; Cole, Deborah
2017-08-01
Objective The aim of the present study was to identify all evidence about the prevalence and severity of clinically measured caries and periodontal disease in Indigenous adults in Australia published in peer-reviewed journals and to summarise trends over time. In addition, we examined whether the studies investigated associations between putative risk factors and levels of caries and periodontal disease. Methods PubMed was searched in September 2014, with no date limitations, for published peer-reviewed articles reporting the prevalence rates and/or severity of caries and periodontal disease in Indigenous adults living in Australia. Articles were excluded if measurement was not based on clinical assessment and if oral disease was reported only in a specific or targeted sample, and not the general population. Results The search identified 18 papers (reporting on 10 primary studies) that met the inclusion criteria. The studies published clinical data about dental caries and/or periodontal disease in Australian Indigenous adults. The studies reported on oral health for Indigenous adults living in rural (40%), urban (10%) and both urban and rural (50%) locations. Included studies showed that virtually all Indigenous adults living in rural locations had periodontal disease. The data also showed caries prevalence ranged from 46% to 93%. Although 10 studies were identified, the peer-reviewed literature was extremely limited and no published studies were identified that provided statistics for a significant proportion of Australia (Victoria, Tasmania, Queensland or the Australian Capital Territory). There were also inconsistencies in how the data were reported between studies, making comparisons difficult. Conclusions This review highlights a lack of robust and contemporary data to inform the development of policies and programs to address the disparities in oral health in Indigenous populations living in many parts of Australia. What is known about the topic? Many studies report that Indigenous people in Australia have poorer general health compared with non-Indigenous people. What does this paper add? This paper documents the available caries and periodontal disease prevalence and experience for Indigenous adults in Australia published in peer-reviewed journals. It demonstrates significant limitations in the data, including no data in several large Australian jurisdictions, inconsistency with reporting methods and most data available being for Indigenous adults living in rural locations. Therefore, the oral health data available in the peer-reviewed literature do not reflect the situation of all Indigenous people living in Australia. What are the implications for practitioners? It is important for oral health practitioners to have access to current and relevant statistics on the oral health of Indigenous Australians. However, we have highlighted significant evidence gaps for this population group within the peer-reviewed literature and identified the limitations of the available data upon which decisions are currently being made. This paper also identifies ways to capture and report oral health data in the future to enable more meaningful comparisons and relevance for use in policy development.
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Spatial distribution of deaths due to Alzheimer's disease in the state of São Paulo, Brazil.
Almeida, Milena Cristina da Silva; Gomes, Camila de Moraes Santos; Nascimento, Luiz Fernando Costa
2014-01-01
Alzheimer's disease is a common cause of dementia and identifying possible spatial patterns of mortality due to this disease may enable preventive actions. The objective of this study was to identify spatial distribution patterns of mortality due to Alzheimer's disease in the state of São Paulo. Ecological and exploratory study conducted in all municipalities in the state of São Paulo. Data on Alzheimer's disease mortality in the state of São Paulo between 2004 and 2009 were obtained from DATASUS (the Department of Informatics in the Brazilian Ministry of Health). Death rates per 100,000 inhabitants were then calculated and spatial analysis was performed by constructing a death rate map, global Moran index and local Moran index, which were used to obtain the Moran map. The kernel technique was also applied. The Terra View 4.0.0 software was used. 13,030 deaths due to Alzheimer were reported in the state of São Paulo (rate of 5.33 deaths/100,000 inhabitants). São José do Rio Preto, Ribeirão Preto, Bauru and Araçatuba had higher rates. The Moran index was I = 0.085 (P < 0.002). The Moran map identified 42 municipalities that merit intervention and the kernel estimator identified a high density of deaths in the northwestern region of the state. Higher densities of deaths due to Alzheimer were concentrated more to the north and northwest of the state of São Paulo. It was possible to identify municipalities that have priority for interventions to reduce the death rates due to this disease.
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Molecular identification of bacteria associated with canine periodontal disease.
Riggio, Marcello P; Lennon, Alan; Taylor, David J; Bennett, David
2011-06-02
Periodontal disease is one of the most common diseases of adult dogs, with up to 80% of animals affected. The aetiology of the disease is poorly studied, although bacteria are known to play a major role. The purpose of this study was to identify the bacteria associated with canine gingivitis and periodontitis and to compare this with the normal oral flora. Swabs were obtained from the gingival margin of three dogs with gingivitis and three orally healthy controls, and subgingival plaque was collected from three dogs with periodontitis. Samples were subjected to routine bacterial culture. The prevalent species identified in the normal, gingivitis and periodontitis groups were uncultured bacterium (12.5% of isolates), Bacteroides heparinolyticus/Pasteurella dagmatis (10.0%) and Actinomyces canis (19.4%), respectively. Bacteria were also identified using culture-independent methods (16S rRNA gene sequencing) and the predominant species identified were Pseudomonas sp. (30.9% of clones analysed), Porphyromonas cangingivalis (16.1%) and Desulfomicrobium orale (12.0%) in the normal, gingivitis and periodontitis groups, respectively. Uncultured species accounted for 13.2%, 2.0% and 10.5%, and potentially novel species for 38.2%, 38.3% and 35.3%, of clones in the normal, gingivitis and periodontitis groups, respectively. This is the first study to use utilise culture-independent methods for the identification of bacteria associated with this disease. It is concluded that the canine oral flora in health and disease is highly diverse and also contains a high proportion of uncultured and, in particular, potentially novel species. Copyright © 2011 Elsevier B.V. All rights reserved.
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Potential role of viruses in white plague coral disease.
Soffer, Nitzan; Brandt, Marilyn E; Correa, Adrienne M S; Smith, Tyler B; Thurber, Rebecca Vega
2014-02-01
White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.
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Burden of disease in Nariño, Colombia, 2010
Trujillo-Montalvo, Elizabeth; Hidalgo-Patiño, Carlos; Hidalgo-Eraso, Angela
2014-01-01
Objective: This study sought to measure burden of disease and identifies health priorities from the Disability Adjusted Life Years (DALYs) indicator. Methods: This is the first study on burden of disease for a department in Colombia by using a standardized methodology. By using the DALYs indicator, burden of disease was identified in the department of Nariño according to the guidelines established by the World Health Organization. Results: The DALYs in the Department of Nariño highlight the emergence of communicable, maternal, perinatal, and nutritional diseases during the first years of life; of accidents and lesions among youth, and non-communicable diseases in older individuals. Also, accidents and lesions are highlighted in men and non-communicable diseases in women. Conclusions: This study is part of the knowledge management process in the Departmental Health Plan for Nariño - Colombia 2012-2015 and contributes to the system of indicators of the 2012 ten-year public health plan. This research evidences that communicable diseases generate the biggest part of the burden of disease in the Department of Nariño, that DALYs due to non-communicable diseases are on the rise, and that accidents and lesions, especially due to violence are an important cause of DALYs in this region, which is higher than that of the country. PMID:25386034
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The expanding universe of inflammatory bowel disease genetics.
Achkar, Jean-Paul; Duerr, Richard
2008-07-01
Genetic factors play an important role in the pathogenesis of inflammatory bowel disease. In this review, we will provide an update on the rapid advances in the discovery of inflammatory bowel disease, primarily Crohn's disease, associated genes. Seven recently published Crohn's disease genome-wide association studies have confirmed prior findings related to the nucleotide-binding oligomerization domain 2 (NOD2) gene and the IBD5 locus. In addition, 10 novel loci have been identified and well replicated. Several promising associations between Crohn's disease and gene variants have been identified and replicated, the two most widely replicated being variants in the IL23R and ATG16L1 genes. These findings highlight and further support the importance of the immune system and its interactions with the intestinal microflora in the pathogenesis of inflammatory bowel disease.
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Zhang, Kunlin; Chang, Suhua; Cui, Sijia; Guo, Liyuan; Zhang, Liuyan; Wang, Jing
2011-07-01
Genome-wide association study (GWAS) is widely utilized to identify genes involved in human complex disease or some other trait. One key challenge for GWAS data interpretation is to identify causal SNPs and provide profound evidence on how they affect the trait. Currently, researches are focusing on identification of candidate causal variants from the most significant SNPs of GWAS, while there is lack of support on biological mechanisms as represented by pathways. Although pathway-based analysis (PBA) has been designed to identify disease-related pathways by analyzing the full list of SNPs from GWAS, it does not emphasize on interpreting causal SNPs. To our knowledge, so far there is no web server available to solve the challenge for GWAS data interpretation within one analytical framework. ICSNPathway is developed to identify candidate causal SNPs and their corresponding candidate causal pathways from GWAS by integrating linkage disequilibrium (LD) analysis, functional SNP annotation and PBA. ICSNPathway provides a feasible solution to bridge the gap between GWAS and disease mechanism study by generating hypothesis of SNP → gene → pathway(s). The ICSNPathway server is freely available at http://icsnpathway.psych.ac.cn/.
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Forecasting Alzheimer's Disease.
ERIC Educational Resources Information Center
Fackelmann, Kathleen
1996-01-01
Suggests that doctors may one day be able to identify healthy people who will develop Alzheimer's disease. Discusses recent studies in which characteristics of a person's writing early in life appear to predict the disease, and brain scans can highlight changes that may precede dementia. (CCM)
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Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su
2015-01-01
It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation.
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2015-01-01
Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. Results In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. Conclusions This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation. PMID:26043779
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Ecologic Niche Modeling and Potential Reservoirs for Chagas Disease, Mexico.
Sánchez-Cordero, Victor; Ben Beard, C.; Ramsey, Janine M.
2002-01-01
Ecologic niche modeling may improve our understanding of epidemiologically relevant vector and parasite-reservoir distributions. We used this tool to identify host relationships of Triatoma species implicated in transmission of Chagas disease. Associations have been documented between the protracta complex (Triatoma: Triatominae: Reduviidae) with packrat species (Neotoma spp.), providing an excellent case study for the broader challenge of developing hypotheses of association. Species pairs that were identified coincided exactly with those in previous studies, suggesting that local interactions between Triatoma and Neotoma species and subspecies have implications at a geographic level. Nothing is known about sylvatic associates of T. barberi, which are considered the primary Chagas vector in Mexico; its geographic distribution coincided closely with that of N. mexicana, suggesting interaction. The presence of the species was confirmed in two regions where it had been predicted but not previously collected. This approach may help in identifying Chagas disease risk areas, planning vector-control strategies, and exploring parasite-reservoir associations for other emerging diseases. PMID:12095431
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FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project.
Beaulieu, Chandree L; Majewski, Jacek; Schwartzentruber, Jeremy; Samuels, Mark E; Fernandez, Bridget A; Bernier, Francois P; Brudno, Michael; Knoppers, Bartha; Marcadier, Janet; Dyment, David; Adam, Shelin; Bulman, Dennis E; Jones, Steve J M; Avard, Denise; Nguyen, Minh Thu; Rousseau, Francois; Marshall, Christian; Wintle, Richard F; Shen, Yaoqing; Scherer, Stephen W; Friedman, Jan M; Michaud, Jacques L; Boycott, Kym M
2014-06-05
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE's impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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Chronic kidney disease of unknown etiology in Sri Lanka
2016-01-01
Introduction In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1–22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. Methods A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Results Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Discussion Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization. PMID:27399161
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Chronic kidney disease of unknown etiology in Sri Lanka.
Rajapakse, Senaka; Shivanthan, Mitrakrishnan Chrishan; Selvarajah, Mathu
2016-07-01
In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization.
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Martínez-Salmeron, J F; Rodrigo, M; de Teresa, J; Nogueras, F; García-Montero, M; de Sola, C; Salmeron, J; Caballero, M
1993-01-01
An epidemiological study of inflammatory bowel disease in the Province of Granada, Spain, was conducted between 1979 and 1988. Altogether, 257 cases were identified: 167 ulcerative colitis, 79 Crohn's disease, and 11 indeterminate colitis. The mean incidence of ulcerative colitis in the 10 year period was 2/10(5) and 0.9/10(5) for Crohn's disease. This is the first epidemiological study in Spain of the incidence of ulcerative colitis and corroborates the results of an earlier population based study on the incidence of Crohn's disease in Spain. PMID:8406155
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Romagnoli, Francesco; Colaiacomo, Maria Chiara; De Milito, Ritanna; Modini, Claudio; Gualdi, Gianfranco; Catani, Marco
2014-01-01
The sigmoidorectal junction (SRJ) has been defined as an anatomical sphincter with particular physiological behavior that regulates sigmoid and rectum evacuation. Its function in clinical conditions, such as diverticular disease has been advocated. The aim of our study is to identify the SRJ and to compare the morphometric and dynamic features of the SRJ between patients with diverticular disease and healthy subjects using MR-defecography. Sixteen individuals, eight with uncomplicated diverticular disease and eight healthy subjects, were studied using MR-defecography to identify the SRJ and to compare the morphometric and dynamic features observed. In each subject studied, MR-defecography was able to identify the SRJ. This resulted in the identification of a discrete anatomical entity with a mean length of 31.23 mm, located in front of the first sacral vertebra (S1) and at a mean distance of 15.55 cm from the anal verge, with a mean wall thickness of 4.45 mm, significantly different from the sigmoid and rectal parietal thickness. The SRJ wall was significantly thicker in patients with diverticular disease than the controls (P = 0.005), showing a unique shape and behavior in dynamic sequences. Our findings support the hypothesis that SRJ plays a critical role in patients with symptomatic diverticular disease; further investigation may clarify whether specific SRJ analysis, such as MR-defecography, would predict inflammatory complications of this diffuse and heterogenic disease.
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[Arterial diseases in women using combined hormonal contraceptives].
Novotná, M; Unzeitig, V; Novotný, T
2002-05-01
To determine the association between myocardial infarction and cerebral stroke and use of combined oral contraceptives. Review of literature. Department of Obstetrics and Gynaecology, Hospital of Merciful Brothers, Brno, Czech Republic. Identification of methodologically sound studies able to address the topic. Studies were identified by Medline database search. Five the most recent and important studies were the main source of information (Oxford Family Planning Association Contraception Study 1984, Royal College of General Practitioners' Study 1994, WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception 1996, 1997, Transnational Study on Oral Contraceptives and the Health of Young Women 1997, Myocardial Infarction and Oral Contraceptives Study, 1997). Generally there was no evidence of a significantly increased risk of arterial wall disease in healthy non smoked users younger than 35 years. No difference between second and third generation oral contraceptives on risk of arterial wall disease were found. In the most of cases of myocardial infarction or stroke one or more risk factor were identified. Two of the most relevant risk factors are smoking and the absence of blood pressure control. The risk of arterial cardiovascular system diseases seems not to be increased at no-risk users (healthy non-smoker younger than 35 years).
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Features of Coping with Disease in Iranian Multiple Sclerosis Patients: a Qualitative Study.
Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas
2018-03-01
Introduction: Coping with disease is of the main components improving the quality of life in multiple sclerosis patients. Identifying the characteristics of this concept is based on the experiences of patients. Using qualitative research is essential to improve the quality of life. This study was conducted to explore the features of coping with the disease in patients with multiple sclerosis. Method: In this conventional content analysis study, eleven multiple sclerosis patients from Iran MS Society in Tehran (Iran) participated. Purposive sampling was used to select participants. Data were gathered using semi structured interviews. To analyze data, a conventional content analysis approach was used to identify meaning units and to make codes and categories. Results: Results showed that features of coping with disease in multiple sclerosis patients consists of (a) accepting the current situation, (b) maintenance and development of human interactions, (c) self-regulation and (d) self-efficacy. Each of these categories is composed of sub-categories and codes that showed the perception and experience of patients about the coping with disease. Conclusion: Accordingly, a unique set of features regarding features of coping with the disease were identified among the patients with multiple sclerosis. Therefore, working to ensure the emergence of, and subsequent reinforcement of these features in MS patients can be an important step in improving the adjustment and quality of their lives.
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Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases.
Torres, Joana; Caprioli, Flavio; Katsanos, Konstantinos H; Lobatón, Triana; Micic, Dejan; Zerôncio, Marco; Van Assche, Gert; Lee, James C; Lindsay, James O; Rubin, David T; Panaccione, Remo; Colombel, Jean-Frédéric
2016-12-01
Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higher risk for complications. It is therefore essential to identify high-risk patients - both at diagnosis and throughout disease course. As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014. Patients with Crohn's disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosing behaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use. Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient. © European Crohn’s and Colitis Organisation 2016.
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The Influence of Genetics on Cystic Fibrosis Phenotypes
Knowles, Michael R.; Drumm, Mitchell
2012-01-01
Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF. PMID:23209180
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2009-01-01
Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays) representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration) in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level. PMID:20003209
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de Albuquerque Seixas, Emerson; Carmello, Beatriz Leone; Kojima, Christiane Akemi; Contti, Mariana Moraes; Modeli de Andrade, Luiz Gustavo; Maiello, José Roberto; Almeida, Fernando Antonio; Martin, Luis Cuadrado
2015-05-01
Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in São Paulo state were analyzed for associations between significant coronary artery diseases (≥70% stenosis in one or more epicardial coronary arteries or ≥50% in the left main coronary artery) and clinical parameters. Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.
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Markunas, Christina A; Johnson, Eric O; Hancock, Dana B
2017-07-01
Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference = 1.28 × 10 -6 vs. enhancers P TissueDifference = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.
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Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross
Ferris, Martin T.; Aylor, David L.; Bottomly, Daniel; Whitmore, Alan C.; Aicher, Lauri D.; Bell, Timothy A.; Bradel-Tretheway, Birgit; Bryan, Janine T.; Buus, Ryan J.; Gralinski, Lisa E.; Haagmans, Bart L.; McMillan, Leonard; Miller, Darla R.; Rosenzweig, Elizabeth; Valdar, William; Wang, Jeremy; Churchill, Gary A.; Threadgill, David W.; McWeeney, Shannon K.; Katze, Michael G.; Pardo-Manuel de Villena, Fernando; Baric, Ralph S.; Heise, Mark T.
2013-01-01
Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss. PMID:23468633
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Risk of early surgery for Crohn's disease: implications for early treatment strategies.
Sands, Bruce E; Arsenault, Joanne E; Rosen, Michael J; Alsahli, Mazen; Bailen, Laurence; Banks, Peter; Bensen, Steven; Bousvaros, Athos; Cave, David; Cooley, Jeffrey S; Cooper, Herbert L; Edwards, Susan T; Farrell, Richard J; Griffin, Michael J; Hay, David W; John, Alex; Lidofsky, Sheldon; Olans, Lori B; Peppercorn, Mark A; Rothstein, Richard I; Roy, Michael A; Saletta, Michael J; Shah, Samir A; Warner, Andrew S; Wolf, Jacqueline L; Vecchio, James; Winter, Harland S; Zawacki, John K
2003-12-01
In this study we aimed to define the rate of early surgery for Crohn's disease and to identify risk factors associated with early surgery as a basis for subsequent studies of early intervention in Crohn's disease. We assembled a retrospective cohort of patients with Crohn's disease diagnosed between 1991 and 1997 and followed for at least 3 yr, who were identified in 16 community and referral-based practices in New England. Chart review was performed for each patient. Details of baseline demographic and disease features were recorded. Surgical history including date of surgery, indication, and procedure were also noted. Risk factors for early surgery (defined as major surgery for Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of diagnosis) were identified by univariate analysis. Multiple logistic regression was used to identify independent risk factors. Of 345 eligible patients, 69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients (4.1%) who had major surgery at the time of diagnosis. Overall, the interval between diagnosis and surgery was short; one half of all patients who required surgery underwent operation within 6 months of diagnosis. Risk factors identified by univariate analysis as significantly associated with early surgery included the following: smoking; disease of small bowel without colonic involvement; nausea and vomiting or abdominal pain on presentation; neutrophil count; and steroid use in the first 6 months. Disease localized to the colon only, blood in the stool, use of 5-aminosalicylate, and lymphocyte count were inversely associated with risk of early surgery. Logistic regression confirmed independent associations with smoking as a positive risk factor and involvement of colon without small bowel as a negative risk factor for early surgery. The rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease, particularly in the first 6 months. These results suggest that improved risk stratification and potent therapies with rapid onset of action are needed to modify the natural history of Crohn's disease.
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Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay
2012-10-01
Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke. The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline. Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively). Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.
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Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay
2012-01-01
Objective Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if a self-reported early menopause (menopause at an age <46) identifies women as at risk for future coronary heart disease or stroke. Methods The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000–2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46) and future coronary heart disease and stroke was assessed in 2509 women (ages 45–84, 987 White, 331 Chinese, 641 Black, 550 Hispanic) from the Multi-Ethnic Study Atherosclerosis, who were free of cardiovascular disease at baseline. Results 693/2509 (28%) of women reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank p=<0.008 and 0.0158). In models adjusted for age, race/ethnicity, Multi-Ethnic Study Atherosclerosis site and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (HR 2.08, 95% CI 1.17, 3.70 and 2.19, 95% CI 1.11, 4.32, respectively). Conclusions Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors. PMID:22692332
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Davis, Ian J.; Wallis, Corrin; Deusch, Oliver; Colyer, Alison; Milella, Lisa; Loman, Nick; Harris, Stephen
2013-01-01
Periodontal disease is the most widespread oral disease in dogs which if left untreated results in significant pain to the pet and loss of dentition. The objective of this study was to identify bacterial species in canine plaque that are significantly associated with health, gingivitis and mild periodontitis (<25% attachment loss). In this survey subgingival plaque samples were collected from 223 dogs with healthy gingiva, gingivitis and mild periodontitis with 72 to 77 samples per health status. DNA was extracted from the plaque samples and subjected to PCR amplification of the V1-V3 region of the 16S rDNA. Pyrosequencing of the PCR amplicons identified a total of 274 operational taxonomic units after bioinformatic and statistical analysis. Porphyromonas was the most abundant genus in all disease stages, particularly in health along with Moraxella and Bergeyella. Peptostreptococcus, Actinomyces, and Peptostreptococcaceae were the most abundant genera in mild periodontitis. Logistic regression analysis identified species from each of these genera that were significantly associated with health, gingivitis or mild periodontitis. Principal component analysis showed distinct community profiles in health and disease. The species identified show some similarities with health and periodontal disease in humans but also major differences. In contrast to human, healthy canine plaque was found to be dominated by Gram negative bacterial species whereas Gram positive anaerobic species predominate in disease. The scale of this study surpasses previously published research and enhances our understanding of the bacterial species present in canine subgingival plaque and their associations with health and early periodontal disease. PMID:24349448
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Davis, Ian J; Wallis, Corrin; Deusch, Oliver; Colyer, Alison; Milella, Lisa; Loman, Nick; Harris, Stephen
2013-01-01
Periodontal disease is the most widespread oral disease in dogs which if left untreated results in significant pain to the pet and loss of dentition. The objective of this study was to identify bacterial species in canine plaque that are significantly associated with health, gingivitis and mild periodontitis (<25% attachment loss). In this survey subgingival plaque samples were collected from 223 dogs with healthy gingiva, gingivitis and mild periodontitis with 72 to 77 samples per health status. DNA was extracted from the plaque samples and subjected to PCR amplification of the V1-V3 region of the 16S rDNA. Pyrosequencing of the PCR amplicons identified a total of 274 operational taxonomic units after bioinformatic and statistical analysis. Porphyromonas was the most abundant genus in all disease stages, particularly in health along with Moraxella and Bergeyella. Peptostreptococcus, Actinomyces, and Peptostreptococcaceae were the most abundant genera in mild periodontitis. Logistic regression analysis identified species from each of these genera that were significantly associated with health, gingivitis or mild periodontitis. Principal component analysis showed distinct community profiles in health and disease. The species identified show some similarities with health and periodontal disease in humans but also major differences. In contrast to human, healthy canine plaque was found to be dominated by Gram negative bacterial species whereas Gram positive anaerobic species predominate in disease. The scale of this study surpasses previously published research and enhances our understanding of the bacterial species present in canine subgingival plaque and their associations with health and early periodontal disease.
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Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance
Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid
2016-01-01
AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428
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Hendricks, Brian; Mark-Carew, Miguella; Conley, Jamison
2017-11-13
Domestic dogs and cats are potentially effective sentinel populations for monitoring occurrence and spread of Lyme disease. Few studies have evaluated the public health utility of sentinel programmes using geo-analytic approaches. Confirmed Lyme disease cases diagnosed by physicians and ticks submitted by veterinarians to the West Virginia State Health Department were obtained for 2014-2016. Ticks were identified to species, and only Ixodes scapularis were incorporated in the analysis. Separate ordinary least squares (OLS) and spatial lag regression models were conducted to estimate the association between average numbers of Ix. scapularis collected on pets and human Lyme disease incidence. Regression residuals were visualised using Local Moran's I as a diagnostic tool to identify spatial dependence. Statistically significant associations were identified between average numbers of Ix. scapularis collected from dogs and human Lyme disease in the OLS (β=20.7, P<0.001) and spatial lag (β=12.0, P=0.002) regression. No significant associations were identified for cats in either regression model. Statistically significant (P≤0.05) spatial dependence was identified in all regression models. Local Moran's I maps produced for spatial lag regression residuals indicated a decrease in model over- and under-estimation, but identified a higher number of statistically significant outliers than OLS regression. Results support previous conclusions that dogs are effective sentinel populations for monitoring risk of human exposure to Lyme disease. Findings reinforce the utility of spatial analysis of surveillance data, and highlight West Virginia's unique position within the eastern United States in regards to Lyme disease occurrence.
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Prabhanjan, Manasa; Suresh, Raviraj V; Murthy, Megha N; Ramachandra, Nallur B
2016-03-01
To identify the role of copy number variations (CNVs) on disease risk genes and its effect on disease phenotypes in type 2 diabetes mellitus (T2DM) in 12 random populations using high throughput arrays. CNV analysis was carried out on a total of 1715 individuals from 12 populations, from ArrayExpress Archive of the European Bioinformatics Institute along with our subjects using Affymetrix Genome Wide SNP 6.0 array. CNV effect on T2DM genes were analyzed using several bioinformatics tools and a molecular protein interaction network was constructed to identify the disease mechanism altered by the CNVs. Analysis showed 34.4% of the total population to be under CNV burden for T2DM, with 83 disease causal and associated genes being under CNV influence. Hotspots were identified on chromosomes 22, 12, 6, 19 and 11.Overlap studies with case cohorts revealed significant disease risk genes such as EGFR, E2F1, PPP1R3A, HLA and TSPAN8. CNVs play a significant role in predisposing T2DM in normal cohorts and contribute to the phenotypic effects. Thus, CNVs should be considered as one of the major contributors in predisposition of the disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Epidemiology of dengue disease in Malaysia (2000-2012): a systematic literature review.
Mohd-Zaki, Abdul Hamid; Brett, Jeremy; Ismail, Ellyana; L'Azou, Maïna
2014-01-01
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions. PROSPERO #CRD42012002293.
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Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases
Fung, Isaac Chun-Hai; Ying, Yuchen; Schaible, Braydon James; Yu, Cynthia Mengxi; Tse, Zion Tsz Ho; Fu, King-Wa
2015-01-01
This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed. PMID:25946020
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Eleven loci with new reproducible genetic associations with allergic disease risk.
Ferreira, Manuel A R; Vonk, Judith M; Baurecht, Hansjörg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; Lu, Yi; Rüschendorf, Franz; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik K E; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Karlsson, Robert; Almqvist, Catarina; Koppelman, Gerard H; Paternoster, Lavinia
2018-04-19
A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities. We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects. We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study. Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10 -6 . Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress T H 2 responses. Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Application of CRISPR/Cas9 Gene Editing System on MDV-1 Genome for the Study of Gene Function.
Zhang, Yaoyao; Tang, Na; Sadigh, Yashar; Baigent, Susan; Shen, Zhiqiang; Nair, Venugopal; Yao, Yongxiu
2018-05-24
Marek's disease virus (MDV) is a member of alphaherpesviruses associated with Marek's disease, a highly contagious neoplastic disease in chickens. Complete sequencing of the viral genome and recombineering techniques using infectious bacterial artificial chromosome (BAC) clones of Marek's disease virus genome have identified major genes that are associated with pathogenicity. Recent advances in CRISPR/Cas9-based gene editing have given opportunities for precise editing of the viral genome for identifying pathogenic determinants. Here we describe the application of CRISPR/Cas9 gene editing approaches to delete the Meq and pp38 genes from the CVI988 vaccine strain of MDV. This powerful technology will speed up the MDV gene function studies significantly, leading to a better understanding of the molecular mechanisms of MDV pathogenesis.
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Alarcon, Pablo; Wieland, Barbara; Mateus, Ana L P; Dewberry, Chris
2014-10-01
The objectives of this study were (1) to explore the factors involved in the decision-making process used by pig farmers for disease control and (2) to investigate pig farmers' attitudes and perceptions about different information sources relating to disease control. In 2011 a qualitative study involving 20 face-to-face interviews with English pig farmers was conducted. The questionnaire was composed of three parts. The first part required farmers to identify two diseases they had experienced and which were difficult to recognize and/or control. They were asked to report how the disease problem was recognized, how the need for control was decided, and what affected the choice of control approach. For the latter, a structure related to the Theory of Planned Behaviour was used. Their verbal responses were classified as associated with: (1) attitude and beliefs, (2) subjective norms, or (3) perceived behavioural control (PBC). In the second part, five key sources of information for disease control (Defra, BPEX, research from academia, internet and veterinarians) and the factors related to barriers to knowledge were investigated. Interviews were recorded and transcribed. A qualitative analysis of the text of the interview transcripts was carried out using templates. Drivers for disease control were 'pig mortality', 'feeling of entering in an economically critical situation', 'animal welfare' and 'feeling of despair'. Veterinarians were perceived by several participating farmers as the most trusted information source on disease control. However, in particular non-sustainable situations, other producers, and especially experiences from abroad, seemed to considerably influence the farmers' decision-making. 'Lack of knowledge', 'farm structure and management barriers' and 'economic constrains' were identified in relation to PBC. Several negative themes, such as 'lack of communication', 'not knowing where to look', and 'information bias' were associated with research from academia. This study identified a range of factors influencing the decision-making process for disease control by pig farmers. In addition, it highlighted the lack of awareness and difficult access of producers to current scientific research outputs. The factors identified should be considered when developing communication strategies to disseminate research findings and advice for disease control. Copyright © 2013 Elsevier B.V. All rights reserved.
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Cluster analysis in phenotyping a Portuguese population.
Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J
2015-09-03
Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.
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Pathak, Jyotishman; Kiefer, Richard C.; Chute, Christopher G.
2012-01-01
The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. One of the key requirements to perform GWAS is the identification of subject cohorts with accurate classification of disease phenotypes. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical data stored in electronic health records (EHRs) to accurately identify subjects with specific diseases for inclusion in cohort studies. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR data and enabling federated querying and inferencing via standardized Web protocols for identifying subjects with Diabetes Mellitus. Our study highlights the potential of using Web-scale data federation approaches to execute complex queries. PMID:22779040
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Familial Lung Cancer: A Brief History from the Earliest Work to the Most Recent Studies
Musolf, Anthony M.; Simpson, Claire L.; de Andrade, Mariza; Mandal, Diptasri; Gaba, Colette; Yang, Ping; Li, Yafang; You, Ming; Kupert, Elena Y.; Anderson, Marshall W.; Schwartz, Ann G.; Pinney, Susan M.; Amos, Christopher I.; Bailey-Wilson, Joan E.
2017-01-01
Lung cancer is the deadliest cancer in the United States, killing roughly one of four cancer patients in 2016. While it is well-established that lung cancer is caused primarily by environmental effects (particularly tobacco smoking), there is evidence for genetic susceptibility. Lung cancer has been shown to aggregate in families, and segregation analyses have hypothesized a major susceptibility locus for the disease. Genetic association studies have provided strong evidence for common risk variants of small-to-moderate effect. Rare and highly penetrant alleles have been identified by linkage studies, including on 6q23–25. Though not common, some germline mutations have also been identified via sequencing studies. Ongoing genomics studies aim to identify additional high penetrance germline susceptibility alleles for this deadly disease. PMID:28106732
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2011-01-01
Background During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. Methods A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Results Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. Conclusions The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/abstract. PMID:21291537
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Ross, Kenneth Andrew
2011-02-03
During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study.
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Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos
2017-05-01
Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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Retinoids and Retinal Diseases
Kiser, Philip D.; Palczewski, Krzysztof
2016-01-01
Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions. PMID:27917399
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Coronary risk stratification of patients undergoing surgery for valvular heart disease.
Hasselbalch, Rasmus Bo; Engstrøm, Thomas; Pries-Heje, Mia; Heitmann, Merete; Pedersen, Frants; Schou, Morten; Mickley, Hans; Elming, Hanne; Steffensen, Rolf; Køber, Lars; Iversen, Kasper
2017-01-15
Multislice computed tomography (MSCT) is a non-invasive, less expensive, low-radiation alternative to coronary angiography (CAG) prior to valvular heart surgery. MSCT has a high negative predictive value for coronary artery disease (CAD) but previous studies of patients with valvular disease have shown that MSCT, as the primary evaluation technique, lead to re-evaluation with CAG in about a third of cases and it is therefore not recommended. If a subgroup of patients with low- to intermediate risk of CAD could be identified and examined with MSCT, it could be cost-effective, reduce radiation and the risk of complications associated with CAG. The study cohort was derived from a national registry of patients undergoing CAG prior to valvular heart surgery. Using logistic regression, we identified significant risk factors for CAD and developed a risk score (CT-valve score). The score was validated on a similar cohort of patients from another registry. The study cohort consisted of 2221 patients, 521 (23.5%) had CAD. The validation cohort consisted of 2575 patients, 771 (29.9%) had CAD. The identified risk factors were male sex, age, smoking, hyperlipidemia, hypertension, aortic valve disease, extracardiac arteriopathy, ejection fraction <30% and diabetes mellitus. CT-valve score could identify a third of the population with a risk about 10%. A score based on risk factors of CAD can identify patients that might benefit from using MSCT as a gatekeeper to CAG prior to heart valve surgery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Corkscrew Collateral Vessels in Buerger Disease: Vasa Vasorum or Vasa Nervorum.
Baş, Ahmet; Dikici, Atilla S; Gülşen, Fatih; Samancı, Cesur; Mihmanlı, İsmail; Beşirli, Kazım; Numan, Furuzan; Kantarci, Fatih
2016-05-01
To investigate the origin of "corkscrew" collateral vessels around the occluded popliteal artery in patients with Buerger disease by Doppler ultrasound (US) and magnetic resonance (MR) imaging in tandem with digital subtraction angiography (DSA). Between January 2013 and June 2015, 42 patients diagnosed with Buerger disease were identified retrospectively. Patients in whom occlusion of the popliteal artery was found on DSA of the lower extremity were subjected to Doppler US and MR imaging prospectively. Fifteen of 42 patients were identified as having the required characteristics, of whom 10 participated in the present study. Ten patients with occlusion of the popliteal artery were selected for inclusion, and 12 lower limbs of these patients were investigated. The study cohort comprised one woman and nine men with a mean age of 41 years ± 10 (standard deviation; range, 39-58 y). Corkscrew collateral vessels identified on DSA examinations were also identified on secondary imaging (Doppler US and MR imaging) in all patients except one in whom the popliteal artery was reconstituted after short-segment occlusion. The origin of the corkscrew collateral vessels was identified as the vasa nervorum of the tibial nerve in nine patients. Data from the present study suggest that corkscrew collateral vessels at the knee level in patients with Buerger disease originate from the vasa nervorum of the tibial nerve rather than the vasa vasorum of the popliteal artery if the latter is occluded. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.
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Canine sterile nodular panniculitis: a retrospective study of 39 dogs.
Contreary, Caitlin L; Outerbridge, Catherine A; Affolter, Verena K; Kass, Philip H; White, Stephen D
2015-12-01
Canine sterile nodular panniculitis (SNP) is an inflammatory disease of the panniculus that is typically managed with immunomodulatory or immunosuppressive treatments. It has been reported to be a cutaneous marker of an underlying systemic disease. To assess the presence or absence of concurrent systemic diseases associated with canine SNP and to document breed predispositions. Thirty nine dogs presented to a veterinary teaching hospital from 1990 to 2012 which met inclusion criteria. Inclusion in this retrospective study required a diagnosis of SNP via histopathological analysis and negative special stains for infectious organisms. Breed distributions of affected dogs were compared to all other dogs examined at this hospital during the study period. Correlations between the histological pattern of panniculitis and the histological presence of dermatitis, clinical presentation of lesions, dog breed and therapeutic outcomes were assessed. Australian shepherd dogs, Brittany spaniels, Dalmatians, Pomeranians and Chihuahuas were significantly over-represented, but correlations between inflammatory patterns of panniculitis and other histological and clinical factors were not identified. Based on the information available in medical records, 32 dogs (82.1%) had no concurrent systemic diseases identified. Four dogs had concurrent polyarthritis, which may be related to SNP through unknown mechanisms. This study identified several novel breed predilections for SNP; it failed to find any clear correlations with associated systemic diseases other than polyarthritis. The histological inflammatory pattern of SNP does not predict therapeutic outcome. © 2015 ESVD and ACVD.
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Prioritization of zoonotic diseases of public health significance in Vietnam.
Trang, Do Thuy; Siembieda, Jennifer; Huong, Nguyen Thi; Hung, Pham; Ky, Van Dang; Bandyopahyay, Santanu; Olowokure, Babatunde
2015-12-30
Prioritization of zoonotic diseases is critical as it facilitates optimization of resources, greater understanding of zoonotic diseases and implementation of policies promoting multisectoral collaboration. This study aimed to establish strategic priorities for zoonotic diseases in Vietnam taking a key stakeholder approach. Two weeks prior to a workshop on zoonotic diseases a questionnaire was developed and posted to key professionals involved in different areas of zoonotic disease management in Vietnam. Respondents were asked to assess the relative priority of 12 zoonotic diseases using a number of evidence-based criteria, and to provide suggestions to strengthen multisectoral collaboration. A response rate of 69% (51/74) was obtained, and 75% (38/51) respondents worked in non-international Vietnamese organizations. Respondents identified the top five diseases for prioritization in Vietnam as: avian influenza, rabies, Streptococcus suis infection, pandemic influenza and foodborne bacterial diseases. The three criteria most used to rank diseases were severity of disease, outbreak potential and public attention. Avian influenza was ranked as the number one priority zoonotic disease in Vietnam by 57% of the respondents, followed by rabies (18%). Respondents identified coordination mechanisms, information sharing and capacity building as the most important areas for strengthening to enhance multisectoral collaboration. This study is the first systematic and broad-based attempt to prioritize zoonotic diseases of public health significance in Vietnam using key stakeholders, and a comparative and transparent method. There is limited literature for policy makers and planners on this topic and the results of this study can be used to guide decision-making.
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I; Conti, David V; Schumacher, Fredrick; Han, Ying; Benlloch, Sara; Hazelett, Dennis J; Wang, Zhaoming; Saunders, Ed; Leongamornlert, Daniel; Lindstrom, Sara; Jugurnauth-Little, Sara; Dadaev, Tokhir; Tymrakiewicz, Malgorzata; Stram, Daniel O; Rand, Kristin; Wan, Peggy; Stram, Alex; Sheng, Xin; Pooler, Loreall C; Park, Karen; Xia, Lucy; Tyrer, Jonathan; Kolonel, Laurence N; Le Marchand, Loic; Hoover, Robert N; Machiela, Mitchell J; Yeager, Merideth; Burdette, Laurie; Chung, Charles C; Hutchinson, Amy; Yu, Kai; Goh, Chee; Ahmed, Mahbubl; Govindasami, Koveela; Guy, Michelle; Tammela, Teuvo L J; Auvinen, Anssi; Wahlfors, Tiina; Schleutker, Johanna; Visakorpi, Tapio; Leinonen, Katri A; Xu, Jianfeng; Aly, Markus; Donovan, Jenny; Travis, Ruth C; Key, Tim J; Siddiq, Afshan; Canzian, Federico; Khaw, Kay-Tee; Takahashi, Atsushi; Kubo, Michiaki; Pharoah, Paul; Pashayan, Nora; Weischer, Maren; Nordestgaard, Borge G; Nielsen, Sune F; Klarskov, Peter; Røder, Martin Andreas; Iversen, Peter; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Stanford, Janet L; Kolb, Suzanne; Holt, Sarah; Knudsen, Beatrice; Coll, Antonio Hurtado; Gapstur, Susan M; Diver, W Ryan; Stevens, Victoria L; Maier, Christiane; Luedeke, Manuel; Herkommer, Kathleen; Rinckleb, Antje E; Strom, Sara S; Pettaway, Curtis; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; Cannon-Albright, Lisa; Cybulski, Cezary; Wokołorczyk, Dominika; Kluźniak, Wojciech; Park, Jong; Sellers, Thomas; Lin, Hui-Yi; Isaacs, William B; Partin, Alan W; Brenner, Hermann; Dieffenbach, Aida Karina; Stegmaier, Christa; Chen, Constance; Giovannucci, Edward L; Ma, Jing; Stampfer, Meir; Penney, Kathryn L; Mucci, Lorelei; John, Esther M; Ingles, Sue A; Kittles, Rick A; Murphy, Adam B; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej M; Blot, William; Signorello, Lisa B; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, Cristina; Wu, Suh-Yuh; Hennis, Anselm; Kibel, Adam S; Rybicki, Benjamin A; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Batra, Jyotsna; Clements, Judith; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Witte, John S; Casey, Graham; Gillanders, Elizabeth M; Seminara, Daniella; Riboli, Elio; Hamdy, Freddie C; Coetzee, Gerhard A; Li, Qiyuan; Freedman, Matthew L; Hunter, David J; Muir, Kenneth; Gronberg, Henrik; Neal, David E; Southey, Melissa; Giles, Graham G; Severi, Gianluca; Cook, Michael B; Nakagawa, Hidewaki; Wiklund, Fredrik; Kraft, Peter; Chanock, Stephen J; Henderson, Brian E; Easton, Douglas F; Eeles, Rosalind A; Haiman, Christopher A
2014-10-01
Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
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Su, Lining; Wang, Chunjie; Zheng, Chenqing; Wei, Huiping; Song, Xiaoqing
2018-04-13
Parkinson's disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3'-untranslated region of genes and are controlled by several miRNAs. Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.
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A graphic method for identification of novel glioma related genes.
Gao, Yu-Fei; Shu, Yang; Yang, Lei; He, Yi-Chun; Li, Li-Peng; Huang, GuaHua; Li, Hai-Peng; Jiang, Yang
2014-01-01
Glioma, as the most common and lethal intracranial tumor, is a serious disease that causes many deaths every year. Good comprehension of the mechanism underlying this disease is very helpful to design effective treatments. However, up to now, the knowledge of this disease is still limited. It is an important step to understand the mechanism underlying this disease by uncovering its related genes. In this study, a graphic method was proposed to identify novel glioma related genes based on known glioma related genes. A weighted graph was constructed according to the protein-protein interaction information retrieved from STRING and the well-known shortest path algorithm was employed to discover novel genes. The following analysis suggests that some of them are related to the biological process of glioma, proving that our method was effective in identifying novel glioma related genes. We hope that the proposed method would be applied to study other diseases and provide useful information to medical workers, thereby designing effective treatments of different diseases.
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Jeff, Janina M; Peloso, Gina M; Do, Ron
2016-04-01
Rare variant association studies (RVAS) target the class of genetic variation with frequencies less than 1%. Recently, investigators have used exome sequencing in RVAS to identify rare alleles responsible for Mendelian diseases but have experienced greater difficulty discovering such alleles for complex diseases. In this review, we describe what we have learned about lipoprotein metabolism and coronary heart disease through the conduct of RVAS. Rare protein-altering genetic variation can provide important insights that are not as easily attainable from common variant association studies. First, RVAS can facilitate gene discovery by identifying novel rare protein-altering variants in specific genes that are associated with disease. Second, rare variant associations can provide supportive evidence for putative drug targets for novel therapies. Finally, rare variants can uncover new pathways and reveal new biologic mechanisms. The field of human genetics has already made tremendous progress in understanding lipoprotein metabolism and the causes of coronary heart disease in the context of rare variants. As next generation sequencing becomes more cost-effective, RVAS with larger sample sizes will be conducted. This will lead to more novel rare variant discoveries and the translation of genomic data into biological knowledge and clinical insights for cardiovascular disease.
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Online Patient Education for Chronic Disease Management: Consumer Perspectives.
Win, Khin Than; Hassan, Naffisah Mohd; Oinas-Kukkonen, Harri; Probst, Yasmine
2016-04-01
Patient education plays an important role in chronic disease management. The aim of this study is to identify patients' preferences in regard to the design features of effective online patient education (OPE) and the benefits. A review of the existing literature was conducted in order to identify the benefits of OPE and its essential design features. These design features were empirically tested by conducting survey with patients and caregivers. Reliability analysis, construct validity and regression analysis were performed for data analysis. The results identified patient-tailored information, interactivity, content credibility, clear presentation of content, use of multimedia and interpretability as the essential design features of online patient education websites for chronic disease management.
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Munroe, Melissa E.; Young, Kendra A.; Kamen, Diane L.; Guthridge, Joel M.; Niewold, Timothy B.; Costenbader, Karen H.; Weisman, Michael H.; Ishimori, Mariko L.; Wallace, Daniel J.; Gilkeson, Gary S.; Karp, David R.; Harley, John B.; Norris, Jill M.; James, Judith A.
2016-01-01
Objective Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential to curtail irreversible inflammatory damage. The objective of this study was to identify factors associated with transition to classified disease that inform SLE risk. Methods Previously identified lupus patient blood relatives with < 4 American College of Rheumatology SLE classification criteria at baseline (n=409) were enrolled in this follow-up study. Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEE) were applied to identify factors anticipating disease transition. Results Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time=6.4 years). Relatives who transitioned displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (p<0.0001) at baseline than non-transitioned relatives. Importantly, they also had elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS), stem cell factor (SCF), and interferon-associated chemokines (p≤0.02), with concurrent decreases in levels of regulatory mediators, tumor growth factor (TGF)-β and interleukin (IL)-10 (p≤0.03). GEE revealed that baseline SLE-CSQ or ACR scores and plasma levels of SCF and TGF-β (p≤0.03), but not autoantibodies, were significant and independent predictors of SLE transition. Conclusions Altered levels of soluble mediators anticipate transition to classified disease in lupus relatives. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials. PMID:27863174
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Smedley, Damian; Kohler, Sebastian; Czeschik, Johanna Christina; ...
2014-07-30
Here, whole-exome sequencing (WES) has opened up previously unheard of possibilities for identifying novel disease genes in Mendelian disorders, only about half of which have been elucidated to date. However, interpretation of WES data remains challenging. As a result, we analyze protein–protein association (PPA) networks to identify candidate genes in the vicinity of genes previously implicated in a disease. The analysis, using a random-walk with restart (RWR) method, is adapted to the setting of WES by developing a composite variant-gene relevance score based on the rarity, location and predicted pathogenicity of variants and the RWR evaluation of genes harboring themore » variants. Benchmarking using known disease variants from 88 disease-gene families reveals that the correct gene is ranked among the top 10 candidates in ≥50% of cases, a figure which we confirmed using a prospective study of disease genes identified in 2012 and PPA data produced before that date. In conclusion, we implement our method in a freely available Web server, ExomeWalker, that displays a ranked list of candidates together with information on PPAs, frequency and predicted pathogenicity of the variants to allow quick and effective searches for candidates that are likely to reward closer investigation.« less
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Events of hospitalization among children with sickle cell disease.
Fosdal, Marian B; Wojner-Alexandrov, Anne W
2007-08-01
Previous research has identified vaso-occlusive pain crisis as the most common reason for hospitalization among pediatric patients with sickle cell disease. We sought to identify contributors to hospitalization and length of stay (LOS) for this patient population. A descriptive design was used to determine factors associated with hospitalization and LOS for patients with sickle cell disease at an urban tertiary care pediatric hospital in the Midwest. Sickle cell disease as a principal or secondary diagnosis during calendar year 2003 was used to identify patients for study inclusion. Data were collected from subjects' medical records and the hospital accounting system. 72 African American subjects, ranging in age from infant to 24 years (mean = 10.3) met study inclusion criteria, and accounted for 186 hospitalizations. Sickle cell pain crisis was the most common diagnosis associated with hospitalization (n = 122). Adolescent age was significantly associated with longer LOS (r = .451; p<.001), and females stayed on average 2.1 days longer than male subjects (p = .001). Age and gender appear to be associated with LOS in pediatric patients with sickle cell disease, although specific factors underlying these findings remain unclear. Further research is necessary to determine how the complex interplay of social, cultural, developmental, and physiologic factors may contribute to the hospitalization experience of children and adolescents with sickle cell disease.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Smedley, Damian; Kohler, Sebastian; Czeschik, Johanna Christina
Here, whole-exome sequencing (WES) has opened up previously unheard of possibilities for identifying novel disease genes in Mendelian disorders, only about half of which have been elucidated to date. However, interpretation of WES data remains challenging. As a result, we analyze protein–protein association (PPA) networks to identify candidate genes in the vicinity of genes previously implicated in a disease. The analysis, using a random-walk with restart (RWR) method, is adapted to the setting of WES by developing a composite variant-gene relevance score based on the rarity, location and predicted pathogenicity of variants and the RWR evaluation of genes harboring themore » variants. Benchmarking using known disease variants from 88 disease-gene families reveals that the correct gene is ranked among the top 10 candidates in ≥50% of cases, a figure which we confirmed using a prospective study of disease genes identified in 2012 and PPA data produced before that date. In conclusion, we implement our method in a freely available Web server, ExomeWalker, that displays a ranked list of candidates together with information on PPAs, frequency and predicted pathogenicity of the variants to allow quick and effective searches for candidates that are likely to reward closer investigation.« less
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Socio-Cultural Aspects of Chagas Disease: A Systematic Review of Qualitative Research
Ventura-Garcia, Laia; Roura, Maria; Pell, Christopher; Posada, Elisabeth; Gascón, Joaquim; Aldasoro, Edelweis; Muñoz, Jose; Pool, Robert
2013-01-01
Background Globally, more than 10 million people are infected with Trypanosoma cruzi, which causes about 20 000 annual deaths. Although Chagas disease is endemic to certain regions of Latin America, migratory flows have enabled its expansion into areas where it was previously unknown. Economic, social and cultural factors play a significant role in its presence and perpetuation. This systematic review aims to provide a comprehensive overview of qualitative research on Chagas disease, both in endemic and non-endemic countries. Methodology/Principal Findings Searches were carried out in ten databases, and the bibliographies of retrieved studies were examined. Data from thirty-three identified studies were extracted, and findings were analyzed and synthesized along key themes. Themes identified for endemic countries included: socio-structural determinants of Chagas disease; health practices; biomedical conceptions of Chagas disease; patient's experience; and institutional strategies adopted. Concerning non-endemic countries, identified issues related to access to health services and health seeking. Conclusions The emergence and perpetuation of Chagas disease depends largely on socio-cultural aspects influencing health. As most interventions do not address the clinical, environmental, social and cultural aspects jointly, an explicitly multidimensional approach, incorporating the experiences of those affected is a potential tool for the development of long-term successful programs. Further research is needed to evaluate this approach. PMID:24069473
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Comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone
Moody, Laura R; Herbst, Allen J; Yoo, Han Sang; Vanderloo, Joshua P
2009-01-01
Identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. Although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both spongiform change and astrocytosis. The use of cuprizone-treated animals as an experimental control during comparative expression profiling allows for the identification of transcripts whose expression increases during prion disease and remains unchanged during cuprizone-triggered neuropathology. In this study, expression profiles from the brains of mice preclinically and clinically infected with Rocky Mountain Laboratory (RML) mouse-adapted scrapie agent and age-matched controls were profiled using Affymetrix gene arrays. In total, 164 genes were differentially regulated during prion infection. Eighty-three of these transcripts have been previously undescribed as differentially regulated during prion disease. A 0.4% cuprizone diet was utilized as a control for comparative expression profiling. Cuprizone treatment induced spongiosis and astrocyte proliferation as indicated by glial fibrillary acidic protein (Gfap) transcriptional activation and immunohistochemistry. Gene expression profiles from brain tissue obtained from cuprizone-treated mice identified 307 differentially regulated transcript changes. After comparative analysis, 17 transcripts unaffected by cuprizone treatment but increasing in expression from preclinical to clinical prion infection were identified. Here we describe the novel use of the prion disease mimetic, cuprizone, to control for cell population changes in the brain during prion infection. PMID:19535908
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The population ecology of infectious diseases: pertussis in Thailand as a case study.
Blackwood, J C; Cummings, D A T; Broutin, H; Iamsirithaworn, S; Rohani, P
2012-12-01
Many of the fundamental concepts in studying infectious diseases are rooted in population ecology. We describe the importance of population ecology in exploring central issues in infectious disease research including identifying the drivers and dynamics of host-pathogen interactions and pathogen persistence, and evaluating the success of public health policies. The use of ecological concepts in infectious disease research is demonstrated with simple theoretical examples in addition to an analysis of case notification data of pertussis, a childhood respiratory disease, in Thailand as a case study. We stress that further integration of these fields will have significant impacts in infectious diseases research.
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Fatalities from occupational diseases in Connecticut.
Morse, T; Storey, E
1999-08-01
Occupational diseases in Connecticut were identified using reports to the Workers' Compensation Commission, Connecticut OSHA, Vital Statistics, and the Tumor Registry. There were 93 identified fatalities from occupational disease in 1995, and 90 in 1994, approximately three times the number of traumatic occupational fatalities. Identified fatalities were predominantly from asbestos-related diseases, including mesothelioma and asbestosis. Most occupational diseases are not readily identifiable with current reporting mechanisms. Based on national estimates, these figures are considered to be an underestimate of the true burden of occupational disease. Increased awareness and reporting of occupational diseases is needed to properly identify and prevent these common conditions.
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Presence of the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease.
Clark-Feoktistova, Y; Ruenes-Domech, C; García-Bacallao, E F; Roblejo-Balbuena, H; Feoktistova, L; Clark-Feoktistova, I; Jay-Herrera, O; Collazo-Mesa, T
2018-06-10
Wilson's disease is characterized by the accumulation of copper in different organs, mainly affecting the liver, brain, and cornea, and is caused by mutations in the ATP7B gene. More than 120 polymorphisms in the ATP7B gene have been reported in the medical literature. The aim of the present study was to identify the conformational changes in the exon 3 region of the ATP7B gene and detect the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease. A descriptive study was conducted at the Centro Nacional de Genética Médica and the Instituto Nacional de Gastroenterología within the time frame of 2007-2012 and included 105 patients with a clinical diagnosis of Wilson's disease. DNA extraction was performed through the salting-out method and the fragment of interest was amplified using the polymerase chain reaction technique. The conformational shift changes in the exon 3 region and the presence of the p.L456V polymorphism were identified through the Single-Strand Conformation Polymorphism analysis. The so-called b and c conformational shift changes, corresponding to the p.L456V polymorphism in the heterozygous and homozygous states, respectively, were identified. The allelic frequency of the p.L456V polymorphism in the 105 Cuban patients that had a clinical diagnosis of Wilson's disease was 41% and liver-related symptoms were the most frequent in the patients with that polymorphism. The p.L456V polymorphism was identified in 64 Cuban patients clinically diagnosed with Wilson's disease, making future molecular study through indirect methods possible. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.
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Cornish, Alex J; Filippis, Ioannis; David, Alessia; Sternberg, Michael J E
2015-09-01
Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. In this study, we integrate protein-protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. The GSC method successfully identifies known disease-cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine.
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Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian
2016-08-08
The therapeutic options for patients with Multiple Sclerosis (MS) have steadily increased due to the approval of new substances that now supplement traditional first-line agents, demanding a paradigm shift in the assessment of disease activity and treatment response in clinical routine. Here, we report the study design of PANGAEA 2.0 (Post-Authorization Non-interventional GermAn treatment benefit study of GilEnyA in MS patients), a non-interventional study in patients with relapsing-remitting MS (RRMS) identify patients with disease activity and monitor their disease course after treatment switch to fingolimod (Gilenya®), an oral medication approved for patients with highly active RRMS. In the first phase of the PANGAEA 2.0 study the disease activity status of patients receiving a disease-modifying therapy (DMT) is evaluated in order to identify patients at risk of disease progression. This evaluation is based on outcome parameters for both clinical disease activity and magnetic resonance imaging (MRI), and subclinical measures, describing disease activity from the physician's and the patient's perspective. In the second phase of the study, 1500 RRMS patients identified as being non-responders and switched to fingolimod (oral, 0.5 mg/daily) are followed-up for 3 years. Data on relapse activity, disability progression, MRI lesions, and brain volume loss will be assessed in accordance to 'no evidence of disease activity-4' (NEDA-4). The modified Rio score, currently validated for the evaluation of treatment response to interferons, will be used to evaluate the treatment response to fingolimod. The MS management software MSDS3D will guide physicians through the complex processes of diagnosis and treatment. A sub-study further analyzes the benefits of a standardized quantitative evaluation of routine MRI scans by a central reading facility. PANGAEA 2.0 is being conducted between June 2015 and December 2019 in 350 neurological practices and centers in Germany, including 100 centers participating in the sub-study. PANGAEA 2.0 will not only evaluate the long-term benefit of a treatment change to fingolimod but also the applicability of new concepts of data acquisition, assessment of MS disease activity and evaluation of treatment response for the in clinical routine. BfArM6532; Trial Registration Date: 20/05/2015.
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[Psychiatric disorders in patients with Cushing's disease before and after neurosurgery].
Gnjidiae, Zivko; Karloviae, Dalibor; Buljan, Danijel; Malencia, Masa; Kovak-Mufiae, Ana; Kostanjsak, Lidija
2011-01-01
Cushing's disease which is a consequence of ACTH-secreting pituitary adenoma leads to hypercortisolism. Cushing's disease is associated with several psychiatric disturbances. The aim of the present study was to identify which psychiatric disorders were present in patients with Cushing's disease over a 2-year period and to monitor their general psychiatric condition. Additionally, the study aimed to examine the relationship between the duration of Cushing's disease, and the severity of psychiatric conditions based on psychiatric rating scales. The study included 39 patients with Cushing's disease that underwent neurosurgery for ACTH-secreting pituitary adenomas. The transsphenoidal approach (the standard microsurgery technique) was performed in all patients. ACTH-secreting pituitary adenomas were confirmed based on immunohistochemistry in all patients. Psychiatric conditions in the patients were identified using the Clinical Global Impression Scale (CGI) and ICD 10 diagnostic criteria at 3 time points: prior to surgery, and 6 and 48 months post surgery. The Cushing's disease patients exhibited statistically significant improvement in their psychiatric condition, according to the CGI, 6 and 48 months post surgery. There wasn't any significant correlation between the duration of Cushing's disease and psychiatric status, as measured by the CGI prior to surgery, 6 months post surgery, or 48 months post surgery. Patients with Cushing's disease had a significant level psychiatric disturbance that remitted after surgery. There wasn't a significant correlation between the duration of Cushing's disease and psychiatric status.
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Drug development for exceptionally rare metabolic diseases: challenging but not impossible.
Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Wied, Christine C Gispen-de; Hoes, Arno W; Leufkens, Hubert G M; de Vrueh, Remco L A
2013-11-15
We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the 'Orphanet database of Rare diseases'. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest.
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Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases.
Witoelar, Aree; Jansen, Iris E; Wang, Yunpeng; Desikan, Rahul S; Gibbs, J Raphael; Blauwendraat, Cornelis; Thompson, Wesley K; Hernandez, Dena G; Djurovic, Srdjan; Schork, Andrew J; Bettella, Francesco; Ellinghaus, David; Franke, Andre; Lie, Benedicte A; McEvoy, Linda K; Karlsen, Tom H; Lesage, Suzanne; Morris, Huw R; Brice, Alexis; Wood, Nicholas W; Heutink, Peter; Hardy, John; Singleton, Andrew B; Dale, Anders M; Gasser, Thomas; Andreassen, Ole A; Sharma, Manu
2017-07-01
Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases. Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes. The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.
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Finding future high-cost cases: comparing prior cost versus diagnosis-based methods.
Ash, A S; Zhao, Y; Ellis, R P; Schlein Kramer, M
2001-01-01
OBJECTIVE: To examine the value of two kinds of patient-level dat a (cost and diagnoses) for identifying a very small subgroup of a general population with high future costs that may be mitigated with medical management. DATA SOURCES: The study used the MEDSTAT Market Scan (R) Research Database, consisting of inpatient and ambulatory health care encounter records for individuals covered by employee- sponsored benefit plans during 1997 and 1998. STUDY DESIGN: Prior cost and a diagnostic cost group (DCG) risk model were each used with 1997 data to identify 0.5-percent-sized "top groups" of people most likely to be expensive in 1998. We compared the distributions of people, cost, and diseases commonly targeted for disease management for people in the two top groups and, as a bench mark, in the full population. PRINCIPAL FINDINGS: the prior cost- and DCG-identified top groups overlapped by only 38 percent. Each top group consisted of people with high year-two costs and high rates of diabetes, heart failure, major lung disease, and depression. The DCG top group identified people who are both somewhat more expensive ($27,292 vs. $25,981) and more likely ( 49.4 percent vs. 43.8 percent ) th an the prior-cost top group to have at least one of the diseases commonly targeted for disease management. The overlap group average cost was $46,219. CONCLUSIONS: Diagnosis-based risk models are at least as powerful as prior cost for identifying people who will be expensive. Combined cost and diagnostic data are even more powerful and more operation ally useful, especially because the diagnostic information identifies the medical problems that may be managed to achieve better out comes and lower costs. PMID:16148969
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Head, Michael G; Fitchett, Joseph R; Moore, David Aj; Atun, Rifat
2015-03-01
This study aimed to assess the research investments made to UK institutions for all infectious disease research and identify the direction of spend by institution. Systematic analysis. Databases and websites were systematically searched for information on relevant studies funded for the period 1997-2010. UK institutions carrying out infectious disease research. None. Twenty academic institutions receiving greatest sum investments across infection are included here, also NHS sites, Sanger Institute, Health Protection Agency and the Medical Research Council. We measured total funding, median award size, disease areas and position of research along the R&D value chain. Included institutions accounted for £2.1 billion across 5003 studies. Imperial College and University of Oxford received the most investment. Imperial College led the most studies. The Liverpool and London Schools of Tropical Medicine had highest median award size, whereas the NHS sites combined had many smaller studies. Sum NHS funding appears to be declining over time, whilst university income is relatively stable. Several institutions concentrate almost exclusively on pre-clinical research. In some areas, there is clearly a leading institution, e.g. Aberdeen and mycology research or UCL and antimicrobial resistance. UK institutions carry out research across a wide range of infectious disease areas. This analysis can identify centres of excellence and help inform future resource allocation for research priorities. Institutions can use this analysis for establishing expertise within their groups, identifying external collaborators and informing local research strategy.
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Turning the pump handle: Evolving methods for integrating the evidence on gene-disease association
USDA-ARS?s Scientific Manuscript database
Recent findings from genome-wide association studies have demonstrated their considerable potential for identifying genetic determinants of common diseases of public health significance such as cancer, heart disease, and diabetes, but they have also highlighted the continued importance of targeted g...
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Towards a Better Understanding of Complex Disease: Identifying Endotypes of Childhood Asthma
Complex disease, where the diagnostic criteria cannot distinguish among differing etiologies, is often difficult to diagnose, treat and study due to the inability to classify individuals into suitable subtypes of the disease. Here, we aim to use and compare a combination of met...
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Hypothyroidism in late-onset Pompe disease.
Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle; Whitley, Chester B; Jarnes Utz, Jeanine
2016-09-01
In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p < 0.001 compared with the general UMMC adult population). Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.
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Familial aggregation of age-related macular degeneration in the Utah population.
Luo, Ling; Harmon, Jennifer; Yang, Xian; Chen, Haoyu; Patel, Shrena; Mineau, Geraldine; Yang, Zhenglin; Constantine, Ryan; Buehler, Jeanette; Kaminoh, Yuuki; Ma, Xiang; Wong, Tien Y; Zhang, Maonian; Zhang, Kang
2008-02-01
We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.
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Contribution of Electronic Medical Records to the Management of Rare Diseases.
Bremond-Gignac, Dominique; Lewandowski, Elisabeth; Copin, Henri
2015-01-01
Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR) in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients' data with ophthalmology-specific EMR. Ophthalmology-specific EMR software (Softalmo software Corilus) was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software-collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease.
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Contribution of Electronic Medical Records to the Management of Rare Diseases
Bremond-Gignac, Dominique; Lewandowski, Elisabeth; Copin, Henri
2015-01-01
Purpose. Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR) in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients' data with ophthalmology-specific EMR. Methods. Ophthalmology-specific EMR software (Softalmo software Corilus) was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. Results. A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. Discussion. EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. Conclusion. Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software-collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease. PMID:26539543
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USDA-ARS?s Scientific Manuscript database
Quantitative trait loci (QTL) in rice play important roles in controlling rice blast disease. In the present study, 10 field isolates of the races IA1, IB1, IB17, and IC1 of U.S. rice blast fungus Magnaporthe oryzae collected in 1996 and 2009 were used to identify blast resistance QTL with a recombi...
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Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.
Marigorta, Urko M; Denson, Lee A; Hyams, Jeffrey S; Mondal, Kajari; Prince, Jarod; Walters, Thomas D; Griffiths, Anne; Noe, Joshua D; Crandall, Wallace V; Rosh, Joel R; Mack, David R; Kellermayer, Richard; Heyman, Melvin B; Baker, Susan S; Stephens, Michael C; Baldassano, Robert N; Markowitz, James F; Kim, Mi-Ok; Dubinsky, Marla C; Cho, Judy; Aronow, Bruce J; Kugathasan, Subra; Gibson, Greg
2017-10-01
Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus protection, thereby linking statistical association to biological mechanism. The TRS approach constitutes a potential strategy for personalized medicine that enhances inference from static genotypic risk assessment.
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Spengler, Jessica R; Kelly Keating, M; McElroy, Anita K; Zivcec, Marko; Coleman-McCray, JoAnn D; Harmon, Jessica R; Bollweg, Brigid C; Goldsmith, Cynthia S; Bergeron, Éric; Keck, James G; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F
2017-12-12
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. In the current study, we inoculated NSG-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low-passage CCHF virus strains isolated from human patients. In humanized mice, lethal disease develops, characterized by histopathological change in the liver and brain. To date, targets of neurological infection and disease have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis, and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggest a role for astrocyte dysfunction in neurological disease and identify key regions of infection in the CNS for future investigations of CCHF. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Taylor, Francesca; Taylor, Celia; Baharani, Jyoti; Nicholas, Johann; Combes, Gill
2016-08-02
As a result of difficulties related to their illness, diagnosis and treatment, patients with end-stage renal disease experience significant emotional and psychological problems, which untreated can have considerable negative impact on their health and wellbeing. Despite evidence that patients desire improved support, management of their psychosocial problems, particularly at the lower-level, remains sub-optimal. There is limited understanding of the specific support that patients need and want, from whom, and when, and also a lack of data on what helps and hinders renal staff in identifying and responding to their patients' support needs, and how barriers to doing so might be overcome. Through this research we therefore seek to determine what, when, and how, support for patients with lower-level emotional and psychological problems should be integrated into the end-stage renal disease pathway. The research will involve two linked, multicentre studies, designed to identify and consider the perspectives of patients at five different stages of the end-stage renal disease pathway (Study 1), and renal staff working with them (Study 2). A convergent, parallel mixed methods design will be employed for both studies, with quantitative and qualitative data collected separately. For each study, the data sets will be analysed separately and the results then compared or combined using interpretive analysis. A further stage of synthesis will employ data-driven thematic analysis to identify: triangulation and frequency of themes across pathway stages; patterns and plausible explanations of effects. There is an important need for this research given the high frequency of lower-level distress experienced by end-stage renal disease patients and lack of progress to date in integrating support for their lower-level psychosocial needs into the care pathway. Use of a mixed methods design across the two studies will generate a holistic patient and healthcare professional perspective that is more likely to identify viable solutions to enable implementation of timely and integrated care. Based on the research outputs, appropriate support interventions will be developed, implemented and evaluated in a linked follow-on study.
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Coats' disease and congenital retinoschisis in a single eye: a case report and DNA analysis.
Berinstein, D M; Hiraoka, M; Trese, M T; Shastry, B S
2001-01-01
The clinical features of Coats' disease and congenital retinoschisis (RS) are distinctly different. Therefore, finding changes consistent with Coats' disease and congenital RS in a single eye is an unusual occurrence. The following report describes two cases with a Coats' telangiectatic lesion in one region of the retina separated by normal retina and the presence of central and peripheral congenital RS. Molecular genetic analysis of the Norrie disease and RS genes failed to identify disease-causing or polymorphic mutations in either of the genes, suggesting that the above condition is clinically and genetically a different disorder. Further studies are needed to identify the genes responsible for the above disorder and associated ocular manifestations. Copyright 2001 S. Karger AG, Basel.
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The Prevalence of Parkinson Disease Among Patients With Hepatitis C Infection.
Golabi, Pegah; Otgonsuren, Munkhzul; Sayiner, Mehmet; Arsalla, Aimal; Gogoll, Trevor; Younossi, Zobair M
HCV has been suspected to potentially cause degenerations in the central nervous system. Parkinson's disease is the second most common neurodegenerative disorder. Our aim was to assess the prevalence of Parkinson's disease among patients with HCV infection. For this study, we used Medicare database from 2005-2010. Medicare database contains information on enrollment, coverage, diagnosis recorded with International Classification of Disease, Ninth Revision (ICD-9). From combined inpatient and outpatient files, Parkinson's disease was identified as the first diagnosis by ICD-9 code 332.0. Other study variables were; age, gender, race (White and No White), and Medicare eligibility status. Simple distribution comparison by HCV status examined with t-test for numerical variables and ?2 test for categorical variables in the main analytical cohort as well as in the propensity score matched cohort. A total of 1,236,734 patients (median age 76 years, 41% male, and 85% White) was identified among over 47 million claims. Of these, 6040 patients (0.5%) were infected with HCV. Overall, 0.8% (N = 49) of the HCV group and 1.3% (N = 16,004) of the Non-HCV group had Parkinson's disease (P < 0.001). When the study groups matched for age, gender and race, the prevalence of Parkinson's disease was similar between HCV and Non-HCV groups (P > 0.05). This study revealed that, among Medicare population, HCV was not associated with Parkinson disease.
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Marengoni, A; Bonometti, F; Nobili, A; Tettamanti, M; Salerno, F; Corrao, S; Iorio, A; Marcucci, M; Mannucci, P M
2010-08-01
The aim of the study was to recognize clusters of diseases among hospitalized elderly and to identify groups of patients at risk of in-hospital death and adverse clinical events according to disease clustering. This was a cross-sectional study conducted in 38 internal medicine and geriatric wards in Italy participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The subjects were 1,332 inpatients aged 65 years or older. Clusters of diseases (i.e., two or more co-occurrent diseases) were identified using the odds ratios (OR) for the associations between pairs of conditions, followed by cluster analysis. Logistic regression models were used to evaluate the effect of disease clusters on in-hospital death and adverse clinical events. A total of 86.7% of the patients were discharged, 8.3% were transferred to another hospital unit, and 5.0% died during hospitalization; 36.4% of the patients had at least one adverse clinical event. Patients affected by the clusters, including heart failure (HF) and either chronic renal failure (CRF) or chronic obstructive pulmonary disease, had a significant association with in-hospital death (OR, 4.3;95% confidence interval [CI], 1.6-11.5; OR, 2.9; 95% CI, 1.1-8.3, respectively), as well as patients affected by CRF and anemia (OR, 6.1; 95% CI, 2.3-16.2). The cluster including HF and CRF was also associated with adverse clinical events (OR, 3.5; 95% CI, 1.5-7.8). The effect of both HF and CRF and anemia and CRF on in-hospital death was additive. Several groups of older patients at risk of in-hospital death and adverse clinical events were identified according to disease clustering. Knowledge of the relationship among co-occurring diseases may help developing strategies to improve clinical practice and preventative interventions.
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Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff; Kyvik, Kirsten Ohm; Skytthe, Axel; Backer, Vibeke; Bønnelykke, Klaus; Thomsen, Simon Francis
2015-01-01
The development of atopic diseases early in life suggests an important role of perinatal risk factors. To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction. © 2014 John Wiley & Sons Ltd.
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Telerheumatology: A Systematic Review.
McDougall, John A; Ferucci, Elizabeth D; Glover, Janis; Fraenkel, Liana
2017-10-01
To identify and summarize the published and gray literature on the use of telemedicine for the diagnosis and management of inflammatory and/or autoimmune rheumatic disease. We performed a registered systematic search (CRD42015025382) for studies using MEDLINE (1946 to July 2015), Embase (1974 to July 2015), Web of Science (1900 to July 2015), and Scopus (1946 to July 2015) databases. We included studies that demonstrated the use of telemedicine for diagnosis and/or management of inflammatory/autoimmune rheumatic disease. Following data extraction, we performed a descriptive analysis. Our literature search identified 1,468 potentially eligible studies. Of these studies, 20 were ultimately included in this review. Studies varied significantly in publication type, quality of evidence, and the reporting of methods. Most demonstrated a high risk of bias. Rheumatoid arthritis was the most commonly studied rheumatic disease (42% of patients). Studies demonstrated conflicting results regarding the effectiveness of telemedicine (18 found it effective, 1 found it effective but possibly harmful, and 1 found it ineffective). A limited number of studies included some component of a cost analysis (n = 6; 16% of patients); all of these found telemedicine to be cost-effective. Studies identified by this systematic review generally found telemedicine to be effective for the diagnosis and management of autoimmune/inflammatory rheumatic disease; however, there is limited evidence to support this conclusion. Further studies are needed to determine the best uses of telemedicine for the diagnosis and management of these conditions. © 2016, American College of Rheumatology.
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Bruse, Shannon; Moreau, Michael; Bromberg, Yana; Jang, Jun-Ho; Wang, Nan; Ha, Hongseok; Picchi, Maria; Lin, Yong; Langley, Raymond J; Qualls, Clifford; Klensney-Tait, Julia; Zabner, Joseph; Leng, Shuguang; Mao, Jenny; Belinsky, Steven A; Xing, Jinchuan; Nyunoya, Toru
2016-01-07
Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15-20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes. We performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro. Our integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.
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Monda, E.; Cheruiyot, R. C.; Mbaka, J.; Alakonya, A.
2018-01-01
Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to be Colletotrichum gloeosporioides as reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, “pepper spots,” and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s) of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang'a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified as Colletotrichum spp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified as Pestalotiopsis spp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicated Colletotrichum gloeosporioides, Colletotrichum boninense, and Pestalotiopsis microspora as the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof. PMID:29681943
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Kimaru, S K; Monda, E; Cheruiyot, R C; Mbaka, J; Alakonya, A
2018-01-01
Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to be Colletotrichum gloeosporioides as reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, "pepper spots," and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s) of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang'a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified as Colletotrichum spp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified as Pestalotiopsis spp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicated Colletotrichum gloeosporioides , Colletotrichum boninense , and Pestalotiopsis microspora as the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof.
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Knight, Andrea; Weiss, Pamela; Morales, Knashawn; Gerdes, Marsha; Rearson, Melissa; Vickery, Michelle; Keren, Ron
2015-12-01
To investigate differences in risk factors for depression and anxiety, such as central nervous system involvement in systemic lupus erythematosus (SLE)/mixed connective tissue disease (MCTD), by comparing youth with SLE/MCTD to peers with type 1 diabetes mellitus (T1D). We conducted a cross-sectional study of 50 outpatient pairs, ages 8 years and above, matching subjects with SLE/MCTD and T1D by sex and age group. We screened for depression, suicidal ideation, and anxiety using the Patient Health Questionnaire-9 and the Screen for Childhood Anxiety Related Emotional Disorders, respectively. We collected parent-reported mental health treatment data. We compared prevalence and treatment rates between subjects with SLE/MCTD and T1D, and identified disease-specific risk factors using logistic regression. Depression symptoms were present in 23%, suicidal ideation in 15%, and anxiety in 27% of participants. Compared with subjects with T1D, subjects with SLE/MCTD had lower adjusted rates of depression and suicidal ideation, yet poorer rates of mental health treatment (24% vs 53%). Non-White race/ethnicity and longer disease duration were independent risk factors for depression and suicidal ideation. Depression was associated with poor disease control in both groups, and anxiety with insulin pump use in subjects with T1D. Depression and anxiety are high and undertreated in youth with SLE/MCTD and T1D. Focusing on risk factors such as race/ethnicity and disease duration may improve their mental health care. Further study of central nervous system and other disease-related factors may identify targets for intervention. Copyright © 2015 Elsevier Inc. All rights reserved.
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Zhe, Shandian; Xu, Zenglin; Qi, Yuan; Yu, Peng
2014-01-01
A key step for Alzheimer's disease (AD) study is to identify associations between genetic variations and intermediate phenotypes (e.g., brain structures). At the same time, it is crucial to develop a noninvasive means for AD diagnosis. Although these two tasks-association discovery and disease diagnosis-have been treated separately by a variety of approaches, they are tightly coupled due to their common biological basis. We hypothesize that the two tasks can potentially benefit each other by a joint analysis, because (i) the association study discovers correlated biomarkers from different data sources, which may help improve diagnosis accuracy, and (ii) the disease status may help identify disease-sensitive associations between genetic variations and MRI features. Based on this hypothesis, we present a new sparse Bayesian approach for joint association study and disease diagnosis. In this approach, common latent features are extracted from different data sources based on sparse projection matrices and used to predict multiple disease severity levels based on Gaussian process ordinal regression; in return, the disease status is used to guide the discovery of relationships between the data sources. The sparse projection matrices not only reveal the associations but also select groups of biomarkers related to AD. To learn the model from data, we develop an efficient variational expectation maximization algorithm. Simulation results demonstrate that our approach achieves higher accuracy in both predicting ordinal labels and discovering associations between data sources than alternative methods. We apply our approach to an imaging genetics dataset of AD. Our joint analysis approach not only identifies meaningful and interesting associations between genetic variations, brain structures, and AD status, but also achieves significantly higher accuracy for predicting ordinal AD stages than the competing methods.
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Gaps in policy-relevant information on burden of disease in children: a systematic review.
Rudan, Igor; Lawn, Joy; Cousens, Simon; Rowe, Alexander K; Boschi-Pinto, Cynthia; Tomasković, Lana; Mendoza, Walter; Lanata, Claudio F; Roca-Feltrer, Arantxa; Carneiro, Ilona; Schellenberg, Joanna A; Polasek, Ozren; Weber, Martin; Bryce, Jennifer; Morris, Saul S; Black, Robert E; Campbell, Harry
Valid information about cause-specific child mortality and morbidity is an essential foundation for national and international health policy. We undertook a systematic review to investigate the geographical dispersion of and time trends in publication for policy-relevant information about children's health and to assess associations between the availability of reliable data and poverty. We identified data available on Jan 1, 2001, and published since 1980, for the major causes of morbidity and mortality in young children. Studies with relevant data were assessed against a set of inclusion criteria to identify those likely to provide unbiased estimates of the burden of childhood disease in the community. Only 308 information units from more than 17,000 papers identified were regarded as possible unbiased sources for estimates of childhood disease burden. The geographical distribution of these information units revealed a pattern of small well-researched populations surrounded by large areas with little available information. No reliable population-based data were identified from many of the world's poorest countries, which account for about a third of all deaths of children worldwide. The number of new studies diminished over the last 10 years investigated. The number of population-based studies yielding estimates of burden of childhood disease from less developed countries was low. The decreasing trend over time suggests reductions in research investment in this sphere. Data are especially sparse from the world's least developed countries with the highest child mortality. Guidelines are needed for the conduct of burden-of-disease studies together with an international research policy that gives increased emphasis to global equity and coverage so that knowledge can be generated from all regions of the world.
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Khan, Sarah; Khoory, Ayesha; Al Zaffin, Dhabia; Al Suwaidi, Meera
2016-11-07
Cardiovascular diseases were the leading cause of death in women in the United Arab Emirates (UAE) in 2010. The UAE is expected to experience a tripling of heart diseases in the next two decades as risk factors for heart diseases increase. Research shows that first year survival rates of younger women suffering from a heart attack are lower than in men. Women present with a wider range of symptoms for heart diseases than men; non-recognition of atypical symptoms may explain the delay in seeking treatment and poor prognosis following heart diseases in women. No known study on awareness of heart diseases among women has been carried out in the Middle Eastern region. Social constructionist and interpretivist epistemological approaches have been considered in this qualitative study to explore the awareness of heart diseases and the health seeking behavior of Emirati women. Convenience sampling was used to recruit 41 Emirati women. Three focus groups and six in-depth semi-structured interviews were conducted to obtain data. Thematic content analysis was applied to the data following transcription and translation of recordings. Emirati women had limited knowledge on heart diseases. Women were generally unaware of the atypical symptoms, commonly experienced by women however they identified most risk factors associated with heart diseases. Lack of awareness of disease severity and symptoms, sociocultural influences and distrust in the healthcare system were considered the main barriers to seeking prompt treatment. This study clearly identified gaps and inaccuracies in knowledge of heart diseases, which could contribute to delayed health seeking action and possibly poorer prognosis among Emirati women. Absence of initiatives to educate women on cardiovascular diseases in UAE has erroneously deemed it a less serious concern among Emirati women. The findings from this study provide clear indications of the need to increase accountability of the healthcare system and to develop culturally relevant, gender specific, age focused, heart diseases related public health awareness campaigns in UAE.
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The supportive care needs of parents caring for a child with a rare disease: A scoping review.
Pelentsov, Lemuel J; Laws, Thomas A; Esterman, Adrian J
2015-10-01
Parents caring for a child with a rare disease report unmet needs, the origins of which are varied and complex. Few studies have systematically attempted to identify the supportive care needs of parents with a child with a rare disease comprehensively. We have used the widely accepted Supportive Care Needs Framework (SCNF) as the structure for this review. The purpose of the current review was to identify the supportive care needs of parents with a child with a rare disease, irrespective of condition. We conducted a scoping study review comprising 29 studies (1990-2014) to identify and examine the research literature related to the supportive care needs of parents, and to compare these needs with the seven domains outlined in the SCNF. Most common needs cited were social needs (72% of papers), followed by informational needs (65% of papers) and emotional needs (62% of papers), with the most common parental needs overall being information about their child's disease, emotional stress, guilt and uncertainty about their child's future health care needs, parents own caring responsibilities and the need for more general support. A paucity of studies exists that explore the supportive care needs of parents of a child with a rare disease. The SCNF only partially reflects the breadth and type of needs of these parents, and a preliminary revised framework has been suggested. Further research is required in this area, particularly empirical research to amend or confirm the suggested new framework. Copyright © 2015 Elsevier Inc. All rights reserved.
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Reflex Cough and Disease Duration as Predictors of Swallowing Dysfunction in Parkinson's Disease.
Troche, Michelle S; Schumann, Beate; Brandimore, Alexandra E; Okun, Michael S; Hegland, Karen W
2016-12-01
Patients with Parkinson's disease (PD) have progressive and pervasive disorders of airway protection. Recent work has highlighted the relationship between reflex and voluntary cough and swallowing safety. The goal of this study was to test the sensitivity and specificity of several airway protective and disease-specific factors for predicting swallowing safety outcomes in PD. Sixty-four participants (44 males) completed measures of voluntary and reflex cough, and swallowing safety. Clinical predictors included disease severity and duration, and cough airflow and sensitivity measures. ROC and Chi-square analyses identified predictors of swallowing safety (penetration-aspiration score) in PD. Disease duration significantly discriminated between patients with normal and abnormal swallowing safety (p = 0.027, sensitivity: 71 %, specificity: 55.4 %). Cough reflex sensitivity significantly discriminated between patients who penetrated above the level of the vocal folds and those with more severe penetration/aspiration (p = 0.021, sensitivity: 71.0 %, specificity 57.6 %). Urge-to-cough sensitivity (log-log linear slope) was the only variable which significantly discriminated between patients with penetration versus aspiration (p = 0.017, sensitivity: 85.7 %, specificity 73.2 %). It is important to identify the factors which influence airway protective outcomes in PD especially given that aspiration pneumonia is a leading cause of death. Results from this study highlight the ecological validity of reflex cough in the study of airway protection and this study further identifies important factors to consider in the screening of airway protective deficits in PD.
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Rivera, Andrea; White, Karen; Stöhr, Heidi; Steiner, Klaus; Hemmrich, Nadine; Grimm, Timo; Jurklies, Bernhard; Lorenz, Birgit; Scholl, Hendrik P. N.; Apfelstedt-Sylla, Eckhart; Weber, Bernhard H. F.
2000-01-01
Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of ∼58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required. PMID:10958763
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Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H
2000-10-01
Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.
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The 100 most cited articles in metastatic spine disease.
Cohen, Jonathan; Alan, Nima; Zhou, James; Kojo Hamilton, D
2016-08-01
OBJECTIVE Despite the growing neurosurgical literature, a subset of pioneering studies have significantly impacted the field of metastatic spine disease. The purpose of this study was to identify and analyze the 100 most frequently cited articles in the field. METHODS A keyword search using the Thomson Reuters Web of Science was conducted to identify articles relevant to the field of metastatic spine disease. The results were filtered based on title and abstract analysis to identify the 100 most cited articles. Statistical analysis was used to characterize journal frequency, past and current citations, citation distribution over time, and author frequency. RESULTS The total number of citations for the final 100 articles ranged from 74 to 1169. Articles selected for the final list were published between 1940 and 2009. The years in which the greatest numbers of top-100 studies were published were 1990 and 2005, and the greatest number of citations occurred in 2012. The majority of articles were published in the journals Spine (15), Cancer (11), and the Journal of Neurosurgery (9). Forty-four individuals were listed as authors on 2 articles, 9 were listed as authors on 3 articles, and 2 were listed as authors on 4 articles in the top 100 list. The most cited article was the work by Batson (1169 citations) that was published in 1940 and described the role of the vertebral veins in the spread of metastases. The second most cited article was Patchell's 2005 study (594 citations) discussing decompressive resection of spinal cord metastases. The third most cited article was the 1978 study by Gilbert that evaluated treatment of epidural spinal cord compression due to metastatic tumor (560 citations). CONCLUSIONS The field of metastatic spine disease has witnessed numerous milestones and so it is increasingly important to recognize studies that have influenced the field. In this bibliographic study the authors identified and analyzed the most influential articles in the field of metastatic spine disease.
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Batista, Dalia; Courkoutsakis, Nickolas A; Oldfield, Edward H; Griffin, Kurt J; Keil, Meg; Patronas, Nickolas J; Stratakis, Constantine A
2005-09-01
We recently showed that pre- and postcontrast spoiled gradient-recalled acquisition in the steady-state (SPGR) was superior to conventional pre- and postcontrast T-1 weighted spin echo (SE) acquisition magnetic resonance imaging (MRI) for the diagnostic evaluation of pituitary tumors in adult patients. The present investigation assessed the use of SPGR vs. SE-MRI in the diagnostic evaluation of ACTH-secreting tumors in children and adolescents with Cushing disease. Data were analyzed retrospectively from a series of patients seen over 7 yr (1997-2004). The setting for this study was a tertiary care referral center. Thirty children with Cushing disease (13 females and 17 males with a mean age of 12 +/- 3 yr) were studied. Imaging results were compared with surgical and pathological findings and the clinical outcome. Twenty-eight patients had microadenomas, and two had macroadenomas; the latter were identified by both MRI techniques. Precontrast SE and SPGR-MRI identified four and six of the microadenomas, respectively. Postcontrast SPGR-MRI identified the location of the tumor in 18 of 28 patients, whereas postcontrast SE-MRI identified the location and accurately estimated the size of the tumor in only five patients (P < 0.001). We conclude that conventional MRI, even with contrast enhancement, mostly failed to identify ACTH-secreting microadenomas in children and adolescents with Cushing disease. Postcontrast SPGR-MRI was superior to SE-MRI and should be used in addition to conventional SE-MRI in the pituitary evaluation of children and adolescents with suspected Cushing disease.
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Soul, Jamie; Hardingham, Timothy E; Boot-Handford, Raymond P; Schwartz, Jean-Marc
2015-01-29
We describe a new method, PhenomeExpress, for the analysis of transcriptomic datasets to identify pathogenic disease mechanisms. Our analysis method includes input from both protein-protein interaction and phenotype similarity networks. This introduces valuable information from disease relevant phenotypes, which aids the identification of sub-networks that are significantly enriched in differentially expressed genes and are related to the disease relevant phenotypes. This contrasts with many active sub-network detection methods, which rely solely on protein-protein interaction networks derived from compounded data of many unrelated biological conditions and which are therefore not specific to the context of the experiment. PhenomeExpress thus exploits readily available animal model and human disease phenotype information. It combines this prior evidence of disease phenotypes with the experimentally derived disease data sets to provide a more targeted analysis. Two case studies, in subchondral bone in osteoarthritis and in Pax5 in acute lymphoblastic leukaemia, demonstrate that PhenomeExpress identifies core disease pathways in both mouse and human disease expression datasets derived from different technologies. We also validate the approach by comparison to state-of-the-art active sub-network detection methods, which reveals how it may enhance the detection of molecular phenotypes and provide a more detailed context to those previously identified as possible candidates.
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Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay
2015-01-01
The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060
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Dietary Patterns and Risk of Gallbladder Disease: A Hospital-based Case-Control Study in Adult Women
Jessri, Mahsa
2015-01-01
ABSTRACT Gallbladder disease is one of the most prevalent gastrointestinal disorders that may result from a complex interaction of genetic and environmental factors. This study examined the association of dietary patterns with gallstone disease among Iranian women. This case-control study was conducted in general teaching hospitals in Tehran, Iran. Participants were 101 female cases and 204 female controls aged 40-65 years who were admitted for problems other than GBD. Dietary patterns were identified using principal components analysis based on food frequency questionnaire. Compared to the control group, cases were less educated, less physically active, and consumed more total energy (p<0.02). Having ≥3 livebirths increased the risk of gallstone by more than 5 times, followed by having rapid weight loss, being single, having familial history of gallstone, and consuming high total energy. Two distinct dietary patterns were identified in women (healthy and unhealthy). After adjustment for several confounding variables, healthy dietary pattern was associated with a decreased risk of gallstone disease (OR=0.14, 95% CI 0.048-0.4) while unhealthy dietary pattern was associated with an increased risk (OR=3.77, 95% CI 1.52-9.36). These findings confirm that dietary pattern approach provides potentially useful and relevant information on the relationship between diet and disease. Identifying risk factors will provide an opportunity for prevention of gallbladder disease in developing countries facing an increased risk of obesity. PMID:25995720
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Periodontal disease in diabetic patients - clinical and histopathological aspects.
Corlan Puşcu, Dorina; Ciuluvică, Radu Constantin; Anghel, Andreea; Mălăescu, Gheorghe Dan; Ciursaş, Adina Nicoleta; Popa, Gabriel Valeriu; Agop Forna, Doriana; Busuioc, Cristina Jana; Siloşi, Izabela
2016-01-01
Periodontal disease is one of the most frequent diseases affecting people all over the world. The relation between periodontal disease and diabetes mellitus raised the interest both of dentists and doctors treating metabolic diseases, as the two conditions influence one another. In our study, we analyzed a number of 75 patients with diabetes mellitus and periodontal disease that presented to the medical consultory for conditions of the dental maxillary system. The clinical study showed that periodontal disease and diabetes may affect young adults as well, still this pathological association more frequently appears after the age of 50. The disease was identified especially in the women living in urban area. The clinical examination of the dental maxillary system identified the presence of gingival ulcerations, dental calculus, gingival bleeding, radicular leftovers with anfractuous margins, fixed prostheses with an inappropriate cervical adjustment. Of the systemic diseases associated to periodontal disease and diabetes mellitus, there was observed that 66.66% of the patients also suffered from cardiovascular diseases (high blood pressure, ischemic cardiopathy, heart failure), and 37.33% suffered from obesity. The histopathological and immunohistochemical tests highlighted the presence of an inflammatory chronic, intense reaction, mainly formed of lymphocytes, plasmocytes, macrophages and granulocytes, heterogeneously disseminated and alteration of the structure of marginal and superficial periodontium. The inflammatory reaction in the patients with periodontal disease and diabetes was more intense than in the patients with periodontal disease without diabetes.
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Spatial statistical analysis of basal stem root disease under natural field epidemic of oil palm
NASA Astrophysics Data System (ADS)
Kamu, Assis; Phin, Chong Khim; Seman, Idris Abu; Wan, Hoong Hak; Mun, Ho Chong
2015-02-01
Oil palm or scientifically known as Elaeis guineensis Jacq. is the most important commodity crop in Malaysia and has greatly contributed to the economy growth of the country. As far as disease is concerned in the industry, Basal Stem Rot (BSR) caused by Ganoderma boninence remains the most important disease. BSR disease is the most widely studied with information available for oil palm disease in Malaysia. However, there is still limited study on the spatial as well as temporal pattern or distribution of the disease especially under natural field epidemic condition in oil palm plantation. The objective of this study is to spatially identify the pattern of BSR disease under natural field epidemic using two geospatial analytical techniques, which are quadrat analysis for the first order properties of partial pattern analysis and nearest-neighbor analysis (NNA) for the second order properties of partial pattern analysis. Two study sites were selected with different age of tree. Both sites are located in Tawau, Sabah and managed by the same company. The results showed that at least one of the point pattern analysis used which is NNA (i.e. the second order properties of partial pattern analysis) has confirmed the disease is complete spatial randomness. This suggests the spread of the disease is not from tree to tree and the age of palm does not play a significance role in determining the spatial pattern of the disease. From the spatial pattern of the disease, it would help in the disease management program and for the industry in the future. The statistical modelling is expected to help in identifying the right model to estimate the yield loss of oil palm due to BSR disease in the future.
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Patterson, Victoria L; Thompson, Brian S; Cherry, Catherine; Wang, Shao-Bin; Chen, Bo; Hoh, Josephine
2016-07-14
Age-related diseases are becoming increasingly prevalent and the burden continues to grow as our population ages. Effective treatments are necessary to lessen the impact of debilitating conditions but remain elusive in many cases. Only by understanding the causes and pathology of diseases associated with aging, can scientists begin to identify potential therapeutic targets and develop strategies for intervention. The most common age-related conditions are neurodegenerative disorders such as Parkinson's disease and blindness. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Genome wide association studies have previously identified loci that are associated with increased susceptibility to this disease and identified two regions of interest: complement factor H (CFH) and the 10q26 locus, where the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HtrA1) genes are located. CFH acts as a negative regulator of the alternative pathway (AP) of the complement system while HtrA1 is an extracellular serine protease. ARMS2 is located upstream of HtrA1 in the primate genome, although the gene is absent in mice. To study the effects of these genes, humanized knock-in mouse lines of Cfh and ARMS2, knockouts of Cfh, HtrA1, HtrA2, HtrA3 and HtrA4 as well as a conditional neural deletion of HtrA2 were generated. Of all the genetically engineered mice produced only mice lacking HtrA2, either systemically or in neural tissues, displayed clear phenotypes. In order to examine these mice thoroughly and systematically, an initial phenotyping schedule was established, consisting of a series of tests related to two main diseases of interest: AMD and Parkinson's. Genetically modified mice can be subjected to appropriate experiments to identify phenotypes that may be related to the associated diseases in humans. A phenotyping regimen with a mitochondrial focus is presented here alongside representative results from the tests of interest.
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Calculating stage duration statistics in multistage diseases.
Komarova, Natalia L; Thalhauser, Craig J
2011-01-01
Many human diseases are characterized by multiple stages of progression. While the typical sequence of disease progression can be identified, there may be large individual variations among patients. Identifying mean stage durations and their variations is critical for statistical hypothesis testing needed to determine if treatment is having a significant effect on the progression, or if a new therapy is showing a delay of progression through a multistage disease. In this paper we focus on two methods for extracting stage duration statistics from longitudinal datasets: an extension of the linear regression technique, and a counting algorithm. Both are non-iterative, non-parametric and computationally cheap methods, which makes them invaluable tools for studying the epidemiology of diseases, with a goal of identifying different patterns of progression by using bioinformatics methodologies. Here we show that the regression method performs well for calculating the mean stage durations under a wide variety of assumptions, however, its generalization to variance calculations fails under realistic assumptions about the data collection procedure. On the other hand, the counting method yields reliable estimations for both means and variances of stage durations. Applications to Alzheimer disease progression are discussed.
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Risk Factors for Chronic Disease in Viet Nam: A Review of the Literature
Rao, Chalapati; Nhung, Nguyen Thi Trang; Marks, Geoffrey; Hoa, Nguyen Phuong
2013-01-01
Introduction Chronic diseases account for most of the disease burden in low- and middle-income countries, particularly those in Asia. We reviewed literature on chronic disease risk factors in Viet Nam to identify patterns and data gaps. Methods All population-based studies published from 2000 to 2012 that reported chronic disease risk factors were considered. We used standard chronic disease terminology to search PubMed and assessed titles, abstracts, and articles for eligibility for inclusion. We summarized relevant study information in tables listing available studies, risk factors measured, and the prevalence of these risk factors. Results We identified 23 studies conducted before 2010. The most common age range studied was 25 to 64 years. Sample sizes varied, and sample frames were national in 5 studies. A combination of behavioral, physical, and biological risk factors was studied. Being overweight or obese was the most common risk factor studied (n = 14), followed by high blood pressure (n = 11) and tobacco use (n = 10). Tobacco and alcohol use were high among men, and tobacco use may be increasing among Vietnamese women. High blood pressure is common; however, people’s knowledge that they have high blood pressure may be low. A high proportion of diets do not meet international criteria for fruit and vegetable consumption. Prevalence of overweight and obesity is increasing. None of the studies evaluated measured dietary patterns or total caloric intake, and only 1 study measured dietary salt intake. Conclusion Risk factors for chronic diseases are common in Viet Nam; however, more recent and context-specific information is required for planning and monitoring interventions to reduce risk factors and chronic disease in this country. PMID:23306076
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Page, Thomas E; Farina, Nicolas; Brown, Anna; Daley, Stephanie; Bowling, Ann; Basset, Thurstine; Livingston, Gill; Knapp, Martin; Murray, Joanna; Banerjee, Sube
2017-03-29
Neurodegenerative diseases, such as dementia, have a profound impact on those with the conditions and their family carers. Consequently, the accurate measurement of family carers' quality of life (QOL) is important. Generic measures may miss key elements of the impact of these conditions, so using disease-specific instruments has been advocated. This systematic review aimed to identify and examine the psychometric properties of disease-specific outcome measures of QOL of family carers of people with neurodegenerative diseases (Alzheimer's disease and other dementias; Huntington's disease; Parkinson's disease; multiple sclerosis; and motor neuron disease). Systematic review. Instruments were identified using 5 electronic databases (PubMed, PsycINFO, Web of Science, Scopus and the International Bibliography of the Social Sciences (IBSS)) and lateral search techniques. Only studies which reported the development and/or validation of a disease-specific measure for adult family carers, and which were written in English, were eligible for inclusion. The methodological quality of the included studies was evaluated using the COnsensus based Standards for the selection of health Measurement Instruments (COSMIN) checklist. The psychometric properties of each instrument were examined. 676 articles were identified. Following screening and lateral searches, a total of 8 articles were included; these reported 7 disease-specific carer QOL measures. Limited evidence was available for the psychometric properties of the 7 instruments. Psychometric analyses were mainly focused on internal consistency, reliability and construct validity. None of the measures assessed either criterion validity or responsiveness to change. There are very few measures of carer QOL that are specific to particular neurodegenerative diseases. The findings of this review emphasise the importance of developing and validating psychometrically robust disease-specific measures of carer QOL. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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Pozet, Astrid; Lejeune, Catherine; Bonnet, Magalie; Dabakuyo, Sandrine; Dion, Michèle; Fagnoni, Philippe; Gaimard, Maryse; Imbert, Geneviève; Nerich, Virginie; Foubert, Audrey; Chotard, Morgane; Bonin, Marie; Anota, Amélie; Bonnetain, Franck
2016-11-03
Medical progress and the lifestyle modification have prolonged life expectancy, despite the development of chronic diseases. Support and care for older subjects are often provided by a network of informal caregivers composed of family, friends and neighbors, who are essential in helping older persons to continue living at home. It has been shown that the extent and diversity of informal tasks may jeopardize the physical, mental and social wellbeing of caregivers. The aim of the Informal Carers of Elderly cohort is to define, through a longitudinal study, profiles of caregivers of older patients with a diagnosis of one of the following diseases: cancer (breast, prostate, colorectal), neurodegenerative diseases (Parkinson's disease, Alzheimer's disease and similar diseases), neurovascular diseases (stroke), sensory diseases (age-related macular degeneration (AMD)) and heart disease (heart failure). Patients must be at least 60 years old and living in the region of Burgundy-Franche-Comte (France). By following the different phases of the caregiving relationship from the announcement of the diagnosis, it will be possible to assess the quality of life of caregivers, coping strategies, levels of anxiety and depression, social support and the extent of their burden. We will also evaluate the efficacy and efficiency of the implementation of a pragmatic intervention by a social worker to help informal caregivers, through a randomized interventional trial nested in the cohort. Qualitative approaches aimed at studying the caregiver/patient relationship, and situations leading to breakdown of the caregiver relationship will be also undertaken. Through an analytical and longitudinal definition of profiles of informal caregivers, this study will gather detailed information on their life courses and their health trajectory by identifying consequences associated with the concept of their role as carers. In addition, the randomized interventional trial will explore the relevance of the implementation of a supportive intervention by a social worker to help caregivers. These data will help to identify strategies that could be used to improve the existing sources of aid and to propose new approaches to help caregivers. This study will provide the opportunity to identify the most relevant means of support adapted to caregivers, and provide an impulse for new health care policies. ClinicalTrials.gov Identifier: NCT02626377 . Retrospectively registered on 9 December 2015. Protocol date/version: 23 October 2014/version 2.
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Pitter, Gisella; Gnavi, Roberto; Romor, Pierantonio; Zanotti, Renzo; Simonato, Lorenzo; Canova, Cristina
2017-01-01
to assess the role of four administrative healthcare databases (pathology reports, copayment exemptions, hospital discharge records, gluten-free food prescriptions) for the identification of possible paediatric cases of celiac disease. population-based observational study with record linkage of administrative healthcare databases. SETTING AND PARTICIPANT S: children born alive in the Friuli Venezia Giulia Region (Northern Italy) to resident mothers in the years 1989-2012, identified using the regional Medical Birth Register. we defined possible celiac disease as having at least one of the following, from 2002 onward: 1. a pathology report of intestinal villous atrophy; 2. a copayment exemption for celiac disease; 3. a hospital discharge record with ICD-9-CM code of celiac disease; 4. a gluten-free food prescription. We evaluated the proportion of subjects identified by each archive and by combinations of archives, and examined the temporal relationship of the different sources in cases identified by more than one source. RESULT S: out of 962 possible cases of celiac disease, 660 (68.6%) had a pathology report, 714 (74.2%) a copayment exemption, 667 (69.3%) a hospital discharge record, and 636 (66.1%) a gluten-free food prescription. The four sources coexisted in 42.2% of subjects, whereas 30.2% were identified by two or three sources and 27.6% by a single source (16.9% by pathology reports, 4.2% by hospital discharge records, 3.9% by copayment exemptions, and 2.6% by gluten-free food prescriptions). Excluding pathology reports, 70.6% of cases were identified by at least two sources. A definition based on copayment exemptions and discharge records traced 80.5% of the 962 possible cases of celiac disease; whereas a definition based on copayment exemptions, discharge records, and gluten-free food prescriptions traced 83.1% of those cases. The temporal relationship of the different sources was compatible with the typical diagnostic pathway of subjects with celiac disease. the four sources were only partially consistent. A relevant proportion of all possible cases of paediatric celiac disease were identified exclusively by pathology reports.
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Biomarkers intersect with the exposome
Rappaport, Stephen M.
2016-01-01
The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment. PMID:22672124
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Families Seek a Greater Role in Search for Rare Disease Treatments
ERIC Educational Resources Information Center
Abbott, Natalie
2011-01-01
Of the nearly 7,000 rare diseases identified by the National Institutes of Health (NIH), only a few hundred currently have treatments. The development of therapies for rare diseases is often hampered by the special challenges of conducting the needed studies for rare disease drugs and medical devices, such as small numbers of patients and the fact…
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ERIC Educational Resources Information Center
Masupe, T. K.; Ndayi, K.; Tsolekile, L.; Delobelle, P.; Puoane, T.
2018-01-01
The colliding epidemics of non-communicable diseases including diabetes with chronic infectious diseases in Sub-Saharan Africa requires contextualized innovative disease management strategies. This qualitative study conducted in a peri-urban township near Cape Town, South Africa aimed to identify and gain in-depth understanding of contextual and…
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Diseases that turn African hair silky.
Ajose, Frances O A
2012-11-01
African hair in its natural state poses tenacious grooming challenges; consequently a large portion of the African cosmetic industry is focused on means to relax the tight curls of African hair to make the hair more manageable. In malnourished and hypoproteinemic states, African hair straightens in an uncomplimentary manner. Recently, we observed that in certain diseases African hair changes to a desirable silky wavy texture. To identify the diseases that turn African hair silky and their parameters we examined 5612 dermatology patients at a tertiary hospital in Nigeria. We then studied the clinical and basic laboratory parameters of those patients whose diseases were accompanied by the silky hair change. Silky hair change similar to the hair of the African neonatal child was observed in five diseases, namely AIDS, rheumatoid arthritis, systemic lupus erythematosus, pulmonary tuberculosis with cachexia, and Behçet's disease. Our study identified retrogression of African hair to the neonatal structure in five diseases. Anemia of chronic illness, high erythrocyte sedimentation rate, and mild hypocalcemia were significant laboratory parameters. This is an important observation, which should excite and advance research into the nature and structure of African hair. The causes of structural hair changes should include these five diseases. © 2012 The International Society of Dermatology.
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Jennings, Jacky M; Stover, Jeffrey A; Bair-Merritt, Megan H; Fichtenberg, Caroline; Munoz, Mary Grace; Maziad, Rafiq; Ketemepi, Sherry Johnson; Zenilman, Jonathan
2009-01-01
Integrated infectious disease surveillance information systems have the potential to provide important new surveillance capacities and business efficiencies for local health departments. We conducted a case study at a large city health department of the primary computer-based infectious disease surveillance information systems during a 10-year period to identify the major challenges for information integration across the systems. The assessment included key informant interviews and evaluations of the computer-based surveillance information systems used for acute communicable diseases, human immunodeficiency virus/acquired immunodeficiency syndrome, sexually transmitted diseases, and tuberculosis. Assessments were conducted in 1998 with a follow-up in 2008. Assessments specifically identified and described the primary computer-based surveillance information system, any duplicative information systems, and selected variables collected. Persistent challenges to information integration across the information systems included the existence of duplicative data systems, differences in the variables used to collect similar information, and differences in basic architecture. The assessments identified a number of challenges for information integration across the infectious disease surveillance information systems at this city health department. The results suggest that local disease control programs use computer-based surveillance information systems that were not designed for data integration. To the extent that integration provides important new surveillance capacities and business efficiencies, we recommend that patient-centric information systems be designed that provide all the epidemiologic, clinical, and research needs in one system. In addition, the systems should include a standard system of elements and fields across similar surveillance systems.
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Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.
Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping
2015-04-01
Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Soundy, Andrew; Condon, Nicola
2015-01-01
Research is required that can synthesize the experiences of patients with Motor Neuron Disease (MND). One value of being able to do this is to understand the psychological experiences and processes involved in maintaining mental well-being and hope. A qualitative thematic synthesis of studies was undertaken. Studies were electronically searched from inception until June 2014. Twenty-nine studies with 342 (175 male) unique individuals with MND were identified. Five themes were identified: (1)The effects of the disease on interactions, relationships, roles and meaningful activities, (2) Responses that relate to the expression of hope, (3) Factors which disable hope, (4) Factors which enable hope, and (5) Cognitive and Practical adaptation that enabled hope, control and coping. Finally, a model of hope enablement was identified that considers the psychological pathways undertaken by a patient which influence mental well-being and hope. Within this review article evidence is provided which illustrates the central importance of relationships and social support for individuals with MND. Further, it has been identified that periods of coping are possible and are likely associated with greater mental well-being for patients with MND.
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Identification of Urban Leprosy Clusters
Paschoal, José Antonio Armani; Paschoal, Vania Del'Arco; Nardi, Susilene Maria Tonelli; Rosa, Patrícia Sammarco; Ismael, Manuela Gallo y Sanches; Sichieri, Eduvaldo Paulo
2013-01-01
Overpopulation of urban areas results from constant migrations that cause disordered urban growth, constituting clusters defined as sets of people or activities concentrated in relatively small physical spaces that often involve precarious conditions. Aim. Using residential grouping, the aim was to identify possible clusters of individuals in São José do Rio Preto, Sao Paulo, Brazil, who have or have had leprosy. Methods. A population-based, descriptive, ecological study using the MapInfo and CrimeStat techniques, geoprocessing, and space-time analysis evaluated the location of 425 people treated for leprosy between 1998 and 2010. Clusters were defined as concentrations of at least 8 people with leprosy; a distance of up to 300 meters between residences was adopted. Additionally, the year of starting treatment and the clinical forms of the disease were analyzed. Results. Ninety-eight (23.1%) of 425 geocoded cases were located within one of ten clusters identified in this study, and 129 cases (30.3%) were in the region of a second-order cluster, an area considered of high risk for the disease. Conclusion. This study identified ten clusters of leprosy cases in the city and identified an area of high risk for the appearance of new cases of the disease. PMID:24288467
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Systematic review with meta-analysis: coffee consumption and the risk of gallstone disease.
Zhang, Y-P; Li, W-Q; Sun, Y-L; Zhu, R-T; Wang, W-J
2015-09-01
Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory. To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease. We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). One case-control study and five prospective cohort studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers. This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease. © 2015 John Wiley & Sons Ltd.
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Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G
2014-10-01
Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.
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Bassola, Barbara; Sansone, Valeria Ada; Lusignani, Maura
2018-06-01
Self-care is a crucial aspect in the management of people with motor neuron disease (MND). Nurses and healthcare professionals must know the processes used by patients in performing self-care to identify problems and help them. Decision-making processes, self-understanding, and political and social support influence the self-care process in chronic diseases. Little is known about the self-care process in MND. The aim of this study was to gain insight on the self-care processes in people with MND. A grounded theory method was chosen for this study. Data from interviews were gathered, and a simultaneous comparative analysis was conducted to identify categories and codes. Twenty-one people with spinal muscular atrophy and amyotrophic lateral sclerosis participated in the study. Five categories were identified as grounded in the data. The process starts from "being yourself in the care," and it develops thanks to "growing and changing" and with a "thinking about the future" approach. "Family role" and "you and who helps you" categories affect the process itself. The self-care process in people with MND is not seen in a daily perspective but changes with the evolution of the disease. For the growing patients with MND, changing, accepting and controlling the disease while deciding autonomously are the foundations of the process.
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Bracht, Thilo; Schweinsberg, Vincent; Trippler, Martin; Kohl, Michael; Ahrens, Maike; Padden, Juliet; Naboulsi, Wael; Barkovits, Katalin; Megger, Dominik A; Eisenacher, Martin; Borchers, Christoph H; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara
2015-05-01
Hepatic fibrosis and cirrhosis are major health problems worldwide. Until now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. To develop noninvasive diagnostic assays for the assessment of liver fibrosis, it is urgently necessary to identify molecules that are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n = 77). Finally, we performed a targeted proteomics approach, multiple reaction monitoring (MRM), to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM), and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.
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Xu, Yanjun; Li, Feng; Wu, Tan; Xu, Yingqi; Yang, Haixiu; Dong, Qun; Zheng, Meiyu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Li, Xia
2017-02-28
Long non-coding RNAs (lncRNAs) play important roles in various biological processes, including the development of many diseases. Pathway analysis is a valuable aid for understanding the cellular functions of these transcripts. We have developed and characterized LncSubpathway, a novel method that integrates lncRNA and protein coding gene (PCG) expression with interactome data to identify disease risk subpathways that functionally associated with risk lncRNAs. LncSubpathway identifies the most relevance regions which are related with risk lncRNA set and implicated with study conditions through simultaneously considering the dysregulation extent of lncRNAs, PCGs and their correlations. Simulation studies demonstrated that the sensitivity and false positive rates of LncSubpathway were within acceptable ranges, and that LncSubpathway could accurately identify dysregulated regions that related with disease risk lncRNAs within pathways. When LncSubpathway was applied to colorectal carcinoma and breast cancer subtype datasets, it identified cancer type- and breast cancer subtype-related meaningful subpathways. Further, analysis of its robustness and reproducibility indicated that LncSubpathway was a reliable means of identifying subpathways that functionally associated with lncRNAs. LncSubpathway is freely available at http://www.bio-bigdata.com/lncSubpathway/.
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Wu, Tan; Xu, Yingqi; Yang, Haixiu; Dong, Qun; Zheng, Meiyu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Li, Xia
2017-01-01
Long non-coding RNAs (lncRNAs) play important roles in various biological processes, including the development of many diseases. Pathway analysis is a valuable aid for understanding the cellular functions of these transcripts. We have developed and characterized LncSubpathway, a novel method that integrates lncRNA and protein coding gene (PCG) expression with interactome data to identify disease risk subpathways that functionally associated with risk lncRNAs. LncSubpathway identifies the most relevance regions which are related with risk lncRNA set and implicated with study conditions through simultaneously considering the dysregulation extent of lncRNAs, PCGs and their correlations. Simulation studies demonstrated that the sensitivity and false positive rates of LncSubpathway were within acceptable ranges, and that LncSubpathway could accurately identify dysregulated regions that related with disease risk lncRNAs within pathways. When LncSubpathway was applied to colorectal carcinoma and breast cancer subtype datasets, it identified cancer type- and breast cancer subtype-related meaningful subpathways. Further, analysis of its robustness and reproducibility indicated that LncSubpathway was a reliable means of identifying subpathways that functionally associated with lncRNAs. LncSubpathway is freely available at http://www.bio-bigdata.com/lncSubpathway/. PMID:28152521
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Using hyperspectral imaging technology to identify diseased tomato leaves
NASA Astrophysics Data System (ADS)
Li, Cuiling; Wang, Xiu; Zhao, Xueguan; Meng, Zhijun; Zou, Wei
2016-11-01
In the process of tomato plants growth, due to the effect of plants genetic factors, poor environment factors, or disoperation of parasites, there will generate a series of unusual symptoms on tomato plants from physiology, organization structure and external form, as a result, they cannot grow normally, and further to influence the tomato yield and economic benefits. Hyperspectral image usually has high spectral resolution, not only contains spectral information, but also contains the image information, so this study adopted hyperspectral imaging technology to identify diseased tomato leaves, and developed a simple hyperspectral imaging system, including a halogen lamp light source unit, a hyperspectral image acquisition unit and a data processing unit. Spectrometer detection wavelength ranged from 400nm to 1000nm. After hyperspectral images of tomato leaves being captured, it was needed to calibrate hyperspectral images. This research used spectrum angle matching method and spectral red edge parameters discriminant method respectively to identify diseased tomato leaves. Using spectral red edge parameters discriminant method produced higher recognition accuracy, the accuracy was higher than 90%. Research results have shown that using hyperspectral imaging technology to identify diseased tomato leaves is feasible, and provides the discriminant basis for subsequent disease control of tomato plants.
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Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.
von Coelln, Rainer; Shulman, Lisa M
2016-12-01
Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.
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Transgenic animal models of neurodegeneration based on human genetic studies
Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko
2011-01-01
The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease. PMID:20931247
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Slater, Helen; Briggs, Andrew; Stinson, Jennifer; Campbell, Jared M
2017-08-01
The objective of this review is to systematically identify, review and synthesize relevant qualitative research on end user and implementer experiences of mobile health (mHealth) technologies developed for noncommunicable chronic disease management in young adults. "End users" are defined as young people aged 15-24 years, and "implementers" are defined as health service providers, clinicians, policy makers and administrators.The two key questions we wish to systematically explore from identified relevant qualitative studies or studies with qualitative components are.
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Suhrcke, Marc; Stuckler, David; Suk, Jonathan E.; Desai, Monica; Senek, Michaela; McKee, Martin; Tsolova, Svetla; Basu, Sanjay; Abubakar, Ibrahim; Hunter, Paul; Rechel, Boika; Semenza, Jan C.
2011-01-01
There is concern among public health professionals that the current economic downturn, initiated by the financial crisis that started in 2007, could precipitate the transmission of infectious diseases while also limiting capacity for control. Although studies have reviewed the potential effects of economic downturns on overall health, to our knowledge such an analysis has yet to be done focusing on infectious diseases. We performed a systematic literature review of studies examining changes in infectious disease burden subsequent to periods of crisis. The review identified 230 studies of which 37 met our inclusion criteria. Of these, 30 found evidence of worse infectious disease outcomes during recession, often resulting from higher rates of infectious contact under poorer living circumstances, worsened access to therapy, or poorer retention in treatment. The remaining studies found either reductions in infectious disease or no significant effect. Using the paradigm of the “SIR” (susceptible-infected-recovered) model of infectious disease transmission, we examined the implications of these findings for infectious disease transmission and control. Key susceptible groups include infants and the elderly. We identified certain high-risk groups, including migrants, homeless persons, and prison populations, as particularly vulnerable conduits of epidemics during situations of economic duress. We also observed that the long-term impacts of crises on infectious disease are not inevitable: considerable evidence suggests that the magnitude of effect depends critically on budgetary responses by governments. Like other emergencies and natural disasters, preparedness for financial crises should include consideration of consequences for communicable disease control. PMID:21695209
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Stengel, Bénédicte; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Édouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Pisoni, Ron L; Robinson, Bruce M; Massy, Ziad A
2016-04-01
Preserving kidney function and improving the transition from chronic kidney disease to end stage is a research and healthcare challenge. The national Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort was established to identify the determinants, biomarkers and practice patterns associated with chronic kidney disease outcomes. The study will include more than 3000 adult patients with moderate to advanced chronic kidney disease from a representative sample of 40 nephrology clinics with respect to regions and legal status, public or private. Patients are recruited during a routine visit and followed for 5 years, before and after starting renal replacement therapy. Patient-level clinical, biological, and lifestyle data are collected annually, as well as provider-level data on clinical practices, coordinated with the International Chronic Kidney Disease Outcomes and Practice Pattern Study. Blood and urine samples are stored in a biobank. Major studied outcomes include survival, patient-reported outcomes, disease progression and hospitalizations. More than 13,000 eligible patients with chronic kidney disease were identified, 60% with stage 3 and 40% with stage 4. Their median age is 72 years [interquartile range, 62-80 years], 60% are men and 38% have diabetes. By the end of December 2015, 2885 patients were included. The CKD-REIN cohort will serve to improve our understanding of chronic kidney disease and provide evidence to improve patient survival and quality of life as well as health care system performances. Copyright © 2016 Association Société de néphrologie. All rights reserved.
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Apikoglu-Rabus, Sule; Yesilyaprak, Gozde; Izzettin, Fikret Vehbi
2016-11-01
Asthma and chronic obstructive pulmonary disease are preventable and treatable chronic airway diseases with high incidence and prevalence. Pharmacists and clinical pharmacy based pharmaceutical care services have positive impact on therapy outcomes. The aim of this study is to describe drug related problems in a cohort of patients with asthma and chronic obstructive pulmonary disease and to assess interventions provided by the pharmacist to address these problems in a community pharmacy. Study population consisted of patients with asthma and chronic obstructive pulmonary disease older than 18 years who visited the study pharmacy during the pre-determined six-month period. The patients whose disease control states were "not fully controlled" were included in our study for further steps. On the first interview, present and potential drug related problems were addressed, interventions were provided. Follow-up interviews were held one month and two months later than the first interview. For the 44 patients with asthma, 59 drug-related problems and 134 causes for these problems were identified. Eighty-four interventions were made to resolve the problems; and 54.2% of the problems were resolved. For the 37 patients with chronic obstructive pulmonary disease, 60 drug-related problems and 128 causes for these problems were identified. Ninety-five interventions were made to resolve the problems; and 63.3% of the problems were resolved. Pharmacists taking part in therapy and management of asthma and chronic obstructive pulmonary disease can help patients be more educated about their disease and medications; and improve disease control and therapy outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Kim, Jae Yoon; Moon, Jun-Cheol; Kim, Hyo Chul; Shin, Seungho; Song, Kitae; Kim, Kyung-Hee; Lee, Byung-Moo
2017-01-01
Premise of the study: Positional cloning in combination with phenotyping is a general approach to identify disease-resistance gene candidates in plants; however, it requires several time-consuming steps including population or fine mapping. Therefore, in the present study, we suggest a new combined strategy to improve the identification of disease-resistance gene candidates. Methods and Results: Downy mildew (DM)–resistant maize was selected from five cultivars using a spreader row technique. Positional cloning and bioinformatics tools were used to identify the DM-resistance quantitative trait locus marker (bnlg1702) and 47 protein-coding gene annotations. Eventually, five DM-resistance gene candidates, including bZIP34, Bak1, and Ppr, were identified by quantitative reverse-transcription PCR (RT-PCR) without fine mapping of the bnlg1702 locus. Conclusions: The combined protocol with the spreader row technique, quantitative trait locus positional cloning, and quantitative RT-PCR was effective for identifying DM-resistance candidate genes. This cloning approach may be applied to other whole-genome-sequenced crops or resistance to other diseases. PMID:28224059
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78 FR 5188 - Proposed Collection; Comment Request: The Jackson Heart Study (JHS)
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-24
... cardiovascular disease in African American men and women. Recruitment of 5,500 JHS participants began in... JHS study, review of their medical records, and interviews with doctors and family to identify disease occurrence. Interviewers will contact doctors and hospitals to ascertain participants' cardiovascular events...
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Coronary Heart Disease Knowledge and Risk Factors among Tri-Ethnic College Students
ERIC Educational Resources Information Center
Koutoubi, Samer; Huffman, Fatma G.; Ciccazzo, Michele W.; Himburg, Susan P.; Johnson, Paulette
2005-01-01
Objectives: Coronary heart disease (CHD) is the leading cause of death in the United States and Europe. This study identified and compared nutritional knowledge associated with CHD risk factors among tri-ethnic college students. Design: A quantitative, cross-sectional, observational study using questionnaires. Setting: University laboratory.…
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Prevalence of obesity among patients with congenital and acquired heart disease.
Shustak, Rachel J; McGuire, Sharda B; October, Tessie W; Phoon, Colin K L; Chun, Anne J L
2012-01-01
Overweight and obesity rates have risen dramatically in the United States, with subsequent detrimental comorbidity risks. The rates for obesity among children with congenital and acquired heart disease have rarely been reported. A retrospective cross-sectional study was conducted to determine the prevalence of overweight and obesity in children with heart disease and to identify subgroups at increased risk. A total of 795 cases were identified from a chart review of patients presenting to an urban center's Pediatric Cardiology Program between 1 January and 31 December 2006. A body mass index (BMI) at the 85th percentile or higher was defined as overweight, and a BMI at the 95th percentile or higher was defined as obese. Subjects with comorbidities affecting body habitus were excluded from the study. Overall, overweight and obesity rates were similar to national data. No significant differences in overweight or obesity rates were detected between heart disease and non-heart disease groups (P = 0.50). According to multivariate analysis, Hispanic ethnicity and male gender were the only predictors of obesity. This study shows that children with heart disease are not immune to the common predictors of obesity such as gender and ethnicity and that the future care of children with heart disease should include general discussions about the risks for obesity.
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The prevalence of diabetic foot disease in the Waikato region.
O'Shea, C; McClintock, J; Lawrenson, R
2017-07-01
The aim of this study was to establish the prevalence of diabetic foot disease by utilising the retinal eye screening register in the Waikato region of New Zealand. Understanding both the prevalence and the degree of foot disease across the general diabetes population will help to determine what podiatry services are required for people with diabetes. 2192 people aged 15years and over, who attended the Waikato Regional Diabetes Service mobile retinal photo screening service for the six-month period between May and November 2014, consented to a foot screen including testing for sensation and pedal pulses. A digital image was taken of the dorsal and plantar aspect of each foot for review by a registered Podiatrist. Thirteen percent of the study sample was identified as having a high-risk foot including active foot complications. 65% were categorised as low risk and a further 22% at moderate risk of diabetic foot disease. Factors identified as significant included age, type of diabetes, duration of diabetes, and smoking. These factors placed people at greater risk of diabetic foot disease. A significant number of people with diabetes are at risk of diabetic foot disease. This study has highlighted the need for targeted podiatry services to address diabetic foot disease. Copyright © 2017 Elsevier B.V. All rights reserved.
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Wen, Tzai-Hung; Chin, Wei Chien Benny
2015-04-14
Respiratory diseases mainly spread through interpersonal contact. Class suspension is the most direct strategy to prevent the spread of disease through elementary or secondary schools by blocking the contact network. However, as university students usually attend courses in different buildings, the daily contact patterns on a university campus are complicated, and once disease clusters have occurred, suspending classes is far from an efficient strategy to control disease spread. The purpose of this study is to propose a methodological framework for generating campus location networks from a routine administration database, analyzing the community structure of the network, and identifying the critical links and nodes for blocking respiratory disease transmission. The data comes from the student enrollment records of a major comprehensive university in Taiwan. We combined the social network analysis and spatial interaction model to establish a geo-referenced community structure among the classroom buildings. We also identified the critical links among the communities that were acting as contact bridges and explored the changes in the location network after the sequential removal of the high-risk buildings. Instead of conducting a questionnaire survey, the study established a standard procedure for constructing a location network on a large-scale campus from a routine curriculum database. We also present how a location network structure at a campus could function to target the high-risk buildings as the bridges connecting communities for blocking disease transmission.
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Clinical characteristics in patients with asymmetric idiopathic pulmonary fibrosis.
Callahan, Sean J; Xia, Meng; Murray, Susan; Flaherty, Kevin R
2016-10-01
A group of patients with idiopathic pulmonary fibrosis (IPF) presents with disease affecting one lung markedly more than the other. At this time, it is unclear how this population differs from those who present with more symmetric disease. We sought to explain the characteristics of the asymmetric group and how their disease progresses. In this retrospective case-control study we accessed an interstitial lung disease (ILD) database and identified 14 asymmetric IPF cases via high-resolution computed tomography (HRCT) scoring of each lung lobe's disease severity. We identified 28 symmetric IPF controls from the same database using the same methods, and compared the clinical features of each group. Patients with asymmetric disease exhibited similar demographics as those in the general IPF population; they were predominantly male (64%), elderly (69 years old), and used tobacco (57%). We found a trend toward significantly increased all-cause mortality in the case population two years following diagnosis (p = 0.089). Pulmonary function tests were significantly lower in the case group at the time of diagnosis, then both groups experienced gradual decline. We found no statistically significant differences in number of IPF exacerbations (cases 43%, controls 39%, p = 0.824) and gastro-esophageal reflux (both groups 50%). Patients with asymmetric IPF resemble patients in the general IPF population but may have a lower overall survival rate. Further systemic factors may be studied to identify reasons for disease asymmetry and clinical decline in this population. Published by Elsevier Ltd.
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Iddamalgoda, Lahiru; Das, Partha S; Aponso, Achala; Sundararajan, Vijayaraghava S; Suravajhala, Prashanth; Valadi, Jayaraman K
2016-01-01
Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods in determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI) methods in conjunction with the K nearest neighbors' could be used in accurately categorizing the genetic factors in disease causation.
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The promise of discovering population-specific disease-associated genes in South Asia.
Nakatsuka, Nathan; Moorjani, Priya; Rai, Niraj; Sarkar, Biswanath; Tandon, Arti; Patterson, Nick; Bhavani, Gandham SriLakshmi; Girisha, Katta Mohan; Mustak, Mohammed S; Srinivasan, Sudha; Kaushik, Amit; Vahab, Saadi Abdul; Jagadeesh, Sujatha M; Satyamoorthy, Kapaettu; Singh, Lalji; Reich, David; Thangaraj, Kumarasamy
2017-09-01
The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identified 81 unique groups, 14 of which had estimated census sizes of more than 1 million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identified multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an underappreciated opportunity for decreasing disease burden among South Asians through discovery of and testing for recessive disease-associated genes.
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The promise of disease gene discovery in South Asia
Nakatsuka, Nathan; Moorjani, Priya; Rai, Niraj; Sarkar, Biswanath; Tandon, Arti; Patterson, Nick; Bhavani, Gandham SriLakshmi; Girisha, Katta Mohan; Mustak, Mohammed S; Srinivasan, Sudha; Kaushik, Amit; Vahab, Saadi Abdul; Jagadeesh, Sujatha M.; Satyamoorthy, Kapaettu; Singh, Lalji; Reich, David; Thangaraj, Kumarasamy
2017-01-01
The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population, but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identify 81 unique groups, of which 14 have estimated census sizes of more than a million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identify multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an under-appreciated opportunity for reducing disease burden among South Asians through the discovery of and testing for recessive disease genes. PMID:28714977
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Stebler, N; Schuepbach-Regula, G; Braam, P; Falzon, L C
2015-09-01
Zoonotic diseases have a significant impact on public health globally. To prevent or reduce future zoonotic outbreaks, there is a constant need to invest in research and surveillance programs while updating risk management strategies. However, given the limited resources available, disease prioritization based on the need for their control and surveillance is important. This study was performed to identify and weight disease criteria for the prioritization of zoonotic diseases in Switzerland using a semi-quantitative research method based on expert opinion. Twenty-eight criteria relevant for disease control and surveillance, classified under five domains, were selected following a thorough literature review, and these were evaluated and weighted by seven experts from the Swiss Federal Veterinary Office using a modified Delphi panel. The median scores assigned to each criterion were then used to rank 16 notifiable and/or emerging zoonoses in Switzerland. The experts weighted the majority of the criteria similarly, and the top three criteria were Severity of disease in humans, incidence and prevalence of the disease in humans and treatment in humans. Based on these weightings, the three highest ranked diseases were Avian Influenza, Bovine Spongiform Encephalitis, and Bovine Tuberculosis. Overall, this study provided a preliminary list of criteria relevant for disease prioritization in Switzerland. These were further evaluated in a companion study which involved a quantitative prioritization method and multiple stakeholders. Copyright © 2015 Elsevier B.V. All rights reserved.
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A HapMap harvest of insights into the genetics of common disease
Manolio, Teri A.; Brooks, Lisa D.; Collins, Francis S.
2008-01-01
The International HapMap Project was designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases. This expectation has been amply fulfilled with just the initial output of genome-wide association studies, identifying nearly 100 loci for nearly 40 common diseases and traits. These associations provided new insights into pathophysiology, suggesting previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. In addition, HapMap-based discoveries have shed new light on the impact of evolutionary pressures on the human genome, suggesting multiple loci important for adapting to disease-causing pathogens and new environments. In this review we examine the origin, development, and current status of the HapMap; its prospects for continued evolution; and its current and potential future impact on biomedical science. PMID:18451988
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Epidemiology of Dengue Disease in Malaysia (2000–2012): A Systematic Literature Review
Mohd-Zaki, Abdul Hamid; Brett, Jeremy; Ismail, Ellyana; L'Azou, Maïna
2014-01-01
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions. Protocol registration PROSPERO #CRD42012002293 PMID:25375211
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Ulcerative colitis in Kuwait: a review of 90 cases.
Al-Shamali, Mohammed A; Kalaoui, Maher; Patty, Istivan; Hasan, Fuad; Khajah, Abdulkareem; Al-Nakib, Basil
2003-01-01
Chronic ulcerative colitis is a disease of unknown etiology. Its incidence is on the rise in various developing countries as has been reported in studies from South-East Asia and the Middle East. There seems to be significant differences in the pattern and the clinical course of this disease in our patient population. The aim of our study is to assess the incidence and the clinical course of the disease in Kuwait. This is a retrospective study of cases identified over a period of 14 years (1985-1999). Three hundred forty-six patients were identified to have chronic ulcerative colitis. Ninety patients were interviewed for this study. Chronic ulcerative colitis is being identified with increasing frequency. Our local incidence was 2.8 per 100,000 persons per year. The disease was seen in both sexes with equal frequency. It peaks at the third decade of life, with no second peak observed in the sixth decade. The disease was of mild to moderate severity in 93% of the cases. The distribution of the disease in the colon showed pancolitis in 45%, left-sided colitis in 14%, proctosigmoiditis in 21% and proctitis in 20%. Arthritis and arthralgia were the most frequent extraintestinal manifestation seen in 31%. Perianal disease, although rare in ulcerative colitis, was seen in 8%. Of interest is the fact that over 14 years of follow-up, none of our patients developed high-grade dysplasia or colorectal cancer. Four patients required total colectomy mainly due to failure of medical therapy. Chronic ulcerative colitis is occurring with increasing frequency similar to that seen in Western countries. The disease observed in our patient population was of mild to moderate severity, with fewer complications than reported in Western countries. It peaks in the third decade with no second peak. None of our patients developed high-grade dysplasia or colorectal carcinoma. Copyright 2003 S. Karger AG, Basel
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Prevalence of celiac disease in siblings of Iranian patients with celiac disease.
Chomeili, Bashir; Aminzadeh, Majid; Hardani, Amir Kamal; Fathizadeh, Payam; Chomeili, Pooya; Azaran, Azarakhsh
2011-01-01
Celiac disease, one of the best-known autoimmune human leukocyte antigen-dependent disorders, has a relatively increased prevalence in first-degree relatives. To determine the prevalence of celiac disease in siblings of patients with confirmed celiac disease. Siblings of confirmed celiac disease patients in our center were identified and enrolled in this study. Their serum immunoglobulin A and tissue transglutaminase antibody-enzyme-linked immunosorbent assay (anti-tissue transglutaminase, immunoglobulin A, and immunoglobulin G) were measured and multiple endoscopic duodenal biopsy specimens were obtained with parental consensus. Celiac disease was confirmed by observation of characteristic histological changes. A total of 49 children (male, 29; female, 20; age, 2-16 years) with confirmed celiac disease in a pediatric gastroenterology ward were studied from 1999 to 2006. We found 30 siblings (female, 16) all shared in both parents. The only measurement available was for immunoglobulin A tissue transglutaminase antibody. A duodenal biopsy was performed in all 30 siblings. Clinical findings such as abdominal pain, fatigue, growth retardation and diarrhea were found in 53.3% of the completely studied siblings, and positive serology without histological changes was identified in four cases. Both serology and biopsy (confirmed new cases) were positive in 2 of the 30 siblings. High prevalence of celiac disease among siblings of patients with confirmed celiac disease necessitates serologic screening (and confirmatory biopsy if indicated) in families having celiac disease. It is advantageous to diagnose the disease as soon as possible because early diagnosis and diet intervention may prevent serious complications such as growth retardation, short stature, chronic diarrhea, and malignancy.
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Lee, Eunjoo; Park, Hyejin; Whyte, James; Kim, Youngae; Park, Sang Youn
2014-12-01
The purpose of this study was to identify the core nursing sensitive outcomes according to the most frequently used five North American Nursing Diagnosis Association-International for patients with cerebrovascular disease using the Nursing Outcomes Classification (NOC). A cross-sectional survey design was used. First, nursing problems were identified through 78 charts review, and then linkages between each of nursing problems and nursing sensitive outcomes were established and validated by an expert group for questionnaires. Second, 80 nurses working in the neurosurgical intensive care unit and neurosurgery departments of five Korean hospitals were asked to evaluate how important each outcome is and how often each outcome used to evaluate patient outcomes using 5-point Likert scale. Although there were some differences in the core outcomes identified for each of the nursing problem, consciousness, cognitive orientation, neurologic status and communication were considered the most critical nursing sensitive outcomes for patients suffering cerebrovascular disease. Core nursing sensitive outcomes of patients suffering cerebrovascular disease using NOC were identified to measure the effectiveness of nursing care. © 2013 Wiley Publishing Asia Pty Ltd.
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Craddock, Nick; Hurles, Matthew E; Cardin, Niall; Pearson, Richard D; Plagnol, Vincent; Robson, Samuel; Vukcevic, Damjan; Barnes, Chris; Conrad, Donald F; Giannoulatou, Eleni; Holmes, Chris; Marchini, Jonathan L; Stirrups, Kathy; Tobin, Martin D; Wain, Louise V; Yau, Chris; Aerts, Jan; Ahmad, Tariq; Andrews, T Daniel; Arbury, Hazel; Attwood, Anthony; Auton, Adam; Ball, Stephen G; Balmforth, Anthony J; Barrett, Jeffrey C; Barroso, Inês; Barton, Anne; Bennett, Amanda J; Bhaskar, Sanjeev; Blaszczyk, Katarzyna; Bowes, John; Brand, Oliver J; Braund, Peter S; Bredin, Francesca; Breen, Gerome; Brown, Morris J; Bruce, Ian N; Bull, Jaswinder; Burren, Oliver S; Burton, John; Byrnes, Jake; Caesar, Sian; Clee, Chris M; Coffey, Alison J; Connell, John M C; Cooper, Jason D; Dominiczak, Anna F; Downes, Kate; Drummond, Hazel E; Dudakia, Darshna; Dunham, Andrew; Ebbs, Bernadette; Eccles, Diana; Edkins, Sarah; Edwards, Cathryn; Elliot, Anna; Emery, Paul; Evans, David M; Evans, Gareth; Eyre, Steve; Farmer, Anne; Ferrier, I Nicol; Feuk, Lars; Fitzgerald, Tomas; Flynn, Edward; Forbes, Alistair; Forty, Liz; Franklyn, Jayne A; Freathy, Rachel M; Gibbs, Polly; Gilbert, Paul; Gokumen, Omer; Gordon-Smith, Katherine; Gray, Emma; Green, Elaine; Groves, Chris J; Grozeva, Detelina; Gwilliam, Rhian; Hall, Anita; Hammond, Naomi; Hardy, Matt; Harrison, Pile; Hassanali, Neelam; Hebaishi, Husam; Hines, Sarah; Hinks, Anne; Hitman, Graham A; Hocking, Lynne; Howard, Eleanor; Howard, Philip; Howson, Joanna M M; Hughes, Debbie; Hunt, Sarah; Isaacs, John D; Jain, Mahim; Jewell, Derek P; Johnson, Toby; Jolley, Jennifer D; Jones, Ian R; Jones, Lisa A; Kirov, George; Langford, Cordelia F; Lango-Allen, Hana; Lathrop, G Mark; Lee, James; Lee, Kate L; Lees, Charlie; Lewis, Kevin; Lindgren, Cecilia M; Maisuria-Armer, Meeta; Maller, Julian; Mansfield, John; Martin, Paul; Massey, Dunecan C O; McArdle, Wendy L; McGuffin, Peter; McLay, Kirsten E; Mentzer, Alex; Mimmack, Michael L; Morgan, Ann E; Morris, Andrew P; Mowat, Craig; Myers, Simon; Newman, William; Nimmo, Elaine R; O'Donovan, Michael C; Onipinla, Abiodun; Onyiah, Ifejinelo; Ovington, Nigel R; Owen, Michael J; Palin, Kimmo; Parnell, Kirstie; Pernet, David; Perry, John R B; Phillips, Anne; Pinto, Dalila; Prescott, Natalie J; Prokopenko, Inga; Quail, Michael A; Rafelt, Suzanne; Rayner, Nigel W; Redon, Richard; Reid, David M; Renwick; Ring, Susan M; Robertson, Neil; Russell, Ellie; St Clair, David; Sambrook, Jennifer G; Sanderson, Jeremy D; Schuilenburg, Helen; Scott, Carol E; Scott, Richard; Seal, Sheila; Shaw-Hawkins, Sue; Shields, Beverley M; Simmonds, Matthew J; Smyth, Debbie J; Somaskantharajah, Elilan; Spanova, Katarina; Steer, Sophia; Stephens, Jonathan; Stevens, Helen E; Stone, Millicent A; Su, Zhan; Symmons, Deborah P M; Thompson, John R; Thomson, Wendy; Travers, Mary E; Turnbull, Clare; Valsesia, Armand; Walker, Mark; Walker, Neil M; Wallace, Chris; Warren-Perry, Margaret; Watkins, Nicholas A; Webster, John; Weedon, Michael N; Wilson, Anthony G; Woodburn, Matthew; Wordsworth, B Paul; Young, Allan H; Zeggini, Eleftheria; Carter, Nigel P; Frayling, Timothy M; Lee, Charles; McVean, Gil; Munroe, Patricia B; Palotie, Aarno; Sawcer, Stephen J; Scherer, Stephen W; Strachan, David P; Tyler-Smith, Chris; Brown, Matthew A; Burton, Paul R; Caulfield, Mark J; Compston, Alastair; Farrall, Martin; Gough, Stephen C L; Hall, Alistair S; Hattersley, Andrew T; Hill, Adrian V S; Mathew, Christopher G; Pembrey, Marcus; Satsangi, Jack; Stratton, Michael R; Worthington, Jane; Deloukas, Panos; Duncanson, Audrey; Kwiatkowski, Dominic P; McCarthy, Mark I; Ouwehand, Willem; Parkes, Miles; Rahman, Nazneen; Todd, John A; Samani, Nilesh J; Donnelly, Peter
2010-04-01
Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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Figueiredo, Cristina Adelaide; Luchs, Adriana; Russo, Denise Hage; de Cassia Compagnoli Carmona, Rita; Afonso, Ana Maria Sardinha; de Oliveira, Maria Isabel; Curti, Suely Pires; de Moraes, José Cassio; Toscano, Cristiana M; Ciccone, Flavia Helena; Timenetsky, Maria do Carmo Sampaio Tavares
2014-06-01
The aim of the present study was to identify the rubella virus (RV) and enterovirus (EV) genotypes detected during the Epidemiological Surveillance on Exanthematic Febrile Diseases (VIGIFEX) study and to perform phylogenetic analysis. Ten RV- and four EV-positive oropharyngeal samples isolated from cell culture were subjected to RT-PCR and sequencing. Genotype 1G and echovirus 9 (E-9) was identified in RV- and EV-positive samples, respectively. The RV 1G genotype has been persisting in Brazil since 2000-2001. No evidence of E-9 being involved in exanthematic illness in Brazil has been reported previously. Differential laboratory diagnosis is essential for management of rash and fever disease.
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Park, Ji Eun; Park, Bumwoo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun
2017-01-01
To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal ( p < 0.001) and supramarginal gyrus ( p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.
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Harahsheh, Ashraf S; O'Byrne, Michael L; Pastor, Bill; Graham, Dionne A; Fulton, David R
2017-11-01
We conducted a study to assess test characteristics of red-flag criteria for identifying cardiac disease causing chest pain and technical charges of low-probability referrals. Accuracy of red-flag criteria was ascertained through study of chest pain Standardized Clinical Assessment and Management Plans (SCAMPs®) data. Patients were divided into 2 groups: Group1 (concerning clinical elements) and Group2 (without). We compared incidence of cardiac disease causing chest pain between these 2 groups. Technical charges of Group 2 were analyzed using the Pediatric Health Information System database. Potential savings for the US population was estimated using National Ambulatory Medical Care Survey data. Fifty-two percent of subjects formed Group 1. Cardiac disease causing chest pain was identified in 8/1656 (0.48%). No heart disease was identified in patients in Group 2 ( P = .03). Applying red-flags in determining need for referral identified patients with cardiac disease causing chest pain with 100% sensitivity. Median technical charges for Group 2, over a 4-year period, were US2014$775 559. Eliminating cardiac testing of low-probability referrals would save US2014$3 775 182 in technical charges annually. Red-flag criteria were an effective screen for children with chest pain. Eliminating cardiac testing in children without red-flags for referral has significant technical charge savings.
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Fukunaga, Landry L; Uehara, Denise L; Tom, Tammy
2011-03-01
Research about the support needs for and barriers to successful disease management of working adults with diabetes is limited. Our objective was to gain an in-depth understanding of how working adults in Hawaii perceive diabetes, barriers to disease management, and the services needed to keep people healthy and working. From November 2008 through March 2009, we conducted focus group interviews with 74 employed adults with diabetes enrolled in the Hawaii Demonstration to Maintain Independence and Employment project. Responses to questions were analyzed within and across groups to identify recurring themes. A third layer of analysis examined themes across responses to all questions, specifically, how barriers related to identified service needs. Employed participants with diabetes experienced pervasive effects on their lives as a result of the disease, although they interpreted these effects positively or negatively. Barriers to disease management, such as additional health issues, social prejudice, and lack of social support, indicated a need to educate the general public about the disease. Participants identified needing social support from other people with diabetes, psychological support to address the emotional side of diabetes, and coordinated teams of specialists to address medication side effects and other health-related barriers to disease management. Many participants discussed the challenge of integrating diabetes management with work and family responsibilities and the need for monetary support. This study provides insight into how employed adults perceived their disease and what they perceived as challenges to successfully managing diabetes. The findings provide future directions for community and workplace diabetes initiatives.
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Fraser, R S; Lumsden, J S; Lillie, B N
2018-05-10
Infectious diseases are a significant issue in animal production systems, including both the dairy and beef cattle industries. Understanding and defining the genetics of infectious disease susceptibility in cattle is an important step in the mitigation of their impact. Collagenous lectins are soluble pattern recognition receptors that form an important part of the innate immune system, which serves as the first line of host defense against pathogens. Polymorphisms in the collagenous lectin genes have been shown in previous studies to contribute to infectious disease susceptibility, and in cattle, mutations in two collagenous lectin genes (MBL1 and MBL2) are associated with mastitis. To further characterize the contribution of variation in the bovine collagenous lectins to infectious disease susceptibility, we used a pooled NGS approach to identify short nucleotide variants (SNVs) in the collagenous lectins (and regulatory DNA) of cattle with (n = 80) and without (n = 40) infectious disease. Allele frequency analysis identified 74 variants that were significantly (p < 5 × 10 -6 ) associated with infectious disease, the majority of which were clustered in a 29-kb segment upstream of the collectin locus on chromosome 28. In silico analysis of the functional effects of all the variants predicted 11 SNVs with a deleterious effect on protein structure and/or function, 148 SNVs that occurred within potential transcription factor binding sites, and 31 SNVs occurring within potential miRNA binding elements. This study provides a detailed look at the genetic variation of the bovine collagenous lectins and identifies potential genetic markers for infectious disease susceptibility.
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Zabana, Yamile; Garcia-Planella, Esther; van Domselaar, Manuel; Mañosa, Míriam; Gordillo, Jordi; López-Sanromán, Antonio; Cabré, Eduard; Domènech, Eugeni
2013-12-01
No studies have specifically searched for predictors of a favourable outcome that would allow a conservative therapeutic approach in adult Crohn's disease (CD). To identify predictors of a favourable disease course over time at CD diagnosis. We identified and included all patients diagnosed with CD between January 1994 and December 2003, who had CD with an inflammatory pattern and no perianal disease at diagnosis, and who were followed up for at least 5 years. Clinical and therapeutic features until December 2008 and losses to follow-up were identified. We defined a favourable outcome as the absence of stricturing and penetrating complications of the disease (including perianal disease), together with the absence of need for anti-TNF therapy or resectional surgery during follow up. One hundred and forty-five patients were included and followed up for a median of 96 months (IQR, 79-140). At diagnosis, location was ileal in 39%, colonic in 28%, and ileocolonic in 32%; 50% of the patients were active smokers, and 41% used immunomodulators. Eighty-two patients (57%) met the criteria for a favourable outcome at the end of follow-up. The only factor associated with a favourable outcome was isolated colonic involvement (P=0.022), with 73% of these patients meeting the criteria for a favourable outcome. A favourable outcome of initially uncomplicated CD is not easily predicted at disease diagnosis by means of clinical or epidemiologic factors. Nevertheless, patients with isolated colonic disease are less likely to have an aggressive course. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.
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Diverticular disease and the risk of colon cancer - a population-based case-control study.
Granlund, J; Svensson, T; Granath, F; Hjern, F; Ekbom, A; Blomqvist, P; Schmidt, P T
2011-09-01
Colon cancer and diverticular disease are most common in the Western world and their incidences tend to increase with advancing age. The association between the diseases remains unclear. To analyse the risk of colon cancer after hospitalisation for diverticular disease. Nationwide case-control study. A total of 41,037 patients with colon cancer during 1992-2006, identified from the Swedish Cancer Register were included. Each case was matched with two control subjects. From the Swedish Inpatient Register, cases and control subjects hospitalised for diverticular disease were identified. Odds ratios (OR) and confidence intervals for receiving a diagnosis of colon cancer after hospital discharge for diverticular disease were calculated. Colon cancer mortality was compared between patients with or without diverticular disease. Within 6months after an admission due to diverticular disease, OR of having a colon cancer diagnosis were up to 31.49 (19.00-52.21). After 12 months, there was no increased risk. The number of discharges for diverticular disease did not affect the risk. Colon cancer mortality did not differ between patients with and without diverticular disease. Diverticular disease does not increase the risk of colon cancer in the long term, and a history of diverticular disease does not affect colon cancer mortality. The increased risk of colon cancer within the first 12months after diagnosing diverticular disease is most likely due to surveillance and misclassification. Examination of the colon should be recommended after a primary episode of symptomatic diverticular disease. © 2011 Blackwell Publishing Ltd.
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Lee, Bradford W.; Kumar, Virender B.; Biswas, Pooja; Ko, Audrey C.; Alameddine, Ramzi M.; Granet, David B.; Ayyagari, Radha; Kikkawa, Don O.; Korn, Bobby S.
2018-01-01
Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents. PMID:29760827
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Lees, P S
1991-01-01
Dozens of epidemiologic studies have been conducted since the late 1940s in an attempt to elucidate the relationship between exposure to chromium compounds and increased rates of certain cancers observed in several industries. The relationship between employment in industries producing chromium compounds from chromite ore and lung cancer has been well established in numerous studies. The relationship between exposure to certain chromium-based pigments and chromic acid and lung cancer, although not as strong, is fairly well accepted. The data concerning emissions from stainless-steel manufacturing and disease are contradictory. Although individual studies have indicated excesses of gastrointestinal and occasionally other cancers in these industries, results are not consistent and not universally accepted. There is general agreement that chromite ore does not have an associated risk of cancer. Although the chromium compound (or compounds) responsible for disease have yet to be identified, there is general agreement that hexavalent species are responsible for these diseases and that the trivalent species are not. Hypotheses about the carcinogenicity of specific chromium compounds generally relate to their solubility in body fluids. These hypotheses, however, have generally been produced as a result of toxicologic, not epidemiologic, investigation. Well-designed epidemiologic studies incorporating detailed assessments of worker exposures have the potential to help elucidate causality, identify specific carcinogenic compounds, and quantify risk in humans, eliminating the need to extrapolate from animal data. Although the need for exposure data crucial to this effort was identified in the earliest epidemiologic studies of chromium, such studies have not been conducted. As a result, little more is known today about the relationship between this chemical and disease in humans than was known 40 years ago. PMID:1935857
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Heritability of Measures of Kidney Disease Among Zuni Indians: The Zuni Kidney Project
MacCluer, Jean W.; Scavini, Marina; Shah, Vallabh O.; Cole, Shelley A.; Laston, Sandra L.; Voruganti, V. Saroja; Paine, Susan S.; Eaton, Alfred J.; Comuzzie, Anthony G.; Tentori, Francesca; Pathak, Dorothy R.; Bobelu, Arlene; Bobelu, Jeanette; Ghahate, Donica; Waikaniwa, Mildred; Zager, Philip G.
2010-01-01
Background The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. Study Design A community-based participatory research approach was used to recruit family members of individuals with kidney disease. Setting & Participants The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. Predictor Outcomes & Measurements Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was ≥0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. Results Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. Limitations Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. Conclusions Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations. PMID:20646805
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Genetic variation associated with cardiovascular risk in autoimmune diseases
Perrotti, Pedro P.; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L.; Lasanta, María L.; Marsal, Sara; Julià, Antonio
2017-01-01
Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity. PMID:28982122
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Boucher, Gabrielle; Beauchamp, Claudine; Trynka, Gosia; Dubois, Patrick C.; Lagacé, Caroline; Stokkers, Pieter C. F.; Hommes, Daan W.; Barisani, Donatella; Palmieri, Orazio; Annese, Vito; van Heel, David A.; Weersma, Rinse K.; Daly, Mark J.; Wijmenga, Cisca; Rioux, John D.
2011-01-01
Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. PMID:21298027
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Which Doctor to Trust: A Recommender System for Identifying the Right Doctors.
Guo, Li; Jin, Bo; Yao, Cuili; Yang, Haoyu; Huang, Degen; Wang, Fei
2016-07-07
Key opinion leaders (KOLs) are people who can influence public opinion on a certain subject matter. In the field of medical and health informatics, it is critical to identify KOLs on various disease conditions. However, there have been very few studies on this topic. We aimed to develop a recommender system for identifying KOLs for any specific disease with health care data mining. We exploited an unsupervised aggregation approach for integrating various ranking features to identify doctors who have the potential to be KOLs on a range of diseases. We introduce the design, implementation, and deployment details of the recommender system. This system collects the professional footprints of doctors, such as papers in scientific journals, presentation activities, patient advocacy, and media exposure, and uses them as ranking features to identify KOLs. We collected the information of 2,381,750 doctors in China from 3,657,797 medical journal papers they published, together with their profiles, academic publications, and funding. The empirical results demonstrated that our system outperformed several benchmark systems by a significant margin. Moreover, we conducted a case study in a real-world system to verify the applicability of our proposed method. Our results show that doctors' profiles and their academic publications are key data sources for identifying KOLs in the field of medical and health informatics. Moreover, we deployed the recommender system and applied the data service to a recommender system of the China-based Internet technology company NetEase. Patients can obtain authority ranking lists of doctors with this system on any given disease.
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Addison, Odessa; Kundi, Rishi; Ryan, Alice S; Goldberg, Andrew P; Patel, Richa; Lal, Brajesh K; Prior, Steven J
2017-08-23
The study is to compare the Modified Physical Performance Test (MPPT) and Short Physical Performance Battery (SPPB) as metrics of mobility and function in older men with peripheral arterial disease (PAD). A total of 51 men (55-87 years) with PAD underwent functional testing including the SPPB, MPPT, Walking Impairment Questionnaire (WIQ), stair ascent, and 6-min walk distance. Individuals were grouped according to SPPB and MPPT scores as not limited on either, limited only on the MPPT, or limited on both. The MPPT identified a higher proportion of patients as being functionally limited than the SPPB (p < 0.001). Men identified as limited only by the MPPT, and not the SPPB, were subsequently confirmed to have lower function on all measures compared to those not identified as limited by either the SPPB or the MPPT (p < 0.02). These findings suggest the MPPT is an appropriate measure to identify early declines in men with PAD and may identify global disability better than SPPB. Implications for rehabilitation Individuals with peripheral arterial disease have low activity levels and are at risk for a loss of independence and global disability. Early detection of decline in mobility and global function would allow for interventions before large changes in ambulatory ability or a loss of functional independence occur. This study shows the Modified Physical Performance Test may be an appropriate test to identify early decline in function in men with peripheral arterial disease.
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Which Doctor to Trust: A Recommender System for Identifying the Right Doctors
Yao, Cuili; Yang, Haoyu; Huang, Degen; Wang, Fei
2016-01-01
Background Key opinion leaders (KOLs) are people who can influence public opinion on a certain subject matter. In the field of medical and health informatics, it is critical to identify KOLs on various disease conditions. However, there have been very few studies on this topic. Objective We aimed to develop a recommender system for identifying KOLs for any specific disease with health care data mining. Methods We exploited an unsupervised aggregation approach for integrating various ranking features to identify doctors who have the potential to be KOLs on a range of diseases. We introduce the design, implementation, and deployment details of the recommender system. This system collects the professional footprints of doctors, such as papers in scientific journals, presentation activities, patient advocacy, and media exposure, and uses them as ranking features to identify KOLs. Results We collected the information of 2,381,750 doctors in China from 3,657,797 medical journal papers they published, together with their profiles, academic publications, and funding. The empirical results demonstrated that our system outperformed several benchmark systems by a significant margin. Moreover, we conducted a case study in a real-world system to verify the applicability of our proposed method. Conclusions Our results show that doctors’ profiles and their academic publications are key data sources for identifying KOLs in the field of medical and health informatics. Moreover, we deployed the recommender system and applied the data service to a recommender system of the China-based Internet technology company NetEase. Patients can obtain authority ranking lists of doctors with this system on any given disease. PMID:27390219
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Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler
2012-02-01
Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups.
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Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg
2015-09-29
The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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An integrative, translational approach to understanding rare and orphan genetically based diseases
Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.
2013-01-01
PhenomeNet is an approach for integrating phenotypes across species and identifying candidate genes for genetic diseases based on the similarity between a disease and animal model phenotypes. In contrast to ‘guilt-by-association’ approaches, PhenomeNet relies exclusively on the comparison of phenotypes to suggest candidate genes, and can, therefore, be applied to study the molecular basis of rare and orphan diseases for which the molecular basis is unknown. In addition to disease phenotypes from the Online Mendelian Inheritance in Man (OMIM) database, we have now integrated the clinical signs from Orphanet into PhenomeNet. We demonstrate that our approach can efficiently identify known candidate genes for genetic diseases in Orphanet and OMIM. Furthermore, we find evidence that mutations in the HIP1 gene might cause Bassoe syndrome, a rare disorder with unknown genetic aetiology. Our results demonstrate that integration and computational analysis of human disease and animal model phenotypes using PhenomeNet has the potential to reveal novel insights into the pathobiology underlying genetic diseases. PMID:23853703
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Symptoms and Treatment | NIH MedlinePlus the Magazine
... of this page please turn JavaScript on. Feature: Parkinson's Disease Symptoms and Treatment Past Issues / Winter 2016 Table ... study to identify abnormal brain rhythms associated with Parkinson's disease. Photo courtesy of Coralie de Hemptinne Deep Brain ...
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Pathomechanisms in Lysosomal Storage Disorders
Walkley, Steven U.; Vanier, Marie T.
2015-01-01
Lysosomal diseases are inherited metabolic disorders caused by defects in a wide spectrum of lysosomal and a few non-lysosomal proteins. In most cases a single type of primary storage material is identified, which has been used to name and classify the disorders: hence the terms sphingolipidoses, gangliosidoses, mucopolysaccharidoses, glycoproteinoses, and so forth. In addition to this primary storage, however, a host of secondary storage products can also be identified, more often than not having no direct link to the primary protein defect. Lipids - glycosphingolipids and phospholipids, as well as cholesterol - are the most ubiquitous and best studied of these secondary storage materials. While in the past typically considered nonspecific and nonconsequential features of these diseases, newer studies suggest direct links between secondary storage and disease pathogenesis and support the view that understanding all aspects of this sequestration process will provide important insights into the cell biology and treatment of lysosomal disease. PMID:19111580
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Gaikwad, Rekha; Warren, Jim
2009-06-01
This article presents a systematic literature review done to evaluate the feasibility and benefits of home-based information and communications technology enabled interventions for chronic disease management, with emphasis on their impact on health outcomes and costs. Relevant articles were retrieved from PubMed and evaluated using quality worksheets with pre-identified inclusion and exclusion criteria. Of the 256 articles retrieved, 27 were found to concord with the study criteria. Evaluation of the identified articles was conducted irrespective of study design, type of home-based intervention or chronic disease involved. The review demonstrates that HBIs applied to chronic disease management improve functional and cognitive patient outcomes and reduce healthcare spending. However, further research is needed to assess benefit in terms of evidence-based outcome indicators (that can provide a basis for meta-analysis), to confirm sustainable cost benefits, and to systematically collect data on physician satisfaction with patient management.
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Identifying Disease Associated miRNAs Based on Protein Domains.
Qin, Gui-Min; Li, Rui-Yi; Zhao, Xing-Ming
2016-01-01
MicroRNAs (miRNAs) are a class of small endogenous non-coding genes, acting as regulators in the post-transcriptional processes. Recently, the miRNAs are found to be widely involved in different types of diseases. Therefore, the identification of disease associated miRNAs can help understand the mechanisms that underlie the disease and identify new biomarkers. However, it is not easy to identify the miRNAs related to diseases due to its extensive involvements in various biological processes. In this work, we present a new approach to identify disease associated miRNAs based on domains, the functional and structural blocks of proteins. The results on real datasets demonstrate that our method can effectively identify disease related miRNAs with high precision.
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[Long-term disease in Danish children reported by the parents].
Nielsen, Anne M; Koefoed, Birgitte Gade; Møller, Ralf; Laursen, Bjarne
2006-01-23
The aim of this study was to report the prevalence and nature of long-term diseases and their consequences in children under the age of 16 in Denmark, and to identify the socio-demographic determinants of disease. Parents and stepparents participating in the Danish Health and Morbidity Survey, 2000, were interviewed at home about long-term diseases, including impairments and sequelae after injury and disease, in children under the age of 16 living at home. Answers were given for 7,670 children, and diseases were coded according to ICD-10 by two doctors. Logistic regression analysis was used to identify the determinants and consequences of disease. A total of 16.2% of children had one or more long-term diseases, boys (17.5%) more frequently than girls (14.8%). The prevalence increased through the first six years of life. A social gradient was seen: children of parents with low socioeconomic status or with little education had a higher prevalence. The most frequent disease was asthma (4.9%). Also frequent were congenital disorders (1.6%), otitis media (1.4%) and hearing impairment (0.6%). Children with long-term disease suffered more frequently than others from poor health in general, recent sick leave and poor thriving. The figures for long-term disease reported by the parents participating in the study were in accordance with what was found in earlier studies, but stigmatising and less severe diseases, as well as periodically recurring diseases, were probably underreported. Attention should be paid to the high prevalence of asthma, to the poorer thriving and to the general health status of children with long-term disease, and to the social inequality in children's health.
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Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W
2016-01-09
Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10(-78)), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10(-18)). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10(-4)). Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time. International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list). Copyright © 2016 Cleynen et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
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Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W
2016-01-01
Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4). Interpretation Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time. Funding International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list). PMID:26490195
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B cells gone rogue: the intersection of diffuse large B cell lymphoma and autoimmune disease.
Koff, Jean L; Flowers, Christopher R
2016-06-01
Diffuse large B cell lymphoma (DLBCL) is characterized by genetic, genomic and clinical heterogeneity. Autoimmune diseases (AIDs) have recently been shown to represent significant risk factors for development of DLBCL. Studies that examined the relationships between AIDs and lymphoma in terms of pathogenesis, genetic lesions, and treatment were identified in the MEDLINE database using combinations of medical subject heading (MeSH) terms. Co-authors independently performed study selection for inclusion based on appropriateness of the study question and nature of the study design and sample size. Expert commentary: Identification of AID as a substantial risk factor for DLBCL raises new questions regarding how autoimmunity influences lymphomagenesis and disease behavior. It will be important to identify whether DLBCL cases arising in the setting of AID harbor inferior prognoses, and, if so, whether they also exhibit certain molecular abnormalities that may be targeted to overcome such a gap in clinical outcomes.
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Lewis, Sarah J; Gardner, Mike; Higgins, Julian; Holly, Jeff M P; Gaunt, Tom R; Perks, Claire M; Turner, Suzanne D; Rinaldi, Sabina; Thomas, Steve; Harrison, Sean; Lennon, Rosie J; Tan, Vanessa; Borwick, Cath; Emmett, Pauline; Jeffreys, Mona; Northstone, Kate; Mitrou, Giota; Wiseman, Martin; Thompson, Rachel; Martin, Richard M
2017-11-01
Background: Human, animal, and cell experimental studies; human biomarker studies; and genetic studies complement epidemiologic findings and can offer insights into biological plausibility and pathways between exposure and disease, but methods for synthesizing such studies are lacking. We, therefore, developed a methodology for identifying mechanisms and carrying out systematic reviews of mechanistic studies that underpin exposure-cancer associations. Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology, and nutrition was assembled. Five 1-day workshops were held to brainstorm ideas; in the intervening periods we carried out searches and applied our methods to a case study to test our ideas. Results: We have developed a two-stage framework, the first stage of which is designed to identify mechanisms underpinning a specific exposure-disease relationship; the second stage is a targeted systematic review of studies on a specific mechanism. As part of the methodology, we also developed an online tool for text mining for mechanism prioritization (TeMMPo) and a new graph for displaying related but heterogeneous data from epidemiologic studies (the Albatross plot). Conclusions: We have developed novel tools for identifying mechanisms and carrying out systematic reviews of mechanistic studies of exposure-disease relationships. In doing so, we have outlined how we have overcome the challenges that we faced and provided researchers with practical guides for conducting mechanistic systematic reviews. Impact: The aforementioned methodology and tools will allow potential mechanisms to be identified and the strength of the evidence underlying a particular mechanism to be assessed. Cancer Epidemiol Biomarkers Prev; 26(11); 1667-75. ©2017 AACR . ©2017 American Association for Cancer Research.
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Asthma, hypersensitivity pneumonitis and other respiratory diseases caused by metalworking fluids.
Rosenman, Kenneth D
2009-04-01
To highlight advances in understanding the respiratory disease associated with metal machining, a common work process involving approximately 1.2 million workers in the USA. Recent studies emphasize that work-related asthma and hypersensitivity pneumonitis continue to be caused by exposure to metalworking fluid. Identification of an individual patient indicates the need for follow-up investigations at the work site to prevent additional disease and/or identify additional effected individuals. Identification of the causal agent for hypersensitivity pneumonitis has centered on microbial contamination of metalworking fluids with a number of studies focusing on Mycobacterium immunogenum. Both asthma and hypersensitivity pneumonitis occur among workers exposed to metalworking fluid. The incidence of these diseases among such workers is unknown. Outbreaks of these conditions continue to be identified among metal machinists. Whether these are true outbreaks associated with some breakdown in workplace controls or, rather the recognition of ongoing endemic disease that is typically misdiagnosed as pneumonia or common adult onset asthma, needs further evaluation. Further work to elucidate the specific causal agent(s) is necessary to affect effective workplace controls. Treating an identified individual case as an index case with a follow-up workplace investigation will only be possible if practicing physicians interact with public health authorities to report newly diagnosed cases.
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Arai, Yuuki; Maeda, Akiko; Hirami, Yasuhiko; Ishigami, Chie; Kosugi, Shinji; Mandai, Michiko; Kurimoto, Yasuo; Takahashi, Masayo
2015-01-01
The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.
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Identifying Degenerative Brain Disease Using Rough Set Classifier Based on Wavelet Packet Method.
Cheng, Ching-Hsue; Liu, Wei-Xiang
2018-05-28
Population aging has become a worldwide phenomenon, which causes many serious problems. The medical issues related to degenerative brain disease have gradually become a concern. Magnetic Resonance Imaging is one of the most advanced methods for medical imaging and is especially suitable for brain scans. From the literature, although the automatic segmentation method is less laborious and time-consuming, it is restricted in several specific types of images. In addition, hybrid techniques segmentation improves the shortcomings of the single segmentation method. Therefore, this study proposed a hybrid segmentation combined with rough set classifier and wavelet packet method to identify degenerative brain disease. The proposed method is a three-stage image process method to enhance accuracy of brain disease classification. In the first stage, this study used the proposed hybrid segmentation algorithms to segment the brain ROI (region of interest). In the second stage, wavelet packet was used to conduct the image decomposition and calculate the feature values. In the final stage, the rough set classifier was utilized to identify the degenerative brain disease. In verification and comparison, two experiments were employed to verify the effectiveness of the proposed method and compare with the TV-seg (total variation segmentation) algorithm, Discrete Cosine Transform, and the listing classifiers. Overall, the results indicated that the proposed method outperforms the listing methods.
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The Experience of Parkinson's Disease: A Systematic Review and Meta-Ethnography
Soundy, Andrew
2014-01-01
There has been little attempt to summarise and synthesise qualitative studies concerning the experience and perception of living with Parkinson's disease. Bringing this information together would provide a background to understand the importance of an individual's social identity on their well-being and hope. Three primary aims were identified (a) understanding the importance of social identity and meaningful activities on individuals' well-being, (b) identifying factors and strategies that influence well-being and hope, and (c) establishing a model that relates to an individual's hope and well-being. Three stages were undertaken including a traditional electronic search, a critical appraisal of articles, and a synthesis of studies. Qualitative articles were included that considered the experience of living with Parkinson's disease. Thirty seven articles were located and included in the review. Five themes were identified and the themes were used to inform development of a new model of hope enablement. The current review furthered understanding of how physical symptoms and the experience of Parkinson's disease affect the individual's well-being and hope. Social identity was established as a key factor that influenced an individual's well-being. Being able to maintain, retain, or develop social identities was essential for the well-being and hope of individuals with Parkinson's disease. Understanding the factors which prevent or can facilitate this is essential. PMID:25525623
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Nalluri, Joseph J; Rana, Pratip; Barh, Debmalya; Azevedo, Vasco; Dinh, Thang N; Vladimirov, Vladimir; Ghosh, Preetam
2017-08-15
In recent studies, miRNAs have been found to be extremely influential in many of the essential biological processes. They exhibit a self-regulatory mechanism through which they act as positive/negative regulators of expression of genes and other miRNAs. This has direct implications in the regulation of various pathophysiological conditions, signaling pathways and different types of cancers. Studying miRNA-disease associations has been an extensive area of research; however deciphering miRNA-miRNA network regulatory patterns in several diseases remains a challenge. In this study, we use information diffusion theory to quantify the influence diffusion in a miRNA-miRNA regulation network across multiple disease categories. Our proposed methodology determines the critical disease specific miRNAs which play a causal role in their signaling cascade and hence may regulate disease progression. We extensively validate our framework using existing computational tools from the literature. Furthermore, we implement our framework on a comprehensive miRNA expression data set for alcohol dependence and identify the causal miRNAs for alcohol-dependency in patients which were validated by the phase-shift in their expression scores towards the early stages of the disease. Finally, our computational framework for identifying causal miRNAs implicated in diseases is available as a free online tool for the greater scientific community.
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Serum Proteome Profiles in Stricturing Crohn’s Disease: A pilot study.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Townsend, Peter; Zhang, Qibin; Shapiro, Jason
Background: Crohn’s disease (CD) is a form of inflammatory bowel disease (IBD) with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of IBD. We performed a pilot study to examine differences in the proteome among patients with stricturing Crohn’s disease, non-stricturing Crohn’s disease, and ulcerative colitis (UC). Methods: Serum samples were selected from the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), an established cohort of patients with IBD. Crohn’s disease patients with surgically-resected stricture were matched with similar patients with Crohn’s disease without known stricture, and withmore » UC. Serum samples from each patient were digested and analyzed using liquid chromatography-mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture. Results: Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the three groups. We quantified 7668 peptides and 897 proteins for analysis. ROC analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides, and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides, and determined their function based on previously published literature. Conclusions: The serum of patients with stricturing CD, non-stricturing CD, and UC are distinguishable via proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.« less
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Husni, M Elaine; Fernandez, Anthony; Hauber, Brett; Singh, Rakesh; Posner, Joshua; Sutphin, Jessie; Ganguli, Arijit
2018-05-31
The perceived bother of skin and joint-related manifestations of psoriatic disease may differ among patients, rheumatologists, and dermatologists. This study identified and compared the patient and dermatologist/rheumatologist-perceived bother of psoriatic disease manifestations. Online surveys were administered to patients with both psoriasis and psoriatic arthritis and to dermatologists and rheumatologists. Object-case best-worst scaling was used to identify the most and least bothersome items from a set of five items in a series of questions. Each item set was drawn from 20 items describing psoriatic disease skin and joint symptoms and impacts on daily activities. Survey responses were analyzed using random-parameters logit models for each surveyed group, yielding a relative-bother weight (RBW) for each item compared with joint pain, soreness, or tenderness. Surveys were completed by 200 patients, 150 dermatologists, and 150 rheumatologists. Patients and physicians agreed that joint pain, soreness, and tenderness are among the most bothersome manifestations of psoriatic disease (RBW 1.00). For patients, painful, inflamed, or broken skin (RBW 1.03) was more bothersome, while both rheumatologists and dermatologists considered painful skin much less bothersome (RBW 0.17 and 0.22, respectively) than joint pain. Relative to joint pain, rheumatologists were more likely to perceive other joint symptoms as bothersome, while dermatologists were more likely to perceive other skin symptoms as bothersome. This study has identified important areas of discordance both between patients and physicians and between rheumatologists and dermatologists about the relative bother of a comprehensive set of psoriatic disease symptoms and functional impacts. Both physician specialists should ask patients which manifestations of psoriatic disease are most bothersome to them, as these discussions may have important implications for drug and other patient management options.
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Lionetti, Elena; Leonardi, Salvatore; Lanzafame, Angela; Garozzo, Maria Teresa; Filippelli, Martina; Tomarchio, Stefania; Ferrara, Viviana; Salpietro, Carmelo; Pulvirenti, Alfredo; Francavilla, Ruggiero; Catassi, Carlo
2014-01-01
AIM: To review and conduct a meta-analysis of the existing literature on the relationship between Helicobacter pylori (H. pylori), atopy and allergic diseases. METHODS: Studies published in English assessing the prevalence of atopy and/or allergic diseases in patients with H. pylori infection and the prevalence of H. pylori infection in patients with atopy and/or allergic diseases were identified through a MEDLINE search (1950-2014). Random-effect model was used for the meta-analysis. RESULTS: Pooled results of case-control studies showed a significant inverse association of H. pylori infection with atopy/allergic disease or with exclusively atopy, but not with allergic disease, whereas pooled results of cross-sectional studies showed only a significant association between allergic disease and H. pylori infection. CONCLUSION: There is some evidence of an inverse association between atopy/allergic diseases and H. pylori infection, although further studied are needed. PMID:25516679
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Korashy, Hesham M; Attafi, Ibraheem M; Famulski, Konrad S; Bakheet, Saleh A; Hafez, Mohammed M; Alsaad, Abdulaziz M S; Al-Ghadeer, Abdul Rahman M
2017-02-01
Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these genes, which could be used as early biomarkers to prevent renal injury. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Huang, Yen-Tsung; Liang, Liming; Moffatt, Miriam F; Cookson, William O C M; Lin, Xihong
2015-07-01
Genome-wide association studies (GWAS) have been a standard practice in identifying single nucleotide polymorphisms (SNPs) for disease susceptibility. We propose a new approach, termed integrative GWAS (iGWAS) that exploits the information of gene expressions to investigate the mechanisms of the association of SNPs with a disease phenotype, and to incorporate the family-based design for genetic association studies. Specifically, the relations among SNPs, gene expression, and disease are modeled within the mediation analysis framework, which allows us to disentangle the genetic effect on a disease phenotype into two parts: an effect mediated through a gene expression (mediation effect, ME) and an effect through other biological mechanisms or environment-mediated mechanisms (alternative effect, AE). We develop omnibus tests for the ME and AE that are robust to underlying true disease models. Numerical studies show that the iGWAS approach is able to facilitate discovering genetic association mechanisms, and outperforms the SNP-only method for testing genetic associations. We conduct a family-based iGWAS of childhood asthma that integrates genetic and genomic data. The iGWAS approach identifies six novel susceptibility genes (MANEA, MRPL53, LYCAT, ST8SIA4, NDFIP1, and PTCH1) using the omnibus test with false discovery rate less than 1%, whereas no gene using SNP-only analyses survives with the same cut-off. The iGWAS analyses further characterize that genetic effects of these genes are mostly mediated through their gene expressions. In summary, the iGWAS approach provides a new analytic framework to investigate the mechanism of genetic etiology, and identifies novel susceptibility genes of childhood asthma that were biologically meaningful. © 2015 WILEY PERIODICALS, INC.
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Mitra, Arkadeep; Basak, Trayambak; Ahmad, Shadab; Datta, Kaberi; Datta, Ritwik; Sengupta, Shantanu; Sarkar, Sagartirtha
2015-06-05
Cardiac hypertrophy and myocardial infarction (MI) are two etiologically different disease forms with varied pathological characteristics. However, the precise molecular mechanisms and specific causal proteins associated with these diseases are obscure to date. In this study, a comparative cardiac proteome profiling was performed in Wistar rat models for diseased and control (sham) groups using two-dimensional difference gel electrophoresis followed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Proteins were identified using Protein Pilot™ software (version 4.0) and were subjected to stringent statistical analysis. Alteration of key proteins was validated by Western blot analysis. The differentially expressed protein sets identified in this study were associated with different functional groups, involving various metabolic pathways, stress responses, cytoskeletal organization, apoptotic signaling and other miscellaneous functions. It was further deciphered that altered energy metabolism during hypertrophy in comparison to MI may be predominantly attributed to induced glucose oxidation level, via reduced phosphorylation of pyruvate dehydrogenase E1 component subunit β (PDHE1-B) protein during hypertrophy. This study reports for the first time the global changes in rat cardiac proteome during two etiologically different cardiac diseases and identifies key signaling regulators modulating ontogeny of these two diseases culminating in heart failure. This study also pointed toward differential activation of PDHE1-B that accounts for upregulation of glucose oxidation during hypertrophy. Downstream analysis of altered proteome and the associated modulators would enhance our present knowledge regarding altered pathophysiology of these two etiologically different cardiac disease forms. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Endometriosis: a high-risk population for major chronic diseases?
Kvaskoff, Marina; Mu, Fan; Terry, Kathryn L.; Harris, Holly R.; Poole, Elizabeth M.; Farland, Leslie; Missmer, Stacey A.
2015-01-01
BACKGROUND Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If these relationships are confirmed, these findings may have important implications in screening practices and in the management and care of endometriosis patients. PMID:25765863
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Methodological considerations in cost of illness studies on Alzheimer disease
2012-01-01
Cost-of-illness studies (COI) can identify and measure all the costs of a particular disease, including the direct, indirect and intangible dimensions. They are intended to provide estimates about the economic impact of costly disease. Alzheimer disease (AD) is a relevant example to review cost of illness studies because of its costliness.The aim of this study was to review relevant published cost studies of AD to analyze the method used and to identify which dimension had to be improved from a methodological perspective. First, we described the key points of cost study methodology. Secondly, cost studies relating to AD were systematically reviewed, focussing on an analysis of the different methods used. The methodological choices of the studies were analysed using an analytical grid which contains the main methodological items of COI studies. Seventeen articles were retained. Depending on the studies, annual total costs per patient vary from $2,935 to $52, 954. The methods, data sources, and estimated cost categories in each study varied widely. The review showed that cost studies adopted different approaches to estimate costs of AD, reflecting a lack of consensus on the methodology of cost studies. To increase its credibility, closer agreement among researchers on the methodological principles of cost studies would be desirable. PMID:22963680
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Huck, O.; Tenenbaum, H.; Davideau, J.-L.
2011-01-01
For ten years, the incidence of preterm birth does not decrease in developed countries despite the promotion of public health programs. Many risk factors have been identified including ethnicity, age, tobacco, and infection. However, almost 50% of preterm birth causes remain unknown. The periodontal diseases are highly prevalent inflammatory and infectious diseases of tooth supporting tissues leading to an oral disability. They influence negatively general health worsening cardiovascular diseases and diabetes. Periodontal diseases have been also suspected to increase the rate of preterm birth, but data remain contradictory. The objective of this review is to present the principal results of epidemiological, biological, and interventional studies on the link between periodontal diseases and preterm birth. The conclusions of this work underline the importance for the physician/obstetrician to identify women at risk for preterm birth and to address these patients to dentist for periodontal examination and treatment in order to limit adverse pregnancy outcomes. PMID:22132334
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Review of patient registries in dermatology.
DiMarco, Gabriella; Hill, Dane; Feldman, Steven R
2016-10-01
Patient registries are datasets containing information on patients with a particular disease or patients who are undergoing a specific treatment. Our objective was to search for and catalog the types of registries being used in dermatology and investigate their characteristics and uses. We searched Google, the Registry of Patient Registries, Orphanet, and ClinicalTrials.gov to compile a list of dermatology disease registries. We also conducted a literature review on the uses of dermatology registries using PubMed. We identified 48 dermatology patient registries, with 23 distinct diseases represented. We also identified 11 registries used for postmarketing surveillance of skin disease. Our search was limited to registries in English. Registries are commonly used for the study of rare dermatologic diseases and for postsurveillance monitoring of systemic therapies in more common dermatologic diseases, such as psoriasis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
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Patel, Minal R; Shah, Khooshbu S; Shallcross, Meagan L
2015-11-25
Patient financial burden with chronic disease poses significant health risks, yet it remains outside the scope of clinical visits. Little is known about how physicians perceive their patients' health-related financial burden in the context of primary care. The purpose of this study was to describe physician experiences with patients' financial burden while managing chronic disease and the communication of these issues. In November 2013, four focus groups were conducted in an academic medical center. A convenience sample of 29 internal and family medicine resident physicians was used in this study. A semi-structured interview protocol was employed by trained facilitators. Coded transcripts were analyzed for themes regarding physicians' experiences with identifying, managing, and communicating financial burden with their patients in the context of primary care. Major themes identified were 1) patient financial burden with chronic care is visible to physicians, 2) patient's financial burden with chronic care and discussing these issues is important to physicians, 3) ability to identify patients who perceive financial burden is imperfect, 4) communication of financial burden with patients is complex and difficult to navigate, 5) strategies utilized to address concerns are not always generalizable, and 6) physicians have ideas for widespread change to make these conversations easier for them. Awareness of physician perspectives in identifying and addressing their patients' disease-related financial burden may better equip researchers and medical educators to develop interventions that aid care teams in better understanding these patient concerns to promote compliance with treatment recommendations.
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2014-01-01
Introduction Cartilage protein distribution and the changes that occur in cartilage ageing and disease are essential in understanding the process of cartilage ageing and age related diseases such as osteoarthritis. The aim of this study was to investigate the peptide profiles in ageing and osteoarthritic (OA) cartilage sections using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Methods The distribution of proteins in young, old and OA equine cartilage was compared following tryptic digestion of cartilage slices and MALDI-MSI undertaken with a MALDI SYNAPT™ HDMS system. Protein identification was undertaken using database searches following multivariate analysis. Peptide intensity differences between young, ageing and OA cartilage were imaged with Biomap software. Analysis of aggrecanase specific cleavage patterns of a crude cartilage proteoglycan extract were used to validate some of the differences in peptide intensity identified. Immunohistochemistry studies validated the differences in protein abundance. Results Young, old and OA equine cartilage was discriminated based on their peptide signature using discriminant analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage oligomeric matrix protein were identified and localised. Fibronectin peptides displayed a stronger intensity in OA cartilage. Age-specific protein markers for collectin-43 and cartilage oligomeric matrix protein were identified. In addition potential fibromodulin and biglycan peptides targeted for degradation in OA were detected. Conclusions MALDI-MSI provided a novel platform to study cartilage ageing and disease enabling age and disease specific peptides in cartilage to be elucidated and spatially resolved. PMID:24886698
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Teixeira, Maria Glória; Siqueira,, João Bosco; Ferreira, Germano L. C.; Bricks, Lucia; Joint, Graham
2013-01-01
A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Brazil reported between 2000 and 2010. The protocol was registered on PROSPERO (CRD42011001826: http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42011001826). Between 31 July and 4 August 2011, the published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database. A total of 714 relevant citations were identified, 51 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Brazil, in this period, was characterized by increases in the geographical spread and incidence of reported cases. The overall increase in dengue disease was accompanied by a rise in the proportion of severe cases. The epidemiological pattern of dengue disease in Brazil is complex and the changes observed during this review period are likely to have been influenced by multiple factors. Several gaps in epidemiological knowledge regarding dengue disease in Brazil were identified that provide avenues for future research, in particular, studies of regional differences, genotype evolution, and age-stratified seroprevalence. Systematic Review Registration PROSPERO registration number: CRD42011001826. PMID:24386496
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Dakin, Stephanie Georgina; Smith, Roger Kenneth Whealands; Heinegård, Dick; Önnerfjord, Patrik; Khabut, Areej; Dudhia, Jayesh
2014-01-01
During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragments released in naturally occurring disease, we hypothesized that stimulation of tendon explants with proinflammatory mediators in vitro would induce fragments of COMP analogous to natural disease. Therefore, normal tendon explants were stimulated with IL-1β and prostaglandin E2, and their effects on the release of COMP and its cleavage patterns were characterized. Analyses of injured tendons identified an altered proteomic composition of the ECM at all stages post injury, showing protein fragments that were specific to disease stage. IL-1β enhanced the proteolytic cleavage and release of COMP from tendon explants, whereas PGE2 had no catabolic effect. Of the cleavage fragments identified in early stage tendon disease, two fragments were generated by an IL-1-mediated mechanism. These fragments provide a platform for the development of neo-epitope assays specific to injury stage for tendon disease. PMID:24398684
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2014-01-01
Introduction The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM). Methods Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist). Results Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease. Conclusions Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed. PMID:24989778
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Understanding and preventing type 1 diabetes through the unique working model of TrialNet.
Battaglia, Manuela; Anderson, Mark S; Buckner, Jane H; Geyer, Susan M; Gottlieb, Peter A; Kay, Thomas W H; Lernmark, Åke; Muller, Sarah; Pugliese, Alberto; Roep, Bart O; Greenbaum, Carla J; Peakman, Mark
2017-11-01
Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.
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Understanding and preventing type 1 diabetes through the unique working model of TrialNet
Anderson, Mark S.; Buckner, Jane H.; Geyer, Susan M.; Gottlieb, Peter A.; Kay, Thomas W. H.; Lernmark, Åke; Muller, Sarah; Pugliese, Alberto; Roep, Bart O.; Greenbaum, Carla J.
2018-01-01
Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches. PMID:28770323
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Chen, T-Y; Hsu, C-C; Feng, I-J; Wang, J-J; Su, S-B; Guo, H-R; Huang, C-C; Lin, H-J
2017-03-01
Physicians have high work stress, responsibility for night shifts and chances of exposure to medical radiation, which may increase the risk for thyroid diseases. We conducted this study to assess the risk for thyroid diseases in physicians, which remain unclear. We used a secondary analysis of the Taiwan National Health Insurance Research Database for this study. After excluding thyroid diseases occurring before 2006 and residents, physicians and general population were identified by matching with age and sex in 2009 in a 1:2 ratio. The risk for thyroid diseases was compared between the physicians and general population and among physicians by tracing their medical histories between 2006 and 2012. In total, 28,649 physicians and 57,298 general population were identified. Physicians had a higher risk for overall thyroid diseases than the general population [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.10-1.47], including individual thyroid disease: thyroid cancer (OR: 1.89; 95% CI: 1.22-2.95), hypothyroidism (OR: 1.64; 95% CI: 1.23-2.18) and thyroiditis (OR: 1.48; 95% CI: 1.00-2.19). We showed that physicians had a significantly higher risk for thyroid diseases than the general population. This reminds us to pay more attention to thyroid diseases in physicians. Further studies about the underlying mechanisms are warranted. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Finkel, Richard S.; Crawford, Thomas O.; Swoboda, Kathryn J.; Kaufmann, Petra; Juhasz, Peter; Li, Xiaohong; Guo, Yu; Li, Rebecca H.; Trachtenberg, Felicia; Forrest, Suzanne J.; Kobayashi, Dione T.; Chen, Karen S.; Joyce, Cynthia L.; Plasterer, Thomas
2012-01-01
Background Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1) gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets. Objective: To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches. Materials and Methods: A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2–12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS) and to a number of secondary clinical measures. Results A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites) and 44 urine metabolites. No transcripts correlated with MHFMS. Discussion In this cross-sectional study, “BforSMA” (Biomarkers for SMA), candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with disease progression, and assess potential impact on clinical trial design. Trial Registry Clinicaltrials.gov NCT00756821. PMID:22558154
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Treatment of dental complications in sickle cell disease.
Mulimani, Priti; Ballas, Samir K; Abas, Adinegara B L; Karanth, Laxminarayan
2016-04-22
Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health.Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. To assess methods of treating dental complications in people with sickle cell disease. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 11 April 2016.Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field.Date of last search: 03 March 2016. We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease. Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review. No randomised controlled studies were identified. This Cochrane review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease.
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Caccamo, Alexandra; Kachur, Rachel; Williams, Samantha P
2017-08-01
Homelessness affects an estimated 1.6 million US youth annually. Compared with housed youth, homeless youth are more likely to engage in high-risk behaviors, including inconsistent condom use, multiple sex partners, survival sex, and alcohol/drug use, putting them at increased sexually transmitted disease (STD) risk. However, there is no national estimate of STD prevalence among this population. We identified 10 peer-reviewed articles (9 unique studies) reporting STD prevalence among homeless US youth (2000-2015). Descriptive and qualitative analyses identified STD prevalence ranges and risk factors among youth. Eight studies reported specific STD prevalence estimates, mainly chlamydia, gonorrhea, and syphilis. Overall STD prevalence among homeless youth ranged from 6% to 32%. STD rates for girls varied from 16.7% to 46%, and from 9% to 13.1% in boys. Most studies were conducted in the Western United States, with no studies from the Southeast or Northeast. Youths who experienced longer periods of homelessness were more likely to engage in high-risk sexual behaviors. Girls had lower rates of condom use and higher rates of STDs; boys were more likely to engage in anal and anonymous sex. Additionally, peer social networks contributed to protective effects on individual sexual risk behavior. Sexually transmitted disease prevalence estimates among homeless youth fluctuated greatly by study. Sexually transmitted disease risk behaviors are associated with unmet survival needs, length of homelessness, and influence of social networks. To promote sexual health and reduce STD rates, we need better estimates of STD prevalence, more geographic diversity of studies, and interventions addressing the behavioral associations identified in our review.
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Caccamo, Alexandra; Kachur, Rachel; Williams, Samantha P.
2018-01-01
Background Homelessness affects an estimated 1.6 million US youth annually. Compared with housed youth, homeless youth are more likely to engage in high-risk behaviors, including inconsistent condom use, multiple sex partners, survival sex, and alcohol/drug use, putting them at increased sexually transmitted disease (STD) risk. However, there is no national estimate of STD prevalence among this population. Methods We identified 10 peer-reviewed articles (9 unique studies) reporting STD prevalence among homeless US youth (2000–2015). Descriptive and qualitative analyses identified STD prevalence ranges and risk factors among youth. Results Eight studies reported specific STD prevalence estimates, mainly chlamydia, gonorrhea, and syphilis. Overall STD prevalence among homeless youth ranged from 6% to 32%. STD rates for girls varied from 16.7% to 46%, and from 9% to 13.1% in boys. Most studies were conducted in the Western United States, with no studies from the Southeast or Northeast. Youths who experienced longer periods of homelessness were more likely to engage in high-risk sexual behaviors. Girls had lower rates of condom use and higher rates of STDs; boys were more likely to engage in anal and anonymous sex. Additionally, peer social networks contributed to protective effects on individual sexual risk behavior. Conclusions Sexually transmitted disease prevalence estimates among homeless youth fluctuated greatly by study. Sexually transmitted disease risk behaviors are associated with unmet survival needs, length of homelessness, and influence of social networks. To promote sexual health and reduce STD rates, we need better estimates of STD prevalence, more geographic diversity of studies, and interventions addressing the behavioral associations identified in our review. PMID:28703725
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Thompson, Wesley K.; McEvoy, Linda K.; Schork, Andrew J.; Zuber, Verena; LeBlanc, Marissa; Bettella, Francesco; Mills, Ian G.; Desikan, Rahul S.; Djurovic, Srdjan; Gautvik, Kaare M.; Dale, Anders M.; Andreassen, Ole A.
2015-01-01
Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. PMID:26695485
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Eyles, Jillian P; Lucas, Barbara R; Patterson, Jillian A; Williams, Matthew J; Weeks, Kate; Fransen, Marlene; Hunter, David J
2014-11-01
To identify baseline characteristics of participants who will respond favorably following 6 months of participation in a chronic disease management program for hip and knee osteoarthritis (OA). This prospective cohort study assessed 559 participants at baseline and following 6 months of participation in the Osteoarthritis Chronic Care Program. Response was defined as the minimal clinically important difference of an 18% and 9-point absolute improvement in the Western Ontario and McMaster Universities Arthritis Index global score. Multivariate logistic regression modeling was used to identify predictors of response. Complete data were available for 308 participants. Those who withdrew within the study period were imputed as nonresponders. Three variables were independently associated with response: signal joint (knee vs hip), sex, and high level of comorbidity. Index joint and sex were significant in the multivariate model, but the model was not a sensitive predictor of response. Strong predictors of response to a chronic disease management program for hip and knee OA were not identified. The significant predictors that were found should be considered in future studies.
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Visualization and Analytics Tools for Infectious Disease Epidemiology: A Systematic Review
Carroll, Lauren N.; Au, Alan P.; Detwiler, Landon Todd; Fu, Tsung-chieh; Painter, Ian S.; Abernethy, Neil F.
2014-01-01
Background A myriad of new tools and algorithms have been developed to help public health professionals analyze and visualize the complex data used in infectious disease control. To better understand approaches to meet these users' information needs, we conducted a systematic literature review focused on the landscape of infectious disease visualization tools for public health professionals, with a special emphasis on geographic information systems (GIS), molecular epidemiology, and social network analysis. The objectives of this review are to: (1) Identify public health user needs and preferences for infectious disease information visualization tools; (2) Identify existing infectious disease information visualization tools and characterize their architecture and features; (3) Identify commonalities among approaches applied to different data types; and (4) Describe tool usability evaluation efforts and barriers to the adoption of such tools. Methods We identified articles published in English from January 1, 1980 to June 30, 2013 from five bibliographic databases. Articles with a primary focus on infectious disease visualization tools, needs of public health users, or usability of information visualizations were included in the review. Results A total of 88 articles met our inclusion criteria. Users were found to have diverse needs, preferences and uses for infectious disease visualization tools, and the existing tools are correspondingly diverse. The architecture of the tools was inconsistently described, and few tools in the review discussed the incorporation of usability studies or plans for dissemination. Many studies identified concerns regarding data sharing, confidentiality and quality. Existing tools offer a range of features and functions that allow users to explore, analyze, and visualize their data, but the tools are often for siloed applications. Commonly cited barriers to widespread adoption included lack of organizational support, access issues, and misconceptions about tool use. Discussion and Conclusion As the volume and complexity of infectious disease data increases, public health professionals must synthesize highly disparate data to facilitate communication with the public and inform decisions regarding measures to protect the public's health. Our review identified several themes: consideration of users' needs, preferences, and computer literacy; integration of tools into routine workflow; complications associated with understanding and use of visualizations; and the role of user trust and organizational support in the adoption of these tools. Interoperability also emerged as a prominent theme, highlighting challenges associated with the increasingly collaborative and interdisciplinary nature of infectious disease control and prevention. Future work should address methods for representing uncertainty and missing data to avoid misleading users as well as strategies to minimize cognitive overload. PMID:24747356
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Visualization and analytics tools for infectious disease epidemiology: a systematic review.
Carroll, Lauren N; Au, Alan P; Detwiler, Landon Todd; Fu, Tsung-Chieh; Painter, Ian S; Abernethy, Neil F
2014-10-01
A myriad of new tools and algorithms have been developed to help public health professionals analyze and visualize the complex data used in infectious disease control. To better understand approaches to meet these users' information needs, we conducted a systematic literature review focused on the landscape of infectious disease visualization tools for public health professionals, with a special emphasis on geographic information systems (GIS), molecular epidemiology, and social network analysis. The objectives of this review are to: (1) identify public health user needs and preferences for infectious disease information visualization tools; (2) identify existing infectious disease information visualization tools and characterize their architecture and features; (3) identify commonalities among approaches applied to different data types; and (4) describe tool usability evaluation efforts and barriers to the adoption of such tools. We identified articles published in English from January 1, 1980 to June 30, 2013 from five bibliographic databases. Articles with a primary focus on infectious disease visualization tools, needs of public health users, or usability of information visualizations were included in the review. A total of 88 articles met our inclusion criteria. Users were found to have diverse needs, preferences and uses for infectious disease visualization tools, and the existing tools are correspondingly diverse. The architecture of the tools was inconsistently described, and few tools in the review discussed the incorporation of usability studies or plans for dissemination. Many studies identified concerns regarding data sharing, confidentiality and quality. Existing tools offer a range of features and functions that allow users to explore, analyze, and visualize their data, but the tools are often for siloed applications. Commonly cited barriers to widespread adoption included lack of organizational support, access issues, and misconceptions about tool use. As the volume and complexity of infectious disease data increases, public health professionals must synthesize highly disparate data to facilitate communication with the public and inform decisions regarding measures to protect the public's health. Our review identified several themes: consideration of users' needs, preferences, and computer literacy; integration of tools into routine workflow; complications associated with understanding and use of visualizations; and the role of user trust and organizational support in the adoption of these tools. Interoperability also emerged as a prominent theme, highlighting challenges associated with the increasingly collaborative and interdisciplinary nature of infectious disease control and prevention. Future work should address methods for representing uncertainty and missing data to avoid misleading users as well as strategies to minimize cognitive overload. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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New Lives: Some Case Studies in Minamata.
ERIC Educational Resources Information Center
Tsurumi, Kazuko
Three case studies of young Japanese adults who fell ill with Minamata disease (a form of methyl-mercury poisoning) are presented and the adjustment of the individuals to the disease is analyzed in terms of a model of creativity. The model distinguishes three types of creativity: identificational (in which one identifies with old ideas and…
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-19
... cardiovascular disease in middle aged and older men and women. Frequency of Response: The participants will be... study, review of their medical records, and interviews with doctors and family to identify disease occurrence. Interviewers will contact doctors and hospitals to ascertain participants' cardiovascular events...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-02-19
... cardiovascular disease in middle aged and older men and women. Frequency of Response: The participants will be... ARIC study, review of their medical records, and interviews with doctors and family to identify disease occurrence. Interviewers will contact doctors and hospitals to ascertain participants' cardiovascular events...
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Lee, Hyeonjeong; Shin, Miyoung
2017-01-01
The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into distinctive associations between pathway activities in case and control samples.
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Wijetunge, S; Ratnatunga, N V I; Abeysekera, T D J; Wazil, A W M; Selvarajah, M
2015-01-01
Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.
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Comparison of disease clusters in two elderly populations hospitalized in 2008 and 2010.
Marengoni, A; Nobili, A; Pirali, C; Tettamanti, M; Pasina, L; Salerno, F; Corrao, S; Iorio, A; Marcucci, M; Franchi, C; Mannucci, P M
2013-01-01
As chronicity represents one of the major challenges in the healthcare of aging populations, the understanding of how chronic diseases distribute and co-occur in this part of the population is needed. The aims of this study were to evaluate and compare patterns of diseases identified with cluster analysis in two samples of hospitalized elderly. Data were obtained from the multicenter 'Registry Politerapie SIMI (REPOSI)' that included people aged 65 or older hospitalized in internal medicine and geriatric wards in Italy during 2008 and 2010. The study sample from the first wave included 1,411 subjects enrolled in 38 hospitals wards, whereas the second wave included 1,380 subjects in 66 wards located in different regions of Italy. To analyze patterns of multimorbidity, a cluster analysis was performed including the same diseases (19 chronic conditions with a prevalence >5%) collected at hospital discharge during the two waves of the registry. Eight clusters of diseases were identified in the first wave of the REPOSI registry and six in the second wave. Several diseases were included in similar clusters in the two waves, such as malignancy and liver cirrhosis; anemia, gastric and intestinal diseases; diabetes and coronary heart disease; chronic obstructive pulmonary disease and prostate hypertrophy. These findings strengthened the idea of an association other than by chance of diseases in the elderly population. Copyright © 2013 S. Karger AG, Basel.
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Safroneeva, E; Vavricka, S; Fournier, N; Seibold, F; Mottet, C; Nydegger, A; Ezri, J; Straumann, A; Rogler, G; Schoepfer, A M
2015-09-01
Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent. © 2015 John Wiley & Sons Ltd.
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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.
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von Bültzingslöwen, Inger; Sollecito, Thomas P; Fox, Philip C; Daniels, Troy; Jonsson, Roland; Lockhart, Peter B; Wray, David; Brennan, Michael T; Carrozzo, Marco; Gandera, Beatrice; Fujibayashi, Takashi; Navazesh, Mahvash; Rhodus, Nelson L; Schiødt, Morten
2007-03-01
The objective of this study was to identify systemic diseases associated with hyposalivation and xerostomia and develop evidence-based management recommendations for hyposalivation/xerostomia. Literature searches covered the English language medical literature from 1966 to 2005. An evidence-based review process was applied to management studies published from 2002 to 2005. Several systemic diseases were identified. From studies published 2002 to 2005, 15 were identified as high-quality studies and were used to support management recommendations: pilocarpine and cevimeline are recommended for treating hyposalivation and xerostomia in primary and secondary Sjögren's syndrome (SS). IFN-alpha lozenges may enhance saliva flow in primary SS patients. Anti-TNF-alpha agents, such as infliximab or etanercept, are not recommended to treat hyposalivation in SS. Dehydroepiandrosterone is not recommended to relieve hyposalivation or xerostomia in primary SS. There was not enough evidence to support any recommendations for the use of local stimulants, lubricants, and protectants for hyposalivation/xerostomia. However, professional judgment and patient preferences may support the use of a specific product for an individual patient. These evidence-based management recommendations should guide the clinician's management decisions for patients with salivary dysfunction related to systemic disease. Future treatment strategies may include new formulations of existing drugs, e.g., local application of pilocarpine. Recent discoveries on gene expression and a better understanding of the etiopathogenesis of SS may open new treatment options in the future.
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Wada, Yasuyo; Hisamatsu, Tadakazu; Naganuma, Makoto; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Yajima, Tomoharu; Kouyama, Keisuke; Iwao, Yasushi; Ogata, Haruhiko; Hibi, Toshifumi; Abe, Takayuki; Kanai, Takanori
2015-12-01
Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis.
Wu, Pensée; Haththotuwa, Randula; Kwok, Chun Shing; Babu, Aswin; Kotronias, Rafail A; Rushton, Claire; Zaman, Azfar; Fryer, Anthony A; Kadam, Umesh; Chew-Graham, Carolyn A; Mamas, Mamas A
2017-02-01
Preeclampsia is a pregnancy-specific disorder resulting in hypertension and multiorgan dysfunction. There is growing evidence that these effects persist after pregnancy. We aimed to systematically evaluate and quantify the evidence on the relationship between preeclampsia and the future risk of cardiovascular diseases. We studied the future risk of heart failure, coronary heart disease, composite cardiovascular disease, death because of coronary heart or cardiovascular disease, stroke, and stroke death after preeclampsia. A systematic search of MEDLINE and EMBASE was performed to identify relevant studies. We used random-effects meta-analysis to determine the risk. Twenty-two studies were identified with >6.4 million women including >258 000 women with preeclampsia. Meta-analysis of studies that adjusted for potential confounders demonstrated that preeclampsia was independently associated with an increased risk of future heart failure (risk ratio [RR], 4.19; 95% confidence interval [CI], 2.09-8.38), coronary heart disease (RR, 2.50; 95% CI, 1.43-4.37), cardiovascular disease death (RR, 2.21; 95% CI, 1.83-2.66), and stroke (RR, 1.81; 95% CI, 1.29-2.55). Sensitivity analyses showed that preeclampsia continued to be associated with an increased risk of future coronary heart disease, heart failure, and stroke after adjusting for age (RR, 3.89; 95% CI, 1.83-8.26), body mass index (RR, 3.16; 95% CI, 1.41-7.07), and diabetes mellitus (RR, 4.19; 95% CI, 2.09-8.38). Preeclampsia is associated with a 4-fold increase in future incident heart failure and a 2-fold increased risk in coronary heart disease, stroke, and death because of coronary heart or cardiovascular disease. Our study highlights the importance of lifelong monitoring of cardiovascular risk factors in women with a history of preeclampsia. © 2017 American Heart Association, Inc.
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Borsi, John P.
2016-01-01
We have sought to replicate and extend the Season-wide Association Study (SeaWAS) of Boland, et al.1 in identifying birth month-disease associations from electronic health records (EHRs). We used methodology similar to that implemented by Boland on three geographically distinct cohorts, for a total of 11.8 million individuals derived from multiple data sources. We were able to identify eleven out of sixteen literature-supported birth month associations as compared to seven of sixteen for SeaWAS. Of the nine novel cardiovascular birth month associations discovered by SeaWAS, we were able to replicate four. None of the novel non-cardiovascular associations discovered by SeaWAS emerged as significant relations in our study. We identified thirty birth month disease associations not previously reported; of those, only six associations were validated in more than one cohort. These results suggest that differences in cohort composition and location can cause consequential variation in results of hypothesis-free searches. PMID:28269826
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2014-01-01
Background The Project on a Framework for Rating Evidence in Public Health (PRECEPT) was initiated and is being funded by the European Centre for Disease Prevention and Control (ECDC) to define a methodology for evaluating and grading evidence and strength of recommendations in the field of public health, with emphasis on infectious disease epidemiology, prevention and control. One of the first steps was to review existing quality appraisal tools (QATs) for individual research studies of various designs relevant to this area, using a question-based approach. Methods Through team discussions and expert consultations, we identified 20 relevant types of public health questions, which were grouped into six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis, risk factors, intervention, and implementation of intervention. Previously published systematic reviews were used and supplemented by expert consultation to identify suitable QATs. Finally, a matrix was constructed for matching questions to study designs suitable to address them and respective QATs. Key features of each of the included QATs were then analyzed, in particular in respect to its intended use, types of questions and answers, presence/absence of a quality score, and if a validation was performed. Results In total we identified 21 QATs and 26 study designs, and matched them. Four QATs were suitable for experimental quantitative study designs, eleven for observational quantitative studies, two for qualitative studies, three for economic studies, one for diagnostic test accuracy studies, and one for animal studies. Included QATs consisted of six to 28 items. Six of the QATs had a summary quality score. Fourteen QATs had undergone at least one validation procedure. Conclusions The results of this methodological study can be used as an inventory of potentially relevant questions, appropriate study designs and QATs for researchers and authorities engaged with evidence-based decision-making in infectious disease epidemiology, prevention and control. PMID:24886571
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Harder, Thomas; Takla, Anja; Rehfuess, Eva; Sánchez-Vivar, Alex; Matysiak-Klose, Dorothea; Eckmanns, Tim; Krause, Gérard; de Carvalho Gomes, Helena; Jansen, Andreas; Ellis, Simon; Forland, Frode; James, Roberta; Meerpohl, Joerg J; Morgan, Antony; Schünemann, Holger; Zuiderent-Jerak, Teun; Wichmann, Ole
2014-05-21
The Project on a Framework for Rating Evidence in Public Health (PRECEPT) was initiated and is being funded by the European Centre for Disease Prevention and Control (ECDC) to define a methodology for evaluating and grading evidence and strength of recommendations in the field of public health, with emphasis on infectious disease epidemiology, prevention and control. One of the first steps was to review existing quality appraisal tools (QATs) for individual research studies of various designs relevant to this area, using a question-based approach. Through team discussions and expert consultations, we identified 20 relevant types of public health questions, which were grouped into six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis, risk factors, intervention, and implementation of intervention. Previously published systematic reviews were used and supplemented by expert consultation to identify suitable QATs. Finally, a matrix was constructed for matching questions to study designs suitable to address them and respective QATs. Key features of each of the included QATs were then analyzed, in particular in respect to its intended use, types of questions and answers, presence/absence of a quality score, and if a validation was performed. In total we identified 21 QATs and 26 study designs, and matched them. Four QATs were suitable for experimental quantitative study designs, eleven for observational quantitative studies, two for qualitative studies, three for economic studies, one for diagnostic test accuracy studies, and one for animal studies. Included QATs consisted of six to 28 items. Six of the QATs had a summary quality score. Fourteen QATs had undergone at least one validation procedure. The results of this methodological study can be used as an inventory of potentially relevant questions, appropriate study designs and QATs for researchers and authorities engaged with evidence-based decision-making in infectious disease epidemiology, prevention and control.
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Knowledge of heart disease among women in an urban emergency setting.
Prendergast, Heather M.; Bunney, E. Bradshaw; Roberson, Thessa; Davis, Theresa
2004-01-01
OBJECTIVE: To test the hypothesis that the higher prevalence of heart disease-related illnesses in women in urban areas may be attributed to lack of knowledge. DESIGN: A prospective survey of 224 women presenting to an urban emergency department. INTERVENTION: All study participants were surveyed about their knowledge of heart disease and associated risk factors. RESULTS: Two-hundred participants correctly completed the surveys. Only 25 (13%) of women correctly identified heart disease as the leading cause of death in women. Similarly, only 12 (6%) of women surveyed felt heart disease was the greatest health issue facing women today. The majority of women felt breast cancer was the most important health issue and responsible for the greatest mortality in women. Only three of the traditional cardiac risk factors were correctly identified by half of the women surveyed: hypercholesteremia (56%), hypertension (54%), and tobacco (52%). Family history was correctly identified by 44%, and only 20% of women felt diabetes was a risk factor for cardiovascular disease. CONCLUSIONS: Despite increased medical education and media time spent on women's health issues, up to 87% of women in this urban population did not know the leading cause of death for their gender. PMID:15303406
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Carss, Keren J; Arno, Gavin; Erwood, Marie; Stephens, Jonathan; Sanchis-Juan, Alba; Hull, Sarah; Megy, Karyn; Grozeva, Detelina; Dewhurst, Eleanor; Malka, Samantha; Plagnol, Vincent; Penkett, Christopher; Stirrups, Kathleen; Rizzo, Roberta; Wright, Genevieve; Josifova, Dragana; Bitner-Glindzicz, Maria; Scott, Richard H; Clement, Emma; Allen, Louise; Armstrong, Ruth; Brady, Angela F; Carmichael, Jenny; Chitre, Manali; Henderson, Robert H H; Hurst, Jane; MacLaren, Robert E; Murphy, Elaine; Paterson, Joan; Rosser, Elisabeth; Thompson, Dorothy A; Wakeling, Emma; Ouwehand, Willem H; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Raymond, F Lucy
2017-01-05
Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease. Copyright © 2017. Published by Elsevier Inc.
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NASA Astrophysics Data System (ADS)
Brown, Heidi E.
Spatially explicit information is increasingly available for infectious disease modeling. However, such information is reluctantly or inappropriately incorporated. My dissertation research uses spatially explicit data to assess relationships between landscape and mosquito species distribution and discusses challenges regarding accurate predictive risk modeling. The goal of my research is to use remotely sensed environmental information and spatial statistical methods to better understand mosquito-borne disease epidemiology for improvement of public health responses. In addition to reviewing the progress of spatial infectious disease modeling, I present four research projects. I begin by evaluating the biases in surveillance data and build up to predictive modeling of mosquito species presence. In the first study I explore how mosquito surveillance trap types influence estimations of mosquito populations. Then. I use county-based human surveillance data and landscape variables to identify risk factors for West Nile virus disease. The third study uses satellite-based vegetation indices to identify spatial variation among West Nile virus vectors in an urban area and relates the variability to virus transmission dynamics. Finally, I explore how information from three satellite sensors of differing spatial and spectral resolution can be used to identify and distinguish mosquito habitat across central Connecticut wetlands. Analyses presented here constitute improvements to the prediction of mosquito distribution and therefore identification of disease risk factors. Current methods for mosquito surveillance data collection are labor intensive and provide an extremely limited, incomplete picture of the species composition and abundance. Human surveillance data offers additional challenges with respect to reporting bias and resolution, but is nonetheless informative in identifying environmental risk factors and disease transmission dynamics. Remotely sensed imagery supports mosquito and human disease surveillance data by providing spatially explicit, line resolution information about environmental factors relevant to vector-borne disease processes. Together, surveillance and remotely sensed environmental data facilitate improved description and modeling of disease transmission. Remote sensing can be used to develop predictive maps of mosquito distribution in relation to disease risk. This has implications for increased accuracy of mosquito control efforts. The projects presented in this dissertation enhance current public health capacities by examining the applications of spatial modeling with respect to mosquito-borne disease.
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Odencrants, Sigrid; Ehnfors, Margareta; Ehrenberg, Anna
2008-07-01
The aim of the study was to describe and compare nutritional status and social and medical characteristics among older patients with chronic obstructive pulmonary disease admitted to an acute care hospital ward for respiratory medicine. Chronic obstructive pulmonary disease is a condition associated with risk of developing malnutrition. A body mass index <20 is predictive of hospitalisation for acute exacerbations of chronic obstructive pulmonary disease. Knowledge about patient characteristics is crucial for the identification of malnourished patients and the development of nursing care for these patients. Quantitative descriptive study. Thirty-three hospitalised women and 17 men with a mean age of 75.7 years (SD 6.9) were consecutively included. A very severe case of chronic obstructive pulmonary disease was indicated in 28 out of 39 patients who underwent a lung function test. Data were collected with measurement of nutritional status using Mini Nutritional Assessment, anthropometry and lung function. Nearly half of the patients (48%) were identified as malnourished, an equal part as at risk for malnutrition and two patients as well nourished. The mean Mini Nutritional Assessment score of 17.2 (SD 3.99) for all patients was near the Mini Nutritional Assessment cut-off score (i.e. 17) for malnutrition. Patients identified as malnourished had a mean body mass index of 18.9 and those at risk for malnutrition had a mean of 23.4. It was more common for those identified as malnourished to live singly, to not live in own property and to be dependent on daily community service. Seven patients identified as malnourished died during the data collection period. This study provides important knowledge about further risks of impaired nutritional status among older patients with chronic obstructive pulmonary disease. This knowledge can provide registered nurses with the necessary knowledge to make them aware of certain patients needing particular kinds of attention.
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Anthropogenic disturbance and the risk of flea-borne disease transmission
Megan M. Friggens; Paul Beier
2010-01-01
Anthropogenic disturbance may lead to the spread of vector-borne diseases through effects on pathogens, vectors, and hosts. Identifying the type and extent of vector response to habitat change will enable better and more accurate management strategies for anthropogenic disease spread. We compiled and analyzed data from published empirical studies to test for patterns...
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Rare deleterious mutations are associated with disease in bipolar disorder families.
Rao, A R; Yourshaw, M; Christensen, B; Nelson, S F; Kerner, B
2017-07-01
Bipolar disorder (BD) is a common, complex and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction. Disease association and disease specificity was determined using 5090 exomes from the Sweden-Schizophrenia (SZ) Population-Based Case-Control Exome Sequencing study. We identified 14 rare and likely deleterious mutations in 14 genes that were shared identity-by-descent among affected family members. The variants were associated with BD (P<0.05 after Bonferroni's correction) and disease specificity was supported by the absence of the mutations in patients with SZ. In addition, we found rare, functional mutations in known causal genes for neuropsychiatric disorders including holoprosencephaly and epilepsy. Our results demonstrate that exome sequencing in multigenerational families with BD is effective in identifying rare genomic variants of potential clinical relevance and also disease modifiers related to coexisting medical conditions. Replication of our results and experimental validation are required before disease causation could be assumed.
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Analysis of single nucleotide polymorphisms in case-control studies.
Li, Yonghong; Shiffman, Dov; Oberbauer, Rainer
2011-01-01
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variants in the human genome. SNPs are known to modify susceptibility to complex diseases. We describe and discuss methods used to identify SNPs associated with disease in case-control studies. An outline on study population selection, sample collection and genotyping platforms is presented, complemented by SNP selection, data preprocessing and analysis.
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Nordenvall, Caroline; Rosvall, Oda; Bottai, Matteo; Everhov, Åsa H; Malmborg, Petter; Smedby, Karin E; Ekbom, Anders; Askling, Johan; Ludvigsson, Jonas F; Myrelid, Pär; Olén, Ola
2018-01-24
The incidence of childhood-onset [< 18 years] inflammatory bowel disease [IBD] is increasing worldwide, and some studies suggest that it represents a more severe disease phenotype. Few nationwide, population-based studies have evaluated the surgical burden in patients with childhood-onset IBD, and whether the improved medical treatment has influenced the need for gastrointestinal surgery. The aim was to examine whether the surgical treatment at any age of patients with childhood-onset IBD has changed over time. In a nationwide cohort study we identified 4695 children [< 18 years] diagnosed with incident IBD in 2002-2014 through the Swedish Patient Register [ulcerative colitis: n = 2295; Crohn's disease: n = 2174; inflammatory bowel disease-unclassified: n = 226]. Abdominal [intestinal resections and colectomies] and perianal surgeries were identified through the Swedish Patient Register. The cumulative incidences of surgeries were calculated using the Kaplan-Meier method. In the cohort, 44% were females and 56% males. The median age at inflammatory bowel disease diagnosis was 15 years and the maximum age at end of follow-up was 31 years. The 3-year cumulative incidence of intestinal surgery was 5% in patients with ulcerative colitis and 7% in patients with Crohn's disease, and lower in children aged < 6 years at inflammatory bowel disease diagnosis [3%] than in those aged 15-17 years at diagnosis [7%]. Calendar period of inflammatory bowel disease diagnosis was not associated with risk of surgery. Over the past 13 years, the risk of surgery in childhood-onset inflammatory bowel disease has remained unchanged. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
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[Notifiable infectious diseases: knowledge and notification among hospital physicians].
Rubio-Cirilo, Laura; Martín-Ríos, M Dolores; de Las Casas-Cámara, Gonzalo; Andrés-Prado, M José; Rodríguez-Caravaca, Gil
2013-12-01
Notifiable infectious diseases represent a public health hazard, which is why they are under surveillance and must be reported. We tried to assess hospital physicians' knowledge of hospital physicians on notifiable infectious diseases and their self-reported attitudes to notification. An observational study was conducted using a questionnaire with 11 multiple choice questions, two yes/no questions and one short-answer question. It was distributed to all senior doctors and residents in 19 medical and surgical departments. A total of 248 questionnaires were sent out, with a response rate of 79.84%. More than three-quarters (76.3%) of the respondents were senior doctors. As regards specific knowledge about whether a particular disease is a notifiable disease, 29.5% identified correctly 100% of the named diseases, 3.2% could not identify any of them. All urgent named notifiable infectious diseases were correctly identified by 25.3% of physicians. Statistically significant differences were found in the knowledge of notifiable diseases knowledge in medical and surgical departments, as well as for senior doctors (P=.047) and residents (P=.035). A high percentage of medical services (40%) and surgical (70%) department reported never failing to notify. When asked about the causes of under-reporting, 72% did not know whether notification was mandatory or not, and 88% did not know what diseases must be notified. Although many respondents are aware that diseases notification is part of their daily activity, many of them admit under-reporting. There is insufficient knowledge about what diseases are considered notifiable infectious diseases and how to notify them. Copyright © 2012 Elsevier España, S.L. All rights reserved.
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LGscore: A method to identify disease-related genes using biological literature and Google data.
Kim, Jeongwoo; Kim, Hyunjin; Yoon, Youngmi; Park, Sanghyun
2015-04-01
Since the genome project in 1990s, a number of studies associated with genes have been conducted and researchers have confirmed that genes are involved in disease. For this reason, the identification of the relationships between diseases and genes is important in biology. We propose a method called LGscore, which identifies disease-related genes using Google data and literature data. To implement this method, first, we construct a disease-related gene network using text-mining results. We then extract gene-gene interactions based on co-occurrences in abstract data obtained from PubMed, and calculate the weights of edges in the gene network by means of Z-scoring. The weights contain two values: the frequency and the Google search results. The frequency value is extracted from literature data, and the Google search result is obtained using Google. We assign a score to each gene through a network analysis. We assume that genes with a large number of links and numerous Google search results and frequency values are more likely to be involved in disease. For validation, we investigated the top 20 inferred genes for five different diseases using answer sets. The answer sets comprised six databases that contain information on disease-gene relationships. We identified a significant number of disease-related genes as well as candidate genes for Alzheimer's disease, diabetes, colon cancer, lung cancer, and prostate cancer. Our method was up to 40% more accurate than existing methods. Copyright © 2015 Elsevier Inc. All rights reserved.
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Drug development for exceptionally rare metabolic diseases: challenging but not impossible
2013-01-01
Background We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Methods All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the ‘Orphanet database of Rare diseases’. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). Results In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). Conclusion For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest. PMID:24237580
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The Data Gap in the EHR for Clinical Research Eligibility Screening.
Butler, Alex; Wei, Wei; Yuan, Chi; Kang, Tian; Si, Yuqi; Weng, Chunhua
2018-01-01
Much effort has been devoted to leverage EHR data for matching patients into clinical trials. However, EHRs may not contain all important data elements for clinical research eligibility screening. To better design research-friendly EHRs, an important step is to identify data elements frequently used for eligibility screening but not yet available in EHRs. This study fills this knowledge gap. Using the Alzheimer's disease domain as an example, we performed text mining on the eligibility criteria text in Clinicaltrials.gov to identify frequently used eligibility criteria concepts. We compared them to the EHR data elements of a cohort of Alzheimer's Disease patients to assess the data gap by usingthe OMOP Common Data Model to standardize the representations for both criteria concepts and EHR data elements. We identified the most common SNOMED CT concepts used in Alzheimer 's Disease trials, andfound 40% of common eligibility criteria concepts were not even defined in the concept space in the EHR dataset for a cohort of Alzheimer 'sDisease patients, indicating a significant data gap may impede EHR-based eligibility screening. The results of this study can be useful for designing targeted research data collection forms to help fill the data gap in the EHR.
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Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases
Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon
2016-01-01
Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688
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Marino, Marta; de Belvis, Antonio; Basso, Danila; Avolio, Maria; Pelone, Ferruccio; Tanzariello, Maria; Ricciardi, Walter
2013-01-01
When an health condition has been identified, the question of whether to continue driving depends not on a medical diagnosis, but on the functional consequences of the illness. The complex nature of physical and mental impairments and their relationship with safe driving make the availability of evidence based tools necessary for health professionals. The review aims at identifying and summarizing scientific findings concerning the relationship between neuropsychological and clinical screening tests and fitness to drive among people with chronic conditions. Studies were searched for driving ability evaluation by road test or simulator, clinical/neuropsychological examinations of participants with chronic diseases or permanent disablement impairing driving performance, primary outcomes as fatal/non-fatal traffic injuries and secondary outcomes as fitness to drive assessment. Twenty-seven studies fulfilled the inclusion criteria. Some studies included more than one clinical condition. The illness investigated were Alzheimer Disease (n=6), Parkinson Disease (n=8), Cardiovascular Accident (n=4), Traumatic Brain Injuries (n=3), Sleep Apnea Syndrome (n=2), Narcolepsy (n=1), Multiple Sclerosis (n=1) and Hepatic Encephalopathy (n=1), comorbidities (n=3). No studies match inclusion criteria about Myasthenia Gravis, Diabetes Mellitus, Renal Diseases, Hearing Disorders and Sight Diseases. No studies referred to primary outcomes. The selected studies provided opposite evidences. It would be reasonable to argue that some clinical and neuropsychological tests are effective in predicting fitness to drive even if contrasting results support that driving performance decreases as a function of clinical and neuropsychological decline in some chronic diseases. Nevertheless we found no evidence that clinical and neuropsychological screening tests would lead to a reduction in motor vehicle crashes involving chronic disabled drivers. It seems necessary to develop tests with proven validity for identifying high-risk drivers so that physicians can provide guidance to their patients in chronic conditions, and also to medical advisory boards working with licensing offices. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links
Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán
2014-01-01
Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186
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Brekelmans, Marjolein P; Fens, Niki; Brinkman, Paul; Bos, Lieuwe D; Sterk, Peter J; Tak, Paul P; Gerlag, Daniëlle M
2016-01-01
To investigate whether exhaled breath analysis using an electronic nose can identify differences between inflammatory joint diseases and healthy controls. In a cross-sectional study, the exhaled breath of 21 rheumatoid arthritis (RA) and 18 psoriatic arthritis (PsA) patients with active disease was compared to 21 healthy controls using an electronic nose (Cyranose 320; Smiths Detection, Pasadena, CA, USA). Breathprints were analyzed with principal component analysis, discriminant analysis, and area under curve (AUC) of receiver operating characteristics (ROC) curves. Volatile organic compounds (VOCs) were identified by gas chromatography and mass spectrometry (GC-MS), and relationships between breathprints and markers of disease activity were explored. Breathprints of RA patients could be distinguished from controls with an accuracy of 71% (AUC 0.75, 95% CI 0.60-0.90, sensitivity 76%, specificity 67%). Breathprints from PsA patients were separated from controls with 69% accuracy (AUC 0.77, 95% CI 0.61-0.92, sensitivity 72%, specificity 71%). Distinction between exhaled breath of RA and PsA patients exhibited an accuracy of 69% (AUC 0.72, 95% CI 0.55-0.89, sensitivity 71%, specificity 72%). There was a positive correlation in RA patients of exhaled breathprints with disease activity score (DAS28) and number of painful joints. GC-MS identified seven key VOCs that significantly differed between the groups. Exhaled breath analysis by an electronic nose may play a role in differential diagnosis of inflammatory joint diseases. Data from this study warrant external validation.
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Using Zebrafish to Test the Genetic Basis of Human Craniofacial Diseases.
Machado, R Grecco; Eames, B Frank
2017-10-01
Genome-wide association studies (GWASs) opened an innovative and productive avenue to investigate the molecular basis of human craniofacial disease. However, GWASs identify candidate genes only; they do not prove that any particular one is the functional villain underlying disease or just an unlucky genomic bystander. Genetic manipulation of animal models is the best approach to reveal which genetic loci identified from human GWASs are functionally related to specific diseases. The purpose of this review is to discuss the potential of zebrafish to resolve which candidate genetic loci are mechanistic drivers of craniofacial diseases. Many anatomic, embryonic, and genetic features of craniofacial development are conserved among zebrafish and mammals, making zebrafish a good model of craniofacial diseases. Also, the ability to manipulate gene function in zebrafish was greatly expanded over the past 20 y, enabling systems such as Gateway Tol2 and CRISPR-Cas9 to test gain- and loss-of-function alleles identified from human GWASs in coding and noncoding regions of DNA. With the optimization of genetic editing methods, large numbers of candidate genes can be efficiently interrogated. Finding the functional villains that underlie diseases will permit new treatments and prevention strategies and will increase understanding of how gene pathways operate during normal development.
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Identifying Group-Specific Sequences for Microbial Communities Using Long k-mer Sequence Signatures
Wang, Ying; Fu, Lei; Ren, Jie; Yu, Zhaoxia; Chen, Ting; Sun, Fengzhu
2018-01-01
Comparing metagenomic samples is crucial for understanding microbial communities. For different groups of microbial communities, such as human gut metagenomic samples from patients with a certain disease and healthy controls, identifying group-specific sequences offers essential information for potential biomarker discovery. A sequence that is present, or rich, in one group, but absent, or scarce, in another group is considered “group-specific” in our study. Our main purpose is to discover group-specific sequence regions between control and case groups as disease-associated markers. We developed a long k-mer (k ≥ 30 bps)-based computational pipeline to detect group-specific sequences at strain resolution free from reference sequences, sequence alignments, and metagenome-wide de novo assembly. We called our method MetaGO: Group-specific oligonucleotide analysis for metagenomic samples. An open-source pipeline on Apache Spark was developed with parallel computing. We applied MetaGO to one simulated and three real metagenomic datasets to evaluate the discriminative capability of identified group-specific markers. In the simulated dataset, 99.11% of group-specific logical 40-mers covered 98.89% disease-specific regions from the disease-associated strain. In addition, 97.90% of group-specific numerical 40-mers covered 99.61 and 96.39% of differentially abundant genome and regions between two groups, respectively. For a large-scale metagenomic liver cirrhosis (LC)-associated dataset, we identified 37,647 group-specific 40-mer features. Any one of the features can predict disease status of the training samples with the average of sensitivity and specificity higher than 0.8. The random forests classification using the top 10 group-specific features yielded a higher AUC (from ∼0.8 to ∼0.9) than that of previous studies. All group-specific 40-mers were present in LC patients, but not healthy controls. All the assembled 11 LC-specific sequences can be mapped to two strains of Veillonella parvula: UTDB1-3 and DSM2008. The experiments on the other two real datasets related to Inflammatory Bowel Disease and Type 2 Diabetes in Women consistently demonstrated that MetaGO achieved better prediction accuracy with fewer features compared to previous studies. The experiments showed that MetaGO is a powerful tool for identifying group-specific k-mers, which would be clinically applicable for disease prediction. MetaGO is available at https://github.com/VVsmileyx/MetaGO. PMID:29774017
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Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis.
Cho, Seoae; Kim, Haseong; Oh, Sohee; Kim, Kyunga; Park, Taesung
2009-12-15
The current trend in genome-wide association studies is to identify regions where the true disease-causing genes may lie by evaluating thousands of single-nucleotide polymorphisms (SNPs) across the whole genome. However, many challenges exist in detecting disease-causing genes among the thousands of SNPs. Examples include multicollinearity and multiple testing issues, especially when a large number of correlated SNPs are simultaneously tested. Multicollinearity can often occur when predictor variables in a multiple regression model are highly correlated, and can cause imprecise estimation of association. In this study, we propose a simple stepwise procedure that identifies disease-causing SNPs simultaneously by employing elastic-net regularization, a variable selection method that allows one to address multicollinearity. At Step 1, the single-marker association analysis was conducted to screen SNPs. At Step 2, the multiple-marker association was scanned based on the elastic-net regularization. The proposed approach was applied to the rheumatoid arthritis (RA) case-control data set of Genetic Analysis Workshop 16. While the selected SNPs at the screening step are located mostly on chromosome 6, the elastic-net approach identified putative RA-related SNPs on other chromosomes in an increased proportion. For some of those putative RA-related SNPs, we identified the interactions with sex, a well known factor affecting RA susceptibility.
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Zhang, Tiejun; Yu, Long-Xi; McCord, Per; Miller, David; Bhamidimarri, Suresh; Johnson, David; Monteros, Maria J.; Ho, Julie; Reisen, Peter; Samac, Deborah A.
2014-01-01
Verticillium wilt, caused by the soilborne fungus, Verticillium alfalfae, is one of the most serious diseases of alfalfa (Medicago sativa L.) worldwide. To identify loci associated with resistance to Verticillium wilt, a bulk segregant analysis was conducted in susceptible or resistant pools constructed from 13 synthetic alfalfa populations, followed by association mapping in two F1 populations consisted of 352 individuals. Simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers were used for genotyping. Phenotyping was done by manual inoculation of the pathogen to replicated cloned plants of each individual and disease severity was scored using a standard scale. Marker-trait association was analyzed by TASSEL. Seventeen SNP markers significantly associated with Verticillium wilt resistance were identified and they were located on chromosomes 1, 2, 4, 7 and 8. SNP markers identified on chromosomes 2, 4 and 7 co-locate with regions of Verticillium wilt resistance loci reported in M. truncatula. Additional markers identified on chromosomes 1 and 8 located the regions where no Verticillium resistance locus has been reported. This study highlights the value of SNP genotyping by high resolution melting to identify the disease resistance loci in tetraploid alfalfa. With further validation, the markers identified in this study could be used for improving resistance to Verticillium wilt in alfalfa breeding programs. PMID:25536106
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Zhang, Tiejun; Yu, Long-Xi; McCord, Per; Miller, David; Bhamidimarri, Suresh; Johnson, David; Monteros, Maria J; Ho, Julie; Reisen, Peter; Samac, Deborah A
2014-01-01
Verticillium wilt, caused by the soilborne fungus, Verticillium alfalfae, is one of the most serious diseases of alfalfa (Medicago sativa L.) worldwide. To identify loci associated with resistance to Verticillium wilt, a bulk segregant analysis was conducted in susceptible or resistant pools constructed from 13 synthetic alfalfa populations, followed by association mapping in two F1 populations consisted of 352 individuals. Simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers were used for genotyping. Phenotyping was done by manual inoculation of the pathogen to replicated cloned plants of each individual and disease severity was scored using a standard scale. Marker-trait association was analyzed by TASSEL. Seventeen SNP markers significantly associated with Verticillium wilt resistance were identified and they were located on chromosomes 1, 2, 4, 7 and 8. SNP markers identified on chromosomes 2, 4 and 7 co-locate with regions of Verticillium wilt resistance loci reported in M. truncatula. Additional markers identified on chromosomes 1 and 8 located the regions where no Verticillium resistance locus has been reported. This study highlights the value of SNP genotyping by high resolution melting to identify the disease resistance loci in tetraploid alfalfa. With further validation, the markers identified in this study could be used for improving resistance to Verticillium wilt in alfalfa breeding programs.
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Thumbi, Samuel M; Bronsvoort, Mark B M de C; Kiara, Henry; Toye, P G; Poole, Jane; Ndila, Mary; Conradie, Ilana; Jennings, Amy; Handel, Ian G; Coetzer, J A W; Steyl, Johan; Hanotte, Olivier; Woolhouse, Mark E J
2013-09-08
Infectious livestock diseases remain a major threat to attaining food security and are a source of economic and livelihood losses for people dependent on livestock for their livelihood. Knowledge of the vital infectious diseases that account for the majority of deaths is crucial in determining disease control strategies and in the allocation of limited funds available for disease control. Here we have estimated the mortality rates in zebu cattle raised in a smallholder mixed farming system during their first year of life, identified the periods of increased risk of death and the risk factors for calf mortality, and through analysis of post-mortem data, determined the aetiologies of calf mortality in this population. A longitudinal cohort study of 548 zebu cattle was conducted between 2007 and 2010. Each calf was followed during its first year of life or until lost from the study. Calves were randomly selected from 20 sub-locations and recruited within a week of birth from different farms over a 45 km radius area centered on Busia in the Western part of Kenya. The data comprised of 481.1 calf years of observation. Clinical examinations, sample collection and analysis were carried out at 5 week intervals, from birth until one year old. Cox proportional hazard models with frailty terms were used for the statistical analysis of risk factors. A standardized post-mortem examination was conducted on all animals that died during the study and appropriate samples collected. The all-cause mortality rate was estimated at 16.1 (13.0-19.2; 95% CI) per 100 calf years at risk. The Cox models identified high infection intensity with Theileria spp., the most lethal of which causes East Coast Fever disease, infection with Trypanosome spp., and helminth infections as measured by Strongyle spp. eggs per gram of faeces as the three important infections statistically associated with infectious disease mortality in these calves. Analysis of post-mortem data identified East Coast Fever as the main cause of death accounting for 40% of all deaths, haemonchosis 12% and heartwater disease 7%. The findings demonstrate the impact of endemic parasitic diseases in indigenous animals expected to be well adapted against disease pressures. Additionally, agreement between results of Cox models using data from simple diagnostic procedures and results from post-mortem analysis underline the potential use such diagnostic data to reduce calf mortality. The control strategies for the identified infectious diseases have been discussed.
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Fort, Meredith P; Castro, Maricruz; Peña, Liz; López Hernández, Sergio Hernán; Arreola Camacho, Gabriel; Ramírez-Zea, Manuel; Martínez, Homero
2015-10-05
A healthy lifestyle intervention was implemented in primary care health centers in urban parts of Tuxtla Gutiérrez, Chiapas, Mexico with an aim of reducing cardiovascular disease risk for patients with type 2 diabetes and/or hypertension. During implementation, research questions emerged. Considerably fewer men participated in the intervention than women, and an opportunity was identified to increase the reach of activities aimed at improving disease self-management through strategies involving family members. A qualitative study was conducted to identify strategies to involve men and engage family members in disease management and risk reduction. Nine men with hypertension and/or type 2 diabetes with limited to no participation in disease self-management and health promotion activities, six families in which at least one family member had a diagnosis of one or both conditions, and nine health care providers from four different government health centers were recruited for the study. Participants took part in semi-structured interviews. During interviews with families, genograms and eco-maps were used to diagram family composition and structure, and capture the nature of patients' relationships to the extended family and community resources. Transcripts were coded and a general inductive analytic approach was used to identify themes related to men's limited participation in health promotion activities, family support and barriers to disease management, and health care providers' recommendations. Participants reported barriers to men's participation in chronic disease management and healthy lifestyle education activities that can be grouped into two categories: internal and external factors. Internal factors are those for which they are able to make the decision on their own and external factors are those that are not related solely to their decision to take part or not. Four primary aspects were identified related to families' relationships with disease: different roles within the family, types of support provided to patients, the opportunity to prevent disease among family members without a diagnosis, and - in some cases - lack of family support or stress-induced by other family members. There was an overlap in recommended strategies for engaging men and family members in chronic disease management activities. There is an opportunity to increase the reach of interventions aimed at improving disease self-management by engaging men and family members. The proposed strategies presented by patients, family members, and providers have implications for health education and service provision at primary care health centers and for future research.
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Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe
2016-01-01
Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691
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Hohman, Timothy J; Bush, William S; Jiang, Lan; Brown-Gentry, Kristin D; Torstenson, Eric S; Dudek, Scott M; Mukherjee, Shubhabrata; Naj, Adam; Kunkle, Brian W; Ritchie, Marylyn D; Martin, Eden R; Schellenberg, Gerard D; Mayeux, Richard; Farrer, Lindsay A; Pericak-Vance, Margaret A; Haines, Jonathan L; Thornton-Wells, Tricia A
2016-02-01
Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1 × ABCB1, PSAP × PEBP4, and GRIN2B × ADRA1A. In addition, we extend a previously identified interaction from an endophenotype analysis between RYR3 × CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this article highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.
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Millen, Barbara E; Quatromoni, Paula A; Pencina, Michael; Kimokoti, Ruth; Nam, Byung-H O; Cobain, Sonia; Kozak, Waldemar; Appugliese, Danielle P; Ordovas, Jose; D'Agostino, Ralph B
2005-11-01
To identify the dietary patterns of adult men and examine their relationships with nutrient intake and chronic disease risk over long-term follow-up. Baseline 145-item food frequency questionnaires from 1,666 Framingham Offspring-Spouse cohort men were used to identify comprehensive dietary patterns. Independent 3-day dietary records at baseline and 8 years later provided estimates of subjects' nutrient intake by dietary pattern. Chronic disease risk factor status was compared at baseline and 16-year follow-up across all male dietary patterns. Cluster analysis was applied to food frequency data to identify non-overlapping male dietary patterns. Analysis of covariance and logistic regression were used to compare nutrient intake, summary nutritional risk scores, and chronic disease risk status at baseline and follow-up by male dietary pattern. Five distinct and comprehensive dietary patterns of Framingham Offspring-Spouse men were identified and ordered according to overall nutritional risk: Transition to Heart Healthy, Higher Starch, Average Male, Lower Variety, and Empty Calories. Nutritional risk was high and varied by dietary pattern; key nutrient contrasts were stable over 8-year follow-up. Chronic disease risk also varied by dietary pattern and specific subgroup differences persisted over 16 years, notably rates of overweight/obesity and smoking. Quantitative cluster analysis applied to food frequency questionnaire data identified five distinct, comprehensive, and stable dietary patterns of adult Framingham Offspring-Spouse cohort men. The close associations between the dietary patterns, nutritional risk, and chronic disease profiles of men emphasize the importance of targeted preventive nutrition interventions to promote health in the male population.
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Establishing the role of rare coding variants in known Parkinson's disease risk loci.
Jansen, Iris E; Gibbs, J Raphael; Nalls, Mike A; Price, T Ryan; Lubbe, Steven; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Williams, Nigel M; Brice, Alexis; Hardy, John; Wood, Nicholas W; Morris, Huw R; Gasser, Thomas; Singleton, Andrew B; Heutink, Peter; Sharma, Manu
2017-11-01
Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks. Copyright © 2017 Elsevier Inc. All rights reserved.
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Genetic advances of type 2 diabetes in Chinese populations.
Yu, Weihui; Hu, Cheng; Jia, Weiping
2012-09-01
In recent decades, the prevalence of type 2 diabetes in China has increased significantly, underscoring the importance of investigating the etiological mechanisms, including genetic determinants, of the disease in Chinese populations. Numerous loci conferring susceptibility to type 2 diabetes (T2D) have been identified worldwide, with most having been identified in European populations. In terms of ethnic heterogeneity in pathogenesis as well as disease predisposition, it is imperative to explore the specific genetic architecture of T2D in Han Chinese. Replication studies of European-derived susceptibility loci have been performed, validating 11 of 32 loci in Chinese populations. Genetic investigations into heritable traits related to glucose metabolism are expected to provide new insights into the pathogenesis of T2D, and such studies have already inferred some new susceptibility loci. Other than replication studies of European-derived loci, efforts have been made to identify specific susceptibility loci in Chinese populations using methods such as genome-wide association studies. These efforts have identified additional new loci for the disease. Genetic studies can facilitate the prediction of risk for T2D and also promote individualized anti-diabetic treatment. Despite many advances in the field of risk prediction and pharmacogenetics, the pace of clinical application of these findings is rather slow. As a result, more studies into the practical utility of these findings remain necessary. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.
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Epigenetics of cartilage diseases.
Gabay, Odile; Clouse, Kathleen A
2016-10-01
Osteoarticular diseases, such as arthritis or osteoarthritis, are multifactorial diseases with an underlying genetic etiology that are challenging to study. Genome-Wide Association studies (GWAS) have identified several genetic loci associated with these diseases. Epigenetics is a complex mechanism of chromatin and gene modulation through DNA methylation, histone deacetylation or microRNA, which might contribute to the inheritability of disease. Some of these mechanisms have been studied for decades in other diseases or as part of the aging process, where epigenetic changes seem to play an important role. With the implementation of better technological tools, such as the Illumina next generation sequencing, altered methylation of DNA has been linked to articular diseases and these mechanisms have been shown to regulate metalloprotease (MMP) expression and cartilage matrix integrity. Some miRNA have also been identified and more extensively characterized, such as delineation of the role played by miR-140 in chondrogenesis, followed by the discovery of numerous miRNA potentially involved in the epigenetic regulation of osteoarthritic disease. Histone deacetylases have long been linked to aging, particularly with respect to the Sirtuin family with Sirt1 as the major player. Because aging is the major risk factor for osteoarthritis, the involvement of Sirtuins in the etiology of osteoarthritis has been suggested and investigated. All of these fine regulations together shed new light on cartilage disease pathophysiology. We present in this short review an update of the role of these pathways in articular diseases. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
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Baerwald, Melinda R; Welsh, Amy B; Hedrick, Ronald P; May, Bernie
2008-01-01
Background Whirling disease, caused by the pathogen Myxobolus cerebralis, afflicts several salmonid species. Rainbow trout are particularly susceptible and may suffer high mortality rates. The disease is persistent and spreading in hatcheries and natural waters of several countries, including the U.S.A., and the economic losses attributed to whirling disease are substantial. In this study, genome-wide expression profiling using cDNA microarrays was conducted for resistant Hofer and susceptible Trout Lodge rainbow trout strains following pathogen exposure with the primary objective of identifying specific genes implicated in whirling disease resistance. Results Several genes were significantly up-regulated in skin following pathogen exposure for both the resistant and susceptible rainbow trout strains. For both strains, response to infection appears to be linked with the interferon system. Expression profiles for three genes identified with microarrays were confirmed with qRT-PCR. Ubiquitin-like protein 1 was up-regulated over 100 fold and interferon regulating factor 1 was up-regulated over 15 fold following pathogen exposure for both strains. Expression of metallothionein B, which has known roles in inflammation and immune response, was up-regulated over 5 fold in the resistant Hofer strain but was unchanged in the susceptible Trout Lodge strain following pathogen exposure. Conclusion The present study has provided an initial view into the genetic basis underlying immune response and resistance of rainbow trout to the whirling disease parasite. The identified genes have allowed us to gain insight into the molecular mechanisms implicated in salmonid immune response and resistance to whirling disease infection. PMID:18218127
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Relationship between paternal somatic health and assisted reproductive technology outcomes.
Eisenberg, Michael L; Li, Shufeng; Wise, Lauren A; Lynch, Courtney D; Nakajima, Steven; Meyers, Stuart A; Behr, Barry; Baker, Valerie L
2016-09-01
To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART). Retrospective cohort study. Academic reproductive medicine center. We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes. None. Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages. In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks). The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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Benson, M
2016-03-01
Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples. © 2015 The Association for the Publication of the Journal of Internal Medicine.
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A Systematic Review of Cardiovascular Disease in Sexual Minorities
Brody, Abraham; Luscombe, Rachel E.; Primiano, Jillian E.; Marusca, Peter; Sitts, Edward M.; Chyun, Deborah
2017-01-01
Background: Mental health and HIV disparities are well documented among sexual minorities, but there is a dearth of research on other chronic conditions. Cardiovascular disease remains the leading cause of death worldwide. Although sexual minorities have high rates of several modifiable risk factors for cardiovascular disease (including stress, tobacco use, and alcohol consumption), there is a paucity of research in this area. Objectives: In this systematic review, we synthesized and critiqued the existing evidence on cardiovascular disease among sexual minority adults. Search Methods: We conducted a thorough literature search of 6 electronic databases for studies published between January 1985 and December 2015 that compared cardiovascular disease risk or prevalence between sexual minority and heterosexual adults. Selection Criteria: We included peer-reviewed English-language studies that compared cardiovascular disease risk or diagnoses between sexual minority and heterosexual individuals older than 18 years. We excluded reviews, case studies, and gray literature. A total of 31 studies met inclusion criteria. Data Collection and Analysis: At least 2 authors independently abstracted data from each study. We performed quality assessment of retrieved studies using the Crowe Critical Appraisal Tool. Main Results: Sexual minority women exhibited greater cardiovascular disease risk related to tobacco use, alcohol consumption, illicit drug use, poor mental health, and body mass index, whereas sexual minority men experienced excess risk related to tobacco use, illicit drug use, and poor mental health. We identified several limitations in the extant literature. The majority of included studies were cross-sectional analyses that used self-reported measures of cardiovascular disease. Even though we observed elevated cardiovascular disease risk, we found few differences in cardiovascular disease diagnoses (including hypertension, diabetes, and high cholesterol). Overall, 23 of the 26 studies that examined cardiovascular disease diagnoses used subjective measures. Only 7 studies used a combination of biomarkers and self-report measures to establish cardiovascular disease risk and diagnoses. Authors’ Conclusions: Social conditions appear to exert a negative effect on cardiovascular disease risk among sexual minorities. Although we found few differences in cardiovascular disease diagnoses, we identified an elevated risk for cardiovascular disease in both sexual minority men and women. There is a need for research that incorporates subjective and objective measures of cardiovascular disease risk. Public Health Implications: Cardiovascular disease is a major health concern for clinicians, public health practitioners, and policymakers. This systematic review supports the need for culturally appropriate interventions that address cardiovascular disease risk in sexual minority adults. PMID:28207331
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Albagha, Omar M E; Visconti, Micaela Rios; Alonso, Nerea; Wani, Sachin; Goodman, Kirsteen; Fraser, William D; Gennari, Luigi; Merlotti, Daniela; Gianfrancesco, Fernando; Esposito, Teresa; Rendina, Domenico; di Stefano, Marco; Isaia, Giancarlo; Brandi, Maria Luisa; Giusti, Francesca; Del Pino-Montes, Javier; Corral-Gudino, Luis; Gonzalez-Sarmiento, Rogelio; Ward, Lynley; Rea, Sarah L; Ratajczak, Thomas; Walsh, John P; Ralston, Stuart H
2013-11-01
Paget's disease of bone (PDB) has a strong genetic component. Here, we investigated possible associations between genetic variants that predispose to PDB and disease severity. Allelic variants identified as predictors of PDB from genome-wide association studies were analyzed in 1940 PDB patients from the United Kingdom, Italy, Western Australia, and Spain. A cumulative risk allele score was constructed by adding the variants together and relating this to markers of disease severity, alone and in combination with SQSTM1 mutations. In SQSTM1-negative patients, risk allele scores in the highest tertile were associated with a 27% increase in disease extent compared with the lowest tertile (p < 0.00001) with intermediate values in the middle tertile (20% increase; p = 0.0007). The effects were similar for disease severity score, which was 15% (p = 0.01) and 25% (p < 0.00001) higher in the middle and upper tertiles, respectively. Risk allele score remained a significant predictor of extent and severity when SQSTM-positive individuals were included, with an effect size approximately one-third of that observed with SQSTM1 mutations. A genetic risk score was developed by combining information from both markers, which identified subgroups of individuals with low, medium, and high levels of severity with a specificity of 70% and sensitivity of 55%. Risk allele scores and SQSTM1 mutations both predict extent and severity of PDB. It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention. © 2013 American Society for Bone and Mineral Research.
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How long do patients with chronic disease expect to live? A systematic review of the literature
Salem, Joseph
2016-01-01
Objective To systematically identify and summarise the literature on perceived life expectancy among individuals with non-cancer chronic disease. Setting Published and grey literature up to and including September 2016 where adults with non-cancer chronic disease were asked to estimate their own life expectancy. Participants From 6837 screened titles, 9 articles were identified that met prespecified criteria for inclusion. Studies came from the UK, Netherlands and USA. A total of 729 participants were included (heart failure (HF) 573; chronic obstructive pulmonary disease (COPD) 89; end-stage renal failure 62; chronic kidney disease (CKD) 5). No papers reporting on other lung diseases, neurodegenerative disease or cirrhosis were found. Primary and secondary outcome measures All measures of self-estimated life expectancy were accepted. Self-estimated life expectancy was compared, where available, with observed survival, physician-estimated life expectancy and model-estimated life expectancy. Meta-analysis was not conducted due to the heterogeneity of the patient groups and study methodologies. Results Among patients with HF, median self-estimated life expectancy was 40% longer than predicted by a validated model. Outpatients receiving haemodialysis were more optimistic about prognosis than their nephrologists and overestimated their chances of surviving 5 years. Patients with HF and COPD were approximately three times more likely to die in the next year than they predicted. Data available for patients with CKD were of insufficient quality to draw conclusions. Conclusions Individuals with chronic disease may have unrealistically optimistic expectations of their prognosis. More research is needed to understand how perceived life expectancy affects behaviour. Meanwhile, clinicians should attempt to identify each patient's prognostic preferences and provide information in a way that they can understand and use to inform their decisions. Trial registration number CRD42015020732. PMID:28039288
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Schiavo, Renata; Leung, May May; Brown, Mason
2014-01-01
Objective This review aims to identify and assess evidence on interventions to communicate risk and promote disease mitigation measures in epidemics and emerging disease outbreak settings. The study focuses on data that are relevant to low and middle-income country (LMIC) settings. Methods We conducted a comprehensive literature search using five major electronic databases (Pubmed Medline, Biomed Central, EMBASE, Science of Citation Index, and Cochrane Library) and other sources to identify relevant studies published from January 2002 to July 2013. The review was guided by the socio-ecological model/perspective of public health and the ideation theory and focused on interventions at the community, healthcare, and multi-sectoral settings, which also reflect key intervention levels of the Ottawa Charter for Health Promotion. Eligible quantitative studies were selected according to specific study criteria and assessed using the Critical Appraisal Skills Program (CASP) framework. Conversely, qualitative studies, reviews, case studies, and editorials were not included. Studies were selected by two independent reviewers. Results Twenty-nine relevant studies from 16 countries were included. Most studies focused on a single intervention or intervention level, rather than multi-sectoral interventions. The majority of the evidence relates to programs aimed at behavioral and social results (or relevant intermediate steps) within a specific population group. Two studies included implications for improvements in health service delivery, two studies examined the intervention’s impact on health systems-related outcomes, and three had also implications for environmental health outcomes. Cost- and health equity-related implications for select evidence were also discussed. Conclusions The paucity of well-designed quantitative evaluations of interventions to communicate health risk and promote disease control measures in LMICs does not allow for any definitive conclusions. Yet, the review identified several promising interventions and areas for future investigation. Among them, community-based and participatory interventions seemed to be central within epidemic and emerging disease settings, particularly in low-resource settings. Yet, evidence on their effectiveness is not conclusive and needs to be explored by future studies. Other promising areas for future investigation include multi-component and multi-sectoral approaches to intervention design. Major research gaps referred to any evaluation of the impact of these kinds of interventions on health policy adoption and/or implementation, and social determinants of health. Research on cost-effectiveness also needs to be strengthened. This review identified several research gaps and questions, and discusses potential future directions for increasing capacity for future and more rigorous assessments. PMID:24649867
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Schiavo, Renata; May Leung, May; Brown, Mason
2014-03-01
This review aims to identify and assess evidence on interventions to communicate risk and promote disease mitigation measures in epidemics and emerging disease outbreak settings. The study focuses on data that are relevant to low and middle-income country (LMIC) settings. We conducted a comprehensive literature search using five major electronic databases (Pubmed Medline, Biomed Central, EMBASE, Science of Citation Index, and Cochrane Library) and other sources to identify relevant studies published from January 2002 to July 2013. The review was guided by the socio-ecological model/perspective of public health and the ideation theory and focused on interventions at the community, healthcare, and multi-sectoral settings, which also reflect key intervention levels of the Ottawa Charter for Health Promotion. Eligible quantitative studies were selected according to specific study criteria and assessed using the Critical Appraisal Skills Program (CASP) framework. Conversely, qualitative studies, reviews, case studies, and editorials were not included. Studies were selected by two independent reviewers. Twenty-nine relevant studies from 16 countries were included. Most studies focused on a single intervention or intervention level, rather than multi-sectoral interventions. The majority of the evidence relates to programs aimed at behavioral and social results (or relevant intermediate steps) within a specific population group. Two studies included implications for improvements in health service delivery, two studies examined the intervention's impact on health systems-related outcomes, and three had also implications for environmental health outcomes. Cost- and health equity-related implications for select evidence were also discussed. The paucity of well-designed quantitative evaluations of interventions to communicate health risk and promote disease control measures in LMICs does not allow for any definitive conclusions. Yet, the review identified several promising interventions and areas for future investigation. Among them, community-based and participatory interventions seemed to be central within epidemic and emerging disease settings, particularly in low-resource settings. Yet, evidence on their effectiveness is not conclusive and needs to be explored by future studies. Other promising areas for future investigation include multi-component and multi-sectoral approaches to intervention design. Major research gaps referred to any evaluation of the impact of these kinds of interventions on health policy adoption and/or implementation, and social determinants of health. Research on cost-effectiveness also needs to be strengthened. This review identified several research gaps and questions, and discusses potential future directions for increasing capacity for future and more rigorous assessments.
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Lee, Sang E; Casado, Banghwa Lee
2017-01-01
The present study examined the knowledge of Alzheimer's disease and correlates of the disease knowledge among Vietnamese Americans. Cross-sectional survey interviews were conducted with 95 middle-aged and older Vietnamese Americans. Vietnamese Americans showed limited knowledge about Alzheimer's disease. Normalization of Alzheimer's disease in old age was prevalent. They lacked knowledge about treatment and cure of Alzheimer's disease. Those who reside longer in the U.S. and are more exposed to Alzheimer's disease are likely to have higher levels of Alzheimer's disease knowledge. Our study identified current Alzheimer's disease knowledge level and status, and areas of misconceptions and knowledge gaps among Vietnamese Americans, calling for urgent needs for educational outreach to improve knowledge about Alzheimer's disease among Vietnamese Americans. Information about who can be more or less knowledgeable about Alzheimer's disease can be used to strategize and tailor outreach efforts for different segments of the Vietnamese American population.
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Natarajan, Sathishkumar; Kim, Hoy-Taek; Thamilarasan, Senthil Kumar; Veerappan, Karpagam; Park, Jong-In; Nou, Ill-Sup
2016-01-01
Powdery mildew is one of the most common fungal diseases in the world. This disease frequently affects melon (Cucumis melo L.) and other Cucurbitaceous family crops in both open field and greenhouse cultivation. One of the goals of genomics is to identify the polymorphic loci responsible for variation in phenotypic traits. In this study, powdery mildew disease assessment scores were calculated for four melon accessions, 'SCNU1154', 'Edisto47', 'MR-1', and 'PMR5'. To investigate the genetic variation of these accessions, whole genome re-sequencing using the Illumina HiSeq 2000 platform was performed. A total of 754,759,704 quality-filtered reads were generated, with an average of 82.64% coverage relative to the reference genome. Comparisons of the sequences for the melon accessions revealed around 7.4 million single nucleotide polymorphisms (SNPs), 1.9 million InDels, and 182,398 putative structural variations (SVs). Functional enrichment analysis of detected variations classified them into biological process, cellular component and molecular function categories. Further, a disease-associated QTL map was constructed for 390 SNPs and 45 InDels identified as related to defense-response genes. Among them 112 SNPs and 12 InDels were observed in powdery mildew responsive chromosomes. Accordingly, this whole genome re-sequencing study identified SNPs and InDels associated with defense genes that will serve as candidate polymorphisms in the search for sources of resistance against powdery mildew disease and could accelerate marker-assisted breeding in melon.
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DGEM--a microarray gene expression database for primary human disease tissues.
Xia, Yuni; Campen, Andrew; Rigsby, Dan; Guo, Ying; Feng, Xingdong; Su, Eric W; Palakal, Mathew; Li, Shuyu
2007-01-01
Gene expression patterns can reflect gene regulations in human tissues under normal or pathologic conditions. Gene expression profiling data from studies of primary human disease samples are particularly valuable since these studies often span many years in order to collect patient clinical information and achieve a large sample size. Disease-to-Gene Expression Mapper (DGEM) provides a beneficial community resource to access and analyze these data; it currently includes Affymetrix oligonucleotide array datasets for more than 40 human diseases and 1400 samples. The data are normalized to the same scale and stored in a relational database. A statistical-analysis pipeline was implemented to identify genes abnormally expressed in disease tissues or genes whose expressions are associated with clinical parameters such as cancer patient survival. Data-mining results can be queried through a web-based interface at http://dgem.dhcp.iupui.edu/. The query tool enables dynamic generation of graphs and tables that are further linked to major gene and pathway resources that connect the data to relevant biology, including Entrez Gene and Kyoto Encyclopedia of Genes and Genomes (KEGG). In summary, DGEM provides scientists and physicians a valuable tool to study disease mechanisms, to discover potential disease biomarkers for diagnosis and prognosis, and to identify novel gene targets for drug discovery. The source code is freely available for non-profit use, on request to the authors.
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Impact of Ambient Humidity on Child Health: A Systematic Review
Gao, Jinghong; Sun, Yunzong; Lu, Yaogui; Li, Liping
2014-01-01
Background and Objectives Changes in relative humidity, along with other meteorological factors, accompany ongoing climate change and play a significant role in weather-related health outcomes, particularly among children. The purpose of this review is to improve our understanding of the relationship between ambient humidity and child health, and to propose directions for future research. Methods A comprehensive search of electronic databases (PubMed, Medline, Web of Science, ScienceDirect, OvidSP and EBSCO host) and review of reference lists, to supplement relevant studies, were conducted in March 2013. All identified records were selected based on explicit inclusion criteria. We extracted data from the included studies using a pre-designed data extraction form, and then performed a quality assessment. Various heterogeneities precluded a formal quantitative meta-analysis, therefore, evidence was compiled using descriptive summaries. Results Out of a total of 3797 identified records, 37 papers were selected for inclusion in this review. Among the 37 studies, 35% were focused on allergic diseases and 32% on respiratory system diseases. Quality assessment revealed 78% of the studies had reporting quality scores above 70%, and all findings demonstrated that ambient humidity generally plays an important role in the incidence and prevalence of climate-sensitive diseases among children. Conclusions With climate change, there is a significant impact of ambient humidity on child health, especially for climate-sensitive infectious diseases, diarrhoeal diseases, respiratory system diseases, and pediatric allergic diseases. However, some inconsistencies in the direction and magnitude of the effects are observed. PMID:25503413
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Formanowicz, Dorota; Gmerek, Łukasz; Krokowicz, Piotr
2016-01-01
Aim of the work was to review systematically the published literature addressing whether quality of life (QoL) and health-related QoL (HRQoL) are influenced by surgery among patients with inflammatory bowel disease (IBD). Electronic databases and published articles were searched to identify relevant studies published in the years 1990–2015. Then, a multistep selection was undertaken to identify articles that met specific selection criteria, such us specific key-words (IBD, HRQoL, ulcerative colitis (UC), Crohn’s disease (CD), and surgery), and the population was assessed (studies concerning patients < 18 years old were excluded). The review included 27 studies that were evaluated in the context of the influence of surgery on QoL and HRQoL. Concluding, with the increase in the incidence of IBD, monitoring of QoL is an important indicator of the health effects at each stage of the surgical treatment. PMID:28337230
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Molinuevo, José Luis; Gramunt, Nina; Gispert, Juan Domingo; Fauria, Karine; Esteller, Manel; Minguillon, Carolina; Sánchez-Benavides, Gonzalo; Huesa, Gema; Morán, Sebastián; Dal-Ré, Rafael; Camí, Jordi
2016-06-01
The preclinical phase of Alzheimer's disease (AD) is optimal for identifying early pathophysiological events and developing prevention programs, which are shared aims of the ALFA project, including the ALFA registry and parent cohort and the nested ALFA+ cohort study. The ALFA parent cohort baseline visit included full cognitive evaluation, lifestyle habits questionnaires, DNA extraction, and MRI. The nested ALFA+ study adds wet and imaging biomarkers for deeper phenotyping. A total of 2743 participants aged 45 to 74 years were included in the ALFA parent cohort. We show that this cohort, mostly composed of cognitively normal offspring of AD patients, is enriched for AD genetic risk factors. The ALFA project represents a valuable infrastructure that will leverage with different studies and trials to prevent AD. The longitudinal ALFA+ cohort will serve to untangle the natural history of the disease and to model the preclinical stages to develop successful trials.
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Brant, Steven R.; Okou, David T.; Simpson, Claire L.; Cutler, David J.; Haritunians, Talin; Bradfield, Jonathan P.; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W.; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J.; Klapproth, Jan-Micheal A.; Quiros, Antonio J.; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S.; Baldassano, Robert N.; Dudley-Brown, Sharon; Cross, Raymond K.; Dassopoulos, Themistocles; Denson, Lee A.; Dhere, Tanvi A.; Dryden, Gerald W.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Hyams, Jeffrey S.; Isaacs, Kim L.; Kader, Howard; Kappelman, Michael D.; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kwon, John H.; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E.; Newberry, Rodney D.; Osuntokun, Bankole O.; Patel, Ashish S.; Saeed, Shehzad A.; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Hakonarson, Hakon; Zwick, Michael E.; McGovern, Dermot P.B.; Kugathasan, Subra
2016-01-01
Background & Aims The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. Methods We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified [IBD-U]) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in meta-analysis with a nominal evidence (P<.05) in each scan were considered to have genome-wide significance. Results We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance associations for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. Conclusions We performed a genome-wide association study of African Americans with IBD and identified loci associated with CD and UC in only this population; we also replicated loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry. PMID:27693347
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Cura, C I; Lucero, R H; Bisio, M; Oshiro, E; Formichelli, L B; Burgos, J M; Lejona, S; Brusés, B L; Hernández, D O; Severini, G V; Velazquez, E; Duffy, T; Anchart, E; Lattes, R; Altcheh, J; Freilij, H; Diez, M; Nagel, C; Vigliano, C; Favaloro, L; Favaloro, R R; Merino, D E; Sosa-Estani, S; Schijman, A G
2012-04-01
Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.
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Non-Malignant Respiratory Disease Among Workers in Industries Using Styrene—A Review of the Evidence
Nett, Randall J.; Cox-Ganser, Jean M.; Hubbs, Ann F.; Ruder, Avima M.; Cummings, Kristin J.; Huang, Yuh-Chin T.; Kreiss, Kathleen
2017-01-01
Background Asthma and obliterative bronchiolitis (OB) cases have occurred among styrene-exposed workers. We aimed to investigate styrene as a risk factor for non-malignant respiratory disease (NMRD). Methods From a literature review, we identified case reports and assessed cross-sectional and mortality studies for strength of evidence of positive association (i.e., strong, intermediate, suggestive, none) between styrene exposure and NMRD-related morbidity and mortality. Results We analyzed 55 articles and two unpublished case reports. Ten OB cases and eight asthma cases were identified. Six (75%) asthma cases had abnormal styrene inhalation challenges. Thirteen (87%) of 15 cross-sectional studies and 12 (50%) of 24 mortality studies provided at least suggestive evidence that styrene was associated with NMRD-related morbidity or mortality. Six (66%) of nine mortality studies assessing chronic obstructive pulmonary disease-related mortality indicated excess mortality. Conclusions Available evidence suggests styrene exposure is a potential risk factor for NMRD. Additional studies of styrene-exposed workers are warranted. PMID:28079275
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Park, Ji Eun; Park, Bumwoo; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun
2017-01-01
Objective To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Materials and Methods Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Results Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Conclusion Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease. PMID:29089831
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Doss, Jayanth; Mo, Huan; Carroll, Robert J.; Crofford, Leslie J.; Denny, Joshua C.
2016-01-01
Objective The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. Methods A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). We tested EHR-derived phenotypes using PheWAS comparing seropositive RA against seronegative RA, yielding disease associations. PheWAS was also performed on RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed and fibromyalgia was specifically evaluated using a validated algorithm. Results There were 2199 individuals identified with RA and either RF or ACPA testing. Of these, 1382 (63%) were seropositive. Seronegative RA was associated with “Myalgia and Myositis” (odds ratio [OR] 2.1, P=3.7×10−10) and back pain. A manual record review showed 80% of Myalgia and Myositis codes were used for fibromyalgia, and follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR=1.8, P=4.0×10−6). Seropositive RA was associated with Chronic Airway Obstruction (OR=2.2, P=1.4×10−4) and tobacco use (OR=2.2, P=7.0×10−4). Conclusion This PheWAS in RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity with chronic airway obstruction and seropositivity with tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. PMID:27589350
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2012-01-01
Background Genome-wide association studies (GWAS) do not provide a full account of the heritability of genetic diseases since gene-gene interactions, also known as epistasis are not considered in single locus GWAS. To address this problem, a considerable number of methods have been developed for identifying disease-associated gene-gene interactions. However, these methods typically fail to identify interacting markers explaining more of the disease heritability over single locus GWAS, since many of the interactions significant for disease are obscured by uninformative marker interactions e.g., linkage disequilibrium (LD). Results In this study, we present a novel SNP interaction prioritization algorithm, named iLOCi (Interacting Loci). This algorithm accounts for marker dependencies separately in case and control groups. Disease-associated interactions are then prioritized according to a novel ranking score calculated from the difference in marker dependencies for every possible pair between case and control groups. The analysis of a typical GWAS dataset can be completed in less than a day on a standard workstation with parallel processing capability. The proposed framework was validated using simulated data and applied to real GWAS datasets using the Wellcome Trust Case Control Consortium (WTCCC) data. The results from simulated data showed the ability of iLOCi to identify various types of gene-gene interactions, especially for high-order interaction. From the WTCCC data, we found that among the top ranked interacting SNP pairs, several mapped to genes previously known to be associated with disease, and interestingly, other previously unreported genes with biologically related roles. Conclusion iLOCi is a powerful tool for uncovering true disease interacting markers and thus can provide a more complete understanding of the genetic basis underlying complex disease. The program is available for download at http://www4a.biotec.or.th/GI/tools/iloci. PMID:23281813
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Gera, G; Freeman, D L; Blackinton, M T; Horak, F B; King, L
2016-02-01
Balance deficits in people with Parkinson's disease can affect any of the multiple systems encompassing balance control. Thus, identification of the specific deficit is crucial in customizing balance rehabilitation. The sensory organization test, a test of sensory integration for balance control, is sometimes used in isolation to identify balance deficits in people with Parkinson's disease. More recently, the Mini-Balance Evaluations Systems Test, a clinical scale that tests multiple domains of balance control, has begun to be used to assess balance in patients with Parkinson's disease. The purpose of our study was to compare the use of Sensory Organization Test and Mini-Balance Evaluations Systems Test in identifying balance deficits in people with Parkinson's disease. 45 participants (27M, 18F; 65.2 ± 8.2 years) with idiopathic Parkinson's disease participated in the cross-sectional study. Balance assessment was performed using the Sensory Organization Test and the Mini-Balance Evaluations Systems Test. People were classified into normal and abnormal balance based on the established cutoff scores (normal balance: Sensory Organization Test >69; Mini-Balance Evaluations Systems Test >73). More subjects were classified as having abnormal balance with the Mini-Balance Evaluations Systems Test (71% abnormal) than with the Sensory Organization Test (24% abnormal) in our cohort of people with Parkinson's disease. There were no subjects with a normal Mini-Balance Evaluations Systems Test score but abnormal Sensory Organization Test score. In contrast, there were 21 subjects who had an abnormal Mini-Balance Evaluations Systems Test score but normal Sensory Organization Test scores. Findings from this study suggest that investigation of sensory integration deficits, alone, may not be able to identify all types of balance deficits found in patients with Parkinson's disease. Thus, a comprehensive approach should be used to test of multiple balance systems to provide customized rehabilitation.
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Combining medical informatics and bioinformatics toward tools for personalized medicine.
Sarachan, B D; Simmons, M K; Subramanian, P; Temkin, J M
2003-01-01
Key bioinformatics and medical informatics research areas need to be identified to advance knowledge and understanding of disease risk factors and molecular disease pathology in the 21 st century toward new diagnoses, prognoses, and treatments. Three high-impact informatics areas are identified: predictive medicine (to identify significant correlations within clinical data using statistical and artificial intelligence methods), along with pathway informatics and cellular simulations (that combine biological knowledge with advanced informatics to elucidate molecular disease pathology). Initial predictive models have been developed for a pilot study in Huntington's disease. An initial bioinformatics platform has been developed for the reconstruction and analysis of pathways, and work has begun on pathway simulation. A bioinformatics research program has been established at GE Global Research Center as an important technology toward next generation medical diagnostics. We anticipate that 21 st century medical research will be a combination of informatics tools with traditional biology wet lab research, and that this will translate to increased use of informatics techniques in the clinic.
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Assessment of Parkinson’s disease risk loci in Greece
Kara, Eleanna; Xiromerisiou, Georgia; Spanaki, Cleanthe; Bozi, Maria; Koutsis, Georgios; Panas, Marios; Dardiotis, Efthimios; Ralli, Styliani; Bras, Jose; Letson, Christopher; Edsall, Connor; Pliner, Hannah; Arepali, Sampath; Kalinderi, Kallirhoe; Fidani, Liana; Bostanjopoulou, Sevasti; Keller, Margaux F; Wood, Nicholas W; Hardy, John; Houlden, Henry; Stefanis, Leonidas; Plaitakis, Andreas; Hernandez, Dena; Hadjigeorgiou, Georgios M; Nalls, Mike A; Singleton, Andrew B
2013-01-01
Genome wide association studies (GWAS) have been shown to be a powerful approach to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson’s disease (PD) have been successful in identifying numerous risk variants pointing to novel pathways potentially implicated in the pathogenesis of PD. Contributing to these GWAS efforts, we performed genotyping of previously identified risk alleles in PD patients and controls from Greece. We showed that previously published risk profiles for Northern European and American populations are also applicable to the Greek population. In addition, while we were largely underpowered to detect individual associations we replicated 5 of 32 previously published risk variants with nominal p-values <0.05. Genome-wide complex trait analysis (GCTA) revealed that known risk loci explain disease risk in 1.27% of Greek PD patients. Collectively, these results indicate that there is likely a substantial genetic component to PD in Greece similarly to other worldwide populations that remains to be discovered. PMID:24080174
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Ng, Siew C; Shi, Hai Yun; Hamidi, Nima; Underwood, Fox E; Tang, Whitney; Benchimol, Eric I; Panaccione, Remo; Ghosh, Subrata; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y; Kaplan, Gilaad G
2018-12-23
Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world. We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We created choropleth maps for the incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI. We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% [95% CI 4·8-17·8] and APC for ulcerative colitis +14·9% [10·4-19·6]) and Taiwan (APC for Crohn's disease +4·0% [1·0-7·1] and APC for ulcerative colitis +4·8% [1·8-8·0]). At the turn of the 21st century, inflammatory bowel disease has become a global disease with accelerating incidence in newly industrialised countries whose societies have become more westernised. Although incidence is stabilising in western countries, burden remains high as prevalence surpasses 0·3%. These data highlight the need for research into prevention of inflammatory bowel disease and innovations in health-care systems to manage this complex and costly disease. None. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Pernat Drobež, Cvetka; Ferkolj, Ivan; Potočnik, Uroš; Repnik, Katja
2018-03-01
Crohn's disease (CD) patients are mostly diagnosed with the uncomplicated inflammatory form of disease; however, the majority will progress to complicated stricturing or penetrating disease over time. It is important to identify patients at risk for disease progression at an early stage. The aim of our study was to examine the role of 33 candidate CD genes as possible predictors of disease progression and their influence on time to progression from an inflammatory to a stricturing or penetrating phenotype. Patients with an inflammatory phenotype at diagnosis were followed for 10 years and 33 CD-associated polymorphisms were genotyped. To test for association with CD, 449 healthy individuals were analyzed as the control group. Ten years after diagnosis, 39.1% of patients had not progressed beyond an inflammatory phenotype, but 60.9% had progressed to complicated disease, with average time to progression being 5.91 years. Association analyses of selected single nucleotide polymorphisms (SNPs) confirmed associations with CD for 12 SNPs. Furthermore, seven loci were associated with disease progression, out of which SNP rs4263839 in the gene TNFSF15 showed the strongest association with disease progression and the frameshift mutation rs2066847 in the gene NOD2 showed the strongest association with time to progression. The results of our study identified specific genetic biomarkers as useful predictors of both disease progression and speed of disease progression in patients with CD.
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A 5-Year Follow-up Study on the Relationship between Obstructive Sleep Apnea and Parkinson Disease.
Sheu, Jau-Jiuan; Lee, Hsin-Chien; Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong
2015-12-15
Sleep disturbances are among the most common nonmotor symptoms of Parkinson disease. However, no large epidemiological data regarding the association between obstructive sleep apnea (OSA) and Parkinson disease have been reported. The goal of this study was to investigate the risk for Parkinson disease during a 5-y follow-up period after a diagnosis of OSA using a population-based dataset. The data for this retrospective longitudinal cohort study were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We identified 1,532 patients with OSA as the study cohort and randomly selected 7,660 patients as the comparison cohort. Each subject was individually followed up for a 5-y period to identify those in whom Parkinson disease subsequently developed. Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-y risk of subsequent Parkinson disease between the study cohort and comparison cohort. Of the 9,192 total patients, Parkinson disease developed in 0.73% during the 5-y follow-up period: 1.24% and 0.63% in the OSA and control cohorts, respectively. After censoring patients who died during the follow-up period and adjusting for socio-demographic characteristics, the hazard ratio (HR) of Parkinson disease during the 5-y follow-up period for patients with OSA was 2.26 (95% confidence interval [CI] = 1.32-3.88) compared with comparison patients. In addition, among females, the adjusted HR of Parkinson disease was 3.54 (95% CI = 1.50-8.34) for patients with OSA compared to patients without OSA. However, among males, there was no significantly increased hazard of Parkinson disease for patients with OSA compared to those without OSA. Female patients with OSA were found to be at a significant risk of subsequent Parkinson disease during a 5-y follow-up period. © 2015 American Academy of Sleep Medicine.
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Wagner, T.; Benbow, M.E.; Brenden, T.O.; Qi, J.; Johnson, R.C.
2008-01-01
Background: Buruli ulcer (BU) disease, caused by infection with the environmental mycobacterium M. ulcerans, is an emerging infectious disease in many tropical and sub-tropical countries. Although vectors and modes of transmission remain unknown, it is hypothesized that the transmission of BU disease is associated with human activities in or around aquatic environments, and that characteristics of the landscape (e.g., land use/cover) play a role in mediating BU disease. Several studies performed at relatively small spatial scales (e.g., within a single village or region of a country) support these hypotheses; however, if BU disease is associated with land use/cover characteristics, either through spatial constraints on vector-host dynamics or by mediating human activities, then large-scale (i.e., country-wide) associations should also emerge. The objectives of this study were to (1) investigate associations between BU disease prevalence in villages in Benin, West Africa and surrounding land use/cover patterns and other map-based characteristics, and (2) identify areas with greater and lower than expected prevalence rates (i.e., disease clusters) to assist with the development of prevention and control programs. Results: Our landscape-based models identified low elevation, rural villages surrounded by forest land cover, and located in drainage basins with variable wetness patterns as being associated with higher BU disease prevalence rates. We also identified five spatial disease clusters. Three of the five clusters contained villages with greater than expected prevalence rates and two clusters contained villages with lower than expected prevalence rates. Those villages with greater than expected BU disease prevalence rates spanned a fairly narrow region of south-central Benin. Conclusion: Our analyses suggest that interactions between natural land cover and human alterations to the landscape likely play a role in the dynamics of BU disease. For example, urbanization, potentially by providing access to protected water sources, may reduce the likelihood of becoming infected with BU disease. Villages located at low elevations may have higher BU disease prevalence rates due to their close spatial proximity to high risk environments. In addition, forest land cover and drainage basins with variable wetness patterns may be important for providing suitable growth conditions for M. ulcerans, influencing the distribution and abundance of vectors, or mediating vector-human interactions. The identification of disease clusters in this study provides direction for future research aimed at better understanding these and other environmental and social determinants involved in BU disease outbreaks. ?? 2008 Wagner et al; licensee BioMed Central Ltd.
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Wagner, Tyler; Benbow, M Eric; Brenden, Travis O; Qi, Jiaguo; Johnson, R Christian
2008-01-01
Background Buruli ulcer (BU) disease, caused by infection with the environmental mycobacterium M. ulcerans, is an emerging infectious disease in many tropical and sub-tropical countries. Although vectors and modes of transmission remain unknown, it is hypothesized that the transmission of BU disease is associated with human activities in or around aquatic environments, and that characteristics of the landscape (e.g., land use/cover) play a role in mediating BU disease. Several studies performed at relatively small spatial scales (e.g., within a single village or region of a country) support these hypotheses; however, if BU disease is associated with land use/cover characteristics, either through spatial constraints on vector-host dynamics or by mediating human activities, then large-scale (i.e., country-wide) associations should also emerge. The objectives of this study were to (1) investigate associations between BU disease prevalence in villages in Benin, West Africa and surrounding land use/cover patterns and other map-based characteristics, and (2) identify areas with greater and lower than expected prevalence rates (i.e., disease clusters) to assist with the development of prevention and control programs. Results Our landscape-based models identified low elevation, rural villages surrounded by forest land cover, and located in drainage basins with variable wetness patterns as being associated with higher BU disease prevalence rates. We also identified five spatial disease clusters. Three of the five clusters contained villages with greater than expected prevalence rates and two clusters contained villages with lower than expected prevalence rates. Those villages with greater than expected BU disease prevalence rates spanned a fairly narrow region of south-central Benin. Conclusion Our analyses suggest that interactions between natural land cover and human alterations to the landscape likely play a role in the dynamics of BU disease. For example, urbanization, potentially by providing access to protected water sources, may reduce the likelihood of becoming infected with BU disease. Villages located at low elevations may have higher BU disease prevalence rates due to their close spatial proximity to high risk environments. In addition, forest land cover and drainage basins with variable wetness patterns may be important for providing suitable growth conditions for M. ulcerans, influencing the distribution and abundance of vectors, or mediating vector-human interactions. The identification of disease clusters in this study provides direction for future research aimed at better understanding these and other environmental and social determinants involved in BU disease outbreaks. PMID:18505567
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In Silico Gene Prioritization by Integrating Multiple Data Sources
Zhou, Yingyao; Shields, Robert; Chanda, Sumit K.; Elston, Robert C.; Li, Jing
2011-01-01
Identifying disease genes is crucial to the understanding of disease pathogenesis, and to the improvement of disease diagnosis and treatment. In recent years, many researchers have proposed approaches to prioritize candidate genes by considering the relationship of candidate genes and existing known disease genes, reflected in other data sources. In this paper, we propose an expandable framework for gene prioritization that can integrate multiple heterogeneous data sources by taking advantage of a unified graphic representation. Gene-gene relationships and gene-disease relationships are then defined based on the overall topology of each network using a diffusion kernel measure. These relationship measures are in turn normalized to derive an overall measure across all networks, which is utilized to rank all candidate genes. Based on the informativeness of available data sources with respect to each specific disease, we also propose an adaptive threshold score to select a small subset of candidate genes for further validation studies. We performed large scale cross-validation analysis on 110 disease families using three data sources. Results have shown that our approach consistently outperforms other two state of the art programs. A case study using Parkinson disease (PD) has identified four candidate genes (UBB, SEPT5, GPR37 and TH) that ranked higher than our adaptive threshold, all of which are involved in the PD pathway. In particular, a very recent study has observed a deletion of TH in a patient with PD, which supports the importance of the TH gene in PD pathogenesis. A web tool has been implemented to assist scientists in their genetic studies. PMID:21731658
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Li, Chunquan; Han, Junwei; Yao, Qianlan; Zou, Chendan; Xu, Yanjun; Zhang, Chunlong; Shang, Desi; Zhou, Lingyun; Zou, Chaoxia; Sun, Zeguo; Li, Jing; Zhang, Yunpeng; Yang, Haixiu; Gao, Xu; Li, Xia
2013-05-01
Various 'omics' technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.
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Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse; Barber, Robert; Beecham, Gary W; Bennett, David A; Buxbaum, Joseph D; Byrd, Goldie S; Carrasquillo, Minerva M; Crane, Paul K; Cruchaga, Carlos; De Jager, Philip; Ertekin-Taner, Nilufer; Evans, Denis; Fallin, M Danielle; Foroud, Tatiana M; Friedland, Robert P; Goate, Alison M; Graff-Radford, Neill R; Hendrie, Hugh; Hall, Kathleen S; Hamilton-Nelson, Kara L; Inzelberg, Rivka; Kamboh, M Ilyas; Kauwe, John S K; Kukull, Walter A; Kunkle, Brian W; Kuwano, Ryozo; Larson, Eric B; Logue, Mark W; Manly, Jennifer J; Martin, Eden R; Montine, Thomas J; Mukherjee, Shubhabrata; Naj, Adam; Reiman, Eric M; Reitz, Christiane; Sherva, Richard; St George-Hyslop, Peter H; Thornton, Timothy; Younkin, Steven G; Vardarajan, Badri N; Wang, Li-San; Wendlund, Jens R; Winslow, Ashley R; Haines, Jonathan; Mayeux, Richard; Pericak-Vance, Margaret A; Schellenberg, Gerard; Lunetta, Kathryn L; Farrer, Lindsay A
2017-07-01
Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10 -8 ) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10 -6 ) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10 -6 ). Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1986 Annual Report.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kaattari, Stephen L.
1987-06-01
Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon of the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon of Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem,and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activatemore » the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's third year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various chemical conjugates of Renibacterium salmoninarum cells and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (cellular proliferation), and the kinetics of mortality after Lethal injections of the bacterium. An important facet of this research is the identification and isolation of virulence factors. These studies are not only important to the dissection of the mechanism of pathogenesis of bacterial kidney disease, but the purification of such a factor(s) will insure the production of a more potent vaccine. The studies completed this year have: (1) identified antigenic material which protect; (2) identified antigenic material which can exacerbate the disease; (3) identified a possibly major mechanism of pathogenesis via the interference with antibody; (4) the general ability to produce delineated a western blot technique for identification of infected fish; (5) described the use of monoclonal antibodies for antigenic analysis; and (6) identified an unusual and dramatic effect of R. salmoninarum cells on phagocytic function.« less
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[Severity assessment strategies based on administrative data using stroke as an example].
Schubert, Ingrid; Hammer, Antje; Köster, Ingrid
2017-10-01
Information on disease severity is relevant for many studies with claims data in health service research, but only limited information is available in routine data. Stroke serves as an example to analyse whether the combination of different information in claims data can provide insight into the severity of a disease. As a first step, a literature search was conducted. Strategies to assess the severity of a disease by means of routine data were examined with regard to approval and applicability to German sickness fund data. In order to apply and extend the identified procedures, the statutory health insurance sample AOK Hessen/KV Hessen (VSH) served as data source. It is an 18.75 % random sample of persons insured by the AOK Hessen, with 2013 being the most recent year. Stroke patients were identified by the ICD-10 GM code I63 and I64. Patients with said diagnoses being coded as a hospital discharge diagnosis in 2012 were included due to an acute event in 2012 (n=944). The follow-up time was one year. Ten studies covering seven different methods to assess stroke severity were identified. Codes for coma (4.2 % of stroke patients in the SHI sample) as well as coma and/or the application of a PEG tube (9.8 % of the stroke patients) were applied as a proxy for disease severity of acute cases. Taking age, sex and comorbidity into consideration, patients in a coma show a significantly increased risk of mortality compared to those without coma. Three operationalisations were chosen as possible proxies for disease severity of stroke in the further course of disease: i) sequelae (hemiplegia, neurological neglect), ii) duration of the index inpatient stay, and iii) nursing care/ care level 3 for the first time after stroke. The latter proxy has the highest explanatory value for SHI costs. The studies identified use many variables mainly based on hospital information in order to describe disease severity. With the exception of coma, these proxies were neither validated nor did the authors provide more detailed grounds for their use. An identified score for stroke severity could not be applied to SHI data. To develop a comparable score requires a linkage of clinical and administrative data. Since routine data include information from all sectors of care, it should be explored whether these data (for example, the patients' care needs) are suitable to assess disease severity. For validation, separate databases and, optimally, primary patient data are necessary. Copyright © 2017. Published by Elsevier GmbH.
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Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis
Newaz, Khalique; Sriram, K.; Bera, Debajyoti
2015-01-01
Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC) to protease-resistant isofrom (rPrPSc). Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are) the prime network pathway(s) that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes) potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs) of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that these immunological pathways occupy influential positions in the PFNs (protein functional networks) that are related to prion disease. Importantly, this functional network involvement is prevalent in all the five different mouse strain-prion strain combinations that we studied. We also conclude that the dysregulation of the core elements of the bow-tie structure, which belongs to PI3K-Akt signaling pathway, leads to dysregulation of the downstream components corresponding to other biological pathways. PMID:26646948
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Personalized Medicine and Infectious Disease Management.
Jensen, Slade O; van Hal, Sebastiaan J
2017-11-01
A recent study identified pathogen factors associated with an increased mortality risk in Staphylococcus aureus bacteremia, using predictive modelling and a combination of genotypic, phenotypic, and clinical data. This study conceptually validates the benefit of personalized medicine and highlights the potential use of whole genome sequencing in infectious disease management. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Karyadi, Danielle M; Geybels, Milan S; Karlins, Eric; Decker, Brennan; McIntosh, Laura; Hutchinson, Amy; Kolb, Suzanne; McDonnell, Shannon K; Hicks, Belynda; Middha, Sumit; FitzGerald, Liesel M; DeRycke, Melissa S; Yeager, Meredith; Schaid, Daniel J; Chanock, Stephen J; Thibodeau, Stephen N; Berndt, Sonja I; Stanford, Janet L; Ostrander, Elaine A
2017-01-03
Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men. In an independent nested case-control study of 7,121 men, there was risk association evidence for TANGO2 p.Ser17Ter and the established HOXB13 p.Gly84Glu variant. Meta-analysis combining the case-control studies identified two additional variants suggestively associated with risk, OR5H14 p.Met59Val and CHAD p.Ala342Asp. The TANGO2 and HOXB13 variants co-occurred in cases more often than expected by chance and never in controls. Finally, TANGO2 p.Ser17Ter was associated with aggressive disease in both case-control studies separately. Our analyses identified three new PCa susceptibility alleles in the TANGO2, OR5H14 and CHAD genes that not only segregate in multiple high-risk families but are also of importance in altering disease risk for men from the general population. This is the first successful study to utilize sequencing in high-risk families for the express purpose of identifying low-frequency, moderately penetrant PCa risk mutations.
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Rochon, Paula A.; Mashari, Azad; Cohen, Ariel; Misra, Anjali; Laxer, Dara; Streiner, David L.; Dergal, Julie M.; Clark, Jocalyn P.; Gold, Jennifer; Binns, Malcolm A.
2004-01-01
Background More than two-thirds of the world's population live in low-income countries, where health priorities are different from those of people living in more affluent parts of the world. We evaluated the relation between the global burden of disease and conditions or diseases studied in randomized controlled trials (RCTs) published in general medical journals. Methods A MEDLINE search identified 373 RCTs that had been published in 6 international peer-reviewed general medical journals in 1999. Manual review excluded non-RCTs, brief reports and trials in which the unit of randomization was not the patient; 286 RCTs remained eligible for analysis. We identified the RCTs that studied any of the 40 leading causes of the global burden of disease. Five of these conditions were considered unsuitable for study with an RCT design and were excluded from subsequent analysis. To provide a practical perspective, we asked 12 experts working with international health organizations to rate the relevance to global health of the articles that studied any of the top 10 causes of the global burden of disease, as measured by disability-adjusted life years (DALYs) and mortality, using a 5-point Likert scale. Results Among the 286 RCTs in our sample, 124 (43.4%) addressed 1 of the 35 leading causes of the global burden of disease. Of these, ischemic heart disease, HIV/AIDS and cerebrovascular disease were the most commonly studied conditions. Ninety articles (31.5%) studied 1 of the top 10 causes of the global burden of disease. The mean rating (and standard deviation) for international health relevance assigned by experts was 2.6 (1.5) out of 5. Only 14 (16%) of the 90 trials received a rating of 4 or greater, indicating high relevance to international health. Almost half of the 40 leading causes of the global burden of disease were not studied by any trial. Interpretation Many conditions or diseases common internationally are underrepresented in RCTs published in leading general medical journals. Trials published in these journals that studied one of these high-priority conditions were generally rated as being of little relevance to international health. PMID:15159365
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Phosphoproteins in extracellular vesicles as candidate markers for breast cancer
Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih; Paez, Juan Sebastian Paez; Pan, Li; Andaluz, Hillary; Wendt, Michael K.; Iliuk, Anton B.; Tao, W. Andy
2017-01-01
The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring. PMID:28270605
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Phosphoproteins in extracellular vesicles as candidate markers for breast cancer.
Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih; Paez, Juan Sebastian Paez; Pan, Li; Andaluz, Hillary; Wendt, Michael K; Iliuk, Anton B; Zhu, Jian-Kang; Tao, W Andy
2017-03-21
The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.
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TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia.
Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Dayan, Sarah; Godard, Chloé; Van Bortel, Inge; De Septenville, Anne; Ciura, Sorana; Brice, Alexis; Kabashi, Edor
2013-10-01
Homozygous mutations in TREM2 have been recently identified by exome sequencing in families presenting with frontotemporal dementia (FTD)-like phenotype. No study has evaluated the exact frequency of TREM2 mutations in cohorts of FTD patients so far. We sequenced TREM2 in 175 patients with pure FTD, mostly French, to test whether mutations could be implicated in the pathogenesis of the disease. No disease-causing mutation was identified in 175 individuals from the French cohort of FTD patients. We did not identify the polymorphism p.R47H (rs75932628), strongly associated with an increased risk of developing Alzheimer's disease. We conclude that TREM2 mutations are extremely rare in patients with pure FTD, although further investigation in larger populations is needed. Copyright © 2013 Elsevier Inc. All rights reserved.
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Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses.
Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Evangelou, Evangelos; Ioannidis, John P A
2016-02-01
Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats. Copyright © 2016. Published by Elsevier Ltd.
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Seasonal temperature is associated with Parkinson's disease prescriptions: an ecological study
NASA Astrophysics Data System (ADS)
Rowell, David; Nghiem, Son; Ramagopalan, Sreeram; Meier, Ute-Christiane
2017-12-01
The aim of this study is to test what effect the weather may have on medications prescribed to treat Parkinson's disease. Twenty-three years of monthly time, series data was sourced from the Pharmaceutical Benefits Scheme (PBS) and the Bureau of Meteorology (BOM). Data were available for eight states and territories and their corresponding capital cities. The dependent variable was the aggregate levodopa equivalent dose (LED) for 51 Parkinson's medications identified on the PBS. Two explanatory variables of interest, temperature and solar exposure, were identified in the BOM data set. Linear and cosinor models were estimated with fixed and random effects, respectively. The prescribed LED was 4.2% greater in January and 4.5% lower in July. Statistical analysis showed that temperature was associated with the prescription of Parkinson medications. Our results suggest seasonality exists in Parkinson's disease symptoms and this may be related to temperature. Further work is needed to confirm these findings and understand the underlying mechanisms as a better understanding of the causes of any seasonal variation in Parkinson's disease may help clinicians and patients manage the disease more effectively.
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Using ontology-based annotation to profile disease research
Coulet, Adrien; LePendu, Paea; Shah, Nigam H
2012-01-01
Background Profiling the allocation and trend of research activity is of interest to funding agencies, administrators, and researchers. However, the lack of a common classification system hinders the comprehensive and systematic profiling of research activities. This study introduces ontology-based annotation as a method to overcome this difficulty. Analyzing over a decade of funding data and publication data, the trends of disease research are profiled across topics, across institutions, and over time. Results This study introduces and explores the notions of research sponsorship and allocation and shows that leaders of research activity can be identified within specific disease areas of interest, such as those with high mortality or high sponsorship. The funding profiles of disease topics readily cluster themselves in agreement with the ontology hierarchy and closely mirror the funding agency priorities. Finally, four temporal trends are identified among research topics. Conclusions This work utilizes disease ontology (DO)-based annotation to profile effectively the landscape of biomedical research activity. By using DO in this manner a use-case driven mechanism is also proposed to evaluate the utility of classification hierarchies. PMID:22494789
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Baron, Morgane; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne; Simionescu, M
2012-01-01
Abstract Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression. PMID:22050954
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USDA-ARS?s Scientific Manuscript database
Mango malformation disease (MMD) has become an important global disease affecting this crop. The aim of this study was to identify the main causal agents of MMD in the Axarquía region of southern Spain and determine their genetic diversity. Fusarium mangiferae was previously described in the Axarquí...
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Differential replication of foot-and-mouth disease viruses in mice determine lethality
USDA-ARS?s Scientific Manuscript database
Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...
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Irina Ćalić; Jennifer Koch; David Carey; Charles Addo-Quaye; John E. Carlson; David B. Neale
2017-01-01
Background: The American Beech tree (Fagus grandifolia Ehrh.), native to eastern North America, is ecologically important and provides high quality wood products. This species is susceptible to beech bark disease (BBD) and is facing high rates of mortality in North America. The disease occurs from an interaction between the woolly beech scale...
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Determinants of initiation and progression of idiopathic pulmonary fibrosis
Kottmann, Robert Matthew; Hogan, Christopher M.; Phipps, Richard P.; Sime, Patricia J.
2013-01-01
IPF is a devastating disease with few therapeutic options. The precise aetiology of IPF remains elusive. However, our understanding of the pathologic processes involved in the initiation and progression of this disease is improving. Data on the mechanisms underlying IPF have been generated from epidemiologic investigations as well as cellular and molecular studies of human tissues. Although no perfect animal model of human IPF exists, pre-clinical animal studies have helped define pathways which are likely important in human disease. Epithelial injury, fibroblast activation and repetitive cycles of injury and abnormal repair are almost certainly key events. Factors which have been associated with initiation and/or progression of IPF include viral infections, abnormal cytokine, chemokine and growth factor production, oxidant stress, autoimmunity, inhalational of toxicants and gastro-oesophageal reflux disease. Furthermore, recent evidence identifies a role for a variety of genetic and epigenetic abnormalities ranging from mutations in surfactant protein C to abnormalities in telomere length and telomerase activity. The challenge remains to identify additional inciting agents and key dysregulated pathways that lead to disease progression so that we can develop targeted therapies to treat or prevent this serious disease. PMID:19740254
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Current thoughts on maternal nutrition and fetal programming of the metabolic syndrome.
Brenseke, Bonnie; Prater, M Renee; Bahamonde, Javiera; Gutierrez, J Claudio
2013-01-01
Chronic diseases such as type 2 diabetes and cardiovascular disease are the leading cause of death and disability worldwide. Although the metabolic syndrome has been defined in various ways, the ultimate importance of recognizing this combination of disorders is that it helps identify individuals at high risk for both type 2 diabetes and cardiovascular disease. Evidence from observational and experimental studies links adverse exposures in early life, particularly relating to nutrition, to chronic disease susceptibility in adulthood. Such studies provide the foundation and framework for the relatively new field of developmental origins of health and disease (DOHaD). Although great strides have been made in identifying the putative concepts and mechanisms relating specific exposures in early life to the risk of developing chronic diseases in adulthood, a complete picture remains obscure. To date, the main focus of the field has been on perinatal undernutrition and specific nutrient deficiencies; however, the current global health crisis of overweight and obesity demands that perinatal overnutrition and specific nutrient excesses be examined. This paper assembles current thoughts on the concepts and mechanisms behind the DOHaD as they relate to maternal nutrition, and highlights specific contributions made by macro- and micronutrients.
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Hayasaka, Daisuke; Nishi, Kodai; Fuchigami, Takeshi; Shiogama, Kazuya; Onouchi, Takanori; Shimada, Satoshi; Tsutsumi, Yutaka; Morita, Kouichi
2016-01-05
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that causes fever, enteritis, thrombocytopenia, and leucopenia and can be fatal in up to 30% of cases. However, the mechanism of severe disease is not fully understood. Molecular imaging approaches, such as positron-emission tomography (PET), are functional in vivo imaging techniques that provide real-time dynamics of disease progression, assessments of pharmacokinetics, and diagnoses for disease progression. Molecular imaging also potentially provides useful approaches to explore the pathogenesis of viral infections. Thus, the purpose of this study was to image the pathological features of SFTSV infection in vivo by PET imaging. In a mouse model, we showed that 18F-FDG accumulations clearly identified the intestinal tract site as a pathological site. We also demonstrated that 18F-FDG PET imaging can assess disease progression and response to antiserum therapy within the same individual. This is the first report demonstrating a molecular imaging strategy for SFTSV infection. Our results provide potentially useful information for preclinical studies such as the elucidation of the mechanism of SFTSV infection in vivo and the assessment of drugs for SFTS treatment.
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Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.
Simpson, Siobhan; Dunning, Mark D; Brownlie, Serena; Patel, Janika; Godden, Megan; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S
2016-01-01
Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.
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Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy
Dunning, Mark D.; Brownlie, Serena
2016-01-01
Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH. PMID:28070514
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Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M
2017-06-01
Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.
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Hyperbaric oxygen treatment for inflammatory bowel disease: a systematic review and analysis
2012-01-01
Background Traditionally, hyperbaric oxygen treatment (HBOT) has been used to treat a limited repertoire of disease, including decompression sickness and healing of problem wounds. However, some investigators have used HBOT to treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Methods Comprehensive searches were conducted in 8 scientific databases through 2011 to identify publications using HBOT in IBD. Human studies and animal models were collated separately. Results Thirteen studies of HBOT in Crohn's disease and 6 studies in ulcerative colitis were identified. In all studies, participants had severe disease refractory to standard medical treatments, including corticosteroids, immunomodulators and anti-inflammatory medications. In patients with Crohn's disease, 31/40 (78%) had clinical improvements with HBOT, while all 39 patients with ulcerative colitis improved. One study in Crohn's disease reported a significant decrease in proinflammatory cytokines (IL-1, IL-6 and TNF-alpha) and one study in ulcerative colitis reported a decrease in IL-6 with HBOT. Adverse events were minimal. Twelve publications reported using HBOT in animal models of experimentally-induced IBD, including several studies reporting decreased markers of inflammation or immune dysregulation, including TNF-alpha (3 studies), IL-1beta (2 studies), neopterin (1 study) and myeloperoxidase activity (5 studies). HBOT also decreased oxidative stress markers including malondialdehyde (3 studies) and plasma carbonyl content (2 studies), except for one study that reported increased plasma carbonyl content. Several studies reported HBOT lowered nitric oxide (3 studies) and nitric oxide synthase (3 studies) and one study reported a decrease in prostaglandin E2 levels. Four animal studies reported decreased edema or colonic tissue weight with HBOT, and 8 studies reported microscopic improvements on histopathological examination. Although most publications reported improvements with HBOT, some studies suffered from limitations, including possible publication and referral biases, the lack of a control group, the retrospective nature and a small number of participants. Conclusions HBOT lowered markers of inflammation and oxidative stress and ameliorated IBD in both human and animal studies. Most treated patients were refractory to standard medical treatments. Additional studies are warranted to investigate the effects of HBOT on biomarkers of oxidative stress and inflammation as well as clinical outcomes in individuals with IBD. PMID:22417628
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Genetic polymorphisms in lung disease: bandwagon or breakthrough?
Iannuzzi, Michael C; Maliarik, Mary; Rybicki, Benjamin
2002-01-01
The study of genetic polymorphisms has touched every aspect of pulmonary and critical care medicine. We review recent progress made using genetic polymorphisms to define pathophysiology, to identify persons at risk for pulmonary disease and to predict treatment response. Several pitfalls are commonly encountered in studying genetic polymorphisms, and this article points out criteria that should be applied to design high-quality genetic polymorphism studies. PMID:11980584
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Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon
2018-01-01
Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.
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Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo
2018-01-01
Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis. PMID:29765977
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Diverticular disease of the right colon.
Radhi, Jasim M; Ramsay, Jennifer A; Boutross-Tadross, Odette
2011-10-06
The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. Single true diverticular disease of the right colon is usually of congenital type and affects younger age group and may be associated with angiodysplasia in some cases. Multiple false diverticuli are more seen in association with caecal carcinoma or large adenomas. These are usually asymptomatic and are more seen in older patients. However this study dose not reflects the true incidence of the disease in the general population.
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Hongoh, Valerie; Gosselin, Pierre; Michel, Pascal; Ravel, André; Waaub, Jean-Philippe; Campagna, Céline; Samoura, Karim
2017-01-01
Prioritizing resources for optimal responses to an ever growing list of existing and emerging infectious diseases represents an important challenge to public health. In the context of climate change, there is increasing anticipated variability in the occurrence of infectious diseases, notably climate-sensitive vector-borne diseases. An essential step in prioritizing efforts is to identify what considerations and concerns to take into account to guide decisions and thus set disease priorities. This study was designed to perform a comprehensive review of criteria for vector-borne disease prioritization, assess their applicability in a context of climate change with a diverse cross-section of stakeholders in order to produce a baseline list of considerations to use in this decision-making context. Differences in stakeholder choices were examined with regards to prioritization of these criteria for research, surveillance and disease prevention and control objectives. A preliminary list of criteria was identified following a review of the literature. Discussions with stakeholders were held to consolidate and validate this list of criteria and examine their effects on disease prioritization. After this validation phase, a total of 21 criteria were retained. A pilot vector-borne disease prioritization exercise was conducted using PROMETHEE to examine the effects of the retained criteria on prioritization in different intervention domains. Overall, concerns expressed by stakeholders for prioritization were well aligned with categories of criteria identified in previous prioritization studies. Weighting by category was consistent between stakeholders overall, though some significant differences were found between public health and non-public health stakeholders. From this exercise, a general model for climate-sensitive vector-borne disease prioritization has been developed that can be used as a starting point for further public health prioritization exercises relating to research, surveillance, and prevention and control interventions in a context of climate change. Multi-stakeholder engagement in prioritization can help broaden the range of criteria taken into account, offer opportunities for early identification of potential challenges and may facilitate acceptability of any resulting decisions.
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Solid, Craig A; Peter, Senaka A; Natwick, Tanya; Guo, Haifeng; Collins, Allan J; Arduino, Jean Marie
2017-01-01
Few studies explore the magnitude of the disease burden and health care utilization imposed by renal disease among patients with hepatitis C virus (HCV). We aimed to describe the characteristics, outcomes, and health care utilization and costs of patients with HCV with and without renal impairment. This retrospective analysis used 2 administrative claims databases: the US commercially insured population in Truven Health MarketScan® data (aged 20-64 years), and the US Medicare fee-for-service population in the Medicare 20% sample (aged ≥65 years). Baseline characteristics and comorbid conditions were identified from claims during 2011; patients were followed for up to 1 year (beginning January 1, 2012) to identify health outcomes of interest and health care utilization and costs. In the MarketScan and Medicare databases, 35,965 and 10,608 patients with HCV were identified, 8.5 and 26.5% with evidence of renal disease (chronic kidney disease [CKD] or end-stage renal disease [ESRD]). Most comorbid conditions and unadjusted outcome rates increased across groups from patients with no evidence of renal disease to non-ESRD CKD to ESRD. Health care utilization followed a similar pattern, as did the costs. Our findings suggest that HCV patients with concurrent renal disease have significantly more comorbidity, a higher likelihood of negative health outcomes, and higher health care utilization and costs. © 2017 S. Karger AG, Basel.
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Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci
Brorsson, Caroline A.; Pociot, Flemming
2014-01-01
Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. PMID:25144376
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Inflammatory bowel disease in children of middle eastern descent.
Naidoo, Christina Mai Ying; Leach, Steven T; Day, Andrew S; Lemberg, Daniel A
2014-01-01
Increasing rates of inflammatory bowel disease (IBD) are now seen in populations where it was once uncommon. The pattern of IBD in children of Middle Eastern descent in Australia has never been reported. This study aimed to investigate the burden of IBD in children of Middle Eastern descent at the Sydney Children's Hospital, Randwick (SCHR). The SCHR IBD database was used to identify patients of self-reported Middle Eastern ethnicity diagnosed between 1987 and 2011. Demographic, diagnosis, and management data was collected for all Middle Eastern children and an age and gender matched non-Middle Eastern IBD control group. Twenty-four patients of Middle Eastern descent were identified. Middle Eastern Crohn's disease patients had higher disease activity at diagnosis, higher use of thiopurines, and less restricted colonic disease than controls. Although there were limitations with this dataset, we estimated a higher prevalence of IBD in Middle Eastern children and they had a different disease phenotype and behavior compared to the control group, with less disease restricted to the colon and likely a more active disease course.
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Inflammatory Bowel Disease in Children of Middle Eastern Descent
Naidoo, Christina Mai Ying; Leach, Steven T.; Day, Andrew S.; Lemberg, Daniel A.
2014-01-01
Increasing rates of inflammatory bowel disease (IBD) are now seen in populations where it was once uncommon. The pattern of IBD in children of Middle Eastern descent in Australia has never been reported. This study aimed to investigate the burden of IBD in children of Middle Eastern descent at the Sydney Children's Hospital, Randwick (SCHR). The SCHR IBD database was used to identify patients of self-reported Middle Eastern ethnicity diagnosed between 1987 and 2011. Demographic, diagnosis, and management data was collected for all Middle Eastern children and an age and gender matched non-Middle Eastern IBD control group. Twenty-four patients of Middle Eastern descent were identified. Middle Eastern Crohn's disease patients had higher disease activity at diagnosis, higher use of thiopurines, and less restricted colonic disease than controls. Although there were limitations with this dataset, we estimated a higher prevalence of IBD in Middle Eastern children and they had a different disease phenotype and behavior compared to the control group, with less disease restricted to the colon and likely a more active disease course. PMID:24987422
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Préaud, Emmanuelle; Largeron, Nathalie
2013-01-01
Human papillomavirus (HPV) has an important role in the aetiology of a range of diseases, including cervical, other anogenital, and head and neck cancers, genital warts and recurrent respiratory papillomatosis. This literature review was conducted to identify the available cost data for non-cervical HPV-related cancers (anal, penile, vulvar, vaginal, head and neck) in Europe and to inform discussion of methodological challenges for future economic research. The literature search was conducted using Medline and key words to identify papers published in English or French between 1 January 2000 and 31 December 2011. Abstracts of major conferences were searched to identify relevant information. Structured methods were used to select references that focused on overall disease management for inclusion in the review. A total of 21 references from seven countries (Denmark, France, Germany, Greece, The Netherlands, Portugal, and the UK) were selected, including 11 references relating to head and neck cancers, five to anogenital cancers, and five to more than one HPV-related disease. Non-cervical cancers accounted for a substantial proportion of the economic burden of HPV-related cancers, and this burden was mainly driven by men (∼70%). A wide range of costs were reported for each disease, particularly head and neck cancers, predominantly due to disease complexity and variation in study design. The main limitation of this study was in the search strategy, which was constrained by the key words, the database searched, and the restriction on language (English/French). Non-cervical cancers attributable to HPV impose a substantial economic burden in Europe, and the burden is greater in men than in women. This review provides useful information for future health-economic studies assessing the impact of HPV vaccination on all HPV-related diseases.
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Albarqouni, Loai; Elessi, Khamis; Abu-Rmeileh, Niveen M E
2018-03-15
Research conducted on conditions responsible for the greatest disease burden should be given the highest priority, particularly in resource-limited settings. The present study aimed to assess the research output in relation to disease burden in Palestine and to identify the conditions which are under- or over-investigated, if any. We searched PubMed and Scopus for reports of original research relevant to human health or healthcare authored by researchers affiliated with Palestinian institutions and published between January 2000 and December 2015. We categorised the condition studied in included articles using the Global Burden of Disease (GBD) taxonomy. Data regarding burden of disease (percentage of deaths and disability-adjusted life years (DALYs)) was obtained from the Palestine profile in the GBD study. We examined the degree of discordance between the observed number of published articles for each disease/condition with the expected number based on the proportion of disease burden of that disease/condition. Our search identified 2469 potentially relevant records, from which 1650 were excluded following the screening of titles and abstracts. Of the remaining 819 full-text articles, we included 511 in our review. Communicable (infectious) diseases (n = 103; 20%) was the condition with the highest number of published studies. However, cancer (n = 15; 3%) and chronic respiratory diseases (n = 15; 3%) were the conditions with the lowest number of published studies. Research output was poorly associated with disease burden, irrespective of whether it was measured in terms of DALYs (rho = -0.116, P = 0.7) or death (rho = 0.217, P = 0.5). Cardiovascular disease, cancer, and maternal and neonatal deaths accounted for more than two-thirds of the total deaths in Palestine (67%), but were infrequently addressed (23%) in published articles. There is evidence of research waste measured by a mismatch between the health burden of certain diseases/conditions and the number of published research reports on those diseases/conditions in Palestine. A national research priority-setting agenda should be developed to meet the local community's need for quality evidence to implement independent and informed health policies.
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Identifying patients with gastroesophageal reflux disease in a managed care organization.
Ofman, J J; Ryu, S; Borenstein, J; Kania, S; Lee, J; Grogg, A; Farup, C; Weingarten, S
2001-09-01
The ability of various strategies to identify patients with gastroesophageal reflux disease (GERD) and the relative economic impact on disease management programs for GERD were studied. A telephone interview was conducted of a random sample of patients enrolled in any of three health plans in a 100,000-member managed care organization who had either a pharmacy claim or an encounter claim during 1997. The telephone interview identified patients with GERD and served as the standard by which the sensitivity, specificity, and predictive values of the following patient-identification strategies were compared: (1) telephone interview, (2) chart review, (3) use of encounter claims, (4) use of pharmacy claims, (5) use of both encounter claims, and pharmacy claims, and (6) use of encounter claims or pharmacy claims. Conservative estimates of costs and projected savings were then used to model the potential return on investment of the strategies. A total of 1186 patients completed the telephone interview, of whom 390 (33%) met the case definition of GERD. The most sensitive method for identifying patients with GERD was using either pharmacy or encounter claims (26%). The most specific strategy with the highest positive predictive value (PPV) (87%) was using both pharmacy and encounter claims, but this approach had a case-detection rate of only 3%. Encounter claims were significantly more sensitive than pharmacy claims and yielded a higher estimate of prevalence. The telephone interview identified the most subjects who could have benefited from a disease management program and cost 84% less than chart review. While use of administrative data (pharmacy and encounter claims) was the least costly strategy, it identified 74% fewer patients expected to benefit from disease management. The efficiency of disease management programs for GERD may depend on the method of patient identification, which in turn may depend on whether PPV or negative predictive value (NPV) should be maximized. If there is a need to identify all cases (i.e., sensitivity and NPV are most important), then telephone interview may provide the greatest opportunity for disease management with the greatest return on investment, but at the expense of enrolling many patients who may not benefit.
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MethylMix 2.0: an R package for identifying DNA methylation genes. | Office of Cancer Genomics
DNA methylation is an important mechanism regulating gene transcription, and its role in carcinogenesis has been extensively studied. Hyper and hypomethylation of genes is a major mechanism of gene expression deregulation in a wide range of diseases. At the same time, high-throughput DNA methylation assays have been developed generating vast amounts of genome wide DNA methylation measurements. We developed MethylMix, an algorithm implemented in R to identify disease specific hyper and hypomethylated genes.
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TCGA study identifies genomic features of cervical cancer
Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified novel genomic and molecular characteristics of cervical cancer that will aid in subclassification of the disease and may help target therapies that are most appropriate for each patient.
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[Fine mapping of complex disease susceptibility loci].
Song, Qingfeng; Zhang, Hongxing; Ma, Yilong; Zhou, Gangqiao
2014-01-01
Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) markers have identified more than 3800 susceptibility loci for more than 660 diseases or traits. However, the most significantly associated variants or causative variants in these loci and their biological functions have remained to be clarified. These causative variants can help to elucidate the pathogenesis and discover new biomarkers of complex diseases. One of the main goals in the post-GWAS era is to identify the causative variants and susceptibility genes, and clarify their functional aspects by fine mapping. For common variants, imputation or re-sequencing based strategies were implemented to increase the number of analyzed variants and help to identify the most significantly associated variants. In addition, functional element, expression quantitative trait locus (eQTL) and haplotype analyses were performed to identify functional common variants and susceptibility genes. For rare variants, fine mapping was carried out by re-sequencing, rare haplotype analysis, family-based analysis, burden test, etc.This review summarizes the strategies and problems for fine mapping.
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NASA Technical Reports Server (NTRS)
1996-01-01
Lymphatic filariasis persists as a major cause of clinical morbidity and a significant impediment to socioeconomic development in various parts of the world including Egypt. In Egypt, filariasis has been endemic since time immemorial. Early epidemiologic studies identified Culex pipiens L. as the main vector of the disease and also showed that the geographic distribution of the disease is highly focal and concentrated in lower Egypt. Between 1950 and 1965, a large scale filariasis control program was carried out by the Egyptian Ministry of Health (EMOH) in the endemic areas. Control efforts led to a steady decrease of the disease in areas of the country previously identified as endemic. However, spot surveys conducted in various parts of the Nile Delta during the 1970's and 1980's revealed that the downward trend of the disease had stopped and that the prevalence and intensity of microfilaraemia had increased.
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Agent-Based Modeling of Chronic Diseases: A Narrative Review and Future Research Directions
Lawley, Mark A.; Siscovick, David S.; Zhang, Donglan; Pagán, José A.
2016-01-01
The United States is experiencing an epidemic of chronic disease. As the US population ages, health care providers and policy makers urgently need decision models that provide systematic, credible prediction regarding the prevention and treatment of chronic diseases to improve population health management and medical decision-making. Agent-based modeling is a promising systems science approach that can model complex interactions and processes related to chronic health conditions, such as adaptive behaviors, feedback loops, and contextual effects. This article introduces agent-based modeling by providing a narrative review of agent-based models of chronic disease and identifying the characteristics of various chronic health conditions that must be taken into account to build effective clinical- and policy-relevant models. We also identify barriers to adopting agent-based models to study chronic diseases. Finally, we discuss future research directions of agent-based modeling applied to problems related to specific chronic health conditions. PMID:27236380
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Agent-Based Modeling of Chronic Diseases: A Narrative Review and Future Research Directions.
Li, Yan; Lawley, Mark A; Siscovick, David S; Zhang, Donglan; Pagán, José A
2016-05-26
The United States is experiencing an epidemic of chronic disease. As the US population ages, health care providers and policy makers urgently need decision models that provide systematic, credible prediction regarding the prevention and treatment of chronic diseases to improve population health management and medical decision-making. Agent-based modeling is a promising systems science approach that can model complex interactions and processes related to chronic health conditions, such as adaptive behaviors, feedback loops, and contextual effects. This article introduces agent-based modeling by providing a narrative review of agent-based models of chronic disease and identifying the characteristics of various chronic health conditions that must be taken into account to build effective clinical- and policy-relevant models. We also identify barriers to adopting agent-based models to study chronic diseases. Finally, we discuss future research directions of agent-based modeling applied to problems related to specific chronic health conditions.
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Identification of mutations in Colombian patients affected with Fabry disease.
Uribe, Alfredo; Mateus, Heidi Eliana; Prieto, Juan Carlos; Palacios, Maria Fernanda; Ospina, Sandra Yaneth; Pasqualim, Gabriela; da Silveira Matte, Ursula; Giugliani, Roberto
2015-12-15
Fabry Disease (FD) is an X-linked inborn error of glycosphingolipid catabolism, caused by a deficiency of the lisosomal α-galactosidase A (AGAL). The disorder leads to a vascular disease secondary to the involvement of kidney, heart and the central nervous system. The mutation analysis is a valuable tool for diagnosis and genetic counseling. Although more than 600 mutations have been identified, most mutations are private. Our objective was to describe the analysis of nine Colombian patients with Fabry disease by automated sequencing of the seven exons of the GLA gene. Two novel mutations were identified in two patients affected with the classical subtype of FD, in addition to other 6 mutations previously reported. The present study confirms the heterogeneity of mutations in Fabry disease and the importance of molecular analysis for genetic counseling, female heterozygotes detection as well as therapeutic decisions. Copyright © 2015 Elsevier B.V. All rights reserved.
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Mammalian polycistronic mRNAs and disease
Karginov, Timofey A.; Hejazi Pastor, Daniel Parviz; Semler, Bert L.; Gomez, Christopher M.
2016-01-01
Our understanding of gene expression has come far since the “one-gene one-polypeptide” hypothesis proposed by Beadle and Tatum. This review addresses the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment. We have carried out a systematic literature review identifying 13 mammalian genes for which there is evidence for polycistronic expression via translation through an Internal Ribosome Entry Site (IRES). Although the canonical mechanism of translation initiation has been studied extensively, this review highlights a process of non-canonical translation, IRES-mediated translation, that is a growing source of understanding complex inheritance, elucidation of disease mechanisms, and discovery of novel therapeutic targets. Identification of additional polycistronic genes may provide new insights into disease therapy and allow for new discoveries of translational and disease mechanisms. PMID:28012572
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The Vascular Wall: a Plastic Hub of Activity in Cardiovascular Homeostasis and Disease.
Awgulewitsch, Cassandra P; Trinh, Linh T; Hatzopoulos, Antonis K
2017-06-01
This review aims to summarize recent findings regarding the plasticity and fate switching among somatic and progenitor cells residing in the vascular wall of blood vessels in health and disease. Cell lineage tracing methods have identified multiple origins of stem cells, macrophages, and matrix-producing cells that become mobilized after acute or chronic injury of cardiovascular tissues. These studies also revealed that in the disease environment, resident somatic cells become plastic, thereby changing their stereotypical identities to adopt proinflammatory and profibrotic phenotypes. Currently, the functional significance of this heterogeneity among reparative cells is unknown. Furthermore, mechanisms that control cellular plasticity and fate decisions in the disease environment are poorly understood. Cardiovascular diseases are responsible for the majority of deaths worldwide. From a therapeutic perspective, these novel discoveries may identify new targets to improve the repair and regeneration of the cardiovascular system.
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A Methylation Panel for Bladder Cancer — EDRN Public Portal
Participate in a prevalidation study for methylation based detection of bladder cancer. In addition, a panel of three markers identified will be evaluated for their ability to a) identify bladder cancer patients from those with benign urologic disease; b) identify patients with superficial (papillary) cancers from those with high grade invasive cancers
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Kane, Jennifer; Landes, Megan; Carroll, Christopher; Nolen, Amy; Sodhi, Sumeet
2017-03-23
Chronic diseases, primarily cardiovascular disease, respiratory disease, diabetes and cancer, are the leading cause of death and disability worldwide. In sub-Saharan Africa (SSA), where communicable disease prevalence still outweighs that of non-communicable disease (NCDs), rates of NCDs are rapidly rising and evidence for primary healthcare approaches for these emerging NCDs is needed. A systematic review and evidence synthesis of primary care approaches for chronic disease in SSA. Quantitative and qualitative primary research studies were included that focused on priority NCDs interventions. The method used was best-fit framework synthesis. Three conceptual models of care for NCDs in low- and middle-income countries were identified and used to develop an a priori framework for the synthesis. The literature search for relevant primary research studies generated 3759 unique citations of which 12 satisfied the inclusion criteria. Eleven studies were quantitative and one used mixed methods. Three higher-level themes of screening, prevention and management of disease were derived. This synthesis permitted the development of a new evidence-based conceptual model of care for priority NCDs in SSA. For this review there was a near-consensus that passive rather than active case-finding approaches are suitable in resource-poor settings. Modifying risk factors among existing patients through advice on diet and lifestyle was a common element of healthcare approaches. The priorities for disease management in primary care were identified as: availability of essential diagnostic tools and medications at local primary healthcare clinics and the use of standardized protocols for diagnosis, treatment, monitoring and referral to specialist care.
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Blood-based protein biomarkers for diagnosis of Alzheimer disease.
Doecke, James D; Laws, Simon M; Faux, Noel G; Wilson, William; Burnham, Samantha C; Lam, Chiou-Peng; Mondal, Alinda; Bedo, Justin; Bush, Ashley I; Brown, Belinda; De Ruyck, Karl; Ellis, Kathryn A; Fowler, Christopher; Gupta, Veer B; Head, Richard; Macaulay, S Lance; Pertile, Kelly; Rowe, Christopher C; Rembach, Alan; Rodrigues, Mark; Rumble, Rebecca; Szoeke, Cassandra; Taddei, Kevin; Taddei, Tania; Trounson, Brett; Ames, David; Masters, Colin L; Martins, Ralph N
2012-10-01
To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. General community-based, prospective, longitudinal study of aging. A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.
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RESPIRATORY INFECTIONS RESEARCH IN AFGHANISTAN: BIBLIOMETRIC ANALYSIS WITH THE DATABASE PUBMED.
Pilsczek, Florian H
2015-01-01
Infectious diseases research in a low-income country like Afghanistan is important. In this study an internet-based database Pubmed was used for bibliometric analysis of infectious diseases research activity. Research publications entries in PubMed were analysed according to number of publications, topic, publication type, and country of investigators. Between 2002-2011, 226 (77.7%) publications with the following research topics were identified: respiratory infections 3 (1.3%); parasites 8 (3.5%); diarrhoea 10 (4.4%); tuberculosis 10 (4.4%); human immunodeficiency virus (HIV) 11 (4.9%); multi-drug resistant bacteria (MDR) 18 (8.0%); polio 31 (13.7%); leishmania 31 (13.7%); malaria 46 (20.4%). From 2002-2011, 11 (4.9%) publications were basic science laboratory-based research studies. Between 2002-2011, 8 (3.5%) publications from Afghan institutions were identified. In conclusion, the internet-based database Pubmed can be consulted to collect data for guidance of infectious diseases research activity of low-income countries. The presented data suggest that infectious diseases research in Afghanistan is limited for respiratory infections research, has few studies conducted by Afghan institutions, and limited laboratory-based research contributions.
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A scientific correlation between dystemprament in Unani medicine and diseases: a systematic review
Miraj, Sepideh; Kiani, Sara
2016-01-01
Background Temperament or mezaj refers to four different humors differentiating in individuals and, as a result, proposes specific therapy for their diseases. Objective The aim of this study was to overview the scientific correlation between temperaments in Unani medicine and diseases. Methods This study was carried out from March 2015 to February 2016. A computerized search of published articles was performed using PubMed, Google Scholar, Scopus and Web of Science, and Medline databases as well as local and regional resources between 1983 and 2014. The search terms used were temperament, dystemprament, diseases, mizaj, sue mizaj. Additional sources were identified through cross-referencing. Results The result of this study indicated the relationship between dystemprament and incidence of some diseases such as muscle diseases, skin diseases, asthma, palpitation, bipolar disorder, hemodialysis hysteria, hypertension, sinusitis, aging, diabetes, diarrhea. However, further studies are needed to prove the role of dystemprament in incidence of other diseases. Conclusion The result of this study indicated the relationship between dystemprament and incidence of some disease such as muscle diseases, skin diseases, asthma, palpitation, bipolar disorder, hemodialysis hysteria, hypertension, sinusitis, aging, diabetes, diarrhea. These results are helpful for patients and physicians to change humors toward equilibrium to avoid diseases. Further studies are required to discover the relationship between dystemprament and other diseases. PMID:28070258
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Diseases of Pacific Coast conifers. Agriculture handbook
DOE Office of Scientific and Technical Information (OSTI.GOV)
Scharpf, R.F.
1993-06-01
The handbook provides basic information needed to identify the common diseases of Pacific Coast conifers. Hosts, distribution, disease cycles, and identifying characteristics are described for more than 150 diseases, including cankers, diebacks, galls, rusts, needle diseases, root diseases, mistletoes, and rots. Diseases in which abiotic factors are involved are also described. For some groups of diseases, a descriptive key to field identification is included.
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Characterization of the canine urinary proteome.
Brandt, Laura E; Ehrhart, E J; Scherman, Hataichanok; Olver, Christine S; Bohn, Andrea A; Prenni, Jessica E
2014-06-01
Urine is an attractive biofluid for biomarker discovery as it is easy and minimally invasive to obtain. While numerous studies have focused on the characterization of human urine, much less research has focused on canine urine. The objectives of this study were to characterize the universal canine urinary proteome (both soluble and exosomal), to determine the overlap between the canine proteome and a representative human urinary proteome study, to generate a resource for future canine studies, and to determine the suitability of the dog as a large animal model for human diseases. The soluble and exosomal fractions of normal canine urine were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS). Biological Networks Gene Ontology (BiNGO) software was utilized to assign the canine urinary proteome to respective Gene Ontology categories, such as Cellular Component, Molecular Function, and Biological Process. Over 500 proteins were confidently identified in normal canine urine. Gene Ontology analysis revealed that exosomal proteins were largely derived from an intracellular location, while soluble proteins included both extracellular and membrane proteins. Exosome proteins were assigned to metabolic processes and localization, while soluble proteins were primarily annotated to specific localization processes. Several proteins identified in normal canine urine have previously been identified in human urine where these proteins are related to various extrarenal and renal diseases. The results of this study illustrate the potential of the dog as an animal model for human disease states and provide the framework for future studies of canine renal diseases. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.
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GeneCOST: a novel scoring-based prioritization framework for identifying disease causing genes.
Ozer, Bugra; Sağıroğlu, Mahmut; Demirci, Hüseyin
2015-11-15
Due to the big data produced by next-generation sequencing studies, there is an evident need for methods to extract the valuable information gathered from these experiments. In this work, we propose GeneCOST, a novel scoring-based method to evaluate every gene for their disease association. Without any prior filtering and any prior knowledge, we assign a disease likelihood score to each gene in correspondence with their variations. Then, we rank all genes based on frequency, conservation, pedigree and detailed variation information to find out the causative reason of the disease state. We demonstrate the usage of GeneCOST with public and real life Mendelian disease cases including recessive, dominant, compound heterozygous and sporadic models. As a result, we were able to identify causative reason behind the disease state in top rankings of our list, proving that this novel prioritization framework provides a powerful environment for the analysis in genetic disease studies alternative to filtering-based approaches. GeneCOST software is freely available at www.igbam.bilgem.tubitak.gov.tr/en/softwares/genecost-en/index.html. buozer@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Wang, Xijun; Zhang, Aihua; Han, Ying; Wang, Ping; Sun, Hui; Song, Gaochen; Dong, Tianwei; Yuan, Ye; Yuan, Xiaoxia; Zhang, Miao; Xie, Ning; Zhang, He; Dong, Hui; Dong, Wei
2012-01-01
Metabolomics is a powerful new technology that allows for the assessment of global metabolic profiles in easily accessible biofluids and biomarker discovery in order to distinguish between diseased and nondiseased status information. Deciphering the molecular networks that distinguish diseases may lead to the identification of critical biomarkers for disease aggressiveness. However, current diagnostic methods cannot predict typical Jaundice syndrome (JS) in patients with liver disease and little is known about the global metabolomic alterations that characterize JS progression. Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication, and therapy. Therefore, the aim of this study is to find the potential biomarkers from JS disease by using a nontarget metabolomics method, and test their usefulness in human JS diagnosis. Multivariate data analysis methods were utilized to identify the potential biomarkers. Interestingly, 44 marker metabolites contributing to the complete separation of JS from matched healthy controls were identified. Metabolic pathways (Impact-value≥0.10) including alanine, aspartate, and glutamate metabolism and synthesis and degradation of ketone bodies were found to be disturbed in JS patients. This study demonstrates the possibilities of metabolomics as a diagnostic tool in diseases and provides new insight into pathophysiologic mechanisms. PMID:22505723
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Themes in the literature related to cardiovascular disease risk reduction.
Cohen, Shannon Munro; Kataoka-Yahiro, Merle
2009-01-01
This article aimed to identify themes in the literature related to patient-healthcare provider beliefs, barriers to adherence, and interventions pertaining to cardiovascular disease risk reduction. Twenty quantitative and qualitative primary research studies including 2 meta-analyses published between 1995 and 2008 were analyzed for themes and practice implications to synthesize existing research on cardiovascular disease risk reduction. Databases searched included EBSCO, CINAHL, MEDLINE, ScienceDirect, HealthSource, and PsychLit using the search terms patient- provider adherence, adherence and shared decision making, adherence and decision support, patient- provider goal setting, and cardiovascular disease risk reduction. The emergent themes found in this literature review included (1) complex medication regimens; (2) risk perception, quality of life, and competing priorities; (3) motivation for change; (4) provider clinical inertia; and (5) goal setting, feedback, and reminders. Studies reporting the highest rates of adherence to cardiovascular disease risk reduction recommendations incorporated patient-provider goal setting and decision support, self-management techniques, and personalized printed communication. Goal setting in cardiovascular disease risk reduction is a relatively unexplored area and is an important component of shared decision making and adherence to cardiovascular disease health recommendations. The following review will address the 5 themes identified in more detail and provide a basis for improved clinical practice.
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Xiao, Qiu; Luo, Jiawei; Liang, Cheng; Cai, Jie; Ding, Pingjian
2017-09-01
MicroRNAs (miRNAs) play crucial roles in post-transcriptional regulations and various cellular processes. The identification of disease-related miRNAs provides great insights into the underlying pathogenesis of diseases at a system level. However, most existing computational approaches are biased towards known miRNA-disease associations, which is inappropriate for those new diseases or miRNAs without any known association information. In this study, we propose a new method with graph regularized non-negative matrix factorization in heterogeneous omics data, called GRNMF, to discover potential associations between miRNAs and diseases, especially for new diseases and miRNAs or those diseases and miRNAs with sparse known associations. First, we integrate the disease semantic information and miRNA functional information to estimate disease similarity and miRNA similarity, respectively. Considering that there is no available interaction observed for new diseases or miRNAs, a preprocessing step is developed to construct the interaction score profiles that will assist in prediction. Next, a graph regularized non-negative matrix factorization framework is utilized to simultaneously identify potential associations for all diseases. The results indicated that our proposed method can effectively prioritize disease-associated miRNAs with higher accuracy compared with other recent approaches. Moreover, case studies also demonstrated the effectiveness of GRNMF to infer unknown miRNA-disease associations for those novel diseases and miRNAs. The code of GRNMF is freely available at https://github.com/XIAO-HN/GRNMF/. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.
Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy
2018-06-01
The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Genetic variants associated with celiac disease and the risk for coronary artery disease.
Jansen, Henning; Willenborg, Christina; Schlesinger, Sabrina; Ferrario, Paola G; König, Inke R; Erdmann, Jeanette; Samani, Nilesh J; Lieb, Wolfgang; Schunkert, Heribert
2015-10-01
Epidemiological evidence suggests that patients with celiac disease are at increased risk for coronary artery disease (CAD). Genetic-epidemiological analyses identified many single nucleotide polymorphisms (SNPs) associated with celiac disease. If there is a causal relation between celiac disease and CAD, one might expect that risk alleles primarily associated with celiac disease also increase the risk of CAD. In this study we identified from literature 41 SNPs that have been previously described to be genome-wide associated with celiac disease (p < 5 × 10(-08)). These SNPs were evaluated for their association with CAD in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) dataset, a meta-analysis comprising genome-wide SNP association data from 22,233 CAD cases and 64,762 controls. 24 out of 41 (58.5 %) risk alleles for celiac disease displayed a positive association with CAD (CAD-OR range 1.001-1.081). The remaining risk alleles for celiac disease (n = 16) revealed CAD-ORs of ≤1.0 (range 0.951-1.0). The proportion of CAD associated alleles was greater but did not differ significantly from the proportion of 50 % expected by chance (p = 0.069). One SNP (rs653178 at the SH2B3/ATXN2 locus) displayed study-wise statistically significant association with CAD with directionality consistent effects on celiac disease and CAD. However, the effect of this locus is most likely driven by pleiotropic effects on multiple other diseases. In conclusion, this genetically based approach provided no convincing evidence that SNPs associated with celiac disease contribute to the risk of CAD. Hence, common non-genetic factors may play a more important role explaining the coincidence of these two complex disease conditions.
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Kaufman, Harvey W; Williams, Fred R; Odeh, Mouneer A
2011-01-01
Employer-sponsored health risk assessments (HRA) may include laboratory tests to provide evidence of disease and disease risks for common medical conditions. We evaluated the ability of HRA-laboratory testing to provide new disease-risk information to participants. We performed a cross-sectional analysis of HRA-laboratory results for participating adult employees and their eligible spouses or their domestic partners, focusing on three common health conditions: hyperlipidemia, diabetes mellitus, and chronic kidney disease. HRA with laboratory results of 52,270 first-time participants were analyzed. Nearly all participants had access to health insurance coverage. Twenty-four percent (12,392) self-reported one or more of these medical conditions: 21.1% (11,017) self-identified as having hyperlipidemia, 4.7% (2,479) self-identified as having diabetes, and 0.7% (352) self-identified as having chronic kidney disease. Overall, 36% (n = 18,540) of participants had laboratory evidence of at least one medical condition newly identified: 30.7% (16,032) had laboratory evidence of hyperlipidemia identified, 1.9% (984) had laboratory evidence of diabetes identified, and 5.5% (2,866) had laboratory evidence of chronic kidney disease identified. Of all participants with evidence of hyperlipidemia 59% (16,030 of 27,047), were newly identified through the HRA. Among those with evidence of diabetes 28% (984 of 3,463) were newly identified. The highest rate of newly identified disease risk was for chronic kidney disease: 89% (2,866 of 3,218) of participants with evidence of this condition had not self-reported it. Men (39%) were more likely than women (33%) to have at least one newly identified condition (p<0.0001). Among men, lower levels of educational achievement were associated with modestly higher rates of newly identified disease risk (p<0.0001); the association with educational achievement among women was unclear. Even among the youngest age range (20 to 29 year olds), nearly 1 in 4 participants (24%) had a newly identified risk for disease. These results support the important role of employer-sponsored laboratory testing as an integral element of HRA for identifying evidence of previously undiagnosed common medical conditions in individuals of all working age ranges, regardless of educational level and gender.
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Pharmacotherapy challenges of Fontan-associated plastic bronchitis: a rare pediatric disease.
Brooks, Kristina; Caruthers, Regine L; Schumacher, Kurt R; Stringer, Kathleen A
2013-09-01
Pediatric pharmacotherapy is often challenging due to the paucity of available clinical data on the safety and efficacy of drugs that are commonly used in children. This quandary is even more prevalent in children with rare diseases. Although extrapolations for dosing and administration are often made from available adult data with similar disease states, this translation becomes even more problematic in rare pediatric diseases. Understanding of rare disease pathophysiology is typically poor, and few, if any, effective therapies have been studied and identified. One condition that illustrates these issues is plastic bronchitis, a rare, most often pediatric disease that is characterized by the production of obstructive bronchial airway casts. This illness primarily occurs in children with congenital heart disease, often after palliative surgery. Plastic bronchitis is a highly clinically relevant and therapeutically challenging problem with a high mortality rate, and, a generally accepted effective pharmacotherapy regimen has yet to be identified. Furthermore, the disease is ill defined, which makes timely identification and treatment of children with plastic bronchitis difficult. The pharmacotherapies currently used to manage this disease are largely anecdotal and vary between the use of macrolide antibiotics, mucolytics, bronchodilators, and inhaled fibrinolytics in a myriad of combinations. The purpose of this review is 2-fold: first, to highlight the dilemma of treating plastic bronchitis, and second, to bring attention to the continuing need for studies of drug therapies used in children so safe and effective drug regimens can be established, particularly for rare diseases. © 2013 Pharmacotherapy Publications, Inc.
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Wijetunge, S.; Ratnatunga, N. V. I.; Abeysekera, T. D. J.; Wazil, A. W. M.; Selvarajah, M.
2015-01-01
Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy. PMID:26628792
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de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos
2015-01-01
The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.
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Chocolate consumption and risk of myocardial infarction: a prospective study and meta-analysis.
Larsson, Susanna C; Åkesson, Agneta; Gigante, Bruna; Wolk, Alicja
2016-07-01
To examine whether chocolate consumption is associated with a reduced risk of ischaemic heart disease, we used data from a prospective study of Swedish adults and we performed a meta-analysis of available prospective data. The Swedish prospective study included 67 640 women and men from the Cohort of Swedish Men and the Swedish Mammography Cohort who had completed a food-frequency questionnaire and were free of cardiovascular disease at baseline. Myocardial infarction (MI) cases were ascertained through linkage with the Swedish National Patient and Cause of Death Registers. PubMed and EMBASE databases were searched from inception until 4 February 2016 to identify prospective studies on chocolate consumption and risk of ischaemic heart disease. The results from eligible studies were combined using a random-effects model. During follow-up (1998-2010), 4417 MI cases were ascertained in the Swedish study. Chocolate consumption was inversely associated with MI risk. Compared with non-consumers, the multivariable relative risk for those who consumed ≥3-4 servings/week of chocolate was 0.87 (95% CI 0.77 to 0.98; p for trend =0.04). Five prospective studies on chocolate consumption and ischaemic heart disease were identified. Together with the Swedish study, the meta-analysis included six studies with a total of 6851 ischaemic heart disease cases. The overall relative risk for the highest versus lowest category of chocolate consumption was 0.90 (95% CI 0.82 to 0.97), with little heterogeneity among studies (I(2)=24.3%). Chocolate consumption is associated with lower risk of MI and ischaemic heart disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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Financial Conflicts Facing Late-Life Remarried Alzheimer's Disease Caregivers
ERIC Educational Resources Information Center
Sherman, Carey Wexler; Bauer, Jean W.
2008-01-01
This qualitative study explores financial conflicts faced by late-life remarried wives providing care for their husbands with Alzheimer's disease. Interviews with 9 women identified intergenerational secrets and tensions regarding financial and inheritance decisions. Participants' remarried spouse status, underlying family boundary ambiguities,…
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Non-isoflavone phytochemicals in soy and their health effects
USDA-ARS?s Scientific Manuscript database
Epidemiological and clinical studies have linked consumption of soy foods with low incidences of a number of chronic diseases; such as cardiovascular diseases, cancer, and osteoporosis. Over the past few decades, enormous research efforts have been made on identifying bioactive components in soy. Is...
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van Manen, Daniëlle; Delaneau, Olivier; Kootstra, Neeltje A.; Boeser-Nunnink, Brigitte D.; Limou, Sophie; Bol, Sebastiaan M.; Burger, Judith A.; Zwinderman, Aeilko H.; Moerland, Perry D.; van 't Slot, Ruben; Zagury, Jean-François; van 't Wout, Angélique B.; Schuitemaker, Hanneke
2011-01-01
Background AIDS develops typically after 7–11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (<2 years) and long-term non-progression (>15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Methods The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. Results Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. Conclusions Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection. PMID:21811574
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Identifying Future Disease Hot Spots: Infectious Disease Vulnerability Index.
Moore, Melinda; Gelfeld, Bill; Okunogbe, Adeyemi; Paul, Christopher
2017-06-01
Recent high-profile outbreaks, such as Ebola and Zika, have illustrated the transnational nature of infectious diseases. Countries that are most vulnerable to such outbreaks might be higher priorities for technical support. RAND created the Infectious Disease Vulnerability Index to help U.S. government and international agencies identify these countries and thereby inform programming to preemptively help mitigate the spread and effects of potential transnational outbreaks. The authors employed a rigorous methodology to identify the countries most vulnerable to disease outbreaks. They conducted a comprehensive review of relevant literature to identify factors influencing infectious disease vulnerability. Using widely available data, the authors created an index for identifying potentially vulnerable countries and then ranked countries by overall vulnerability score. Policymakers should focus on the 25 most-vulnerable countries with an eye toward a potential "disease belt" in the Sahel region of Africa. The infectious disease vulnerability scores for several countries were better than what would have been predicted on the basis of economic status alone. This suggests that low-income countries can overcome economic challenges and become more resilient to public health challenges, such as infectious disease outbreaks.
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The construction of learning objects on communicable diseases for community health agents.
Pacheco, Kátia Cilene Ferreira; Azambuja, Marcelo Schenk de; Bonamigo, Andrea Wander
2018-06-07
To describe the creation of a learning object about communicable diseases and their identification, monitoring, and prevention for community health agents. The qualitative, exploratory, case study conducted in the North District Management Zone - Baltazar of the Universidade Federal de Ciências da Saúde de Porto Alegre, from October to January 2015 2016. The study had 58 participants and consisted of the stages field research, Bardin's content analysis, and design of the learning object. The profile of the professionals working in the location was established. These agents identified the most commonly found diseases and stressed their needs in relation to a technological resource. The identified needs were considered to define the content and structure the learning object. The learning object is an alternative method for sharing knowledge on communicable diseases. The tool allows the combination of technology with teaching, which makes the learning process and the work of the community health agents more rewarding and productive.
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Update on Huntington's disease: advances in care and emerging therapeutic options.
Zielonka, Daniel; Mielcarek, Michal; Landwehrmeyer, G Bernhard
2015-03-01
Huntington's disease (HD) is the most common hereditary neurodegenerative disorder. Despite the fact that both the gene and the mutation causing this monogenetic disorder were identified more than 20 years ago, disease-modifying therapies for HD have not yet been established. While intense preclinical research and large cohort studies in HD have laid foundations for tangible improvements in understanding HD and caring for HD patients, identifying targets for therapeutic interventions and developing novel therapeutic modalities (new chemical entities and advanced therapies using DNA and RNA molecules as therapeutic agents) continues to be an ongoing process. The authors review recent achievements in HD research and focus on approaches towards disease-modifying therapies, ranging from huntingtin-lowering strategies to improving huntingtin clearance that may be promoted by posttranslational HTT modifications. The nature and number of upcoming clinical studies/trials in HD is a reason for hope for HD patients and their families. Copyright © 2014 Elsevier Ltd. All rights reserved.
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The complexity of epigenetic diseases.
Brazel, Ailbhe Jane; Vernimmen, Douglas
2016-01-01
Over the past 30 years, a plethora of pathogenic mutations affecting enhancer regions and epigenetic regulators have been identified. Coupled with more recent genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) implicating major roles for regulatory mutations in disease, it is clear that epigenetic mechanisms represent important biomarkers for disease development and perhaps even therapeutic targets. Here, we discuss the diversity of disease-causing mutations in enhancers and epigenetic regulators, with a particular focus on cancer. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.