A supervised learning approach for Crohn's disease detection using higher-order image statistics and a novel shape asymmetry measure.

PubMed

Mahapatra, Dwarikanath; Schueffler, Peter; Tielbeek, Jeroen A W; Buhmann, Joachim M; Vos, Franciscus M

2013-10-01

Increasing incidence of Crohn's disease (CD) in the Western world has made its accurate diagnosis an important medical challenge. The current reference standard for diagnosis, colonoscopy, is time-consuming and invasive while magnetic resonance imaging (MRI) has emerged as the preferred noninvasive procedure over colonoscopy. Current MRI approaches assess rate of contrast enhancement and bowel wall thickness, and rely on extensive manual segmentation for accurate analysis. We propose a supervised learning method for the identification and localization of regions in abdominal magnetic resonance images that have been affected by CD. Low-level features like intensity and texture are used with shape asymmetry information to distinguish between diseased and normal regions. Particular emphasis is laid on a novel entropy-based shape asymmetry method and higher-order statistics like skewness and kurtosis. Multi-scale feature extraction renders the method robust. Experiments on real patient data show that our features achieve a high level of accuracy and perform better than two competing methods.

[Application of iodine metabolism analysis methods in thyroid diseases].

PubMed

Han, Jian-hua; Qiu, Ling

2013-08-01

The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases.

Evaluation of the impacts of climate change on disease vectors through ecological niche modelling.

PubMed

Carvalho, B M; Rangel, E F; Vale, M M

2017-08-01

Vector-borne diseases are exceptionally sensitive to climate change. Predicting vector occurrence in specific regions is a challenge that disease control programs must meet in order to plan and execute control interventions and climate change adaptation measures. Recently, an increasing number of scientific articles have applied ecological niche modelling (ENM) to study medically important insects and ticks. With a myriad of available methods, it is challenging to interpret their results. Here we review the future projections of disease vectors produced by ENM, and assess their trends and limitations. Tropical regions are currently occupied by many vector species; but future projections indicate poleward expansions of suitable climates for their occurrence and, therefore, entomological surveillance must be continuously done in areas projected to become suitable. The most commonly applied methods were the maximum entropy algorithm, generalized linear models, the genetic algorithm for rule set prediction, and discriminant analysis. Lack of consideration of the full-known current distribution of the target species on models with future projections has led to questionable predictions. We conclude that there is no ideal 'gold standard' method to model vector distributions; researchers are encouraged to test different methods for the same data. Such practice is becoming common in the field of ENM, but still lags behind in studies of disease vectors.

Current Applications of Chromatographic Methods in the Study of Human Body Fluids for Diagnosing Disorders.

PubMed

Jóźwik, Jagoda; Kałużna-Czaplińska, Joanna

2016-01-01

Currently, analysis of various human body fluids is one of the most essential and promising approaches to enable the discovery of biomarkers or pathophysiological mechanisms for disorders and diseases. Analysis of these fluids is challenging due to their complex composition and unique characteristics. Development of new analytical methods in this field has made it possible to analyze body fluids with higher selectivity, sensitivity, and precision. The composition and concentration of analytes in body fluids are most often determined by chromatography-based techniques. There is no doubt that proper use of knowledge that comes from a better understanding of the role of body fluids requires the cooperation of scientists of diverse specializations, including analytical chemists, biologists, and physicians. This article summarizes current knowledge about the application of different chromatographic methods in analyses of a wide range of compounds in human body fluids in order to diagnose certain diseases and disorders.

Control of black walnut root rot diseases in nurseries.

Treesearch

Kenneth J. Jr. Kessler

1982-01-01

Current nursery methods used to control black walnut root rot diseases are considered in terms of integrated pest management. Suggestions for future root rot control research studies and procedures to minimize root rot problems are provided.

Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types.

PubMed

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.

[SWOT Analysis of the National Survey on Current Status of Major Human Parasitic Diseases in China].

PubMed

ZHU, Hui-hui; ZHOU, Chang-hai; CHEN, Ying-dan; ZANG, Wei; XIAO, Ning; ZHOU, Xiao-nong

2015-10-01

The National Survey on Current Status of Major Human Parasitic Diseases in China has been carried out since 2014 under the organization of the National Health and Family Planning Commission of the People's Republic of China. The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (NIPD, China CDC) provided technical support and was responsible for quality control in this survey. This study used SWOT method to analyze the strengths, weaknesses, opportunities and threats that were encountered by he NIPD, China CDC during the completion of the survey. Accordingly, working strategies were proposed to facilitate the future field work.

Direct current electrotherapy for internal haemorrhoids: experience in a tertiary health institution

PubMed Central

Olatoke, Samuel; Adeoti, Moses; Agodirin, Olayide; Ajape, Abdulwahab; Agbola, John

2014-01-01

Introduction Haemorrhoids disease is one of the most frequently occurring disabling conditions of the anorectum. We re-present the method, advantages and results of using direct current electrotherapy in the treatment of haemorrhoids. Methods Symptomatic grades 1, 2 or 3 internal and mixed haemorroids were treated. Exposure and evaluation was with an operative proctoscope which visualized one-eighth of the anal canal at a time. All diseased segments were treated per visit, indicators of successful treatment were, darkening of the treated segment, immediate shrinking of the haemorrhoid and ceasation of popping sound of gas release at the probe tip. Patients were followed up for two weeks. No bowel preparations, medications, anesthesia nor admission was required. Results Four hundred and fifty six segments were exposed, 252(55.3%) were diseased. eight patients with either grades 2 or 3 diseases required two treatment visits. The most common symptom was rectal bleeding (94.7%), followed by prolapsed but manually reduced hemorrhoids (68%). Prolapse of tuft of haemorrhoidal tissue with spontaneous return was seen in 59.6%, anal pain in 29.8%, and itching in 3.5%. the median number treated segments per patient was 4. No complication was encountered. All patients treated remained symptom free at a mean duration of follow up of 16 months. Conclusion Direct current electrotherapy is an effective, painless and safe out-patient treatment method for grades 1 to 3 internal and mixed hemorrhoid disease. PMID:25419283

Progress in the molecular diagnosis of Lyme disease.

PubMed

Ružić-Sabljić, Eva; Cerar, Tjaša

2017-01-01

Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

Projections of the Current and Future Disease Burden of Hepatitis C Virus Infection in Malaysia

PubMed Central

McDonald, Scott A.; Dahlui, Maznah; Mohamed, Rosmawati; Naning, Herlianna; Shabaruddin, Fatiha Hana; Kamarulzaman, Adeeba

2015-01-01

Background The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods. Methods An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed. Results In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039. Conclusions The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia. PMID:26042425

Current Literature on Venereal Disease, 1973. Number One. Abstracts and Bibliography.

ERIC Educational Resources Information Center

Center for Disease Control (DHEW/PHS), Atlanta, GA.

This report presents a survey of recently published literature in the field of venereal disease. The five main topics covered are a) diagnosis and management of syphilis and other treponematoses, b) gonorrhea, c) minor venereal and related diseases, d) public health methods, and e) behavioral studies. The material in each of these sections…

The Problem of Rarity: Estimation of Prevalence in Rare Disease.

PubMed

Auvin, Stéphane; Irwin, John; Abi-Aad, Paul; Battersby, Alysia

2018-05-01

From a disease's first description to its wider recognition, factors such as changes over time in diagnostic criteria, available therapies, and subsequent mortality rates may influence diagnosed prevalence of rare diseases. To propose a novel methodology for estimating the true prevalence of rare diseases using current incidence adjusted to changing diagnostic practice over time. This article focuses on rare diseases whose diagnosis may have changed over time, and raises the hypothesis that prevalence calculated from current incidence may be higher than diagnosed prevalence, which may lag behind the current disease definition and diagnostic methods. A rare epileptic encephalopathy, Dravet syndrome (DS), is explored as an illustrative example. A targeted literature review was performed for DS to identify all reported incidence, prevalence, and mortality and depict how diagnostic practice has evolved over time. A conceptual model was developed to calculate prevalence derived from current incidence figures alone (incidence-derived prevalence) or incidence adjusted with factors that cause a diagnostic drag (diagnostic awareness-adjusted prevalence). We identified sufficient publications of incidence and prevalence to test the conceptual model. For pediatric patients with DS, diagnosed prevalence in the field (as reported in current literature) matches incidence-derived prevalence, whereas for adult patients, it is overestimated by incidence-derived prevalence, but not by diagnostic awareness-adjusted prevalence. Care should be taken with current incidence-derived prevalence figures to not overstate the prevalence in rare diseases, as methodological challenges in counting small populations, coupled with advances in rare disease discovery, may cause discrepancies. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Current management of Parkinson's disease.

PubMed

Salawu, F; Olokoba, A; Danburam, A

2010-01-01

Although Parkinson's disease (PD) is still incurable, a large number of different treatments have become available to improve the quality of life and physical and psychological morbidity, and its early treatment is of prime importance. This article reviews the current situation of PD. This review was based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. The subject headings and keywords used were Parkinson's disease and therapeutic advances. Only articles written in English were included.The management of PD has evolved rapidly over the last 10 years with the advent of new drugs and new classes of drugs, but the currently available treatment methods are all symptomatic ones. However, some of these may have marginal disease-modifying effects. Progress in manufacture of newer drugs has markedly improved the treatment of early PD; however, the management of advanced Parkinson's symptoms remains a challenge. Currently no treatment has been proven to slow the progression of PD. Although symptomatic therapy can provide benefit for many years, PD will eventually result in significant morbidity.

Transgenesis and paratransgenesis to control insect-borne diseases: Current status and future challenges

PubMed Central

Coutinho-Abreu, Iliano V.; Zhu, Kun Yan; Ramalho-Ortigao, Marcelo

2009-01-01

Insect-borne diseases cause significant human morbidity and mortality. Current control and preventive methods against vector-borne diseases rely mainly on insecticides. The emergence of insecticide resistance in many disease vectors highlights the necessity to develop new strategies to control these insects. Vector transgenesis and paratransgenesis are novel strategies that aim at reducing insect vectorial capacity, or seek to eliminate transmission of pathogens such as Plasmodium sp., Trypanosoma sp., and Dengue virus currently being developed. Vector transgenesis relies on direct genetic manipulation of disease vectors making them incapable of functioning as vectors of a given pathogen. Paratransgenesis focuses on utilizing genetically modified insect symbionts to express molecules within the vector that are deleterious to pathogens they transmit. Despite the many successes achieved in developing such techniques in the last several years, many significant barriers remain and need to be overcome prior to any of these approaches become a reality. Here, we highlight the current status of these strategies, pointing out advantages and constraints, and also explore issues that need to be resolved before the establishment of transgenesis and paratransgenesis as tools to prevent vector-borne diseases. PMID:19819346

Scale invariant texture descriptors for classifying celiac disease

PubMed Central

Hegenbart, Sebastian; Uhl, Andreas; Vécsei, Andreas; Wimmer, Georg

2013-01-01

Scale invariant texture recognition methods are applied for the computer assisted diagnosis of celiac disease. In particular, emphasis is given to techniques enhancing the scale invariance of multi-scale and multi-orientation wavelet transforms and methods based on fractal analysis. After fine-tuning to specific properties of our celiac disease imagery database, which consists of endoscopic images of the duodenum, some scale invariant (and often even viewpoint invariant) methods provide classification results improving the current state of the art. However, not each of the investigated scale invariant methods is applicable successfully to our dataset. Therefore, the scale invariance of the employed approaches is explicitly assessed and it is found that many of the analyzed methods are not as scale invariant as they theoretically should be. Results imply that scale invariance is not a key-feature required for successful classification of our celiac disease dataset. PMID:23481171

Methods to assess Drosophila heart development, function and aging

PubMed Central

Ocorr, Karen; Vogler, Georg; Bodmer, Rolf

2014-01-01

In recent years the Drosophila heart has become an established model of many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure. PMID:24727147

Standard methods for fungal brood disease research

PubMed Central

Jensen, Annette Bruun; Aronstein, Kathrine; Flores, José Manuel; Vojvodic, Svjetlana; Palacio, María Alejandra; Spivak, Marla

2013-01-01

Summary Chalkbrood and stonebrood are two fungal diseases associated with honey bee brood. Chalkbrood, caused by Ascosphaera apis, is a common and widespread disease that can result in severe reduction of emerging worker bees and thus overall colony productivity. Stonebrood is caused by Aspergillus spp. that are rarely observed, so the impact on colony health is not very well understood. A major concern with the presence of Aspergillus in honey bees is the production of airborne conidia, which can lead to allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, or even invasive aspergillosis in lung tissues upon inhalation by humans. In the current chapter we describe the honey bee disease symptoms of these fungal pathogens. In addition, we provide research methodologies and protocols for isolating and culturing, in vivo and in vitro assays that are commonly used to study these host pathogen interactions. We give guidelines on the preferred methods used in current research and the application of molecular techniques. We have added photographs, drawings and illustrations to assist bee-extension personnel and bee scientists in the control of these two diseases. PMID:24198438

Neuronopathic Lysosomal Storage Diseases: Clinical and Pathologic Findings

ERIC Educational Resources Information Center

Prada, Carlos E.; Grabowski, Gregory A.

2013-01-01

Background: The lysosomal--autophagocytic system diseases (LASDs) affect multiple body systems including the central nervous system (CNS). The progressive CNS pathology has its onset at different ages, leading to neurodegeneration and early death. Methods: Literature review provided insight into the current clinical neurological findings,…

Cacao diseases: A history of old enemies and new encounters

USDA-ARS?s Scientific Manuscript database

This book reviews the current knowledge of cacao pathogens and their management methods. Topics discussed include the history, biology, and genetic diversity of Moniliophthora (causing witches’ broom and frosty pod rot) and Phytophthora species (causing black pod rot) that cause diseases resulting i...

FDTD-based Transcranial Magnetic Stimulation model applied to specific neurodegenerative disorders.

PubMed

Fanjul-Vélez, Félix; Salas-García, Irene; Ortega-Quijano, Noé; Arce-Diego, José Luis

2015-01-01

Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

When can nutritional therapy impact liver disease?

PubMed

Bozeman, Matthew C; Benns, Matthew V; McClave, Stephen A; Miller, Keith R; Jones, Christopher M

2014-10-01

This article reviews the current literature regarding nutritional therapy in liver disease, with an emphasis on patients progressing to liver failure as well as surgical patients. Mechanisms of malnutrition and sarcopenia in liver failure patients as well as nutritional assessment, nutritional requirements of this patient population, and goals and methods of therapy are discussed. Additionally, recommendations for feeding, micronutrient, branched chain amino acid supplementation, and the use of pre- and probiotics are included. The impact of these methods can have on patients with advanced disease and those undergoing surgical procedures will be emphasized.

Common periodontal diseases of children and adolescents.

PubMed

Al-Ghutaimel, Hayat; Riba, Hisham; Al-Kahtani, Salem; Al-Duhaimi, Saad

2014-01-01

Background. Since 2000, studies, experiments, and clinical observations revealed high prevalence of periodontal diseases among children and adolescents. Therefore, this paper was designed to provide an update for dental practitioners on epidemiology, microbiology, pathology, prevention, diagnosis, and treatment of periodontal diseases in children and adolescents. Methods. This paper reviews the current literature concerning periodontal diseases in pediatric dentistry. It includes MEDLINE database search using key terms: "periodontal diseases in children," "Periodontal diseasesin adolescents," "periodontal diseases risk factors," "microbiology of periodontal diseases," "classification of periodontal diseases," "epidemiology of periodontal diseases," and "treatment of periodontal diseases." Articles were evaluated by title and/or abstract and relevance to pediatric dentistry. Sixty-five citations were selected by this method and by the references within the chosen articles. A review of the comprehensive textbooks on pediatric dentistry and periodontology was done. Some recommendations were based on the opinions of experienced researchers and clinicians, when data were inconclusive.

[Current status and clinical application prospect of Akabane's test].

PubMed

Wang, Wenjie; Du, Yanjun

2016-06-12

The Akabane's test is one of the meridian diagnostic methods. Compared with the current meridian diagnostic methods, it has the advantages of convenience and efficiency, but it also has several disadvantages such as the accuracy is difficult to control, the outcome interpretation is limited, etc. In this paper, the influence factors of Akabane's test were analyzed one by one, especially proposed personal opinion on outcome interpretation, which could ascertain the location and nature of disease, leading to disease syndrome. With accurate syndrome, the treatment plan could be established. The application prospect of Akabane's test was initially explored, and it was proposed that wearable automation equipment could be one of the development directions.

Chagas disease diagnostic applications: present knowledge and future steps

PubMed Central

Balouz, Virginia; Agüero, Fernán; Buscaglia, Carlos A.

2017-01-01

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery. PMID:28325368

Aptamers: novel diagnostic and therapeutic tools for diabetes mellitus and metabolic diseases.

PubMed

Hu, Jingping; Ye, Mao; Zhou, Zhiguang

2017-03-01

Diabetes mellitus is one of the most common chronic diseases that threatens human health in worldwide populations. Despite enormous efforts invested in the study of diabetes mellitus, the development of precise diagnoses and treatments for this disease remains difficult due to the limitations of current techniques. Therefore, new methods are currently being developed. Aptamers are oligonucleotides that bind to specific target molecules and have been widely applied as diagnostic and therapeutic tools. In recent years, aptamers have been utilized in the study of diabetes mellitus and metabolic diseases. In this review, we highlight recent developments and new perspectives on aptamers in the field of diabetes mellitus and other metabolic diseases. Aptamers could potentially provide the means for efficient diagnoses and therapies against diabetes mellitus.

Direct current electrotherapy for internal haemorrhoids: experience in a tertiary health institution.

PubMed

Olatoke, Samuel; Adeoti, Moses; Agodirin, Olayide; Ajape, Abdulwahab; Agbola, John

2014-01-01

Haemorrhoids disease is one of the most frequently occurring disabling conditions of the anorectum. We re-present the method, advantages and results of using direct current electrotherapy in the treatment of haemorrhoids. Symptomatic grades 1, 2 or 3 internal and mixed haemorroids were treated. Exposure and evaluation was with an operative proctoscope which visualized one-eighth of the anal canal at a time. All diseased segments were treated per visit, indicators of successful treatment were, darkening of the treated segment, immediate shrinking of the haemorrhoid and ceasation of popping sound of gas release at the probe tip. Patients were followed up for two weeks. No bowel preparations, medications, anesthesia nor admission was required. Four hundred and fifty six segments were exposed, 252(55.3%) were diseased. eight patients with either grades 2 or 3 diseases required two treatment visits. The most common symptom was rectal bleeding (94.7%), followed by prolapsed but manually reduced hemorrhoids (68%). Prolapse of tuft of haemorrhoidal tissue with spontaneous return was seen in 59.6%, anal pain in 29.8%, and itching in 3.5%. the median number treated segments per patient was 4. No complication was encountered. All patients treated remained symptom free at a mean duration of follow up of 16 months. Direct current electrotherapy is an effective, painless and safe out-patient treatment method for grades 1 to 3 internal and mixed hemorrhoid disease.

Current status of nuclear cardiology: a limited review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Botvinick, E.H.; Dae, M.; Hattner, R.S.

1985-11-01

To summarize the current status of nuclear cardiology, the authors will focus on areas that the emphasize the specific advantages of nuclear cardiology methods: (a) their benign, noninvasive nature, (b) their pathophysiologic nature, and (c) the ease of their computer manipulation and analysis, permitting quantitative evaluation. The areas covered include: (a) blood pool scintigraphy and parametric imaging, (b) pharmacologic intervention for the diagnosis of ischemic heart disease, (c) scintigraphic studies for the diagnosis and prognosis of coronary artery disease, and (d) considerations of cost effectiveness.

Evaluating disease management program effectiveness: an introduction to time-series analysis.

PubMed

Linden, Ariel; Adams, John L; Roberts, Nancy

2003-01-01

Currently, the most widely used method in the disease management (DM) industry for evaluating program effectiveness is referred to as the "total population approach." This model is a pretest-posttest design, with the most basic limitation being that without a control group, there may be sources of bias and/or competing extraneous confounding factors that offer a plausible rationale explaining the change from baseline. Furthermore, with the current inclination of DM programs to use financial indicators rather than program-specific utilization indicators as the principal measure of program success, additional biases are introduced that may cloud evaluation results. This paper presents a non-technical introduction to time-series analysis (using disease-specific utilization measures) as an alternative, and more appropriate, approach to evaluating DM program effectiveness than the current total population approach.

Foreign animal disease outbreaks, the animal welfare implications for Canada: Risks apparent from international experience

PubMed Central

Whiting, Terry L.

2003-01-01

Any outbreak of an Office International des Épizooties List A disease, such as classical swine fever or foot and mouth disease, has severe consequences for animal welfare, livestock production, exports of animals and animal products, and the environment. The public concern with the animal welfare effects of methods of disease eradication that result in the destruction of large numbers of uninfected animals has initiated a reconsideration of disease eradication policy in Europe. In many recent List A disease epizootics, the financial cost of addressing animal welfare concerns in healthy animals has greatly exceeded the cost of stamping out disease in infected herds. In the event of a similar incursion in Canada, the number of animals subject to welfare slaughter will be far greater than the number of infected animals killed. Current national disease eradication plans in Canada do not address the animal welfare component of disease control methods. PMID:14601676

Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

PubMed

Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

2016-01-01

To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350 cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

Using Propidium Monoazide as an Enrichment Step to Remove Extraneous DMA and Non-Viable Organisms for Cryptosporidium Genotyping

EPA Science Inventory

Cryptosporidium is an important protozoan parasite that continues to cause waterborne disease outbreaks worldwide. Current methods to monitor for Cryptosporidium oocysts in water are microscopy-based USEPA Methods 1622 and 1623. These methods assess total levels of oocysts in s...

Smoking-attributable medical expenditures by age, sex, and smoking status estimated using a relative risk approach☆

PubMed Central

Maciosek, Michael V.; Xu, Xin; Butani, Amy L.; Pechacek, Terry F.

2015-01-01

Objective To accurately assess the benefits of tobacco control interventions and to better inform decision makers, knowledge of medical expenditures by age, gender, and smoking status is essential. Method We propose an approach to distribute smoking-attributable expenditures by age, gender, and cigarette smoking status to reflect the known risks of smoking. We distribute hospitalization days for smoking-attributable diseases according to relative risks of smoking-attributable mortality, and use the method to determine national estimates of smoking-attributable expenditures by age, sex, and cigarette smoking status. Sensitivity analyses explored assumptions of the method. Results Both current and former smokers ages 75 and over have about 12 times the smoking-attributable expenditures of their current and former smoker counterparts 35–54 years of age. Within each age group, the expenditures of formers smokers are about 70% lower than current smokers. In sensitivity analysis, these results were not robust to large changes to the relative risks of smoking-attributable mortality which were used in the calculations. Conclusion Sex- and age-group-specific smoking expenditures reflect observed disease risk differences between current and former cigarette smokers and indicate that about 70% of current smokers’ excess medical care costs is preventable by quitting. PMID:26051203

Antibacterial activity of plant defensins against alfalfa crown rot pathogens

USDA-ARS?s Scientific Manuscript database

Alfalfa (Medicago sativa) is the fourth most widely grown crop in the United States. Alfalfa crown rot is a disease complex that severely decreases alfalfa stand density and productivity in all alfalfa-producing areas. Currently, there are no viable methods of disease control. Plant defensins are sm...

An extended set of yeast-based functional assays accurately identifies human disease mutations

PubMed Central

Sun, Song; Yang, Fan; Tan, Guihong; Costanzo, Michael; Oughtred, Rose; Hirschman, Jodi; Theesfeld, Chandra L.; Bansal, Pritpal; Sahni, Nidhi; Yi, Song; Yu, Analyn; Tyagi, Tanya; Tie, Cathy; Hill, David E.; Vidal, Marc; Andrews, Brenda J.; Boone, Charles; Dolinski, Kara; Roth, Frederick P.

2016-01-01

We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease- and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods. PMID:26975778

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations

PubMed Central

Caprilli, R; Gassull, M A; Escher, J C; Moser, G; Munkholm, P; Forbes, A; Hommes, D W; Lochs, H; Angelucci, E; Cocco, A; Vucelic, B; Hildebrand, H; Kolacek, S; Riis, L; Lukas, M; de Franchis, R; Hamilton, M; Jantschek, G; Michetti, P; O'Morain, C; Anwar, M M; Freitas, J L; Mouzas, I A; Baert, F; Mitchell, R; Hawkey, C J

2006-01-01

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease. PMID:16481630

Probing amyloid protein aggregation with optical superresolution methods: from the test tube to models of disease

PubMed Central

Kaminski, Clemens F.; Kaminski Schierle, Gabriele S.

2016-01-01

Abstract. The misfolding and self-assembly of intrinsically disordered proteins into insoluble amyloid structures are central to many neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Optical imaging of this self-assembly process in vitro and in cells is revolutionizing our understanding of the molecular mechanisms behind these devastating conditions. In contrast to conventional biophysical methods, optical imaging and, in particular, optical superresolution imaging, permits the dynamic investigation of the molecular self-assembly process in vitro and in cells, at molecular-level resolution. In this article, current state-of-the-art imaging methods are reviewed and discussed in the context of research into neurodegeneration. PMID:27413767

Targeting thyroid diseases with TSH receptor analogs.

PubMed

Galofré, Juan C; Chacón, Ana M; Latif, Rauf

2013-12-01

The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Discrimination of inflammatory bowel disease using Raman spectroscopy and linear discriminant analysis methods

NASA Astrophysics Data System (ADS)

Ding, Hao; Cao, Ming; DuPont, Andrew W.; Scott, Larry D.; Guha, Sushovan; Singhal, Shashideep; Younes, Mamoun; Pence, Isaac; Herline, Alan; Schwartz, David; Xu, Hua; Mahadevan-Jansen, Anita; Bi, Xiaohong

2016-03-01

Inflammatory bowel disease (IBD) is an idiopathic disease that is typically characterized by chronic inflammation of the gastrointestinal tract. Recently much effort has been devoted to the development of novel diagnostic tools that can assist physicians for fast, accurate, and automated diagnosis of the disease. Previous research based on Raman spectroscopy has shown promising results in differentiating IBD patients from normal screening cases. In the current study, we examined IBD patients in vivo through a colonoscope-coupled Raman system. Optical diagnosis for IBD discrimination was conducted based on full-range spectra using multivariate statistical methods. Further, we incorporated several feature selection methods in machine learning into the classification model. The diagnostic performance for disease differentiation was significantly improved after feature selection. Our results showed that improved IBD diagnosis can be achieved using Raman spectroscopy in combination with multivariate analysis and feature selection.

Targeting the neurovascular unit for treatment of neurological disorders.

PubMed

Vangilder, Reyna L; Rosen, Charles L; Barr, Taura L; Huber, Jason D

2011-06-01

Drug discovery for CNS disorders has been restricted by the inability for therapeutic agents to cross the blood-brain barrier (BBB). Moreover, current drugs aim to correct neuron cell signaling, thereby neglecting pathophysiological changes affecting other cell types of the neurovascular unit (NVU). Components of the NVU (pericytes, microglia, astrocytes, and neurons, and basal lamina) act as an intricate network to maintain the neuronal homeostatic microenvironment. Consequently, disruptions to this intricate cell network lead to neuron malfunction and symptoms characteristic of CNS diseases. A lack of understanding in NVU signaling cascades may explain why current treatments for CNS diseases are not curative. Current therapies treat symptoms by maintaining neuron function. Refocusing drug discovery to sustain NVU function may provide a better method of treatment by promoting neuron survival. In this review, we will examine current therapeutics for common CNS diseases, describe the importance of the NVU in cerebral homeostasis and discuss new possible drug targets and technologies that aim to improve treatment and drug delivery to the diseased brain. Copyright © 2011 Elsevier Inc. All rights reserved.

Uncovering the hidden: complexity and strategies for diagnosing latent tuberculosis.

PubMed

Flores-Valdez, Mario Alberto

2017-10-24

Tuberculosis produces two clinical manifestations: active and latent (non-apparent) disease. The latter is estimated to affect one-third of the world population and constitutes a source of continued transmission should the disease emerge from its hidden state (reactivation). Methods to diagnose latent TB have been evolving and aim to detect the disease in people who are truly infected with M. tuberculosis , versus those where other mycobacteria, or even other pathologies not related to TB, are present. The current use of proteomic and transcriptomic approaches may lead to improved detection methods in the coming years.

Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

PubMed Central

Maya, Lisandro; Villarreal, Francisco J.

2009-01-01

In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694

A bridging study for oxytetracycline in the edible fillet of rainbow trout: Analysis by a liquid chromatographic method and the official microbial inhibition assay

USGS Publications Warehouse

Stehly, G.R.; Gingerich, W.H.; Kiessling, C.R.; Cutting, J.H.

1999-01-01

Oxytetracycline (OTC) is a drug approved by the U.S. Food and Drug Administration (FDA) to control certain diseases in salmonids and catfish. OTC is also a likely control agent for diseases of other fish species and for other diseases of salmonids and catfish not currently on the label. One requirement for FDA to extend and expand the approval of this antibacterial agent to other fish species is residue depletion studies. The current regulatory method for OTC in fish tissue, based on microbial inhibition, lacks sensitivity and specificity. To conduct residue depletion studies for OTC in fish with a liquid chromatographic method, a bridging study was required to determine its relationship with the official microbial inhibition assay. Triplicate samples of rainbow trout fillet tissue fortified with OTC at 0.3, 0.6, 1.2, 2.4, 4.8, and 9.6 ppm and fillet tissue with incurred OTC at approximately 0.75, 1.5, and 3.75 ppm were analyzed by high-performance liquid chromatography (HPLC) and the microbial inhibition assay. The results indicated that the 2 methods are essentially identical in the tested range, with mean coefficients of variation of 1.05% for the HPLC method and 3.94% for the microbial inhibition assay.

Development of rapid hemocyte-based extraction methods for detection of hepatitis A virus and murine norovirus in contaminated oysters

USDA-ARS?s Scientific Manuscript database

The human enteric pathogens, hepatitis A virus and human norovirus, have been shown to contaminate molluscan shellfish and cause foodborne disease in consumers. Rapid viral extraction methods are needed to replace current time consuming methods, which use whole oysters or dissected tissues. In our ...

Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload.

PubMed

Koehl, Bérengère; Missud, Florence; Holvoet, Laurent; Ithier, Ghislaine; Sakalian-Black, Oliver; Haouari, Zinedine; Lesprit, Emmanuelle; Baruchel, André; Benkerrou, Malika

2017-03-14

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion. At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

NMR metabolomics analysis of the effect of elevated CO2 on wheat resistance to Fusarium head blight

USDA-ARS?s Scientific Manuscript database

Fusarium head blight (FHB), primarily induced by the filamentous ascomycete Fusarium graminearum (Fg), is one of the most damaging diseases in wheat and other small grain cereals worldwide. Current methods for disease control include utilization of less susceptible cultivars and treatment with fungi...

Virology, Immunology, and Clinical Course of HIV Infection.

ERIC Educational Resources Information Center

McCutchan, J. Allen

1990-01-01

Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

Characterizing and mapping resistance in synthetic-derived wheat to Rhizoctonia root rot in a green bridge environment

USDA-ARS?s Scientific Manuscript database

Root rot caused by Rhizoctonia species is an economically important soilborne disease of spring planted wheat in growing regions of the Pacific Northwest (PNW). The main method of controlling the disease currently is through tillage, which deters farmers from adopting the benefits of minimal tillage...

Common Periodontal Diseases of Children and Adolescents

PubMed Central

Al-Kahtani, Salem; Al-Duhaimi, Saad

2014-01-01

Background. Since 2000, studies, experiments, and clinical observations revealed high prevalence of periodontal diseases among children and adolescents. Therefore, this paper was designed to provide an update for dental practitioners on epidemiology, microbiology, pathology, prevention, diagnosis, and treatment of periodontal diseases in children and adolescents. Methods. This paper reviews the current literature concerning periodontal diseases in pediatric dentistry. It includes MEDLINE database search using key terms: “periodontal diseases in children,” “Periodontal diseasesin adolescents,” “periodontal diseases risk factors,” “microbiology of periodontal diseases,” “classification of periodontal diseases,” “epidemiology of periodontal diseases,” and “treatment of periodontal diseases.” Articles were evaluated by title and/or abstract and relevance to pediatric dentistry. Sixty-five citations were selected by this method and by the references within the chosen articles. A review of the comprehensive textbooks on pediatric dentistry and periodontology was done. Some recommendations were based on the opinions of experienced researchers and clinicians, when data were inconclusive. PMID:25053946

Palliative Care in Huntington Disease: Personal Reflections and a Review of the Literature

PubMed Central

Tarolli, Christopher G.; Chesire, Amy M.; Biglan, Kevin M.

2017-01-01

Background Huntington disease is a fatal, autosomal dominant, neurodegenerative disorder manifest by the triad of a movement disorder, behavioral disturbances, and dementia. At present, no curative or disease modifying therapies exist for the condition and current treatments are symptomatic. Palliative care is an approach to care that focuses on symptom relief, patient and caregiver support, and end of life care. There is increasing evidence of the benefit of palliative care throughout the course of neurodegenerative conditions including Parkinson disease and amyotrophic lateral sclerosis. However, beyond its application at the end of life, little is known about the role of palliative care in Huntington disease. Methods In this article, we discuss what is known about palliative care in Huntington disease, specifically related to early disease burden, caregiver burnout, advance care planning, and end of life care. Results We provide a review of the current literature and discuss our own care practices. Discussion We conclude by discussing questions that remain unanswered and positing ideas for future work in the field. PMID:28428907

CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations

PubMed Central

Fogleman, Sarah; Santana, Casey; Bishop, Casey; Miller, Alyssa; Capco, David G

2016-01-01

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient’s nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy. PMID:27725916

Stem cell and genetic therapies for the fetus.

PubMed

Pearson, Erik G; Flake, Alan W

2013-02-01

The prenatal diagnosis and management of congenital disease has made significant progress over the previous decade. Currently, fetal therapy (including open surgery and fetoscopic intervention) provides therapeutic options for a range of congenital anomalies; however, it is restricted to the treatment of fetal pathophysiology. Improvements in prenatal screening and the early diagnosis of genetic disease allow for preemptive treatment of anticipated postnatal disease by stem cell or genetic therapy. While currently awaiting clinical application, in utero stem cell therapy has made significant advances in overcoming the engraftment and immunologic barriers in both murine and pre-clinical large animal models. Likewise, proof in principle for fetal gene therapy has been demonstrated in rodent and large animal systems as a method to prevent the onset of inherited genetic disease; however, safety and ethical risks still need to be addressed prior to human application. In this review, we examine the current status and future direction of stem cell and genetic therapy for the fetus. Copyright © 2013. Published by Elsevier Inc.

Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

PubMed Central

George, Mark S; Aston-Jones, Gary

2010-01-01

Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies. PMID:19693003

Chromosome preference of disease genes and vectorization for the prediction of non-coding disease genes.

PubMed

Peng, Hui; Lan, Chaowang; Liu, Yuansheng; Liu, Tao; Blumenstein, Michael; Li, Jinyan

2017-10-03

Disease-related protein-coding genes have been widely studied, but disease-related non-coding genes remain largely unknown. This work introduces a new vector to represent diseases, and applies the newly vectorized data for a positive-unlabeled learning algorithm to predict and rank disease-related long non-coding RNA (lncRNA) genes. This novel vector representation for diseases consists of two sub-vectors, one is composed of 45 elements, characterizing the information entropies of the disease genes distribution over 45 chromosome substructures. This idea is supported by our observation that some substructures (e.g., the chromosome 6 p-arm) are highly preferred by disease-related protein coding genes, while some (e.g., the 21 p-arm) are not favored at all. The second sub-vector is 30-dimensional, characterizing the distribution of disease gene enriched KEGG pathways in comparison with our manually created pathway groups. The second sub-vector complements with the first one to differentiate between various diseases. Our prediction method outperforms the state-of-the-art methods on benchmark datasets for prioritizing disease related lncRNA genes. The method also works well when only the sequence information of an lncRNA gene is known, or even when a given disease has no currently recognized long non-coding genes.

Chromosome preference of disease genes and vectorization for the prediction of non-coding disease genes

PubMed Central

Peng, Hui; Lan, Chaowang; Liu, Yuansheng; Liu, Tao; Blumenstein, Michael; Li, Jinyan

2017-01-01

Disease-related protein-coding genes have been widely studied, but disease-related non-coding genes remain largely unknown. This work introduces a new vector to represent diseases, and applies the newly vectorized data for a positive-unlabeled learning algorithm to predict and rank disease-related long non-coding RNA (lncRNA) genes. This novel vector representation for diseases consists of two sub-vectors, one is composed of 45 elements, characterizing the information entropies of the disease genes distribution over 45 chromosome substructures. This idea is supported by our observation that some substructures (e.g., the chromosome 6 p-arm) are highly preferred by disease-related protein coding genes, while some (e.g., the 21 p-arm) are not favored at all. The second sub-vector is 30-dimensional, characterizing the distribution of disease gene enriched KEGG pathways in comparison with our manually created pathway groups. The second sub-vector complements with the first one to differentiate between various diseases. Our prediction method outperforms the state-of-the-art methods on benchmark datasets for prioritizing disease related lncRNA genes. The method also works well when only the sequence information of an lncRNA gene is known, or even when a given disease has no currently recognized long non-coding genes. PMID:29108274

A Primer on Wastewater Treatment, July 1976 Edition.

ERIC Educational Resources Information Center

Environmental Protection Agency, Washington, DC. Office of Public Affairs.

This general information pamphlet is concerned with the types of wastewater treatment systems, the need for further treatment, and advanced methods of treating waste. Current methods are described, illustrated and evaluated. Pollution problems from oxygen-demanding wastes, disease-causing agents, plant nutrients, synthetic chemicals, inorganic…

[Nutritional status of adults with cystic fibrosis - current methods of assessment].

PubMed

Szabla, Anna; Skorupa, Wojciech; Milewska, Magdalena; Weker, Halina

2015-11-01

Cystic fibrosis (CF) is one of the most frequent monogenic disease in the Caucasian population, inherited in an autosomal recessive pattern. This is a multiple organ disease and its main manifestations include pulmonary and gastrointestinal dysfunction. The exocrine pancreatic deficiency results in impaired digestion and absorption what may lead to malnutrition and vitamins and minerals deficiencies. The life expectancy of cystic fibrosis patients has been increasing over the past years, so there is a need to verify usefulness of existing or create new methods of nutritional status assessment. The aim of this paper was presentation current data on the methods of assessment and monitoring of nutritional status. Particular attention has been paid to appropriate nutritional support in prevention and treatment of malnutrition patients with cystic fibrosis. On the basis of recent literature we can conclude that the advanced nutritional status assessment is recommended in patient with CF by using anthropometrical methods, body composition analysis and biochemical data. Good nutritional status is connected with pulmonary functions, quality and life length. © 2015 MEDPRESS.

Oxidative Stress in Kidney Diseases: The Cause or the Consequence?

PubMed

Krata, Natalia; Zagożdżon, Radosław; Foroncewicz, Bartosz; Mucha, Krzysztof

2018-06-01

Exaggerated oxidative stress (OS) is usually considered as a disturbance in regular function of an organism. The excessive levels of OS mediators may lead to major damage within the organism's cells and tissues. Therefore, the OS-associated biomarkers may be considered as new diagnostic tools of various diseases. In nephrology, researchers are looking for alternative methods replacing the renal biopsy in patients with suspicion of chronic kidney disease (CKD). Currently, CKD is a frequent health problem in world population, which can lead to progressive loss of kidney function and eventually to end-stage renal disease. The course of CKD depends on the primary disease. It is assumed that one of the factors influencing the course of CKD might be OS. In the current work, we review whether monitoring the OS-associated biomarkers in nephrology patients can support the decision-making process regarding diagnosis, prognostication and treatment initiation.

New magnetic resonance imaging methods in nephrology

PubMed Central

Zhang, Jeff L.; Morrell, Glen; Rusinek, Henry; Sigmund, Eric; Chandarana, Hersh; Lerman, Lilach O.; Prasad, Pottumarthi Vara; Niles, David; Artz, Nathan; Fain, Sean; Vivier, Pierre H.; Cheung, Alfred K.; Lee, Vivian S.

2013-01-01

Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics. PMID:24067433

Ensemble positive unlabeled learning for disease gene identification.

PubMed

Yang, Peng; Li, Xiaoli; Chua, Hon-Nian; Kwoh, Chee-Keong; Ng, See-Kiong

2014-01-01

An increasing number of genes have been experimentally confirmed in recent years as causative genes to various human diseases. The newly available knowledge can be exploited by machine learning methods to discover additional unknown genes that are likely to be associated with diseases. In particular, positive unlabeled learning (PU learning) methods, which require only a positive training set P (confirmed disease genes) and an unlabeled set U (the unknown candidate genes) instead of a negative training set N, have been shown to be effective in uncovering new disease genes in the current scenario. Using only a single source of data for prediction can be susceptible to bias due to incompleteness and noise in the genomic data and a single machine learning predictor prone to bias caused by inherent limitations of individual methods. In this paper, we propose an effective PU learning framework that integrates multiple biological data sources and an ensemble of powerful machine learning classifiers for disease gene identification. Our proposed method integrates data from multiple biological sources for training PU learning classifiers. A novel ensemble-based PU learning method EPU is then used to integrate multiple PU learning classifiers to achieve accurate and robust disease gene predictions. Our evaluation experiments across six disease groups showed that EPU achieved significantly better results compared with various state-of-the-art prediction methods as well as ensemble learning classifiers. Through integrating multiple biological data sources for training and the outputs of an ensemble of PU learning classifiers for prediction, we are able to minimize the potential bias and errors in individual data sources and machine learning algorithms to achieve more accurate and robust disease gene predictions. In the future, our EPU method provides an effective framework to integrate the additional biological and computational resources for better disease gene predictions.

A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells.

PubMed

Christensen, Chloe L; Choy, Francis Y M

2017-02-24

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient's cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient's cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed.

Attractor Signaling Models for Discovery of Combinatorial Therapies

DTIC Science & Technology

2014-11-01

acquired!drug!resistance!still!makes!the!5-year!survival!rate!for!this! disease ! less!than!15%.!Over!the!years,!many!specific!mechanisms!associated!with!drug...Moreover, it has been suggested that a biological system in a chronic or therapy- resistant disease state can be seen as a network that has become...therapeutic methods for complex diseases such as cancer. Even if our knowledge of biological networks is incomplete, rapid progress is currently being

Nanotechnology in diagnosis and treatment of coronary artery disease.

PubMed

Karimi, Mahdi; Zare, Hossein; Bakhshian Nik, Amirala; Yazdani, Narges; Hamrang, Mohammad; Mohamed, Elmira; Sahandi Zangabad, Parham; Moosavi Basri, Seyed Masoud; Bakhtiari, Leila; Hamblin, Michael R

2016-01-01

Nanotechnology could provide a new complementary approach to treat coronary artery disease (CAD) which is now one of the biggest killers in the Western world. The course of events, which leads to atherosclerosis and CAD, involves many biological factors and cellular disease processes which may be mitigated by therapeutic methods enhanced by nanotechnology. Nanoparticles can provide a variety of delivery systems for cargoes such as drugs and genes that can address many problems within the arteries. In order to improve the performance of current stents, nanotechnology provides different nanomaterial coatings, in addition to controlled-release nanocarriers, to prevent in-stent restenosis. Nanotechnology can increase the efficiency of drugs, improve local and systematic delivery to atherosclerotic plaques and reduce the inflammatory or angiogenic response after intravascular intervention. Nanocarriers have potential for delivery of imaging and diagnostic agents to precisely targeted destinations. This review paper will cover the current applications and future outlook of nanotechnology, as well as the main diagnostic methods, in the treatment of CAD.

Nanotechnology in diagnosis and treatment of coronary artery disease

PubMed Central

Karimi, Mahdi; Zare, Hossein; Bakhshian Nik, Amirala; Yazdani, Narges; Hamrang, Mohammad; Mohamed, Elmira; Sahandi Zangabad, Parham; Moosavi Basri, Seyed Masoud; Bakhtiari, Leila; Hamblin, Michael R

2016-01-01

Nanotechnology could provide a new complementary approach to treat coronary artery disease (CAD) which is now one of the biggest killers in the Western world. The course of events, which leads to atherosclerosis and CAD, involves many biological factors and cellular disease processes which may be mitigated by therapeutic methods enhanced by nanotechnology. Nanoparticles can provide a variety of delivery systems for cargoes such as drugs and genes that can address many problems within the arteries. In order to improve the performance of current stents, nanotechnology provides different nanomaterial coatings, in addition to controlled-release nanocarriers, to prevent in-stent restenosis. Nanotechnology can increase the efficiency of drugs, improve local and systematic delivery to atherosclerotic plaques and reduce the inflammatory or angiogenic response after intravascular intervention. Nanocarriers have potential for delivery of imaging and diagnostic agents to precisely targeted destinations. This review paper will cover the current applications and future outlook of nanotechnology, as well as the main diagnostic methods, in the treatment of CAD. PMID:26906471

Harnessing Aptamers to Overcome Challenges in Gluten Detection

PubMed Central

Miranda-Castro, Rebeca; de-los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J.; Lobo-Castañón, María Jesús

2016-01-01

Celiac disease is a lifelong autoimmune disorder triggered by foods containing gluten, the storage protein in wheat, rye, and barley. The rapidly escalating number of patients diagnosed with this disease poses a great challenge to both food industry and authorities to guarantee food safety for all. Therefore, intensive efforts are being made to establish minimal disease-eliciting doses of gluten and consequently to improve gluten-free labeling. These efforts depend to a high degree on the availability of methods capable of detecting the protein in food samples at levels as low as possible. Current analytical approaches rely on the use of antibodies as selective recognition elements. With limited sensitivity, these methods exhibit some deficiencies that compromise the accuracy of the obtained results. Aptamers provide an ideal alternative for designing biosensors for fast and selective measurement of gluten in foods. This article highlights the challenges in gluten detection, the current status of the use of aptamers for solving this problem, and what remains to be done to move these systems into commercial applications. PMID:27104578

Investigation on uric acid biosensor model for enzyme layer thickness for the application of arthritis disease diagnosis.

PubMed

Parthasarathy, P; Vivekanandan, S

2018-12-01

Uric acid biosensors for arthritis disease has been developed for the specific selection of uricase enzyme film thickness coated over the TiO 2 -CeO 2 nano-composite matrix is modelled mathematically. This model is purely based on R-diffusion conditions with irreversible first-order catalytic reactions. By arithmetical method, the impact of the thickness of enzyme layer on the current response of the biosensor was explored. This article displays a structure for choice of the enzyme layer thickness, guaranteeing the adequately stable sensitivity of a biosensor in a required extent of the maximal enzymatic rate. The numerical outcomes showed subjective and sensible quantitative information for oxidation current due to uric acid also shows the maximum change in the biosensor current response due to the change in membrane thickness, which will be more suitable for uric acid biosensor for the application of arthritis disease diagnosis.

Interactive Introductory Nutrition Course Focusing on Disease Prevention Increased Whole-Grain Consumption by College Students

ERIC Educational Resources Information Center

Ha, Eun-Jeong; Caine-Bish, Natalie

2011-01-01

Objective: To estimate current consumption of whole grains in college students and determine whether there would be an increase in whole-grain consumption after the students completed an interactive introductory nutrition course focusing on disease prevention. Methods: Eighty college students, 18-24 years old, participated in the study. Grain and…

Speech Motor Sequence Learning: Acquisition and Retention in Parkinson Disease and Normal Aging

ERIC Educational Resources Information Center

Whitfield, Jason A.; Goberman, Alexander M.

2017-01-01

Purpose: The aim of the current investigation was to examine speech motor sequence learning in neurologically healthy younger adults, neurologically healthy older adults, and individuals with Parkinson disease (PD) over a 2-day period. Method: A sequential nonword repetition task was used to examine learning over 2 days. Participants practiced a…

Fungicide Injection to Control Dutch Elm Disease: Understanding the Options

Treesearch

Linda Haugen; Mark Stennes

1999-01-01

In some situations, injecting trees with fungicides is an effective treatment for the management of Dutch elm disease (DED). Several injection products are on the market, and various means of application are recommended. Each product and method has pros and cons. The "best" product depends on the individual tree? its current condition, the objectives of the...

Rural-Urban Disparities in Health-Related Quality of Life within Disease Categories of Veterans

ERIC Educational Resources Information Center

Weeks, William B.; Wallace, Amy E.; Wang, Stanley; Lee, Austin; Kazis, Lewis E.

2006-01-01

Context: Compared to their urban counterparts, rural veterans have been found to have lower health-related quality of life. Purpose: To determine whether these disparities persist when examining disease categories of rural and urban veterans. Methods: We obtained survey data on 748,216 veterans who were current or anticipated Veterans Health…

Changes to Articulatory Kinematics in Response to Loudness Cues in Individuals with Parkinson's Disease

ERIC Educational Resources Information Center

Darling, Meghan; Huber, Jessica E.

2011-01-01

Purpose: Individuals with Parkinson's disease (PD) exhibit differences in displacement and velocity of the articulators as compared with older adults. The purpose of the current study was to examine effects of 3 loudness cues on articulatory movement patterns in individuals with PD. Method: Nine individuals diagnosed with idiopathic PD and 9 age-…

Effects of an Extended Version of the Lee Silverman Voice Treatment on Voice and Speech in Parkinson's Disease

ERIC Educational Resources Information Center

Spielman, Jennifer; Ramig, Lorraine O.; Mahler, Leslie; Halpern, Angela; Gavin, William J.

2007-01-01

Purpose: The present study examined vocal SPL, voice handicap, and speech characteristics in Parkinson's disease (PD) following an extended version of the Lee Silverman Voice Treatment (LSVT), to help determine whether current treatment dosages can be altered without compromising clinical outcomes. Method: Twelve participants with idiopathic PD…

Surgical treatment of haemorrhoidal disease – the current situation in Poland

PubMed Central

Dziki, Lukasz; Trzcinski, Radzislaw; Buczynski, Jaroslaw; Kreisel, Anna; Skoneczny, Mariusz; Dziki, Adam

2016-01-01

Introduction In cases of haemorrhoidal disease resistant to conservative treatment, surgical treatment is necessary to relieve the symptoms. Aim To investigate the current methods used by Polish surgeons. Material and methods Surveys were distributed to members of the Association of Polish Surgeons (APS), in which participants were asked a number of closed-ended questions regarding haemorrhoidal disease and the way they treated suffering patients Results Out of the 1523 members of APS who received questionnaires, responses were received from 807 (52.9%) members. The Milligan-Morgan technique was indicated by 72.5% of surgeons as a leading surgical treatment, followed by Ligasure (15.5%), Ferguson (3.5%), DGHL (3.5%), other methods (3.5%), Parks (1.7%), and Longo (0%). The majority of participants (93%) indicated from 0 to 1 life threatening complications, 5% – from 2 to 3, and 2% > 4. A total of 83% of participants use a single dose of antibiotics prior to surgery. Conclusions The Milligan-Morgan technique is the preferred method. The majority of procedures are performed in regional hospitals and university departments, and less commonly in private practices. The vast majority of surgeons in Poland are not convinced about the stapler technique, justifying this fact with the possibility of developing serious complications PMID:27350838

Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease

PubMed Central

Jacques, ZANEVELD; Feng, WANG; Xia, WANG; Rui, CHEN

2013-01-01

Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine. PMID:23393028

Novel Methods in Disease Biogeography: A Case Study with Heterosporosis

PubMed Central

Escobar, Luis E.; Qiao, Huijie; Lee, Christine; Phelps, Nicholas B. D.

2017-01-01

Disease biogeography is currently a promising field to complement epidemiology, and ecological niche modeling theory and methods are a key component. Therefore, applying the concepts and tools from ecological niche modeling to disease biogeography and epidemiology will provide biologically sound and analytically robust descriptive and predictive analyses of disease distributions. As a case study, we explored the ecologically important fish disease Heterosporosis, a relatively poorly understood disease caused by the intracellular microsporidian parasite Heterosporis sutherlandae. We explored two novel ecological niche modeling methods, the minimum-volume ellipsoid (MVE) and the Marble algorithm, which were used to reconstruct the fundamental and the realized ecological niche of H. sutherlandae, respectively. Additionally, we assessed how the management of occurrence reports can impact the output of the models. Ecological niche models were able to reconstruct a proxy of the fundamental and realized niche for this aquatic parasite, identifying specific areas suitable for Heterosporosis. We found that the conceptual and methodological advances in ecological niche modeling provide accessible tools to update the current practices of spatial epidemiology. However, careful data curation and a detailed understanding of the algorithm employed are critical for a clear definition of the assumptions implicit in the modeling process and to ensure biologically sound forecasts. In this paper, we show how sensitive MVE is to the input data, while Marble algorithm may provide detailed forecasts with a minimum of parameters. We showed that exploring algorithms of different natures such as environmental clusters, climatic envelopes, and logistic regressions (e.g., Marble, MVE, and Maxent) provide different scenarios of potential distribution. Thus, no single algorithm should be used for disease mapping. Instead, different algorithms should be employed for a more informed and complete understanding of the pathogen or parasite in question. PMID:28770215

A molecular insight into papaya leaf curl-a severe viral disease.

PubMed

Varun, Priyanka; Ranade, S A; Saxena, Sangeeta

2017-11-01

Papaya leaf curl disease (PaLCuD) caused by papaya leaf curl virus (PaLCuV) not only affects yield but also plant growth and fruit size and quality of papaya and is one of the most damaging and economically important disease. Management of PaLCuV is a challenging task due to diversity of viral strains, the alternate hosts, and the genomic complexities of the viruses. Several management strategies currently used by plant virologists to broadly control or eliminate the viruses have been discussed. In the absence of such strategies in the case of PaLCuV at present, the few available options to control the disease include methods like removal of affected plants from the field, insecticide treatments against the insect vector (Bemisia tabaci), and gene-specific control through transgenic constructs. This review presents the current understanding of papaya leaf curl disease, genomic components including satellite DNA associated with the virus, wide host and vector range, and management of the disease and suggests possible generic resistance strategies.

Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation

PubMed Central

2013-01-01

Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases. PMID:24341630

Rapid detection of hepatitis A virus and murine norovirus in hemocytes of contaminated oysters

USDA-ARS?s Scientific Manuscript database

The human enteric pathogens, hepatitis A virus and human norovirus, have been shown to contaminate molluscan shellfish and cause foodborne disease in consumers. Rapid viral extraction methods are needed to replace current time consuming methods, which use whole oysters or dissected tissues. In our ...

Designing and Implementation of Fuzzy Case-based Reasoning System on Android Platform Using Electronic Discharge Summary of Patients with Chronic Kidney Diseases

PubMed Central

Tahmasebian, Shahram; Langarizadeh, Mostafa; Ghazisaeidi, Marjan; Mahdavi-Mazdeh, Mitra

2016-01-01

Introduction: Case-based reasoning (CBR) systems are one of the effective methods to find the nearest solution to the current problems. These systems are used in various spheres as well as industry, business, and economy. The medical field is not an exception in this regard, and these systems are nowadays used in the various aspects of diagnosis and treatment. Methodology: In this study, the effective parameters were first extracted from the structured discharge summary prepared for patients with chronic kidney diseases based on data mining method. Then, through holding a meeting with experts in nephrology and using data mining methods, the weights of the parameters were extracted. Finally, fuzzy system has been employed in order to compare the similarities of current case and previous cases, and the system was implemented on the Android platform. Discussion: The data on electronic discharge records of patients with chronic kidney diseases were entered into the system. The measure of similarity was assessed using the algorithm provided in the system, and then compared with other known methods in CBR systems. Conclusion: Developing Clinical fuzzy CBR system used in Knowledge management framework for registering specific therapeutic methods, Knowledge sharing environment for experts in a specific domain and Powerful tools at the point of care. PMID:27708490

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

PubMed

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

2018-06-01

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

Brightness-preserving fuzzy contrast enhancement scheme for the detection and classification of diabetic retinopathy disease.

PubMed

Datta, Niladri Sekhar; Dutta, Himadri Sekhar; Majumder, Koushik

2016-01-01

The contrast enhancement of retinal image plays a vital role for the detection of microaneurysms (MAs), which are an early sign of diabetic retinopathy disease. A retinal image contrast enhancement method has been presented to improve the MA detection technique. The success rate on low-contrast noisy retinal image analysis shows the importance of the proposed method. Overall, 587 retinal input images are tested for performance analysis. The average sensitivity and specificity are obtained as 95.94% and 99.21%, respectively. The area under curve is found as 0.932 for the receiver operating characteristics analysis. The classifications of diabetic retinopathy disease are also performed here. The experimental results show that the overall MA detection method performs better than the current state-of-the-art MA detection algorithms.

Assessing nutritional status in children with chronic liver disease.

PubMed

Taylor, Rachel M; Dhawan, Anil

2005-12-01

The metabolic changes compounded by anorexia associated with chronic liver disease adversely affect growth in children. In many cases, this requires the administration of artificial nutritional support. It is important in this group of patients that those who are becoming nutritionally depleted are identified quickly and in those receiving artificial nutritional support, the effectiveness is monitored. The current review is an examination of methods available to assess nutritional status. These include anthropometry, methods available in the laboratory and a selection of less commonly used methods undergoing evaluation at research level. A brief discussion accompanies each technique, outlining the limitations of its use in children with chronic liver disease. The review concludes with an outline of how nutritional status should be assessed in this group of children, and suggests further research.

Ocular biomarkers of Alzheimer's disease.

PubMed

Heaton, George R; Davis, Benjamin M; Turner, Lisa A; Cordeiro, Maria F

2015-01-01

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterised clinically by a progressive decline in executive functions, memory and cognition. Classic neuropathological hallmarks of AD include intracellular hyper-phosphorylated tau protein which forms neurofibrillary tangles (NFT), and extracellular deposits of amyloid β (Aβ) protein, the primary constituent of senile plaques (SP). The gradual process of pathogenic amyloid accumulation is thought to occur 10-20 years prior to symptomatic manifestation. Advance detection of these deposits therefore offers a highly promising avenue for prodromal AD diagnosis. Currently, the most sophisticated method of 'probable AD' diagnosis is via neuroimaging or cerebral spinal fluid (CSF) biomarker analysis. Whilst these methods have reported a high degree of diagnostic specificity and accuracy, they fall significantly short in terms of practicality; they are often highly invasive, expensive or unsuitable for large-scale population screening. In recent years, ocular screening has received substantial attention from the scientific community due to its potential for non-invasive and inexpensive central nervous system (CNS) imaging. In this appraisal we build upon our previous reviews detailing ocular structural and functional changes in AD (Retinal manifestations of Alzheimer's disease, Alzheimer's disease and Retinal Neurodegeneration) and consider their use as biomarkers. In addition, we present an overview of current advances in the use of fluorescent reporters to detect AD pathology through non-invasive retinal imaging.

Plant pathogen nanodiagnostic techniques: forthcoming changes?

PubMed Central

Khiyami, Mohammad A.; Almoammar, Hassan; Awad, Yasser M.; Alghuthaymi, Mousa A.; Abd-Elsalam, Kamel A.

2014-01-01

Plant diseases are among the major factors limiting crop productivity. A first step towards managing a plant disease under greenhouse and field conditions is to correctly identify the pathogen. Current technologies, such as quantitative polymerase chain reaction (Q-PCR), require a relatively large amount of target tissue and rely on multiple assays to accurately identify distinct plant pathogens. The common disadvantage of the traditional diagnostic methods is that they are time consuming and lack high sensitivity. Consequently, developing low-cost methods to improve the accuracy and rapidity of plant pathogens diagnosis is needed. Nanotechnology, nano particles and quantum dots (QDs) have emerged as essential tools for fast detection of a particular biological marker with extreme accuracy. Biosensor, QDs, nanostructured platforms, nanoimaging and nanopore DNA sequencing tools have the potential to raise sensitivity, specificity and speed of the pathogen detection, facilitate high-throughput analysis, and to be used for high-quality monitoring and crop protection. Furthermore, nanodiagnostic kit equipment can easily and quickly detect potential serious plant pathogens, allowing experts to help farmers in the prevention of epidemic diseases. The current review deals with the application of nanotechnology for quicker, more cost-effective and precise diagnostic procedures of plant diseases. Such an accurate technology may help to design a proper integrated disease management system which may modify crop environments to adversely affect crop pathogens. PMID:26740775

An efficient 3-D eddy-current solver using an independent impedance method for transcranial magnetic stimulation.

PubMed

De Geeter, Nele; Crevecoeur, Guillaume; Dupre, Luc

2011-02-01

In many important bioelectromagnetic problem settings, eddy-current simulations are required. Examples are the reduction of eddy-current artifacts in magnetic resonance imaging and techniques, whereby the eddy currents interact with the biological system, like the alteration of the neurophysiology due to transcranial magnetic stimulation (TMS). TMS has become an important tool for the diagnosis and treatment of neurological diseases and psychiatric disorders. A widely applied method for simulating the eddy currents is the impedance method (IM). However, this method has to contend with an ill conditioned problem and consequently a long convergence time. When dealing with optimal design problems and sensitivity control, the convergence rate becomes even more crucial since the eddy-current solver needs to be evaluated in an iterative loop. Therefore, we introduce an independent IM (IIM), which improves the conditionality and speeds up the numerical convergence. This paper shows how IIM is based on IM and what are the advantages. Moreover, the method is applied to the efficient simulation of TMS. The proposed IIM achieves superior convergence properties with high time efficiency, compared to the traditional IM and is therefore a useful tool for accurate and fast TMS simulations.

The Challenges and Advances in Diagnosis of Vector-Borne Diseases: Where Do We Stand?

PubMed

Kuleš, Josipa; Potocnakova, Lenka; Bhide, Katarina; Tomassone, Laura; Fuehrer, Hans-Peter; Horvatić, Anita; Galan, Asier; Guillemin, Nicolas; Nižić, Petra; Mrljak, Vladimir; Bhide, Mangesh

2017-05-01

Vector-borne diseases (VBD) are of major importance to human and animal health. In recent years, VBD have been emerging or re-emerging in many geographical areas, alarming new disease threats and economic losses. The precise diagnosis of many of these diseases still remains a major challenge because of the lack of comprehensive data available on accurate and reliable diagnostic methods. Here, we conducted a systematic and in-depth review of the former, current, and upcoming techniques employed for the diagnosis of VBD.

Current status of treating neurodegenerative disease with induced pluripotent stem cells.

PubMed

Pen, A E; Jensen, U B

2017-01-01

Degenerative diseases of the brain have proven challenging to treat, let alone cure. One of the treatment options is the use of stem cell therapy, which has been under investigation for several years. However, treatment with stem cells comes with a number of drawbacks, for instance the source of these cells. Currently, a number of options are tested to produce stem cells, although the main issues of quantity and ethics remain for most of them. Over recent years, the potential of induced pluripotent stem cells (iPSCs) has been widely investigated and these cells seem promising for production of numerous different tissues both in vitro and in vivo. One of the major advantages of iPSCs is that they can be made autologous and can provide a sufficient quantity of cells by culturing, making the use of other stem cell sources unnecessary. As the first descriptions of iPSC production with the transcription factors Sox2, Klf4, Oct4 and C-Myc, called the Yamanaka factors, a variety of methods has been developed to convert somatic cells from all germ layers to pluripotent stem cells. Improvement of these methods is necessary to increase the efficiency of reprogramming, the quality of pluripotency and the safety of these cells before use in human trials. This review focusses on the current accomplishments and remaining challenges in the production and use of iPSCs for treatment of neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A new low-cost procedure for detecting nucleic acids in low-incidence samples: a case study of detecting spores of Paenibacillus larvae from bee debris.

PubMed

Ryba, Stepan; Kindlmann, Pavel; Titera, Dalibor; Haklova, Marcela; Stopka, Pavel

2012-10-01

American foulbrood, because of its virulence and worldwide spread, is currently one of the most dangerous diseases of honey bees. Quick diagnosis of this disease is therefore vitally important. For its successful eradication, however, all the hives in the region must be tested. This is time consuming and costly. Therefore, a fast and sensitive method of detecting American foulbrood is needed. Here we present a method that significantly reduces the number of tests needed by combining batches of samples from different hives. The results of this method were verified by testing each sample. A simulation study was used to compare the efficiency of the new method with testing all the samples and to develop a decision tool for determining when best to use the new method. The method is suitable for testing large numbers of samples (over 100) when the incidence of the disease is low (10% or less).

Salicylic and jasmonic acid pathways are necessary for defence against Dickeya solani as revealed by a novel method for Blackleg disease screening of in vitro grown potato.

PubMed

Burra, D D; Mühlenbock, P; Andreasson, E

2015-09-01

Potato is major crop ensuring food security in Europe, and blackleg disease is increasingly causing losses in yield and during storage. Recently, one blackleg pathogen, Dickeya solani has been shown to be spreading in Northern Europe that causes aggressive disease development. Currently, identification of tolerant commercial potato varieties has been unsuccessful; this is confounded by the complicated etiology of the disease and a strong environmental influence on disease development. There is currently a lack of efficient testing systems. Here, we describe a system for quantification of blackleg symptoms on shoots of sterile in vitro potato plants, which saves time and space compared to greenhouse and existing field assays. We found no evidence for differences in infection between the described in vitro-based screening method and existing greenhouse assays. This system facilitates efficient screening of blackleg disease response of potato plants independent of other microorganisms and variable environmental conditions. We therefore used the in vitro screening method to increase understanding of plant mechanisms involved in blackleg disease development by analysing disease response of hormone- related (salicylic and jasmonic acid) transgenic potato plants. We show that both jasmonic (JA) and salicylic (SA) acid pathways regulate tolerance to blackleg disease in potato, a result unlike previous findings in Arabidopsis defence response to necrotrophic bacteria. We confirm this by showing induction of a SA marker, pathogenesis-related protein 1 (StPR1), and a JA marker, lipoxygenase (StLOX), in Dickeya solani infected in vitro potato plants. We also observed that tubers of transgenic potato plants were more susceptible to soft rot compared to wild type, suggesting a role for SA and JA pathways in general tolerance to Dickeya. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

A Semi-Supervised Learning Algorithm for Predicting Four Types MiRNA-Disease Associations by Mutual Information in a Heterogeneous Network.

PubMed

Zhang, Xiaotian; Yin, Jian; Zhang, Xu

2018-03-02

Increasing evidence suggests that dysregulation of microRNAs (miRNAs) may lead to a variety of diseases. Therefore, identifying disease-related miRNAs is a crucial problem. Currently, many computational approaches have been proposed to predict binary miRNA-disease associations. In this study, in order to predict underlying miRNA-disease association types, a semi-supervised model called the network-based label propagation algorithm is proposed to infer multiple types of miRNA-disease associations (NLPMMDA) by mutual information derived from the heterogeneous network. The NLPMMDA method integrates disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity information of miRNAs and diseases to construct a heterogeneous network. NLPMMDA is a semi-supervised model which does not require verified negative samples. Leave-one-out cross validation (LOOCV) was implemented for four known types of miRNA-disease associations and demonstrated the reliable performance of our method. Moreover, case studies of lung cancer and breast cancer confirmed effective performance of NLPMMDA to predict novel miRNA-disease associations and their association types.

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.

PubMed

Braverman, Nancy E; Raymond, Gerald V; Rizzo, William B; Moser, Ann B; Wilkinson, Mark E; Stone, Edwin M; Steinberg, Steven J; Wangler, Michael F; Rush, Eric T; Hacia, Joseph G; Bose, Mousumi

2016-03-01

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care. Copyright © 2015 Elsevier Inc. All rights reserved.

Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

PubMed Central

Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

2016-01-01

INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

Nutraceuticals and their preventive or potential therapeutic value in Parkinson's disease.

PubMed

Chao, Jianfei; Leung, Yen; Wang, Mingfu; Chang, Raymond Chuen-Chung

2012-07-01

Parkinson's disease (PD) is the second most common aging-related disorder in the world, after Alzheimer's disease. It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and other parts of the brain, leading to motor impairment, cognitive impairment, and dementia. Current treatment methods, such as L-dopa therapy, are focused only on relieving symptoms and delaying progression of the disease. To date, there is no known cure for PD, making prevention of PD as important as ever. More than a decade of research has revealed a number of major risk factors, including oxidative stress and mitochondrial dysfunction. Moreover, numerous nutraceuticals have been found to target and attenuate these risk factors, thereby preventing or delaying the progression of PD. These nutraceuticals include vitamins C, D, E, coenzyme Q10, creatine, unsaturated fatty acids, sulfur-containing compounds, polyphenols, stilbenes, and phytoestrogens. This review examines the role of nutraceuticals in the prevention or delay of PD as well as the mechanisms of action of nutraceuticals and their potential applications as therapeutic agents, either alone or in combination with current treatment methods. © 2012 International Life Sciences Institute.

Current Experimental Studies of Gene Therapy in Parkinson's Disease

PubMed Central

Lin, Jing-ya; Xie, Cheng-long; Zhang, Su-fang; Yuan, Weien; Liu, Zhen-Guo

2017-01-01

Parkinson's disease (PD) was characterized by late-onset, progressive dopamine neuron loss and movement disorders. The progresses of PD affected the neural function and integrity. To date, most researches had largely addressed the dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia hampered the use of the drug. And the mechanism of PD is so complicated that it's hard to solve the problem by just add drugs. Researchers began to focus on the genetic underpinnings of Parkinson's disease, searching for new method that may affect the neurodegeneration processes in it. In this paper, we reviewed current delivery methods used in gene therapies for PD, we also summarized the primary target of the gene therapy in the treatment of PD, such like neurotrophic factor (for regeneration), the synthesis of neurotransmitter (for prolong the duration of L-dopa), and the potential proteins that might be a target to modulate via gene therapy. Finally, we discussed RNA interference therapies used in Parkinson's disease, it might act as a new class of drug. We mainly focus on the efficiency and tooling features of different gene therapies in the treatment of PD. PMID:28515689

Advances in the microbial etiology and pathogenesis of early childhood caries

PubMed Central

Hajishengallis, Evlambia; Parsaei, Yassmin; Klein, Marlise I.; Koo, Hyun

2016-01-01

Early childhood caries (ECC) is one of the most prevalent infectious diseases affecting children worldwide. ECC is an aggressive form of dental caries, which left untreated, can result in rapid and extensive cavitation in teeth (rampant caries) that is painful and costly to treat. Furthermore, it affects mostly children from impoverished background, and thus constitutes a major challenge in public health. The disease is a prime example of the consequences arising from complex, dynamic interactions between microorganisms, host and diet, leading to the establishment of highly pathogenic (cariogenic) biofilms. To date, there are no effective methods to identify those at risk of developing ECC or control the disease in affected children. Recent advances in deep-sequencing technologies, novel imaging methods and (meta)proteomics-metabolomics approaches provide an unparalleled potential to reveal new insights to illuminate our current understanding about the etiology and pathogenesis of the disease. In this concise review, we provide a broader perspective about the etiology and pathogenesis of ECC based on previous and current knowledge on biofilm matrix, microbial diversity and host-microbe interactions which could have direct implications for developing new approaches for improved risk assessment and prevention of this devastating and costly childhood health condition. PMID:26714612

Nano-sized Contrast Agents to Non-Invasively Detect Renal Inflammation by Magnetic Resonance Imaging

PubMed Central

Thurman, Joshua M.; Serkova, Natalie J.

2013-01-01

Several molecular imaging methods have been developed that employ nano-sized contrast agents to detect markers of inflammation within tissues. Renal inflammation contributes to disease progression in a wide range of autoimmune and inflammatory diseases, and a biopsy is currently the only method of definitively diagnosing active renal inflammation. However, the development of new molecular imaging methods that employ contrast agents capable of detecting particular immune cells or protein biomarkers will allow clinicians to evaluate inflammation throughout the kidneys, and to assess a patient's response to immunomodulatory drugs. These imaging tools will improve our ability to validate new therapies and to optimize the treatment of individual patients with existing therapies. This review describes the clinical need for new methods of monitoring renal inflammation, and recent advances in the development of nano-sized contrast agents for detection of inflammatory markers of renal disease. PMID:24206601

Advances in fish vaccine delivery.

PubMed

Plant, Karen P; Lapatra, Scott E

2011-12-01

Disease prevention is essential to the continued development of aquaculture around the world. Vaccination is the most effective method of combating disease and currently there are a number of vaccines commercially available for use in fish. The majority of aquatic vaccines are delivered by injection, which is by far the most effective method when compared to oral or immersion deliveries. However it is labor intensive, costly and not feasible for large numbers of fish under 20 g. Attempts to develop novel oral and immersion delivery methods have resulted in varying degrees of success but may have great potential for the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diagnosis and Updates in Celiac Disease.

PubMed

Shannahan, Sarah; Leffler, Daniel A

2017-01-01

Celiac disease is an autoimmune disorder induced by gluten in genetically susceptible individuals. It can result in intraintestinal and extraintestinal manifestations of disease including diarrhea, weight loss, anemia, osteoporosis, or lymphoma. Diagnosis of celiac disease is made through initial serologic testing and then confirmed by histopathologic examination of duodenal biopsies. Generally celiac disease is a benign disorder with a good prognosis in those who adhere to a gluten-free diet. However, in refractory disease, complications may develop that warrant additional testing with more advanced radiologic and endoscopic methods. This article reviews the current strategy to diagnose celiac disease and the newer modalities to assess for associated complications. Copyright © 2016 Elsevier Inc. All rights reserved.

Current Dilemmas in Defining the Boundaries of Disease.

PubMed

Doust, Jenny; Jean Walker, Mary; Rogers, Wendy A

2017-08-01

Boorse's biostatistical theory states that diseases should be defined in ways that reflect disturbances of biological function and that are objective and value free. We use three examples from contemporary medicine that demonstrate the complex issues that arise when defining the boundaries of disease: polycystic ovary syndrome, chronic kidney disease, and myocardial infarction. We argue that the biostatistical theory fails to provide sufficient guidance on where the boundaries of disease should be drawn, contains ambiguities relating to choice of reference class, and is out of step with medical processes for identifying disease boundaries. Although proponents of the biostatistical theory might regard these practical issues as irrelevant to the aim of providing a theoretical account of disease, we take them to indicate the need for a theoretical account that is adequate for current needs-including limiting new forms of medicalization that are driven by the identification of disease based on dysfunction. Our processes for determining the boundaries for disease need to recognize that there is no value-free method for making these decisions. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of water-based foam and inert-gas mass emergency depopulation methods.

PubMed

Alphin, R L; Rankin, M K; Johnson, K J; Benson, E R

2010-03-01

Current control strategies for avian influenza (AI) and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. Selection of the best method of emergency mass depopulation involves maximizing human health and safety while minimizing disease spread and animal welfare concerns. Proper selection must ensure that the method is compatible with the species, age, housing type, and disposal options. No one single method is appropriate for all situations. Gassing is one of the accepted methods for euthanatizing poultry. Whole-house, partial-house, or containerized gassing procedures are currently used. The use of water-based foam was developed for emergency mass depopulation and was conditionally approved by the United States Department of Agriculture in 2006. Research has been done comparing these different methods; parameters such as time to brain death, consistency of time to brain death, and pretreatment and posttreatment corticosterone stress levels were considered. In Europe, the use of foam with carbon dioxide is preferred over conventional water-based foam. A recent experiment comparing CO2 gas, foam with CO2 gas, and foam without CO2 gas depopulation methods was conducted with the use of electroencephalometry results. Foam was as consistent as CO2 gassing and more consistent than argon-CO2 gassing. There were no statistically significant differences between foam methods.

Pregnancy and mesenchimal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).

PubMed

Radetskaya, L S; Makatsariya, A D; Bitsadze, V O; Khizroeva, J K

2018-07-01

The objective of this article is to attract the attention of clinical physicians to the rare but extremely relevant clinical pathology of mesenchymal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia) and especially specific characteristics of such diseases during pregnancy. Connective tissue pathology can cover different organs and systems, symptoms of the same disease can vary in different patients thus making diagnostics significantly difficult. Here clinical diagnostic criteria and methods of molecular diagnostics of diseases are described. The pathogenesis of mesenchymal dysplasias is not currently well understood. For the patients with mesenchymal dysplasias pregnancy is fraught with high risk of life-threatening complications. The preferred delivery method for such patients is caesarean section.

Decision support for evidence-based integration of disease control: A proof of concept for malaria and schistosomiasis

PubMed Central

Graeden, Ellie; Kerr, Justin; Sorrell, Erin M.; Katz, Rebecca

2018-01-01

Managing infectious disease requires rapid and effective response to support decision making. The decisions are complex and require understanding of the diseases, disease intervention and control measures, and the disease-relevant characteristics of the local community. Though disease modeling frameworks have been developed to address these questions, the complexity of current models presents a significant barrier to community-level decision makers in using the outputs of the most scientifically robust methods to support pragmatic decisions about implementing a public health response effort, even for endemic diseases with which they are already familiar. Here, we describe the development of an application available on the internet, including from mobile devices, with a simple user interface, to support on-the-ground decision-making for integrating disease control programs, given local conditions and practical constraints. The model upon which the tool is built provides predictive analysis for the effectiveness of integration of schistosomiasis and malaria control, two diseases with extensive geographical and epidemiological overlap, and which result in significant morbidity and mortality in affected regions. Working with data from countries across sub-Saharan Africa and the Middle East, we present a proof-of-principle method and corresponding prototype tool to provide guidance on how to optimize integration of vertical disease control programs. This method and tool demonstrate significant progress in effectively translating the best available scientific models to support practical decision making on the ground with the potential to significantly increase the efficacy and cost-effectiveness of disease control. Author summary Designing and implementing effective programs for infectious disease control requires complex decision-making, informed by an understanding of the diseases, the types of disease interventions and control measures available, and the disease-relevant characteristics of the local community. Though disease modeling frameworks have been developed to address these questions and support decision-making, the complexity of current models presents a significant barrier to on-the-ground end users. The picture is further complicated when considering approaches for integration of different disease control programs, where co-infection dynamics, treatment interactions, and other variables must also be taken into account. Here, we describe the development of an application available on the internet with a simple user interface, to support on-the-ground decision-making for integrating disease control, given local conditions and practical constraints. The model upon which the tool is built provides predictive analysis for the effectiveness of integration of schistosomiasis and malaria control, two diseases with extensive geographical and epidemiological overlap. This proof-of-concept method and tool demonstrate significant progress in effectively translating the best available scientific models to support pragmatic decision-making on the ground, with the potential to significantly increase the impact and cost-effectiveness of disease control. PMID:29649260

Pharmacological and phytochemical screening of Palestinian traditional medicinal plants Erodium laciniatum and Lactuca orientalis.

PubMed

Jaradat, Nidal; AlMasri, Motasem; Zaid, Abdel Naser; Othman, Dua'a Ghazi

2017-09-01

Various epidemiological studies showed that herbal remedies containing polyphenols may protect against various diseases such as cancers, vascular diseases and inflammatory pathologies. Currently, such groups of bioactive compounds have become a subject of many antimicrobials and antioxidant investigations. Accordingly, the current study aimed to conduct biological and phytochemical screening for two Palestinian traditional medicinal plants, Erodium laciniatum and Lactuca orientalis. Current plants phytoconstituents and their antioxidant activities were evaluated by using standard phytochemical methods; meanwhile, antimicrobial activities were estimated by using several types of American Type Culture Collection and multidrug resistant clinical isolates by using agar diffusion well-variant, agar diffusion disc-variant and broth microdilution methods. Phytochemical screenings showed that L. orientalis and E. laciniatum contain mixtures of secondary and primary metabolites Moreover, total flavonoid, tannins and phenols content in E. laciniatum extract were higher than the L. orientalis extracts with almost the same antioxidant potentials. Additionally, both plants organic and aqueous extracts showed various potentials of antimicrobial activity Conclusions: Overall, the studied species have a mixture of phytochemicals, flavonoids, phenols and tannins also have antioxidant and antimicrobial activities which approved their folk uses in treatments of infectious and Alzheimer diseases and simultaneously can be used as therapeutic agents in the pharmaceutical industries.

Rare high-impact disease variants: properties and identifications.

PubMed

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.

Immunoprevalence to Six Waterborne Pathogens in Beachgoers at Boquerón Beach, Puerto Rico: Application of a Microsphere-Based Salivary Antibody Multiplex Immunoassay

EPA Science Inventory

Waterborne infectious diseases are a major public health concern worldwide. Few methods have been established that are capable of measuring human exposure to multiple waterborne pathogens simultaneously using non-invasive samples such as saliva. Most current methods measure expos...

Wolbachia: A biological control strategy against arboviral diseases.

PubMed

Mohanty, Ipsita; Rath, Animesha; Mahapatra, Namita; Hazra, Rupenangshu K

2016-01-01

Vector-borne diseases particularly those transmitted by mosquitoes like Dengue are among the leading causes of mortality and morbidity in human population. There are no effective vaccines or treatment against dengue fever till date and the control methods are limited. So, new approaches are urgently in need to reverse these trends. Vector control is currently the primary intervention tool. Strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. Wolbachia an endosymbiont of arthropod vectors is being explored as a novel ecofriendly control strategy. Studies in Drosophila have shown that Wolbachia can confer resistance to diverse RNA viruses and protect flies from virus-induced mortality. This review was focused on biology of the Wolbachia and its implication as a control measure for arboviral diseases mainly Dengue and Chikungunya.

Quantitative Pulmonary Imaging Using Computed Tomography and Magnetic Resonance Imaging

PubMed Central

Washko, George R.; Parraga, Grace; Coxson, Harvey O.

2011-01-01

Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic, and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy and function. In this review we will focus on two of them, x-ray computed tomography and magnetic resonance imaging. Following a brief introduction of each method we detail some of the most recent work being done to characterize smoking-related lung disease and the clinical applications of such knowledge. PMID:22142490

Cardiac gene therapy: Recent advances and future directions.

PubMed

Mason, Daniel; Chen, Yu-Zhe; Krishnan, Harini Venkata; Sant, Shilpa

2015-10-10

Gene therapy has the potential to serve as an adaptable platform technology for treating various diseases. Cardiovascular disease is a major cause of mortality in the developed world and genetic modification is steadily becoming a more plausible method to repair and regenerate heart tissue. Recently, new gene targets to treat cardiovascular disease have been identified and developed into therapies that have shown promise in animal models. Some of these therapies have advanced to clinical testing. Despite these recent successes, several barriers must be overcome for gene therapy to become a widely used treatment of cardiovascular diseases. In this review, we evaluate specific genetic targets that can be exploited to treat cardiovascular diseases, list the important delivery barriers for the gene carriers, assess the most promising methods of delivering the genetic information, and discuss the current status of clinical trials involving gene therapies targeted to the heart. Copyright © 2015 Elsevier B.V. All rights reserved.

A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells

PubMed Central

Christensen, Chloe L.; Choy, Francis Y. M.

2017-01-01

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient’s cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient’s cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed. PMID:28933359

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Salazar, Jennifer; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

2017-05-01

The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.

Overall, the goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning willmore » be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. Finally, ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.« less

[Laboratory diagnosis of toxoplasmosis].

PubMed

Strhársky, J; Mad'arová, L; Klement, C

2009-04-01

Under Central European climatic conditions, toxoplasmosis is one of the most common human parasitic diseases. A wide range of methods for both direct and indirect detection of the causative agent are currently available for the laboratory diagnosis of toxoplasmosis. The purpose of the article is to review the history of the discovery of the causative agent of toxoplasmosis and how laboratory diagnostic methods were developed and improved. The main emphasis is placed on current options in the diagnosis of Toxoplasma gondii, more precisely on the serodiagnosis and new trends in molecular biology-based techniques.

Current practice in laboratory diagnostics of autoimmune diseases in Croatia. 
Survey of the Working group for laboratory diagnostics of autoimmune diseases of the Croatian Society of Medical Biochemistry and Laboratory Medicine

PubMed Central

Kuna, Andrea Tešija; Đerek, Lovorka; Kozmar, Ana; Drvar, Vedrana

2016-01-01

Introduction With the trend of increasing incidence of autoimmune diseases, laboratories are faced with exponential growth of the requests for tests relating the diagnosis of these diseases. Unfortunately, the lack of laboratory personnel experienced in this specific discipline of laboratory diagnostic, as well as an unawareness of a method limitation often results in confusion for clinicians. The aim was to gain insight into number and type of Croatian laboratories that perform humoral diagnostics with the final goal to improve and harmonize laboratory diagnostics of autoimmune diseases in Croatia. Materials and methods In order to get insight into current laboratory practice two questionnaires, consisting of 42 questions in total, were created. Surveys were conducted using SurveyMonkey application and were sent to 88 medical biochemistry laboratories in Croatia for the first survey. Out of 33 laboratories that declared to perform diagnostic from the scope, 19 were selected for the second survey based on the tests they pleaded to perform. The survey comprised questions regarding autoantibody hallmarks of systemic autoimmune diseases while regarding organ-specific autoimmune diseases was limited to diseases of liver, gastrointestinal and nervous system. Results Response rate was high with 80 / 88 (91%) laboratories which answered the first questionnaire, and 19 / 19 (1.0) for the second questionnaire. Obtained results of surveys indicate high heterogeneity in the performance of autoantibody testing among laboratories in Croatia. Conclusions Results indicate the need of creating recommendations and algorithms in order to harmonize the approach to laboratory diagnostics of autoimmune diseases in Croatia. PMID:27812306

The Prediction of Drug-Disease Correlation Based on Gene Expression Data.

PubMed

Cui, Hui; Zhang, Menghuan; Yang, Qingmin; Li, Xiangyi; Liebman, Michael; Yu, Ying; Xie, Lu

2018-01-01

The explosive growth of high-throughput experimental methods and resulting data yields both opportunity and challenge for selecting the correct drug to treat both a specific patient and their individual disease. Ideally, it would be useful and efficient if computational approaches could be applied to help achieve optimal drug-patient-disease matching but current efforts have met with limited success. Current approaches have primarily utilized the measureable effect of a specific drug on target tissue or cell lines to identify the potential biological effect of such treatment. While these efforts have met with some level of success, there exists much opportunity for improvement. This specifically follows the observation that, for many diseases in light of actual patient response, there is increasing need for treatment with combinations of drugs rather than single drug therapies. Only a few previous studies have yielded computational approaches for predicting the synergy of drug combinations by analyzing high-throughput molecular datasets. However, these computational approaches focused on the characteristics of the drug itself, without fully accounting for disease factors. Here, we propose an algorithm to specifically predict synergistic effects of drug combinations on various diseases, by integrating the data characteristics of disease-related gene expression profiles with drug-treated gene expression profiles. We have demonstrated utility through its application to transcriptome data, including microarray and RNASeq data, and the drug-disease prediction results were validated using existing publications and drug databases. It is also applicable to other quantitative profiling data such as proteomics data. We also provide an interactive web interface to allow our Prediction of Drug-Disease method to be readily applied to user data. While our studies represent a preliminary exploration of this critical problem, we believe that the algorithm can provide the basis for further refinement towards addressing a large clinical need.

Host-microbe interactions in distal airways: relevance to chronic airway diseases.

PubMed

Martin, Clémence; Burgel, Pierre-Régis; Lepage, Patricia; Andréjak, Claire; de Blic, Jacques; Bourdin, Arnaud; Brouard, Jacques; Chanez, Pascal; Dalphin, Jean-Charles; Deslée, Gaetan; Deschildre, Antoine; Gosset, Philippe; Touqui, Lhousseine; Dusser, Daniel

2015-03-01

This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways. Copyright ©ERS 2015.

Using Image Processing to Determine Emphysema Severity

NASA Astrophysics Data System (ADS)

McKenzie, Alexander; Sadun, Alberto

2010-10-01

Currently X-rays and computerized tomography (CT) scans are used to detect emphysema, but other tests are required to accurately quantify the amount of lung that has been affected by the disease. These images clearly show if a patient has emphysema, but are unable by visual scan alone, to quantify the degree of the disease, as it presents as subtle, dark spots on the lung. Our goal is to use these CT scans to accurately diagnose and determine emphysema severity levels in patients. This will be accomplished by performing several different analyses of CT scan images of several patients representing a wide range of severity of the disease. In addition to analyzing the original CT data, this process will convert the data to one and two bit images and will then examine the deviation from a normal distribution curve to determine skewness. Our preliminary results show that this method of assessment appears to be more accurate and robust than the currently utilized methods, which involve looking at percentages of radiodensities in the air passages of the lung.

Iron deposition quantification: Applications in the brain and liver.

PubMed

Yan, Fuhua; He, Naying; Lin, Huimin; Li, Ruokun

2018-06-13

Iron has long been implicated in many neurological and other organ diseases. It is known that over and above the normal increases in iron with age, in certain diseases there is an excessive iron accumulation in the brain and liver. MRI is a noninvasive means by which to image the various structures in the brain in three dimensions and quantify iron over the volume of the object of interest. The quantification of iron can provide information about the severity of iron-related diseases as well as quantify changes in iron for patient follow-up and treatment monitoring. This article provides an overview of current MRI-based methods for iron quantification, specifically for the brain and liver, including: signal intensity ratio, R 2 , R2*, R2', phase, susceptibility weighted imaging and quantitative susceptibility mapping (QSM). Although there are numerous approaches to measuring iron, R 2 and R2* are currently preferred methods in imaging the liver and QSM has become the preferred approach for imaging iron in the brain. 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Celiac Disease: Diagnosis.

PubMed

Byrne, Greg; Feighery, Conleth F

2015-01-01

Historically the diagnosis of celiac disease has relied upon clinical, serological, and histological evidence. In recent years the use of sensitive serological methods has meant an increase in the diagnosis of celiac disease. The heterogeneous nature of the disorder presents a challenge in the study and diagnosis of the disease with patients varying from subclinical or latent disease to patients with overt symptoms. Furthermore the related gluten-sensitive disease dermatitis herpetiformis, while distinct in some respects, shares clinical and serological features with celiac disease. Here we summarize current best practice for the diagnosis of celiac disease and briefly discuss newer approaches. The advent of next-generation assays for diagnosis and newer clinical protocols may result in more sensitive screening and ultimately the possible replacement of the intestinal biopsy as the gold standard for celiac disease diagnosis.

Current Advances in Detection and Treatment of Babesiosis

PubMed Central

Mosqueda, J; Olvera-Ramírez, A; Aguilar-Tipacamú, G; Cantó, GJ

2012-01-01

Babesiosis is a disease with a world-wide distribution affecting many species of mammals principally cattle and man. The major impact occurs in the cattle industry where bovine babesiosis has had a huge economic effect due to loss of meat and beef production of infected animals and death. Nowadays to those costs there must be added the high cost of tick control, disease detection, prevention and treatment. In almost a century and a quarter since the first report of the disease, the truth is: there is no a safe and efficient vaccine available, there are limited chemotherapeutic choices and few low-cost, reliable and fast detection methods. Detection and treatment of babesiosis are important tools to control babesiosis. Microscopy detection methods are still the cheapest and fastest methods used to identify Babesia parasites although their sensitivity and specificity are limited. Newer immunological methods are being developed and they offer faster, more sensitive and more specific options to conventional methods, although the direct immunological diagnoses of parasite antigens in host tissues are still missing. Detection methods based on nucleic acid identification and their amplification are the most sensitive and reliable techniques available today; importantly, most of those methodologies were developed before the genomics and bioinformatics era, which leaves ample room for optimization. For years, babesiosis treatment has been based on the use of very few drugs like imidocarb or diminazene aceturate. Recently, several pharmacological compounds were developed and evaluated, offering new options to control the disease. With the complete sequence of the Babesia bovis genome and the B. bigemina genome project in progress, the post-genomic era brings a new light on the development of diagnosis methods and new chemotherapy targets. In this review, we will present the current advances in detection and treatment of babesiosis in cattle and other animals, with additional reference to several apicomplexan parasites. PMID:22360483

Incidence of bacterial diseases associated with irrigation methods on onions (Allium cepa).

PubMed

Chorolque, A; Pozzo Ardizzi, C; Pellejero, G; Aschkar, G; García Navarro, F J; Jiménez Ballesta, R

2018-04-24

In the last decade, diseases of bacterial origin in onions have increased and this has led to significant losses in production. These diseases are currently observed in both the Old and New Worlds. The aim of the experimental work reported here was to evaluate whether the irrigation method influences the incidence of diseases of bacterial origin. In cases where the inoculum was natural, the initial incidence of Soft Bacterial Rot was not manifested in any treatment in the first year, whereas at the end of the conservation period all treatments had increased incidences of infection. Sprinkler irrigation (8%) was statistically differentiated from the other treatments, for which the final incidence was similar (4.5%). For all irrigation treatments, the final incidence of Bacterial Soft Rot decreased or remained stable towards the end of the cycle, with the exception of sprinkler irrigation in 2015, which increased. It can be inferred from the results that the irrigation method does have an influence on the incidence of diseases of bacterial origin in the post-harvest stage for onions. This article is protected by copyright. All rights reserved.

Work package 4 report: Broodfish testing for bacterial infections

USGS Publications Warehouse

Michel, Christian; Elliott, Diane G.; Jansson, Eva; Urdaci, Maria; Midtlyng, Paul J.

2005-01-01

This report summarises current scientific information and experience obtained with various methods for testing of salmonid broodfish or spawn for bacterial kidney disease (BKD - Renibacterium salmoninarum infection) in order to prevent vertical transmission of the organism to the offspring. Assessment is also being performed for Flavobacterium psychrophilum infections causing rainbow trout fry syndrome (RTFS) or bacterial coldwater disease (CWD), and for Piscirickettsia salmonis infection causing salmon rickettsial syndrome (SRS) in salmonid fish species. Methods for screening to document the absence of BKD in fish populations are well established. Some of them have also proven successful for testing individual fish from infected populations in order to avoid vertical transmission of the infectious agent. Several diagnostic methods for flavobacteriosis and piscirickettsiosis have also been established but none of them, as yet, has been validated for use in programmes to prevent vertical transmission of disease. Priority subjects for further research in order to improve the management and control of these vertically transmissible fish diseases are suggested.

Personalized Exposure Assessment: Promising Approaches for Human Environmental Health Research

PubMed Central

Weis, Brenda K.; Balshaw, David; Barr, John R.; Brown, David; Ellisman, Mark; Lioy, Paul; Omenn, Gilbert; Potter, John D.; Smith, Martyn T.; Sohn, Lydia; Suk, William A.; Sumner, Susan; Swenberg, James; Walt, David R.; Watkins, Simon; Thompson, Claudia; Wilson, Samuel H.

2005-01-01

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a “toolbox” of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure–disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs. PMID:16002370

Review of methods to prevent and reduce the risk of Lyme disease.

PubMed

Lindsay, L R; Ogden, N H; Schofield, S W

2015-06-04

Cases of Lyme disease and areas with self-sustaining populations of vector ticks are increasing in Canada. This trend is expected to continue. Preventing Lyme disease will therefore become relevant to an increasing number of Canadians. To summarize methods for reducing the risk of tick bites and preventing transmission once a tick is feeding. A literature search was conducted to identify methods to reduce the risk of tick bites and the abundance of vector ticks, as well as the risk of becoming infected with the Lyme disease pathogen, Borrelia burgdorferi (BB), if bitten by a vector tick. Current approaches to reducing the risk of tick bites or preventing infection with BB once bitten are largely reliant on the individual. They include use of topical repellents, use of protective clothing, avoidance of risk areas and removing ticks soon (ideally within a day) after they attach. These methods are efficacious, but constrained by user adherence. Other approaches such as landscape modification or the use of acaricides to control ticks, have shown promise in other countries, but have not been widely adopted in Canada. Lyme disease will continue to present a threat in Canada. In additional to the existing interventions for prevention of tick bites and Lyme disease, there is a need for new tools to help reduce the risk of Lyme disease to Canadians.

Mathematical methods for protein science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, W.; Istrail, S.; Atkins, J.

1997-12-31

Understanding the structure and function of proteins is a fundamental endeavor in molecular biology. Currently, over 100,000 protein sequences have been determined by experimental methods. The three dimensional structure of the protein determines its function, but there are currently less than 4,000 structures known to atomic resolution. Accordingly, techniques to predict protein structure from sequence have an important role in aiding the understanding of the Genome and the effects of mutations in genetic disease. The authors describe current efforts at Sandia to better understand the structure of proteins through rigorous mathematical analyses of simple lattice models. The efforts have focusedmore » on two aspects of protein science: mathematical structure prediction, and inverse protein folding.« less

Extrapolation-Based References Improve Motion and Eddy-Current Correction of High B-Value DWI Data: Application in Parkinson's Disease Dementia.

PubMed

Nilsson, Markus; Szczepankiewicz, Filip; van Westen, Danielle; Hansson, Oskar

2015-01-01

Conventional motion and eddy-current correction, where each diffusion-weighted volume is registered to a non diffusion-weighted reference, suffers from poor accuracy for high b-value data. An alternative approach is to extrapolate reference volumes from low b-value data. We aim to compare the performance of conventional and extrapolation-based correction of diffusional kurtosis imaging (DKI) data, and to demonstrate the impact of the correction approach on group comparison studies. DKI was performed in patients with Parkinson's disease dementia (PDD), and healthy age-matched controls, using b-values of up to 2750 s/mm2. The accuracy of conventional and extrapolation-based correction methods was investigated. Parameters from DTI and DKI were compared between patients and controls in the cingulum and the anterior thalamic projection tract. Conventional correction resulted in systematic registration errors for high b-value data. The extrapolation-based methods did not exhibit such errors, yielding more accurate tractography and up to 50% lower standard deviation in DKI metrics. Statistically significant differences were found between patients and controls when using the extrapolation-based motion correction that were not detected when using the conventional method. We recommend that conventional motion and eddy-current correction should be abandoned for high b-value data in favour of more accurate methods using extrapolation-based references.

Lung function imaging methods in Cystic Fibrosis pulmonary disease.

PubMed

Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

2017-05-17

Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

A simple method for measuring porcine circovirus 2 whole virion particles and standardizing vaccine formulation.

PubMed

Zanotti, Cinzia; Amadori, Massimo

2015-03-01

Porcine Circovirus 2 (PCV2) is involved in porcine circovirus-associated disease, that causes great economic losses to the livestock industry worldwide. Vaccination against PCV2 proved to be very effective in reducing disease occurrence and it is currently performed on a large scale. Starting from a previous model concerning Foot-and Mouth Disease Virus antigens, we developed a rapid and simple method to quantify PCV2 whole virion particles in inactivated vaccines. This procedure, based on sucrose gradient analysis and fluorometric evaluation of viral genomic content, allows for a better standardization of the antigen payload in vaccine batches. It also provides a valid indication of virion integrity. Most important, such a method can be applied to whole virion vaccines regardless of the production procedures, thus enabling meaningful comparisons on a common basis. In a future batch consistency approach to PCV2 vaccine manufacture, our procedure represents a valuable tool to improve in-process controls and to guarantee conformity of the final product with passmarks for approval. This might have important repercussions in terms of reduced usage of animals for vaccine batch release, in the framework of the current 3Rs policy. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

An Ultrasonographic Periodontal Probe

NASA Astrophysics Data System (ADS)

Bertoncini, C. A.; Hinders, M. K.

2010-02-01

Periodontal disease, commonly known as gum disease, affects millions of people. The current method of detecting periodontal pocket depth is painful, invasive, and inaccurate. As an alternative to manual probing, an ultrasonographic periodontal probe is being developed to use ultrasound echo waveforms to measure periodontal pocket depth, which is the main measure of periodontal disease. Wavelet transforms and pattern classification techniques are implemented in artificial intelligence routines that can automatically detect pocket depth. The main pattern classification technique used here, called a binary classification algorithm, compares test objects with only two possible pocket depth measurements at a time and relies on dimensionality reduction for the final determination. This method correctly identifies up to 90% of the ultrasonographic probe measurements within the manual probe's tolerance.

Cluster and Multiple Correspondence Analyses in Rheumatology: Paths to Uncovering Relationships in a Sea of Data.

PubMed

Han, Lu; Benseler, Susanne M; Tyrrell, Pascal N

2018-05-01

Rheumatic diseases encompass a wide range of conditions caused by inflammation and dysregulation of the immune system resulting in organ damage. Research in these heterogeneous diseases benefits from multivariate methods. The aim of this review was to describe and evaluate current literature in rheumatology regarding cluster analysis and correspondence analysis. A systematic review showed an increase in studies making use of these 2 methods. However, standardization in how these methods are applied and reported is needed. Researcher expertise was determined to be the main barrier to considering these approaches, whereas education and collaborating with a biostatistician were suggested ways forward. Copyright © 2018 Elsevier Inc. All rights reserved.

Gene-Environment Interactions in Cardiovascular Disease

PubMed Central

Flowers, Elena; Froelicher, Erika Sivarajan; Aouizerat, Bradley E.

2011-01-01

Background Historically, models to describe disease were exclusively nature-based or nurture-based. Current theoretical models for complex conditions such as cardiovascular disease acknowledge the importance of both biologic and non-biologic contributors to disease. A critical feature is the occurrence of interactions between numerous risk factors for disease. The interaction between genetic (i.e. biologic, nature) and environmental (i.e. non-biologic, nurture) causes of disease is an important mechanism for understanding both the etiology and public health impact of cardiovascular disease. Objectives The purpose of this paper is to describe theoretical underpinnings of gene-environment interactions, models of interaction, methods for studying gene-environment interactions, and the related concept of interactions between epigenetic mechanisms and the environment. Discussion Advances in methods for measurement of genetic predictors of disease have enabled an increasingly comprehensive understanding of the causes of disease. In order to fully describe the effects of genetic predictors of disease, it is necessary to place genetic predictors within the context of known environmental risk factors. The additive or multiplicative effect of the interaction between genetic and environmental risk factors is often greater than the contribution of either risk factor alone. PMID:21684212

Optical Diagnostics for Classifying Stages of Dental Erythema

NASA Astrophysics Data System (ADS)

Davis, Matthew J.; Splinter, Robert; Lockhart, Peter; Brennan, Michael; Fox, Philip C.

2003-02-01

Periodontal disease is a term used to describe an inflammatory disease affecting the tissues surrounding and supporting the teeth. Periodontal diseases are some of the most common chronic disorders, which affect humans in all parts of the world. Treatment usually involves the removal of plaque and calculus by scaling and polishing the tooth. In some cases a surgical reduction of hyperplastic tissue, may also be required. In addition, periodontitis is a risk factor for systemic disorders such as cardiovascular disease and diabetes. Current detection methods are qualitative, inaccurate, and often do not detect the periodontal disease in its early, reversible stages. Therefore, an early detection method should be implemented identifying the relationship of periodontal disease with erythema. In order to achieve this purpose we are developing an optical erythema meter to diagnose the periodontal disease in its reversible, gingival stage. The discrimination between healthy and diseased gum tissue was made by using the reflection of two illuminating wavelengths provided by light emitting diodes operating at wavelengths that target the absorption and reflection spectra of the highlights of each particular tissue type (healthy or diseased, and what kind of disease). Three different color gels could successfully be distinguished with a statistical significance of P < 0.05.

Using mixed methods to investigate factors influencing reporting of livestock diseases: a case study among smallholders in Bolivia.

PubMed

Limon, Georgina; Lewis, Elisa G; Chang, Yu-Mei; Ruiz, Hugo; Balanza, Maria Elba; Guitian, Javier

2014-02-01

Livestock disease surveillance is particularly challenging in resource-scarce settings, where disease events are often unreported. Surveillance performance is determined as much by the quantifiable biological attributes of the disease, as it is by motivations and barriers perceived by livestock keepers for disease reporting. Mixed methods designs, which integrate the collection, analysis and interpretation of qualitative and quantitative data in a single study, are increasingly used across different disciplines. These designs allow for a deeper exploration of the topic under investigation, than can be achieved by either approach alone. In this study a mixed methods design was used in order to gain a greater understanding of the factors that influence reporting of livestock diseases in Bolivia. There is a need to strengthen passive surveillance in this country, among other reasons as part of an eradication programme for Foot and Mouth Disease (FMD). Findings revealed livestock keepers in the study area were extremely unlikely to report the occurrence of livestock health events to the Official Veterinary Services (OVS). Communication outside the local community occurs more often through alternative routes and this is positively correlated with disease awareness. The main barriers to disease reporting identified were a lack of institutional credibility and the conflicting priorities of the OVS and livestock keepers. As for other animal and human diseases across the developing world, passive surveillance of livestock diseases in Bolivia should be enhanced; this is urgent in view of the current FMD eradication programme. Increasing timeliness and smallholders' participation requires a detailed understanding of their likely actions and perceived barriers towards disease reporting. These insights are most likely to be developed through a holistic mixed methods approach of quantitative and qualitative analyses. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

A mind map for managing minimal residual disease in acute myeloid leukemia.

PubMed

Benton, Christopher B; Ravandi, Farhad

2017-11-01

Advances in detecting traces of leukemia that were previously unidentifiable have increasingly led to the incorporation of information about residual disease into clinical decision making for patients with leukemia in both the postinduction and consolidation settings. This review discusses current concepts related to minimal residual disease (MRD), which is defined as submicroscopic disease detected during morphologic complete remission. The focus is on acute myeloid leukemia (AML). Basic methods for detecting MRD include flow cytometry, reverse transcription-polymerase chain reaction, and mutation analysis. Several studies using these assays have demonstrated prognostic implications based on MRD-positive vs MRD-negative status. As our understanding of the biological factors responsible for MRD in AML evolves, residual disease should be evaluated in the context of other prognostic markers. Current therapeutic options for managing MRD in AML are limited, and the clinical implications of a positive MRD test result can be significant. Regarding individual patients, an evidence-based approach must be applied while the institution- and assay-specific differences that currently exist are considered. Challenges associated with MRD assessment, such as the limited standardization of available assays and the paucity of effective agents to eradicate MRD, will need to be overcome before physicians who treat leukemia can use MRD as a tool for clinical management.

"RCL-Pooling Assay": A Simplified Method for the Detection of Replication-Competent Lentiviruses in Vector Batches Using Sequential Pooling.

PubMed

Corre, Guillaume; Dessainte, Michel; Marteau, Jean-Brice; Dalle, Bruno; Fenard, David; Galy, Anne

2016-02-01

Nonreplicative recombinant HIV-1-derived lentiviral vectors (LV) are increasingly used in gene therapy of various genetic diseases, infectious diseases, and cancer. Before they are used in humans, preparations of LV must undergo extensive quality control testing. In particular, testing of LV must demonstrate the absence of replication-competent lentiviruses (RCL) with suitable methods, on representative fractions of vector batches. Current methods based on cell culture are challenging because high titers of vector batches translate into high volumes of cell culture to be tested in RCL assays. As vector batch size and titers are continuously increasing because of the improvement of production and purification methods, it became necessary for us to modify the current RCL assay based on the detection of p24 in cultures of indicator cells. Here, we propose a practical optimization of this method using a pairwise pooling strategy enabling easier testing of higher vector inoculum volumes. These modifications significantly decrease material handling and operator time, leading to a cost-effective method, while maintaining optimal sensibility of the RCL testing. This optimized "RCL-pooling assay" ameliorates the feasibility of the quality control of large-scale batches of clinical-grade LV while maintaining the same sensitivity.

Advances in Audio-Based Systems to Monitor Patient Adherence and Inhaler Drug Delivery.

PubMed

Taylor, Terence E; Zigel, Yaniv; De Looze, Céline; Sulaiman, Imran; Costello, Richard W; Reilly, Richard B

2018-03-01

Hundreds of millions of people worldwide have asthma and COPD. Current medications to control these chronic respiratory diseases can be administered using inhaler devices, such as the pressurized metered dose inhaler and the dry powder inhaler. Provided that they are used as prescribed, inhalers can improve patient clinical outcomes and quality of life. Poor patient inhaler adherence (both time of use and user technique) is, however, a major clinical concern and is associated with poor disease control, increased hospital admissions, and increased mortality rates, particularly in low- and middle-income countries. There are currently limited methods available to health-care professionals to objectively and remotely monitor patient inhaler adherence. This review describes recent sensor-based technologies that use audio-based approaches that show promising opportunities for monitoring inhaler adherence in clinical practice. This review discusses how one form of sensor-based technology, audio-based monitoring systems, can provide clinically pertinent information regarding patient inhaler use over the course of treatment. Audio-based monitoring can provide health-care professionals with quantitative measurements of the drug delivery of inhalers, signifying a clear clinical advantage over other methods of assessment. Furthermore, objective audio-based adherence measures can improve the predictability of patient outcomes to treatment compared with current standard methods of adherence assessment used in clinical practice. Objective feedback on patient inhaler adherence can be used to personalize treatment to the patient, which may enhance precision medicine in the treatment of chronic respiratory diseases. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia.

PubMed

McDonald, Scott A; Dahlui, Maznah; Mohamed, Rosmawati; Naning, Herlianna; Shabaruddin, Fatiha Hana; Kamarulzaman, Adeeba

2015-01-01

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods. An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed. In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039. The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.

Constructing an integrated gene similarity network for the identification of disease genes.

PubMed

Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin

2017-09-20

Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .

Longitudinal study of the association between smoking as a periodontitis risk and salivary biomarkers related to periodontitis.

PubMed

Kibayashi, Miyuki; Tanaka, Muneo; Nishida, Nobuko; Kuboniwa, Masae; Kataoka, Kosuke; Nagata, Hideki; Nakayama, Kunio; Morimoto, Kanehisa; Shizukuishi, Satoshi

2007-05-01

Insufficient data exist regarding the long-term influence of lifestyle factors including smoking on periodontal health. The objective of this study was to examine the prospective association between smoking and periodontal disease progression and the effects of smoking on salivary biomarkers related to periodontitis. Probing depth (PD) was measured at health checkups of workers in 1999 and 2003; additionally, lifestyle information was obtained through a questionnaire. In 2003, 219 of 256 (86%) workers examined at baseline completed PD measurements; saliva samples were also collected. Change in PD was used for assessment of periodontitis progression when three or more sites displayed an increase of >or=2 mm over 4 years. Salivary biomarker levels were determined by real-time polymerase chain reaction and enzyme assay. Statistical methods included bivariate and multivariate regression analyses. In the multiple logistic model, in which lifestyle-related factors served as independent variables, significant variables were current smoking and hours of sleep; respective odds ratios were 2.3 and 2.1. Additionally, 38.5% of periodontal disease progression was attributable to current smoking. Moreover, pack-years of smoking showed a dose-response relationship with disease progression. Levels of salivary markers including prostaglandin E(2), lactoferrin, albumin, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were significantly lower in current smokers than in non-current smokers. However, no meaningful differences in the proportions of six periodontal pathogens were observed between current and non-current smokers. Smoking exerted the greatest influence on periodontitis risk among lifestyle factors. Smoking may suppress the host-defense system, which may promote periodontal disease progression.

Shape-based diagnosis of the aortic valve

NASA Astrophysics Data System (ADS)

Ionasec, Razvan Ioan; Tsymbal, Alexey; Vitanovski, Dime; Georgescu, Bogdan; Zhou, S. Kevin; Navab, Nassir; Comaniciu, Dorin

2009-02-01

Disorders of the aortic valve represent a common cardiovascular disease and an important public-health problem worldwide. Pathological valves are currently determined from 2D images through elaborate qualitative evalu- ations and complex measurements, potentially inaccurate and tedious to acquire. This paper presents a novel diagnostic method, which identies diseased valves based on 3D geometrical models constructed from volumetric data. A parametric model, which includes relevant anatomic landmarks as well as the aortic root and lea ets, represents the morphology of the aortic valve. Recently developed robust segmentation methods are applied to estimate the patient specic model parameters from end-diastolic cardiac CT volumes. A discriminative distance function, learned from equivalence constraints in the product space of shape coordinates, determines the corresponding pathology class based on the shape information encoded by the model. Experiments on a heterogeneous set of 63 patients aected by various diseases demonstrated the performance of our method with 94% correctly classied valves.

iPcc: a novel feature extraction method for accurate disease class discovery and prediction

PubMed Central

Ren, Xianwen; Wang, Yong; Zhang, Xiang-Sun; Jin, Qi

2013-01-01

Gene expression profiling has gradually become a routine procedure for disease diagnosis and classification. In the past decade, many computational methods have been proposed, resulting in great improvements on various levels, including feature selection and algorithms for classification and clustering. In this study, we present iPcc, a novel method from the feature extraction perspective to further propel gene expression profiling technologies from bench to bedside. We define ‘correlation feature space’ for samples based on the gene expression profiles by iterative employment of Pearson’s correlation coefficient. Numerical experiments on both simulated and real gene expression data sets demonstrate that iPcc can greatly highlight the latent patterns underlying noisy gene expression data and thus greatly improve the robustness and accuracy of the algorithms currently available for disease diagnosis and classification based on gene expression profiles. PMID:23761440

Urine Metabolomics Analysis for Biomarker Discovery and Detection of Jaundice Syndrome in Patients With Liver Disease*

PubMed Central

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

[Novel current and future therapy options for treatment of dry eye disease].

PubMed

Messmer, E M

2018-02-01

Dry eye disease was redefined by the dry eye workshop (DEWS II) in May 2017. According to the new definition "dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms". The current definition encompasses etiological factors, such as instability and hyperosmolarity of the tear film, ocular surface inflammation and damage as well as a new aspect compared to the former definition, neurosensory abnormalities. Recent and future therapeutic options for dry eye focus on treatment of the aforementioned pathogenetic events. New tear substitutes, medications and devices to stimulate tear production, innovative anti-inflammatory treatment, medications to influence corneal innervation and new methods for treatment of Meibomian gland dysfunction are already available or will be available in the near future.

Clinical Applications Involving CNS Gene Transfer

PubMed Central

Kantor, Boris; McCown, Thomas; Leone, Paola; Gray, Steven J.

2015-01-01

Diseases of the central nervous system (CNS) have traditionally been the most difficult to treat by traditional pharmacological methods, due mostly to the blood–brain barrier and the difficulties associated with repeated drug administration targeting the CNS. Viral vector gene transfer represents a way to permanently provide a therapeutic protein within the nervous system after a single administration, whether this be a gene replacement strategy for an inherited disorder or a disease-modifying protein for a disease such as Parkinson's. Gene therapy approaches for CNS disorders has evolved considerably over the last two decades. Although a breakthrough treatment has remained elusive, current strategies are now considerably safer and potentially much more effective. This chapter will explore the past, current, and future status of CNS gene therapy, focusing on clinical trials utilizing adeno-associated virus and lentiviral vectors. PMID:25311921

Seaweed Polysaccharides - New Therapeutic Insights Against the Inflammatory Response in Diabetic Nephropathy.

PubMed

Vaishnudevi, Durairaj; Viswanathan, Pragasam

2017-01-01

The higher risk of diabetic nephropathy (DN) leads to end stage renal diseases worldwide, which is associated with chronic inflammation. Currently, the available treatments are limited, lack of efficacy and safety. Therefore, we are in need of novel targets and advanced treatments to reduce the necessity for the renal replacement therapy and burden of this disease management. Object/Methods: In this review, we performed through an inflammatory mechanism that contribute to DN, will provide a key point to the finding off novel therapeutic agents. In addition, we discuss the current anti-inflammatory drugs, an alternative approach of seaweed polysaccharides and also exploring the future perspective of anti-inflammatory natural seaweed compounds. Currently, seaweeds are taking majority of attention from scientists for targeting the various diseases. This will become a more significant part of the pipeline and alternate medicines for anti-inflammatory and chronic diseases. The potential benefits of natural seaweed novel compounds in inhibiting inflammatory pathways would be useful for the prevention of diabetic nephropathy. Thus, this therapy manifests the clinical benefits of these compounds in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug Target Prediction and Repositioning Using an Integrated Network-Based Approach

PubMed Central

Emig, Dorothea; Ivliev, Alexander; Pustovalova, Olga; Lancashire, Lee; Bureeva, Svetlana; Nikolsky, Yuri; Bessarabova, Marina

2013-01-01

The discovery of novel drug targets is a significant challenge in drug development. Although the human genome comprises approximately 30,000 genes, proteins encoded by fewer than 400 are used as drug targets in the treatment of diseases. Therefore, novel drug targets are extremely valuable as the source for first in class drugs. On the other hand, many of the currently known drug targets are functionally pleiotropic and involved in multiple pathologies. Several of them are exploited for treating multiple diseases, which highlights the need for methods to reliably reposition drug targets to new indications. Network-based methods have been successfully applied to prioritize novel disease-associated genes. In recent years, several such algorithms have been developed, some focusing on local network properties only, and others taking the complete network topology into account. Common to all approaches is the understanding that novel disease-associated candidates are in close overall proximity to known disease genes. However, the relevance of these methods to the prediction of novel drug targets has not yet been assessed. Here, we present a network-based approach for the prediction of drug targets for a given disease. The method allows both repositioning drug targets known for other diseases to the given disease and the prediction of unexploited drug targets which are not used for treatment of any disease. Our approach takes as input a disease gene expression signature and a high-quality interaction network and outputs a prioritized list of drug targets. We demonstrate the high performance of our method and highlight the usefulness of the predictions in three case studies. We present novel drug targets for scleroderma and different types of cancer with their underlying biological processes. Furthermore, we demonstrate the ability of our method to identify non-suspected repositioning candidates using diabetes type 1 as an example. PMID:23593264

Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models.

PubMed

Reavill, Drury R; Schmidt, Robert E

2012-01-01

Mycobacteriosis is a serious disease across many animal species. Approximately more than 120 species are currently recognized in the genus Mycobacterium. This article describes the zoonotic potential of mycobacteria and mycobacteriosis in fish, amphibians, rodents, rabbits, and ferrets. It considers clinical signs; histology; molecular methods of identification, such as polymerase chain reaction and DNA sequencing; routes of infection; and disease progression. Studying the disease in animals may aid in understanding the pathogenesis of mycobacterial infections in humans and identify better therapy and preventative options such as vaccines.

Human susceptibility to legionnaires' disease.

PubMed

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.

[Device-aided therapies in advanced Parkinson's disease].

PubMed

Timofeeva, A A

Advanced stages of Parkinson's disease (PD) is a consequence of the severe neurodegenerative process and are characterized by the development of motor fluctuations and dyskinesia, aggravation of non-motor symptoms. Treatment with peroral and transdermal drugs can't provide an adequate control of PD symptoms and quality-of-life of the patients at this stage of disease. Currently, three device-aided therapies: deep brain stimulation (DBS), intrajejunal infusion of duodopa, subcutaneous infusion of apomorphine can be used in treatment of patients with advanced stages of PD. Timely administration of device-aided therapies and right choice of the method determine, to a large extent, the efficacy and safety of their use. Despite the high efficacy of all three methods with respect to the fluctuation of separate symptoms, each method has its own peculiarities. The authors reviewed the data on the expediency of using each method according to the severity of motor and non-motor symptoms, patient's age, PD duration, concomitant pathology and social support of the patients.

Droplet Digital PCR-Based Chimerism Analysis for Primary Immunodeficiency Diseases.

PubMed

Okano, Tsubasa; Tsujita, Yuki; Kanegane, Hirokazu; Mitsui-Sekinaka, Kanako; Tanita, Kay; Miyamoto, Satoshi; Yeh, Tzu-Wen; Yamashita, Motoi; Terada, Naomi; Ogura, Yumi; Takagi, Masatoshi; Imai, Kohsuke; Nonoyama, Shigeaki; Morio, Tomohiro

2018-04-01

In the current study, we aimed to accurately evaluate donor/recipient or male/female chimerism in samples from patients who underwent hematopoietic stem cell transplantation (HSCT). We designed the droplet digital polymerase chain reaction (ddPCR) for SRY and RPP30 to detect the male/female chimerism. We also developed mutation-specific ddPCR for four primary immunodeficiency diseases. The accuracy of the male/female chimerism analysis using ddPCR was confirmed by comparing the results with those of conventional methods (fluorescence in situ hybridization and short tandem repeat-PCR) and evaluating dilution assays. In particular, we found that this method was useful for analyzing small samples. Thus, this method could be used with patient samples, especially to sorted leukocyte subpopulations, during the early post-transplant period. Four mutation-specific ddPCR accurately detected post-transplant chimerism. ddPCR-based male/female chimerism analysis and mutation-specific ddPCR were useful for all HSCT, and these simple methods contribute to following the post-transplant chimerism, especially in disease-specific small leukocyte fractions.

Association between exposure to antimicrobial household products and allergic symptoms

PubMed Central

Hong, Soyoung; Kwon, Ho-Jang; Choi, Won-Jun; Lim, Wan Ryung; Kim, Jeonghoon; Kim, KyooSang

2014-01-01

Objectives Antimicrobial chemicals are used in a variety of household and personal care products. Exposure to antimicrobial household products has been hypothesized to lead to allergic diseases in children. Methods We investigated antimicrobial household product exposure and allergic symptoms in Korean children. An antimicrobial exposure (AE) score was derived. To examine the symptoms of allergic diseases (current wheeze, current rhinitis, and current eczema) in the past 12 months, we used a questionnaire based on the core module of the International Study of Asthma and Allergies in Children. Complete data for the analysis were available for 25,805 of the 35,590 (72.5%) children. Results The prevalence of current allergic diseases was as follows: wheeze, 5.6%; allergic rhinitis, 32.6%; and eczema, 17.7%. The mean (standard deviation) AE score was 14.3 (9.3) (range: 0-40). Compared with subjects with a low AE score (reference), subjects with a high AE score (fourth quartile) were more likely to have symptoms of wheezing and allergic rhinitis (adjusted odds ratio [aOR] for wheezing 1.24, 95% confidence interval [CI], 1.05-1.45, p for trend=0.24; aOR for allergic rhinitis 1.30, 95% CI, 1.20-1.40, p<0.01). Conclusions These findings suggest that frequent use of antimicrobial household products was associated with current wheeze and current allergic rhinitis. PMID:25420879

Into the environment of mosquito-borne disease: A spatial analysis of vector distribution using traditional and remotely sensed methods

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.

The Evolution of Genetics: Alzheimer's and Parkinson's Diseases.

PubMed

Singleton, Andrew; Hardy, John

2016-06-15

Genetic discoveries underlie the majority of the current thinking in neurodegenerative disease. This work has been driven by the significant gains made in identifying causal mutations; however, the translation of genetic causes of disease into pathobiological understanding remains a challenge. The application of a second generation of genetics methods allows the dissection of moderate and mild genetic risk factors for disease. This requires new thinking in two key areas: what constitutes proof of pathogenicity, and how do we translate these findings to biological understanding. Here we describe the progress and ongoing evolution in genetics. We describe a view that rejects the tradition that genetic proof has to be absolute before functional characterization and centers on a multi-dimensional approach integrating genetics, reference data, and functional work. We also argue that these challenges cannot be efficiently met by traditional hypothesis-driven methods but that high content system-wide efforts are required. Published by Elsevier Inc.

Current and emerging technologies in melanoma diagnosis: the state of the art

PubMed Central

Psaty, Estee L.; Halpern, Allan C.

2017-01-01

Relative to other specialties, dermatologists have been slow to adopt advanced technologic diagnostic aids. After all, most skin disease can be diagnosed by simple visual inspection, and the skin is readily accessible for a diagnostic biopsy. Diagnostic aids such as total body photography and dermoscopy improve the clinician's ability to diagnose melanoma beyond unaided visual inspection, however, and are now considered mainstream methods for early detection. Emerging technologies such as in vivo reflectance confocal microscopy are currently being investigated to determine their utility for noninvasive diagnosis of melanoma. This review summarizes the currently available cutaneous imaging devices and new frontiers in noninvasive diagnosis of skin disease. We anticipate that multimodal systems that combine different imaging technologies will further improve our ability to detect, at the bedside, melanoma at an earlier stage. PMID:19095152

Improving colorectal cancer screening: fact and fantasy

NASA Astrophysics Data System (ADS)

Van Dam, Jacques

2008-02-01

Premalignant diseases of the gastrointestinal tract, such as Barrett's esophagus, long-standing ulcerative colitis, and adenomatous polyps, have a significantly increased risk for development of adenocarcinoma, most often through an intermediate stage of dysplasia. Adenocarcinoma of the colon is the second most common cancer in the United States. Because patients with colorectal cancer often present with advanced disease, the outcomes are associated with significant morbidity and mortality. Effective methods of early detection are essential. As non-polypoid dysplasia is not visible using conventional endoscopy, surveillance of patients with Barrett's esophagus and ulcerative colitis is performed via a system in which multiple random biopsies are obtained at prescribed intervals. Sampling error and missed diagnoses occur frequently and render current screening methods inadequate. Also, the examination of a tissue biopsy is time consuming and costly, and significant intra- and inter-observer variation may occur. The newer methods discussed herein demonstrate the potential to solve these problems by early detection of disease with high sensitivity and specificity. Conventional endoscopy is based on the observation of white light reflected off the tissue surface. Subtle changes in color and shadow reveal structural changes. New developments in optical imaging go beyond white light, exploiting other properties of light. Several promising methods will be discussed at this meeting and shall be briefly discussed below. However, few such imaging modalities have arrived at our clinical practice. Some much more practical methods to improve colorectal cancer screening are currently being evaluated for their clinical impact. These methods seek to overcome limitations other than those of detecting dysplasia not visible under white light endoscopy. The current standard practice of colorectal cancer screening utilizes colonoscopy, an uncomfortable, sometimes difficult medical procedure. Efforts to improve the practice of colonoscopy will be described. Another limitation of the current practice is the inability to detect polypoid neoplasia that is hidden from view under white light imaging by the natural folds that occur within the colon. A device to overcome this limitation will also be described. Efforts to improve colorectal cancer screening (and thereby decrease the death rate of this second leading cause of cancer death in the United States) are progressing in many arenas. The researcher, basic or clinical, should maintain an up to date overview of the field and how each new technological advance is likely to have a role in the screening and early detection of colorectal cancer.

A mixed-methods needs assessment of adult diabetes mellitus (type II) and hypertension care in Toledo, Belize.

PubMed

Dekker, Annette M; Amick, Ashley E; Scholcoff, Cecilia; Doobay-Persaud, Ashti

2017-02-28

Non-communicable diseases, including diabetes mellitus and hypertension, continue to disproportionately burden low- and middle-income countries. However, little research has been done to establish current practices and management of chronic disease in these settings. The objective of this study was to examine current clinical management and identify potential gaps in care of patients with diabetes mellitus and hypertension in the district of Toledo, Belize. The study used a mixed methodology to assess current practices and identify gaps in diabetes mellitus and hypertension care. One hundred and twenty charts of the general clinic population were reviewed to establish disease epidemiology. One hundred and seventy-eight diabetic and hypertensive charts were reviewed to assess current practices. Twenty providers completed questionnaires regarding diabetes mellitus and hypertension management. Twenty-five individuals with diabetes mellitus and/or hypertension answered a questionnaire and in-depth interview. The prevalence of diabetes mellitus and hypertension was 12%. Approximately 51% (n = 43) of patients with hypertension were at blood pressure goal and 26% (n = 21) diabetic patients were at glycemic goal based on current guidelines. Of the patients with uncontrolled diabetes, 49% (n = 29) were on two oral agents and only 10% (n = 6) were on insulin. Providers stated that barriers to appropriate management include concerns prescribing insulin and patient health literacy. Patients demonstrated a general understanding of the concept of chronic illness, however lacked specific knowledge regarding disease processes and self-management strategies. This study provides an initial overview of diabetes mellitus and hypertension management in a diverse patient population in rural Belize. Results indicate areas for future investigation and possible intervention, including barriers to insulin use and opportunities for lifestyle-specific disease education for patients.

White-Nose Syndrome Disease Severity and a Comparison of Diagnostic Methods.

PubMed

McGuire, Liam P; Turner, James M; Warnecke, Lisa; McGregor, Glenna; Bollinger, Trent K; Misra, Vikram; Foster, Jeffrey T; Frick, Winifred F; Kilpatrick, A Marm; Willis, Craig K R

2016-03-01

White-nose syndrome is caused by the fungus Pseudogymnoascus destructans and has killed millions of hibernating bats in North America but the pathophysiology of the disease remains poorly understood. Our objectives were to (1) assess non-destructive diagnostic methods for P. destructans infection compared to histopathology, the current gold-standard, and (2) to evaluate potential metrics of disease severity. We used data from three captive inoculation experiments involving 181 little brown bats (Myotis lucifugus) to compare histopathology, quantitative PCR (qPCR), and ultraviolet fluorescence as diagnostic methods of P. destructans infection. To assess disease severity, we considered two histology metrics (wing area with fungal hyphae, area of dermal necrosis), P. destructans fungal load (qPCR), ultraviolet fluorescence, and blood chemistry (hematocrit, sodium, glucose, pCO2, and bicarbonate). Quantitative PCR was most effective for early detection of P. destructans, while all three methods were comparable in severe infections. Correlations among hyphae and necrosis scores, qPCR, ultraviolet fluorescence, blood chemistry, and hibernation duration indicate a multi-stage pattern of disease. Disruptions of homeostasis occurred rapidly in late hibernation. Our results provide valuable information about the use of non-destructive techniques for monitoring, and provide novel insight into the pathophysiology of white-nose syndrome, with implications for developing and implementing potential mitigation strategies.

Nanotechnology: a promising method for oral cancer detection and diagnosis.

PubMed

Chen, Xiao-Jie; Zhang, Xue-Qiong; Liu, Qi; Zhang, Jing; Zhou, Gang

2018-06-11

Oral cancer is a common and aggressive cancer with high morbidity, mortality, and recurrence rate globally. Early detection is of utmost importance for cancer prevention and disease management. Currently, tissue biopsy remains the gold standard for oral cancer diagnosis, but it is invasive, which may cause patient discomfort. The application of traditional noninvasive methods-such as vital staining, exfoliative cytology, and molecular imaging-is limited by insufficient sensitivity and specificity. Thus, there is an urgent need for exploring noninvasive, highly sensitive, and specific diagnostic techniques. Nano detection systems are known as new emerging noninvasive strategies that bring the detection sensitivity of biomarkers to nano-scale. Moreover, compared to current imaging contrast agents, nanoparticles are more biocompatible, easier to synthesize, and able to target specific surface molecules. Nanoparticles generate localized surface plasmon resonances at near-infrared wavelengths, providing higher image contrast and resolution. Therefore, using nano-based techniques can help clinicians to detect and better monitor diseases during different phases of oral malignancy. Here, we review the progress of nanotechnology-based methods in oral cancer detection and diagnosis.

Protective immunity of Nile tilapia against Ichthyophthirius

USDA-ARS?s Scientific Manuscript database

Tilapia are currently cultured in different types of production systems ranging from pond, tank, cage, flowing water and intensive water reuse culture systems. Intensification of tilapia culture requires methods to prevent and control diseases to minimize the loss. Ichthyophthirius multifiliis (I...

Biotherapeutics as alternatives to antibiotics

USDA-ARS?s Scientific Manuscript database

Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

DIGITAL IMAGE ANALYSIS OF ZOSTERA MARINA LEAF INJURY

EPA Science Inventory

Current methods for assessing leaf injury in Zostera marina (eelgrass) utilize subjective indexes for desiccation injury and wasting disease. Because of the subjective nature of these measures, they are inherently imprecise making them difficult to use in quantifying complex leaf...

Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease.

PubMed Central

Urnovitz, H B; Murphy, W H

1996-01-01

Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated. PMID:8665478

The human mycobiome in health and disease

PubMed Central

2013-01-01

The mycobiome, referring primarily to the fungal biota in an environment, is an important component of the human microbiome. Despite its importance, it has remained understudied. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal importance. An integrative analysis of current studies shows that different body sites harbor specific fungal populations, and that diverse mycobiome patterns are associated with various diseases. By interfacing with other biomes, as well as with the host, the mycobiome probably contributes to the progression of fungus-associated diseases and plays an important role in health and disease. PMID:23899327

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening

PubMed Central

Smith, Alec S.T.; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A.; Kim, Deok-Ho

2016-01-01

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. PMID:28007615

Biomaterials for the Treatment of Alzheimer's Disease.

PubMed

Hadavi, Darya; Poot, André A

2016-01-01

Alzheimer's disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood-brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies. One of the interesting areas for the latter subject is biomaterials and their applications. This interest originates from the fact that biomaterials are very useful for the delivery of therapeutic agents, such as drugs, proteins, and/or cells, in order to treat diseases and regenerate tissues. Recently, manufacturing of nano-sized delivery systems has increased the efficacy and delivery potential of biomaterials. In this article, we review the latest developments with regard to the use of biomaterials for the treatment of AD, including nanoparticles and liposomes for delivery of therapeutic compounds and scaffolds for cell delivery strategies.

[Current status and prospect of photodynamic therapy in laryngeal diseases].

PubMed

Zhang, C; Jiang, J Q

2018-04-07

Laryngeal diseases are closely related to the swallowing and speech function of the patients.Protecting and restoring laryngeal function, while curing lesions, is vital to patients' quality of life.Photodynamic therapy (PDT) is a minimally invasive method which is widely used in the treatment of tumor, precancerous lesions, and inflammatory diseases.In recent years, it has been shown to have a protective effect on normal structures. This article reviews the clinical outcomes of laryngeal diseases treated with PDT since 1990 in order to evaluate its efficacy and significance. The complete remission rate of early-stage laryngeal tumors and precancerous lesions after PDT is 77.6%(249/321), and a promising effect on recurrent laryngeal papillomatosis has been observed thus far. The prolonged adverse effects of the first-generation photosensitizers have limited the application of PDT. With the improvement of photosensitizers and treatment strategies, PDT promises to be a safe, effective, and minimally invasive treatment method for laryngeal diseases.

Reconsidering the methodology of “stress” research in inflammatory bowel disease

PubMed Central

Keefer, Laurie; Keshavarzian, Ali; Mutlu, Ece

2009-01-01

Background and Aims The goals of this paper are: 1) to critically review and analyze the methodology of the studies since 1990 linking stress to inflammatory bowel disease; and 2) to make recommendations for future research in this area of research. Methods Articles were restricted to empirical reports in the English language with human subjects. Eleven empirical articles were able to answer “How is psychological stress related to inflammation and/or the expression or course of inflammatory bowel disease?” Results Studies varied by choice of participant groups, method for classifying disease activity, choice of design, and definition and measurement of stress. Only half of the studies supported the hypothesis that stress affected IBD in some way. Conclusions Current methodological limitations in the stress and gut inflammation research have made it difficult for us to ascertain the role of stress in inflammatory bowel disease. Authors provide a checklist of items to consider when designing future studies. PMID:21172210

Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

PubMed

Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

2016-04-01

The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

In vivo and in vitro disease modeling with CRISPR/Cas9.

PubMed

Kato, Tomoko; Takada, Shuji

2017-01-01

In the past few years, extensive progress has been made in the development of genome-editing technology. Among several genome-editing tools, the clustered regularly interspaced short palindrome repeat-associated Cas9 nuclease (CRISPR/Cas9) system is particularly widely used owing to the ease of sequence-specific nuclease construction and the highly efficient introduction of mutations. The CRISPR/Cas9 system was originally constructed to induce small insertion and deletion mutations, but various methods have been developed to introduce point mutations, deletions, insertions, chromosomal translocations and so on. These methods should be useful for the reconstruction of disease-causing mutations in cultured cell lines and living organisms to elucidate disease pathogenesis and for disease prevention, treatment and drug discovery. This review summarizes the current technical aspects of the CRISPR/Cas9 system for disease modeling in cultured cells and living organisms, mainly mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Biological Control of Mosquito Vectors: Past, Present, and Future.

PubMed

Benelli, Giovanni; Jeffries, Claire L; Walker, Thomas

2016-10-03

Mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs) is available for most of these diseases andvectorcontrolisstillthemainformofprevention. Thelimitationsoftraditionalinsecticide-based strategies, particularly the development of insecticide resistance, have resulted in significant efforts to develop alternative eco-friendly methods. Biocontrol strategies aim to be sustainable and target a range of different mosquito species to reduce the current reliance on insecticide-based mosquito control. In thisreview, weoutline non-insecticide basedstrategiesthat havebeenimplemented orare currently being tested. We also highlight the use of mosquito behavioural knowledge that can be exploited for control strategies.

A neurite quality index and machine vision software for improved quantification of neurodegeneration.

PubMed

Romero, Peggy; Miller, Ted; Garakani, Arman

2009-12-01

Current methods to assess neurodegradation in dorsal root ganglion cultures as a model for neurodegenerative diseases are imprecise and time-consuming. Here we describe two new methods to quantify neuroprotection in these cultures. The neurite quality index (NQI) builds upon earlier manual methods, incorporating additional morphological events to increase detection sensitivity for the detection of early degeneration events. Neurosight is a machine vision-based method that recapitulates many of the strengths of NQI while enabling high-throughput screening applications with decreased costs.

Counting glomeruli and podocytes: rationale and methodologies

PubMed Central

Puelles, Victor G.; Bertram, John F.

2015-01-01

Purpose of review There is currently much interest in the numbers of both glomeruli and podocytes. This interest stems from greater understanding of the effects of suboptimal fetal events on nephron endowment, the associations between low nephron number and chronic cardiovascular and kidney disease in adults, and the emergence of the podocyte depletion hypothesis. Recent findings Obtaining accurate and precise estimates of glomerular and podocyte number has proven surprisingly difficult. When whole kidneys or large tissue samples are available, design-based stereological methods are considered gold-standard because they are based on principles that negate systematic bias. However, these methods are often tedious and time-consuming, and oftentimes inapplicable when dealing with small samples such as biopsies. Therefore, novel methods suitable for small tissue samples, and innovative approaches to facilitate high through put measurements, such as magnetic resonance imaging (MRI) to estimate glomerular number and flow cytometry to estimate podocyte number, have recently been described. Summary This review describes current gold-standard methods for estimating glomerular and podocyte number, as well as methods developed in the past 3 years. We are now better placed than ever before to accurately and precisely estimate glomerular and podocyte number, and to examine relationships between these measurements and kidney health and disease. PMID:25887899

Cancer research in need of a scientific revolution: Using 'paradigm shift' as a method of investigation.

PubMed

Wion, Didier; Appaix, Florence; Burruss, Meriwether; Berger, Francois; van der Sanden, Boudewijn

2015-09-01

Despite important human and financial resources and considerable accumulation of scientific publications, patents, and clinical trials, cancer research has been slow in achieving a therapeutic revolution similar to the one that occurred in the last century for infectious diseases. It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of 'paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the 'paradigm shift' method in cancer research requires identifying its founding paradigms. In this review, two of these founding paradigms will be discussed: (i) the reification of cancer as a tumour mass and (ii) the translation of the concepts issued from infectious disease in cancer research. We show how these founding paradigms can generate biases that lead to over-diagnosis and over-treatment and also hamper the development of curative cancer therapies. We apply the 'paradigm shift' method to produce perspective reversals consistent with current experimental evidence. The 'paradigm shift' method enlightens the existence of a tumour physiologic-prophylactic-pathologic continuum. It integrates the target/antitarget concept and that cancer is also an extracellular disease. The 'paradigm shift' method has immediate implications for cancer prevention and therapy. It could be a general method of investigation for other diseases awaiting therapy.

Mastitis detection: current trends and future perspectives.

PubMed

Viguier, Caroline; Arora, Sushrut; Gilmartin, Niamh; Welbeck, Katherine; O'Kennedy, Richard

2009-08-01

Bovine mastitis, the most significant disease of dairy herds, has huge effects on farm economics due to reduction in milk production and treatment costs. Traditionally, methods of detection have included estimation of somatic cell counts, an indication of inflammation, measurement of biomarkers associated with the onset of the disease (e.g. the enzymes N-acetyl-beta-D-glucosaminidase and lactate dehydrogenase) and identification of the causative microorganisms, which often involves culturing methods. These methods have their limitations and there is a need for new rapid, sensitive and reliable assays. Recently, significant advances in the identification of nucleic acid markers and other novel biomarkers and the development of sensor-based platforms have taken place. These novel strategies have shown promise, and their advantages over the conventional tests are discussed.

Opportunities for Improved Chagas Disease Vector Control Based on Knowledge, Attitudes and Practices of Communities in the Yucatan Peninsula, Mexico

PubMed Central

Rosecrans, Kathryn; Cruz-Martin, Gabriela; King, Ashley; Dumonteil, Eric

2014-01-01

Background Chagas disease is a vector-borne parasitic disease of major public health importance. Current prevention efforts are based on triatomine vector control to reduce transmission to humans. Success of vector control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to improved vector control strategies in the Yucatan peninsula, Mexico. Methodology/principal findings We employed a sequence of qualitative and quantitative research methods to investigate knowledge, attitudes and practices surrounding Chagas disease, triatomines and vector control in three rural communities. Our combined data show that community members are well aware of triatomines and are knowledgeable about their habits. However, most have a limited understanding of the transmission dynamics and clinical manifestations of Chagas disease. While triatomine control is not a priority for community members, they frequently use domestic insecticide products including insecticide spray, mosquito coils and plug-in repellents. Families spend about $32 US per year on these products. Alternative methods such as yard cleaning and window screens are perceived as desirable and potentially more effective. Screens are nonetheless described as unaffordable, in spite of a cost comparable to the average annual spending on insecticide products. Conclusion/Significance Further education campaigns and possibly financing schemes may lead families to redirect their current vector control spending from insecticide products to window screens. Also, synergism with mosquito control efforts should be further explored to motivate community involvement and ensure sustainability of Chagas disease vector control. PMID:24676038

Immunomodulation: the future cure for allergic diseases.

PubMed

Tsitoura, Daphne C; Tassios, Yannis

2006-11-01

Allergies are the result of aberrant immune reactivity against common innocuous environmental proteins (allergens). A pivotal component of allergic pathogenesis is the generation of allergen-specific Th cells with an effector phenotype. These Th cells activate a complex immune cascade that triggers the release of potent mediators and enhances the mobilization of several inflammatory cells types, which in turn elicit the acute allergic reactions and promote the development of chronic inflammation. The current therapies for allergic diseases focus primarily on pharmacological control of symptoms and suppression of inflammation. This approach is beneficial, but not curative, since the underlying immune pathology is not inhibited. In an attempt to develop more effective therapeutic strategies, the scientific interest has been directed toward methods down-modulating the immune mechanisms that initiate and maintain the allergic cascade. Today, the only widely used disease-modifying form of allergy treatment is the specific immunotherapy with allergen extracts. More recently the use of anti-IgE has been approved for patients with allergic asthma. Other immunomodulatory methods being currently explored are the administration of microbial adjuvants that inhibit Th2 reactivity and the design of molecules that interrupt the activity of key allergic cytokines, chemokines, or other Th2 effector mediators.

The lab without walls: a deployable approach to tropical infectious diseases.

PubMed

Inglis, Timothy J J

2013-04-01

The Laboratory Without Walls is a modular field application of molecular biology that provides clinical laboratory support in resource-limited, remote locations. The current repertoire arose from early attempts to deliver clinical pathology and public health investigative services in remote parts of tropical Australia, to address the shortcomings of conventional methods when faced with emerging infectious diseases. Advances in equipment platforms and reagent chemistry have enabling rapid progress, but also ensure the Laboratory Without Walls is subject to continual improvement. Although new molecular biology methods may lead to more easily deployable clinical laboratory capability, logistic and technical governance issues continue to act as important constraints on wider implementation.

Prediction of potential disease-associated microRNAs based on random walk.

PubMed

Xuan, Ping; Han, Ke; Guo, Yahong; Li, Jin; Li, Xia; Zhong, Yingli; Zhang, Zhaogong; Ding, Jian

2015-06-01

Identifying microRNAs associated with diseases (disease miRNAs) is helpful for exploring the pathogenesis of diseases. Because miRNAs fulfill function via the regulation of their target genes and because the current number of experimentally validated targets is insufficient, some existing methods have inferred potential disease miRNAs based on the predicted targets. It is difficult for these methods to achieve excellent performance due to the high false-positive and false-negative rates for the target prediction results. Alternatively, several methods have constructed a network composed of miRNAs based on their associated diseases and have exploited the information within the network to predict the disease miRNAs. However, these methods have failed to take into account the prior information regarding the network nodes and the respective local topological structures of the different categories of nodes. Therefore, it is essential to develop a method that exploits the more useful information to predict reliable disease miRNA candidates. miRNAs with similar functions are normally associated with similar diseases and vice versa. Therefore, the functional similarity between a pair of miRNAs is calculated based on their associated diseases to construct a miRNA network. We present a new prediction method based on random walk on the network. For the diseases with some known related miRNAs, the network nodes are divided into labeled nodes and unlabeled nodes, and the transition matrices are established for the two categories of nodes. Furthermore, different categories of nodes have different transition weights. In this way, the prior information of nodes can be completely exploited. Simultaneously, the various ranges of topologies around the different categories of nodes are integrated. In addition, how far the walker can go away from the labeled nodes is controlled by restarting the walking. This is helpful for relieving the negative effect of noisy data. For the diseases without any known related miRNAs, we extend the walking on a miRNA-disease bilayer network. During the prediction process, the similarity between diseases, the similarity between miRNAs, the known miRNA-disease associations and the topology information of the bilayer network are exploited. Moreover, the importance of information from different layers of network is considered. Our method achieves superior performance for 18 human diseases with AUC values ranging from 0.786 to 0.945. Moreover, case studies on breast neoplasms, lung neoplasms, prostatic neoplasms and 32 diseases further confirm the ability of our method to discover potential disease miRNAs. A web service for the prediction and analysis of disease miRNAs is available at http://bioinfolab.stx.hk/midp/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Future Prospects of Health Management Systems Using Cellular Phones

PubMed Central

Kim, Hun-Sung; Hwang, Yunji; Lee, Jae-Ho; Oh, Hye Young; Kim, Yi-Jun; Kwon, Hyeon Yoon; Kang, Hyoseung; Kim, Hyunah; Park, Rae Woong

2014-01-01

Abstract Background: Cellular phones enable communication between healthcare providers and patients for prevention, diagnosis, and treatment of diseases. However, few studies have examined the user-friendliness or effectiveness of cellular phone-based medical informatics (CPBMI) for healthcare. Materials and Methods: This study investigated the use of CPBMI to identify its current status within the medical field, advantages and disadvantages, practicability, clinical effectiveness, costs, and cost-saving potential. Results: CPBMI was validated in terms of practicality and provision of medical benefits. It is critical to use CPBMI in accordance with the different features of each disease and condition. Use of CPBMI is expected to be especially useful for patients with chronic disease. Conclusions: We discussed the current status of the clinical use, benefits, and risks of CPBMI. CPBMI and information technology–based health management tools are anticipated to become useful and effective components of healthcare management in the future. PMID:24693986

Gene transfer into the kidney: current status and limitations.

PubMed

Moullier, P; Salvetti, A; Champion-Arnaud, P; Ronco, P M

1997-01-01

Gene therapy is obviously a controversial issue and a wave of suspicion has dampened the initial enthusiasm raised by this new therapeutic approach. It has now become fashionable to downplay the potential for gene therapy in most fields including kidney-related diseases. In our opinion, this is an unfair and unrealistic view of the future. In fact, gene therapy of well-selected kidney diseases will certainly become feasible, but a large data base on vectors and transfer methods both in the normal kidney and in disease models has first to be collected. Any significant progress in the biology of the vectors, in the cellular interactions of the newly introduced DNA, and in the regulation and persistency of the transgene should be rapidly translated to the kidney in relevant experimental models. Herein, we present the use and current limitations of gene transfer to the kidney and the potential therapeutic perspectives.

Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities.

PubMed

Pistollato, Francesca; Ohayon, Elan L; Lam, Ann; Langley, Gillian R; Novak, Thomas J; Pamies, David; Perry, George; Trushina, Eugenia; Williams, Robin S B; Roher, Alex E; Hartung, Thomas; Harnad, Stevan; Barnard, Neal; Morris, Martha Clare; Lai, Mei-Chun; Merkley, Ryan; Chandrasekera, P Charukeshi

2016-06-28

Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies.

Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods

PubMed Central

Lăpădat, AM; Jianu, IR; Ungureanu, BS; Florescu, LM; Gheonea, DI; Sovaila, S; Gheonea, IA

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application. Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed. PMID:28255371

Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities

PubMed Central

Pistollato, Francesca; Ohayon, Elan L.; Lam, Ann; Langley, Gillian R.; Novak, Thomas J.; Pamies, David; Perry, George; Trushina, Eugenia; Williams, Robin S.B.; Roher, Alex E.; Hartung, Thomas; Harnad, Stevan; Barnard, Neal; Morris, Martha Clare; Lai, Mei-Chun; Merkley, Ryan; Chandrasekera, P. Charukeshi

2016-01-01

Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies. PMID:27229915

Trends in technology, trade and consumption likely to impact on microbial food safety.

PubMed

Quested, T E; Cook, P E; Gorris, L G M; Cole, M B

2010-05-30

Current and potential future trends in technology, consumption and trade of food that may impact on food-borne disease are analysed and the key driving factors identified focusing on the European Union and, to a lesser extent, accounting for the United States and global issues. Understanding of factors is developed using system-based methods and their impact is discussed in relation to current events and predictions of future trends. These factors come from a wide range of spheres relevant to food and include political, economic, social, technological, regulatory and environmental drivers. The degree of certainty in assessing the impact of important driving factors is considered in relation to food-borne disease. The most important factors driving an increase in the burden of food-borne disease in the next few decades were found to be the anticipated doubling of the global demand for food and of the international trade in food next to a significantly increased consumption of certain high-value food commodities such as meat and poultry and fresh produce. A less important factor potentially increasing the food-borne disease burden would be the increased demand for convenience foods. Factors that may contribute to a reduction in the food-borne disease burden were identified as the ability of governments around the world to take effective regulatory measures as well as the development and use of new food safety technologies and detection methods. The most important factor in reducing the burden of food-borne disease was identified as our ability to first detect and investigate a food safety issue and then to develop effective control measures. Given the global scale of impact on food safety that current and potentially future trends have, either by potentially increasing or decreasing the food-borne disease burden, it is concluded that a key role is fulfilled by intergovernmental organisations and by international standard setting bodies in coordinating the establishment and rolling-out of effective measures that, on balance, help ensure long-term consumer protection and fair international trade. Copyright 2010 Elsevier B.V. All rights reserved.

Triple burden of disease and out of pocket healthcare expenditure of women in India

PubMed Central

Ladusingh, Laishram; Mohanty, Sanjay Kumar

2018-01-01

Aim Women, unlike men, are subjected to triple burden of disease, namely, non-communicable and communicable diseases and reproductive health related diseases. To assess prevalence of triple burden of disease of currently married women and to contrast out of pocket maternal care expenditure of these diseases in India. Subject and methods This study uses nationally representative unit level data from the 71st round (2014) of the National Sample Survey Organisation. Descriptive statistics and bivariate analysis are employed to assess triple burden of diseases by background of currently married women. Mean out of pocket (OOP) expenditure for healthcare care by demographic and household characteristics of women are also compared by type of diseases. Two parts model is adopted for assessment of determents of out of pocket healthcare expenditure of women. Results Overall medical and non-medical expenses of non–communicable disease are much higher than those of other disease and disability, reproductive health related and communicable diseases. OOP expenditure for treatment of non-communicable diseases, reproductive health and related diseases and other disease and disability are significantly higher than the inpatient treatment of communicable diseases and the differences are statistically significant. Conclusion Out of pocket expenditure for treatment of non-communicable diseases is the highest, followed by that of other diseases & disability, then reproductive health related diseases and the least is for communicable diseases. OOP expenditures for maternal healthcare in private health facilities are much higher than in public health facilities regardless of types of disease. Women from households having insurance of any member spent less than that of women from households not having health insurance. There is an urgent need to expand the outreach of the public health system in India to rural areas. PMID:29746506

Endobronchial Ultrasound (EBUS) - Update 2017.

PubMed

Darwiche, Kaid; Özkan, Filiz; Wolters, Celina; Eisenmann, Stephan

2018-02-01

Endobronchial ultrasound (EBUS) has revolutionized the diagnosis of lung cancer over the last decade. This minimally invasive diagnostic method has also become increasingly important in the case of other diseases such as sarcoidosis, thereby helping to avoid unnecessary diagnostic interventions. This review article provides an update regarding EBUS and discusses current and future developments of this method. © Georg Thieme Verlag KG Stuttgart · New York.

[Current situation of human resources of parasitic disease control and prevention organizations in Henan Province].

PubMed

Ya-Lan, Zhang; Yan-Kun, Zhu; Wei-Qi, Chen; Yan, Deng; Peng, Li

2018-01-10

To understand the current status of human resources of parasitic disease control and prevention organizations in Henan Province, so as to provide the reference for promoting the integrative ability of the prevention and control of parasitic diseases in Henan Province. The questionnaires were designed and the method of census was adopted. The information, such as the amounts, majors, education background, technical titles, working years, and turnover in each parasitic disease control and prevention organization was collected by the centers for disease control and prevention (CDCs) at all levels. The data were descriptively analyzed. Totally 179 CDCs were investigated, in which only 19.0% (34/179) had the independent parasitic diseases control institution (department) . There were only 258 full-time staffs working on parasitic disease control and prevention in the whole province, in which only 61.9% (159/258) were health professionals. Those with junior college degree or below in the health professionals accounted for 60.3% (96/159) . Most of them (42.1%) had over 20 years of experience, but 57.9% (92/159) of their technical post titles were at primary level or below. The proportion of the health professionals is low in the parasitic disease control and prevention organizations in Henan Province. The human resource construction for parasitic disease control and prevention at all levels should be strengthened.

Examining the relationship between infectious diseases and flooding in Europe

PubMed Central

Brown, Lisa; Murray, Virginia

2013-01-01

Introduction Many infectious diseases are sensitive to climatic changes; specifically, flooding. This systematic literature review aimed to strengthen the quality and completeness of evidence on infectious diseases following flooding, relevant to Europe. Methods A systematic literature review from 2004–2012 was performed. Focused searches of the following databases were conducted: Medline, Scopus, PubMed, Cochrane Library, and Evidence Aid. Personal communications with key informants were also reviewed. Results Thirty-eight studies met the inclusion criteria. Evidence suggested that water-borne, rodent-borne, and vector-borne diseases have been associated with flooding in Europe, although at a lower incidence than developing countries. Conclusion Disease surveillance and early warning systems, coupled with effective prevention and response capabilities, can reduce current and future vulnerability to infectious diseases following flooding. PMID:28228994

Towards tailored and targeted adherence assessment to optimise asthma management

PubMed Central

van Boven, Job FM; Trappenburg, Jaap CA; van der Molen, Thys; Chavannes, Niels H

2015-01-01

In this paper, we aim to emphasise the need for a more comprehensive and tailored approach to manage the broad nature of non-adherence, to personalise current asthma management. Although currently several methods are available to measure the extent of asthma patients’ adherence, the vast majority do not incorporate confirmation of the actual inhalation, dose and inhalation technique. Moreover, most current measures lack detailed information on the individual consequences of non-adherence and on when and how to take action if non-adherence is identified. Notably, one has to realise there are several forms of non-adherence (erratic non-adherence, intelligent non-adherence and unwitting non-adherence), each requiring a different approach. To improve asthma management, more accurate methods are needed that integrate measures of non-adherence, asthma disease control and patient preferences. Integrating information from the latest inhaler devices and patient-reported outcomes using mobile monitoring- and feedback systems (‘mHealth’) is considered a promising strategy, but requires careful implementation. Key issues to be considered before large-scale implementation include patient preferences, large heterogeneity in patient and disease characteristics, economic consequences, and long-term persistence with new digital technologies. PMID:26181850

Pain in Neurodegenerative Disease: Current Knowledge and Future Perspectives

PubMed Central

de Tommaso, Marina; Arendt-Nielsen, Lars; Defrin, Ruth; Kunz, Miriam; Pickering, Gisele; Valeriani, Massimiliano

2016-01-01

Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD related disorders, motor neuron diseases (MND), Huntington's disease (HD), spinocerebellar ataxia (SCA), and spinal muscular atrophy (SMA), is mainly addressed to motor and cognitive impairment, with special care to vital functions as breathing and feeding. Many of these patients complain of painful symptoms though their origin is variable, and their presence is frequently not considered in the treatment guidelines, leaving their management to the decision of the clinicians alone. However, studies focusing on pain frequency in such disorders suggest a high prevalence of pain in selected populations from 38 to 75% in AD, 40% to 86% in PD, and 19 to 85% in MND. The methods of pain assessment vary between studies so the type of pain has been rarely reported. However, a prevalent nonneuropathic origin of pain emerged for MND and PD. In AD, no data on pain features are available. No controlled therapeutic trials and guidelines are currently available. Given the relevance of pain in neurodegenerative disorders, the comprehensive understanding of mechanisms and predisposing factors, the application and validation of specific scales, and new specific therapeutic trials are needed. PMID:27313396

Clostridium difficile infection in patients with inflammatory bowel disease

PubMed Central

Saidel-Odes, Lisa; Borer, Abraham; Odes, Selwyn

2011-01-01

Clostridium difficile infection in patients with inflammatory bowel disease has become a serious clinical problem over the past few years. This review is focused on the current changes in epidemiology, pertinent clinical aspects, standard and newer diagnostic methods, established and novel therapies, and prevention of infection. There is emphasis on the importance of clinical awareness, rapid detection by stool testing, and appropriate antibiotic therapy, while newer technologies, antibiotics and other treatments are explored. PMID:24713726

Computer-assisted initial diagnosis of rare diseases

PubMed Central

Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

2016-01-01

Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

Preventing the transmission of pathogenic mitochondrial DNA mutations: Can we achieve long-term benefits from germ-line gene transfer?

PubMed

Samuels, David C; Wonnapinij, Passorn; Chinnery, Patrick F

2013-03-01

Mitochondrial medicine is one of the few areas of genetic disease where germ-line transfer is being actively pursued as a treatment option. All of the germ-line transfer methods currently under development involve some carry-over of the maternal mitochondrial DNA (mtDNA) heteroplasmy, potentially delivering the pathogenic mutation to the offspring. Rapid changes in mtDNA heteroplasmy have been observed within a single generation, and so any 'leakage' of mutant mtDNA could lead to mtDNA disease in future generations, compromising the reproductive health of the first generation, and leading to repeated interventions in subsequent generations. To determine whether this is a real concern, we developed a model of mtDNA heteroplasmy inheritance by studying 87 mother-child pairs, and predicted the likely outcome of different levels of 'mutant mtDNA leakage' on subsequent maternal generations. This showed that, for a clinical threshold of 60%, reducing the proportion of mutant mtDNA to <5% dramatically reduces the chance of disease recurrence in subsequent generations, but transmitting >5% mutant mtDNA was associated with a significant chance of disease recurrence. Mutations with a lower clinical threshold were associated with a higher risk of recurrence. Our findings provide reassurance that, at least from an mtDNA perspective, methods currently under development have the potential to effectively eradicate pathogenic mtDNA mutations from subsequent generations.

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017.

PubMed

Greenwood, John; Hammarlund-Udenaes, Margareta; Jones, Hazel C; Stitt, Alan W; Vandenbroucke, Roosmarijn E; Romero, Ignacio A; Campbell, Matthew; Fricker, Gert; Brodin, Birger; Manninga, Heiko; Gaillard, Pieter J; Schwaninger, Markus; Webster, Carl; Wicher, Krzysztof B; Khrestchatisky, Michel

2017-11-07

This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers.

A literature review of studies using qualitative research to explore chronic neuromuscular disease.

PubMed

LaDonna, Kori A

2011-06-01

Although most neuromuscular disease research articles reflect traditional quantitative approaches, qualitative methods are becoming more prevalent in the neuromuscular literature. Arguably, qualitative research provides rich data that may be used to generate patient-centered outcome measures or influence current standards of care. The purpose of this article is to explore the qualitative literature pertaining to individuals and families living with chronic neuromuscular disease in order to suggest implications for practice. Fifty-six qualitative articles addressing seven research themes including Illness Experience; Work, Recreation, and Services; Assisted Ventilation; Caregiving; Genetics; Communication and Information Seeking; and Palliative Care were identified.

Measuring molecular biomarkers in epidemiologic studies: laboratory techniques and biospecimen considerations.

PubMed

Erickson, Heidi S

2012-09-28

The future of personalized medicine depends on the ability to efficiently and rapidly elucidate a reliable set of disease-specific molecular biomarkers. High-throughput molecular biomarker analysis methods have been developed to identify disease risk, diagnostic, prognostic, and therapeutic targets in human clinical samples. Currently, high throughput screening allows us to analyze thousands of markers from one sample or one marker from thousands of samples and will eventually allow us to analyze thousands of markers from thousands of samples. Unfortunately, the inherent nature of current high throughput methodologies, clinical specimens, and cost of analysis is often prohibitive for extensive high throughput biomarker analysis. This review summarizes the current state of high throughput biomarker screening of clinical specimens applicable to genetic epidemiology and longitudinal population-based studies with a focus on considerations related to biospecimens, laboratory techniques, and sample pooling. Copyright © 2012 John Wiley & Sons, Ltd.

Age-related macular degeneration: current treatments

PubMed Central

Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

2009-01-01

Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

Cross-cultural adaptation and validation of the Behcet’s Disease Current Activity Form in Korea

PubMed Central

Choi, Hyo Jin; Seo, Mi Ryoung; Ryu, Hee Jung; Baek, Han Joo

2015-01-01

Background/Aims: This study was undertaken to perform a cross-cultural adaptation of the Behcet’s Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet’s disease (BD). Methods: A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient’s/clinician’s perception of disease activity and the Korean version of the Behcet’s Disease Quality of Life (BDQOL). Results: For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient’s/clinician’s perception of disease activity p < 0.05). Conclusions: The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients. PMID:26354066

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

PubMed

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Real-time point-of-care measurement of impaired renal function in a rat acute injury model employing exogenous fluorescent tracer agents

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Fitch, Richard M.; Galen, Karen P.; Wojdyla, Jolette K.; Poreddy, Amruta R.; Freskos, John N.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Demirjian, Sevag G.

2013-02-01

Renal function assessment is needed for the detection of acute kidney injury and chronic kidney disease. Glomerular filtration rate (GFR) is now widely accepted as the best indicator of renal function, and current clinical guidelines advocate its use in the staging of kidney disease. The optimum measure of GFR is by the use of exogenous tracer agents. However current clinically employed agents lack sensitivity or are cumbersome to use. An exogenous GFR fluorescent tracer agent, whose elimination rate could be monitored noninvasively through skin would provide a substantial improvement over currently available methods. We developed a series of novel aminopyrazine analogs for use as exogenous fluorescent GFR tracer agents that emit light in the visible region for monitoring GFR noninvasively over skin. In rats, these compounds are eliminated by the kidney with urine recovery greater than 90% of injected dose, are not broken down or metabolized in vivo, are not secreted by the renal tubules, and have clearance values similar to a GFR reference compound, iothalamate. In addition, biological half-life of these compounds measured in rats by noninvasive optical methods correlated with plasma derived methods. In this study, we show that this noninvasive methodology with our novel fluorescent tracer agents can detect impaired renal function. A 5/6th nephrectomy rat model is employed.

Evaluating disease management program effectiveness: an introduction to survival analysis.

PubMed

Linden, Ariel; Adams, John L; Roberts, Nancy

2004-01-01

Currently, the most widely used method in the disease management industry for evaluating program effectiveness is the "total population approach." This model is a pretest-posttest design, with the most basic limitation being that without a control group, there may be sources of bias and/or competing extraneous confounding factors that offer plausible rationale explaining the change from baseline. Survival analysis allows for the inclusion of data from censored cases, those subjects who either "survived" the program without experiencing the event (e.g., achievement of target clinical levels, hospitalization) or left the program prematurely, due to disenrollement from the health plan or program, or were lost to follow-up. Additionally, independent variables may be included in the model to help explain the variability in the outcome measure. In order to maximize the potential of this statistical method, validity of the model and research design must be assured. This paper reviews survival analysis as an alternative, and more appropriate, approach to evaluating DM program effectiveness than the current total population approach.

Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research

PubMed Central

Gupta, Veer; Henriksen, Kim; Edwards, Melissa; Jeromin, Andreas; Lista, Simone; Bazenet, Chantal; Soares, Holly; Lovestone, Simon; Hampel, Harald; Montine, Thomas; Blennow, Kaj; Foroud, Tatiana; Carrillo, Maria; Graff-Radford, Neill; Laske, Christoph; Breteler, Monique; Shaw, Leslie; Trojanowski, John Q.; Schupf, Nicole; Rissman, Robert A.; Fagan, Anne M.; Oberoi, Pankaj; Umek, Robert; Weiner, Michael W.; Grammas, Paula; Posner, Holly; Martins, Ralph

2015-01-01

The lack of readily available biomarkers is a significant hindrance towards progressing to effective therapeutic and preventative strategies for Alzheimer’s disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field in order to foster cross-validation across cohorts and laboratories. PMID:25282381

[How often is breast fibroadenomatosis asymptomatic?].

PubMed

Li, L A; Martyniuk, V V; Neĭshtadt, E L

1999-01-01

The results of clinico-morphological examinations of 386 women having no complains of discomfort in the mammary glands are presented. Methods of palpation, mammography and morphological investigation have detected fibroadenomatosis without subjective symptoms of the disease in 38%, 67% and 78% of the patients correspondingly. This variant of the disease is called asymptomatic since the woman can not notice it and so it is out of the field of attention of oncologists. High incidence of asymptomatic fibroadenomatosis requires a revision of the current assessment of it as a disease because it does not take into account a variant of the disease when the patient has no complains of painful indurations in the mammary glands.

Cutting Edge Methods for Non-Invasive Disease Diagnosis Using E-Tongue and E-Nose Devices

PubMed Central

Fitzgerald, Jessica

2017-01-01

Biomimetic cross-reactive sensor arrays (B-CRSAs) have been used to detect and diagnose a wide variety of diseases including metabolic disorders, mental health diseases, and cancer by analyzing both vapor and liquid patient samples. Technological advancements over the past decade have made these systems selective, sensitive, and affordable. To date, devices for non-invasive and accurate disease diagnosis have seen rapid improvement, suggesting a feasible alternative to current standards for medical diagnostics. This review provides an overview of the most recent B-CRSAs for diagnostics (also referred to electronic noses and tongues in the literature) and an outlook for future technological development. PMID:29215588

Combination therapeutics in complex diseases.

PubMed

He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

2016-12-01

The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Intestinal Microbiota: Facts and Fiction.

PubMed

Kverka, Miloslav; Tlaskalová-Hogenová, Helena

2017-01-01

In humans, the gut microbiota forms a complex ecosystem consisting of a vast number of bacteria, Archaea, fungi and viruses. It represents a major stimulus to the development of the immune system and many other physiological functions, so that it may shape the individual's susceptibility to infectious and immune-mediated diseases. The emergence of new '-omics' methods recently revolutionized the way we study the host-microbe interactions, but they also raised new questions and issues. In this review, we discuss the impact of these new data on the current and future therapies for chronic inflammatory diseases. We also outline the major conceptual, technical and interpretational issues that recently led to some misleading conclusions and discuss in brief the current research directions in the field. © 2017 S. Karger AG, Basel.

Harnessing the potential of noninvasive in vivo preclinical imaging of the immune system: challenges and prospects.

PubMed

Diken, Mustafa; Pektor, Stefanie; Miederer, Matthias

2016-10-01

Preclinical imaging has become a powerful method for investigation of in vivo processes such as pharmacokinetics of therapeutic substances and visualization of physiologic and pathophysiological mechanisms. These are important aspects to understand diseases and develop strategies to modify their progression with pharmacologic interventions. One promising intervention is the application of specifically tailored nanoscale particles that modulate the immune system to generate a tumor targeting immune response. In this complex interaction between immunomodulatory therapies, the immune system and malignant disease, imaging methods are expected to play a key role on the way to generate new therapeutic strategies. Here, we summarize examples which demonstrate the current potential of imaging methods and develop a perspective on the future value of preclinical imaging of the immune system.

Molecular diagnosis of Papaya meleira virus (PMeV) from leaf samples of Carica papaya L. using conventional and real-time RT-PCR.

PubMed

Abreu, Paolla M V; Piccin, João G; Rodrigues, Silas P; Buss, David S; Ventura, José A; Fernandes, Patricia M B

2012-03-01

Papaya meleira virus (PMeV) is the causal agent of papaya sticky disease. This study describes two methods for molecular diagnosis of PMeV using conventional and real-time PCR. These methods were shown to be more efficient than current methods of viral detection using extraction of PMeV dsRNA and observation of symptoms in the field. The methods described here were used to evaluate the effect of inoculation of papaya plants with purified PMeV dsRNA on the progress of PMeV infection. A single inoculation with PMeV dsRNA was observed to delay the progress of the virus infection by several weeks. The possibility of vertical transmission of PMeV was also investigated. No evidence was found for PMeV transmission through seeds collected from diseased fruit. The implications of these results for the epidemiology of PMeV and the management of papaya sticky disease are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells.

PubMed

D'Antonio, Matteo; Woodruff, Grace; Nathanson, Jason L; D'Antonio-Chronowska, Agnieszka; Arias, Angelo; Matsui, Hiroko; Williams, Roy; Herrera, Cheryl; Reyna, Sol M; Yeo, Gene W; Goldstein, Lawrence S B; Panopoulos, Athanasia D; Frazer, Kelly A

2017-04-11

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated. Currently the methods for deriving and characterizing iPSCs are time consuming, expensive, and, in some cases, descriptive but not quantitative. Here we set out to develop a set of simple methods that reduce cost and increase throughput in the characterization of iPSC lines. Specifically, we outline methods for high-throughput quantification of surface markers, gene expression analysis of in vitro differentiation potential, and evaluation of karyotype with markedly reduced cost. Published by Elsevier Inc.

Genetics of gallstone disease.

PubMed

Rebholz, Charlotte; Krawczyk, Marcin; Lammert, Frank

2018-04-10

Gallstone disease (GD) belongs to the most frequent disorders in gastroenterology and causes high costs in our health-care systems. Gallstones are uncommon in children but frequent in adults, in particular in women, and are triggered by exogenous risk factors. Here, we summarize the current knowledge concerning the contribution of inherited predisposition to gallstone risk. In this review, we present the current data and recent research on the genetics of gallstone disease. Several GD-predisposing gene variants have been reported, with most prominent effects being conferred by a common variant (p.D19H) of the hepatic and intestinal cholesterol transporter ABCG5/G8. A smaller group of patients might develop gallstones primarily due low phosphatidylcholine concentrations in bile as a result of loss-of-function mutations of the ABCB4 transporter (low phospholipid-associated cholelithiasis syndrome). Regardless of the origin, the risk factors for gallstones lead to the supersaturation of bile with insoluble compounds, in particular cholesterol. As result, cholesterol stones develop and present the most frequent type of gallstones. Laparoscopic cholecystectomy with low morbidity and mortality is currently the most common and effective method for the therapy of symptomatic gallbladder stones. Gallstone disease represents a multifactorial condition and previous studies have identified the major genetic contributors to gallstone formation. The increasing knowledge about the pathomechanisms of hepatobiliary metabolism and GD as well as the identification of additional risk factors might help to overcome the current invasive therapy by specific lifestyle intervention and precise molecular treatment. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Comparison of characteristics of chronic kidney diseases between Tibet plateau and plain areas

PubMed Central

Zhou, Yan; Deng, Yong-Ming; Li, Chuan; Gong, Yun-Bing; Mao, Zhi-Guo; Wu, Jun; Li, Su-Zhi; Liu, Zhi-Hong; Tang, Zheng

2014-01-01

Background: The purpose of the current study was to investigate the pathological characteristics of chronic kidney diseases in the Tibet plateau and the plain. Methods: 77 cases from the Tibet plateau and 154 cases from the plain of renal biopsied patients with chronic kidney diseases were compared in a randomized, and parallel controlled manner. Pathological characteristics were defined according to the standards of WHO and associated classifications. Results: The ration of sex was shown that most of patients in the plateau region were female, whereas those in the plain were male. The characteristics of pathological types were shown that the patients in the plateau region were primarily minimal change disease, but IgA nephropathy was rare; meanwhile, the proportional lupus nephritis (LN) ratio of the secondary glomerulonephritis in the plateau region was significantly lower than those in the plain region. Conclusions: The current data demonstrated that the most common kidney disease in the Tibet Plateau region is still the primary glomerulonephritis as the same as those in the plain region. However, the primary glomerular disease in the plateau region is minimal change disease, and the most common clinical manifestations are the nephrotic syndrome. The IgA nephropathy in the plain is the most frequent disease. In terms of the secondary renal diseases, Henoch-Schnolein purpura nephritis are dominated in the plateau region, whereas LN-based diseases are frequently found in the plain. There is a statistical significance existed between those two groups. PMID:25337266

Non-invasive prediction of forthcoming cirrhosis-related complications

PubMed Central

Kang, Wonseok; Kim, Seung Up; Ahn, Sang Hoon

2014-01-01

In patients with chronic liver diseases, identification of significant liver fibrosis and cirrhosis is essential for determining treatment strategies, assessing therapeutic response, and stratifying long-term prognosis. Although liver biopsy remains the reference standard for evaluating the extent of liver fibrosis in patients with chronic liver diseases, several non-invasive methods have been developed as alternatives to liver biopsies. Some of these non-invasive methods have demonstrated clinical accuracy for diagnosing significant fibrosis or cirrhosis in many cross-sectional studies with the histological fibrosis stage as a reference standard. However, non-invasive methods cannot be fully validated through cross-sectional studies since liver biopsy is not a perfect surrogate endpoint marker. Accordingly, recent studies have focused on assessing the performance of non-invasive methods through long-term, longitudinal, follow-up studies with solid clinical endpoints related to advanced stages of liver fibrosis and cirrhosis. As a result, current view is that these alternative methods can independently predict future cirrhosis-related complications, such as hepatic decompensation, liver failure, hepatocellular carcinoma, or liver-related death. The clinical role of non-invasive models seems to be shifting from a simple tool for predicting the extent of fibrosis to a surveillance tool for predicting future liver-related events. In this article, we will summarize recent longitudinal studies of non-invasive methods for predicting forthcoming complications related to liver cirrhosis and discuss the clinical value of currently available non-invasive methods based on evidence from the literature. PMID:24627597

Segmentation and labeling of the ventricular system in normal pressure hydrocephalus using patch-based tissue classification and multi-atlas labeling

NASA Astrophysics Data System (ADS)

Ellingsen, Lotta M.; Roy, Snehashis; Carass, Aaron; Blitz, Ari M.; Pham, Dzung L.; Prince, Jerry L.

2016-03-01

Normal pressure hydrocephalus (NPH) affects older adults and is thought to be caused by obstruction of the normal flow of cerebrospinal fluid (CSF). NPH typically presents with cognitive impairment, gait dysfunction, and urinary incontinence, and may account for more than five percent of all cases of dementia. Unlike most other causes of dementia, NPH can potentially be treated and the neurological dysfunction reversed by shunt surgery or endoscopic third ventriculostomy (ETV), which drain excess CSF. However, a major diagnostic challenge remains to robustly identify shunt-responsive NPH patients from patients with enlarged ventricles due to other neurodegenerative diseases. Currently, radiologists grade the severity of NPH by detailed examination and measurement of the ventricles based on stacks of 2D magnetic resonance images (MRIs). Here we propose a new method to automatically segment and label different compartments of the ventricles in NPH patients from MRIs. While this task has been achieved in healthy subjects, the ventricles in NPH are both enlarged and deformed, causing current algorithms to fail. Here we combine a patch-based tissue classification method with a registration-based multi-atlas labeling method to generate a novel algorithm that labels the lateral, third, and fourth ventricles in subjects with ventriculomegaly. The method is also applicable to other neurodegenerative diseases such as Alzheimer's disease; a condition considered in the differential diagnosis of NPH. Comparison with state of the art segmentation techniques demonstrate substantial improvements in labeling the enlarged ventricles, indicating that this strategy may be a viable option for the diagnosis and characterization of NPH.

[Current knowledge on the strain typing of the pathogenic fungus Histoplasma capsulatum var. capsulatum: a review of the findings].

PubMed

Reyes-Montes, M del R; Taylor, M L; Curiel-Quesada, E; Mesa-Arango, A C

2000-12-01

The classification of microbial strains is currently based on different typing methods, which must meet certain criteria in order to be widely used. Phenotypic and genotypic methods are being employed in the epidemiology of several fungal diseases. However, some problems associated to the phenotypic methods have fostered genotyping procedures, from DNA polymorphic diversity to gene sequencing studies, all aiming to differentiate and to relate fungal isolates or strains. Through these studies, it is possible to identify outbreaks, to detect nosocomial infection transmission, and to determine the source of infection, as well as to recognize virulent isolates. This paper is aimed at analyzing the methods recently used to type Histoplasma capsulatum, causative agent of the systemic mycosis known as histoplasmosis, in order to recommend those that yield reproducible and accurate results.

A practical method to rapidly dissolve metallic stents.

PubMed

Bradshaw, Scott H; Kennedy, Lloyd; Dexter, David F; Veinot, John P

2009-01-01

Metallic stents are commonly used in many clinical applications including peripheral vascular disease intervention, biliary obstruction, endovascular repair of aneurysms, and percutaneous coronary interventions. In the examination of vascular stent placement, it is important to determine if the stent is open or has become obstructed. This is increasingly important in the era of drug-eluting stent usage in coronary arteries. We describe a practical, rapid and cost-effective method to dissolve most metallic stents leaving the vascular and luminal tissues intact. This practical method may replace the laborious and expensive plastic embedding methods currently utilized.

Root removal to improve disease management in replanted Washington red raspberry fields

USDA-ARS?s Scientific Manuscript database

Washington leads the nation in the production of red raspberries for processing. Soilborne pathogens are a production constraint in this $61 million industry with growers relying on preplant soil fumigation for their management. However, current fumigation methods can be ineffective, leading to repl...

Serological diagnosis of Besnoitia bennetti infection in donkeys

USDA-ARS?s Scientific Manuscript database

Besnoitiosis is an emerging infectious disease of donkeys in the United States for which there are currently no serologic methods of diagnosis. A study was performed to evaluate physical examination findings and three serologic assays for the detection of B. bennetti infection in donkeys. A prospect...

WATERBORNE DISEASES AND MICROBIAL QUALITY MONITORING FOR RECREATIONAL WATER BODIES USING REGULATORY METHODS

EPA Science Inventory

This chapter will provide the reader with a historical perspective of microbial water quality and monitoring of recreational waters, with special attention to marine environments. It will review the regulations that are currently in effect in the United States and discuss critic...

Analysis strategies for longitudinal attachment loss data.

PubMed

Beck, J D; Elter, J R

2000-02-01

The purpose of this invited review is to describe and discuss methods currently in use to quantify the progression of attachment loss in epidemiological studies of periodontal disease, and to make recommendations for specific analytic methods based upon the particular design of the study and structure of the data. The review concentrates on the definition of incident attachment loss (ALOSS) and its component parts; measurement issues including thresholds and regression to the mean; methods of accounting for longitudinal change, including changes in means, changes in proportions of affected sites, incidence density, the effect of tooth loss and reversals, and repeated events; statistical models of longitudinal change, including the incorporation of the time element, use of linear, logistic or Poisson regression or survival analysis, and statistical tests; site vs person level of analysis, including statistical adjustment for correlated data; the strengths and limitations of ALOSS data. Examples from the Piedmont 65+ Dental Study are used to illustrate specific concepts. We conclude that incidence density is the preferred methodology to use for periodontal studies with more than one period of follow-up and that the use of studies not employing methods for dealing with complex samples, correlated data, and repeated measures does not take advantage of our current understanding of the site- and person-level variables important in periodontal disease and may generate biased results.

Prospects for automated diagnosis of verbal autopsies.

PubMed

Garenne, Michel

2014-02-04

Verbal autopsy is a method for assessing probable causes of death from lay reporting of signs, symptoms and circumstances by family members or caregivers of a deceased person. Several methods of automated diagnoses of causes of death from standardized verbal autopsy questionnaires have been developed recently (Inter-VA, Tariff, Random Forest and King-Lu). Their performances have been assessed in a series of papers in BMC Medicine. Overall, and despite high specificity, the current strategies of automated computer diagnoses lead to relatively low sensitivity and positive predictive values, even for causes which are expected to be easily assessed by interview. Some methods have even abnormally low sensitivity for selected diseases of public health importance and could probably be improved. Ways to improve the current strategies are proposed: more detailed questionnaires; using more information on disease duration; stratifying for large groups of causes of death by age, sex and main category; using clusters of signs and symptoms rather than quantitative scores or ranking; separating indeterminate causes; imputing unknown cause with appropriate methods. Please see related articles: http://www.biomedcentral.com/1741-7015/12/5; http://www.biomedcentral.com/1741-7015/12/19; http://www.biomedcentral.com/1741-7015/12/20; http://www.biomedcentral.com/1741-7015/12/21; http://www.biomedcentral.com/1741-7015/12/22; http://www.biomedcentral.com/1741-7015/12/23.

Review of the Clinical Evidence for the Use of DEBIRI in the Treatment of Colorectal Metastatic Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, Shamar, E-mail: youn1862@umn.edu; D’Souza, Donna; Flanagan, Siobhan

2017-04-15

Colorectal cancer is a common malignancy that most commonly metastasizes to the liver. There has been considerable effort in developing new treatment options for these patients. One method that has been developed for the treatment of colorectal metastases to the liver is irinotecan-loaded drug-eluting bead (DEBIRI) embolization. This article reviews the current literature on DEBIRI and discusses the state of current knowledge and possible areas of future investigation.

Risk assessment of vector-borne diseases for public health governance.

PubMed

Sedda, L; Morley, D W; Braks, M A H; De Simone, L; Benz, D; Rogers, D J

2014-12-01

In the context of public health, risk governance (or risk analysis) is a framework for the assessment and subsequent management and/or control of the danger posed by an identified disease threat. Generic frameworks in which to carry out risk assessment have been developed by various agencies. These include monitoring, data collection, statistical analysis and dissemination. Due to the inherent complexity of disease systems, however, the generic approach must be modified for individual, disease-specific risk assessment frameworks. The analysis was based on the review of the current risk assessments of vector-borne diseases adopted by the main Public Health organisations (OIE, WHO, ECDC, FAO, CDC etc…). Literature, legislation and statistical assessment of the risk analysis frameworks. This review outlines the need for the development of a general public health risk assessment method for vector-borne diseases, in order to guarantee that sufficient information is gathered to apply robust models of risk assessment. Stochastic (especially spatial) methods, often in Bayesian frameworks are now gaining prominence in standard risk assessment procedures because of their ability to assess accurately model uncertainties. Risk assessment needs to be addressed quantitatively wherever possible, and submitted with its quality assessment in order to enable successful public health measures to be adopted. In terms of current practice, often a series of different models and analyses are applied to the same problem, with results and outcomes that are difficult to compare because of the unknown model and data uncertainties. Therefore, the risk assessment areas in need of further research are identified in this article. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

SemaTyP: a knowledge graph based literature mining method for drug discovery.

PubMed

Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

2018-05-30

Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

Serious unexpected sinus infection discovered by CT scanning for presumed neurological disease.

PubMed

Swift, A C; Gill, G V

1994-03-01

Serious infection in the paranasal sinuses may present with symptoms suggestive of neurological disease and thus lead to delay in the diagnosis and subsequent treatment. We present three such cases in whom the initial diagnoses had been acute optic neuritis, a posterior communicating aneurysm and an intracranial space occupying lesion. The fourth patient had meningitis but the paranasal sinuses had not initially been considered as a possible source of infection. The current methods of diagnosing sinusitis are discussed.

Novel strategies for controlling Streptococcus pyogenes infection and associated diseases: from potential peptide vaccines to antibody immunotherapy.

PubMed

Pandey, Manisha; Sekuloski, Silvana; Batzloff, Michael R

2009-07-01

Infections caused by group A streptococcus (GAS) represent a public health problem in both developing and developed countries. The current available methods of prevention are either inadequate or ineffective, which is highlighted by the resurgence in invasive GAS infections over the past two decades. The management of GAS and associated diseases requires new and improved approaches. This review discusses various potential approaches in controlling GAS infections, ranging from prophylactic vaccines to antibody immunotherapy.

A case of nosocomial Legionnaires' disease: The importance of early diagnosis, adequate prevention and eradication measures.

PubMed

Lucardie, A; Rogiers, Ph; Floré, K

2016-02-03

This case-report describes a patient with confirmed nosocomial Legionnaires' disease, a diagnosis which should be suspected when pneumonia does not respond to empiric therapy with beta-lactam antibiotics, or develops in the presence of certain risk factors. Culture is currently the golden standard for diagnosis, although the use of more modern techniques, such as a combination of urinary antigen testing and polymerase chain reaction, are on the rise. Specific detection and eradication methods are discussed.

Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening.

PubMed

Smith, Alec S T; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A; Kim, Deok-Ho

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. Published by Elsevier Inc.

[Oxidative stress. Should it be measured in the diabetic patient?].

PubMed

Villa-Caballero, L; Nava-Ocampo, A A; Frati-Munari, A C; Ponce-Monter, H

2000-01-01

Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species production and the antioxidant systems, with negative effects on carbohydrates, lipids, and proteins. It is also involved in the progression of different chronic diseases and apoptosis. Diabetes mellitus is associated to a high oxidative stress level through different biochemical pathways, i.e. protein glycosylation, glucose auto-oxidation, and the polyol pathway, mainly induced by hyperglycemia. Oxidative stress could also be involved in the pathogenesis of atherosclerotic lesions and other chronic diabetic complications. Measurement of oxidative stress could be useful to investigate its role in the initiation and development processes of chronic diabetic complications and also to evaluate preventive actions, including antioxidative therapy. Different attempts have been made to obtain a practical, accurate, specific, and sensitive method to evaluate oxidative stress in clinical practice. However, this ideal method is not currently available to date and the usefulness of the current methods needs to be confirmed in daily practice. We suggest quantifying oxidated and reduced glutation (GSSG/GSH) and the thiobarbituric reactive substances (TBARS) with currently alternatives. Currently available alternative methods while we await better options.

Examining the relationship between infectious diseases and flooding in Europe: A systematic literature review and summary of possible public health interventions.

PubMed

Brown, Lisa; Murray, Virginia

2013-01-01

Introduction Many infectious diseases are sensitive to climatic changes; specifically, flooding. This systematic literature review aimed to strengthen the quality and completeness of evidence on infectious diseases following flooding, relevant to Europe. Methods A systematic literature review from 2004-2012 was performed. Focused searches of the following databases were conducted: Medline, Scopus, PubMed, Cochrane Library, and Evidence Aid. Personal communications with key informants were also reviewed. Results Thirty-eight studies met the inclusion criteria. Evidence suggested that water-borne, rodent-borne, and vector-borne diseases have been associated with flooding in Europe, although at a lower incidence than developing countries. Conclusion Disease surveillance and early warning systems, coupled with effective prevention and response capabilities, can reduce current and future vulnerability to infectious diseases following flooding.

Diagnosis of dry eye disease and emerging technologies

PubMed Central

Zeev, Maya Salomon-Ben; Miller, Darby Douglas; Latkany, Robert

2014-01-01

Dry eye is one of the most commonly encountered problems in ophthalmology. Signs can include punctate epithelial erosions, hyperemia, low tear lakes, rapid tear break-up time, and meibomian gland disease. Current methods of diagnosis include a slit-lamp examination with and without different stains, including fluorescein, rose bengal, and lissamine green. Other methods are the Schirmer test, tear function index, tear break-up time, and functional visual acuity. Emerging technologies include meniscometry, optical coherence tomography, tear film stability analysis, interferometry, tear osmolarity, the tear film normalization test, ocular surface thermography, and tear biomarkers. Patient-specific considerations involve relevant history of autoimmune disease, refractive surgery or use of oral medications, and allergies or rosacea. Other patient considerations include clinical examination for lid margin disease and presence of lagophthalmos or blink abnormalities. Given a complex presentation and a variety of signs and symptoms, it would be beneficial if there was an inexpensive, readily available, and reproducible diagnostic test for dry eye. PMID:24672224

Sociobehavioural research methods for the introduction of vaccines in the Diseases of the Most Impoverished Programme.

PubMed

Kaljee, Linda M; Pack, Rob; Pach, Al; Nyamete, Andrew; Stanton, Bonita F

2004-09-01

Participation in vaccination campaigns worldwide, particularly the Expanded Programme on Immunization, has increased significantly in recent years. However, there remain multiple and integrated behavioural, sociocultural and political-economic barriers to vaccination. The Diseases of the Most Impoverished (DOMI) Programme has undertaken shigellosis disease-burden studies and oral cholera and typhoid Vi polysaccharide vaccine trials in seven Asian countries. As part of these projects, sociobehavioural studies have been undertaken to determine the potential demand for vaccines for these diseases and the obstacles and enabling factors that may affect acceptance, delivery, and use of vaccines. A theoretical model of acceptance of vaccination and a triangulation of qualitative and quantitative methods have been used for fully elucidating the range of issues relating to vaccination for shigellosis, cholera, and typhoid fever. In this paper, the theoretical and methodological basis of the DOMI projects has been reviewed in a context of current sociobehavioural research on the acceptability and desirability of vaccination.

Whole-Genome Sequencing in Outbreak Analysis

PubMed Central

Turner, Stephen D.; Riley, Margaret F.; Petri, William A.; Hewlett, Erik L.

2015-01-01

SUMMARY In addition to the ever-present concern of medical professionals about epidemics of infectious diseases, the relative ease of access and low cost of obtaining, producing, and disseminating pathogenic organisms or biological toxins mean that bioterrorism activity should also be considered when facing a disease outbreak. Utilization of whole-genome sequencing (WGS) in outbreak analysis facilitates the rapid and accurate identification of virulence factors of the pathogen and can be used to identify the path of disease transmission within a population and provide information on the probable source. Molecular tools such as WGS are being refined and advanced at a rapid pace to provide robust and higher-resolution methods for identifying, comparing, and classifying pathogenic organisms. If these methods of pathogen characterization are properly applied, they will enable an improved public health response whether a disease outbreak was initiated by natural events or by accidental or deliberate human activity. The current application of next-generation sequencing (NGS) technology to microbial WGS and microbial forensics is reviewed. PMID:25876885

Mito-magneto: A Tool for Nanoparticle Mediated Mitochondria Isolation†

PubMed Central

Banik, Bhabatosh; Askins, Brett W.; Dhar, Shanta

2016-01-01

The field of intracellular organelle targeting using nanoparticles (NPs) is mushrooming rapidly. Thus, the area of nanotechnology-enabled targeting of mitochondrion, the cellular powerhouse, for diseases characterized by mitochondrial dysfunctions such as cancer, diseases of the central nervous system, cardiovascular diseases is also growing at a rapid pace. Optimization of NP’s ability to target the mitochondria requires quantification of the particles in this subcellular organelle and isolation of mitochondria from cells. Conventional gradient centrifugation used in currently available methods may not be appropriate for NP containing mitochondria isolation as these particles undergo Brownian motion under centrifugal forces yielding irreproducible results. There is only one method for centrifugation free mitochondria isolation, however this method requires immune-precipitation. Thus, a reliable centrifugation and immune-precipitation free method is urgently needed to support this growing field of nanotechnology-based mitochondria targeting. Here, we report a mitochondria-targeted magnetic NP, Mito-magneto, to avoid centrifugation and immune precipitation methods for isolation of functional, respiration active pure mitochondria which can be used to analyze and quantify mitochondria targeting properties of various NPs to provide an important tool for the growing field of “mitochondrial nanomedicine”. PMID:27735003

Directional spatial frequency analysis of lipid distribution in atherosclerotic plaque

NASA Astrophysics Data System (ADS)

Korn, Clyde; Reese, Eric; Shi, Lingyan; Alfano, Robert; Russell, Stewart

2016-04-01

Atherosclerosis is characterized by the growth of fibrous plaques due to the retention of cholesterol and lipids within the artery wall, which can lead to vessel occlusion and cardiac events. One way to evaluate arterial disease is to quantify the amount of lipid present in these plaques, since a higher disease burden is characterized by a higher concentration of lipid. Although therapeutic stimulation of reverse cholesterol transport to reduce cholesterol deposits in plaque has not produced significant results, this may be due to current image analysis methods which use averaging techniques to calculate the total amount of lipid in the plaque without regard to spatial distribution, thereby discarding information that may have significance in marking response to therapy. Here we use Directional Fourier Spatial Frequency (DFSF) analysis to generate a characteristic spatial frequency spectrum for atherosclerotic plaques from C57 Black 6 mice both treated and untreated with a cholesterol scavenging nanoparticle. We then use the Cauchy product of these spectra to classify the images with a support vector machine (SVM). Our results indicate that treated plaque can be distinguished from untreated plaque using this method, where no difference is seen using the spatial averaging method. This work has the potential to increase the effectiveness of current in-vivo methods of plaque detection that also use averaging methods, such as laser speckle imaging and Raman spectroscopy.

ESEA: Discovering the Dysregulated Pathways based on Edge Set Enrichment Analysis

PubMed Central

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

2015-01-01

Pathway analyses are playing an increasingly important role in understanding biological mechanism, cellular function and disease states. Current pathway-identification methods generally focus on only the changes of gene expression levels; however, the biological relationships among genes are also the fundamental components of pathways, and the dysregulated relationships may also alter the pathway activities. We propose a powerful computational method, Edge Set Enrichment Analysis (ESEA), for the identification of dysregulated pathways. This provides a novel way of pathway analysis by investigating the changes of biological relationships of pathways in the context of gene expression data. Simulation studies illustrate the power and performance of ESEA under various simulated conditions. Using real datasets from p53 mutation, Type 2 diabetes and lung cancer, we validate effectiveness of ESEA in identifying dysregulated pathways. We further compare our results with five other pathway enrichment analysis methods. With these analyses, we show that ESEA is able to help uncover dysregulated biological pathways underlying complex traits and human diseases via specific use of the dysregulated biological relationships. We develop a freely available R-based tool of ESEA. Currently, ESEA can support pathway analysis of the seven public databases (KEGG; Reactome; Biocarta; NCI; SPIKE; HumanCyc; Panther). PMID:26267116

A computational method for drug repositioning using publicly available gene expression data.

PubMed

Shabana, K M; Abdul Nazeer, K A; Pradhan, Meeta; Palakal, Mathew

2015-01-01

The identification of new therapeutic uses of existing drugs, or drug repositioning, offers the possibility of faster drug development, reduced risk, lesser cost and shorter paths to approval. The advent of high throughput microarray technology has enabled comprehensive monitoring of transcriptional response associated with various disease states and drug treatments. This data can be used to characterize disease and drug effects and thereby give a measure of the association between a given drug and a disease. Several computational methods have been proposed in the literature that make use of publicly available transcriptional data to reposition drugs against diseases. In this work, we carry out a data mining process using publicly available gene expression data sets associated with a few diseases and drugs, to identify the existing drugs that can be used to treat genes causing lung cancer and breast cancer. Three strong candidates for repurposing have been identified- Letrozole and GDC-0941 against lung cancer, and Ribavirin against breast cancer. Letrozole and GDC-0941 are drugs currently used in breast cancer treatment and Ribavirin is used in the treatment of Hepatitis C.

Disease quantification in dermatology: in vivo near-infrared spectroscopy measures correlate strongly with the clinical assessment of psoriasis severity

NASA Astrophysics Data System (ADS)

Greve, Tanja Maria; Kamp, Søren; Jemec, Gregor B. E.

2013-03-01

Accurate documentation of disease severity is a prerequisite for clinical research and the practice of evidence-based medicine. The quantification of skin diseases such as psoriasis currently relies heavily on clinical scores. Although these clinical scoring methods are well established and very useful in quantifying disease severity, they require an extensive clinical experience and carry a risk of subjectivity. We explore the opportunity to use in vivo near-infrared (NIR) spectra as an objective and noninvasive method for local disease severity assessment in 31 psoriasis patients in whom selected plaques were scored clinically. A partial least squares (PLS) regression model was used to analyze and predict the severity scores on the NIR spectra of psoriatic and uninvolved skin. The correlation between predicted and clinically assigned scores was R=0.94 (RMSE=0.96), suggesting that in vivo NIR provides accurate clinical quantification of psoriatic plaques. Hence, NIR may be a practical solution to clinical severity assessment of psoriasis, providing a continuous, linear, numerical value of severity.

State-of-the-Art Fluorescence Fluctuation-Based Spectroscopic Techniques for the Study of Protein Aggregation

PubMed Central

Kinjo, Masataka

2018-01-01

Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are devastating proteinopathies with misfolded protein aggregates accumulating in neuronal cells. Inclusion bodies of protein aggregates are frequently observed in the neuronal cells of patients. Investigation of the underlying causes of neurodegeneration requires the establishment and selection of appropriate methodologies for detailed investigation of the state and conformation of protein aggregates. In the current review, we present an overview of the principles and application of several methodologies used for the elucidation of protein aggregation, specifically ones based on determination of fluctuations of fluorescence. The discussed methods include fluorescence correlation spectroscopy (FCS), imaging FCS, image correlation spectroscopy (ICS), photobleaching ICS (pbICS), number and brightness (N&B) analysis, super-resolution optical fluctuation imaging (SOFI), and transient state (TRAST) monitoring spectroscopy. Some of these methodologies are classical protein aggregation analyses, while others are not yet widely used. Collectively, the methods presented here should help the future development of research not only into protein aggregation but also neurodegenerative diseases. PMID:29570669

Towards an eco-phylogenetic framework for infectious disease ecology.

PubMed

Fountain-Jones, Nicholas M; Pearse, William D; Escobar, Luis E; Alba-Casals, Ana; Carver, Scott; Davies, T Jonathan; Kraberger, Simona; Papeş, Monica; Vandegrift, Kurt; Worsley-Tonks, Katherine; Craft, Meggan E

2018-05-01

Identifying patterns and drivers of infectious disease dynamics across multiple scales is a fundamental challenge for modern science. There is growing awareness that it is necessary to incorporate multi-host and/or multi-parasite interactions to understand and predict current and future disease threats better, and new tools are needed to help address this task. Eco-phylogenetics (phylogenetic community ecology) provides one avenue for exploring multi-host multi-parasite systems, yet the incorporation of eco-phylogenetic concepts and methods into studies of host pathogen dynamics has lagged behind. Eco-phylogenetics is a transformative approach that uses evolutionary history to infer present-day dynamics. Here, we present an eco-phylogenetic framework to reveal insights into parasite communities and infectious disease dynamics across spatial and temporal scales. We illustrate how eco-phylogenetic methods can help untangle the mechanisms of host-parasite dynamics from individual (e.g. co-infection) to landscape scales (e.g. parasite/host community structure). An improved ecological understanding of multi-host and multi-pathogen dynamics across scales will increase our ability to predict disease threats. © 2017 Cambridge Philosophical Society.

Haplotype Reconstruction in Large Pedigrees with Many Untyped Individuals

NASA Astrophysics Data System (ADS)

Li, Xin; Li, Jing

Haplotypes, as they specify the linkage patterns between dispersed genetic variations, provide important information for understanding the genetics of human traits. However haplotypes are not directly available from current genotyping platforms, and hence there are extensive investigations of computational methods to recover such information. Two major computational challenges arising in current family-based disease studies are large family sizes and many ungenotyped family members. Traditional haplotyping methods can neither handle large families nor families with missing members. In this paper, we propose a method which addresses these issues by integrating multiple novel techniques. The method consists of three major components: pairwise identical-bydescent (IBD) inference, global IBD reconstruction and haplotype restoring. By reconstructing the global IBD of a family from pairwise IBD and then restoring the haplotypes based on the inferred IBD, this method can scale to large pedigrees, and more importantly it can handle families with missing members. Compared with existing methods, this method demonstrates much higher power to recover haplotype information, especially in families with many untyped individuals.

A solid phase enzyme-linked immunosorbent assay for the antigenic detection of Legionella pneumophila (serogroup 1): A compliment for the space station diagnostic capability

NASA Technical Reports Server (NTRS)

Hejtmancik, Kelly E.

1987-01-01

It is necessary that an adequate microbiology capability be provided as part of the Health Maintenance Facility (HMF) to support expected microbial disease events and environmental monitoring during long periods of space flight. The application of morphological and biochemical studies to confirm the presence of certain bacterial and fungal disease agents are currently available and under consideration. This confirmation would be facilitated through employment of serological methods to aid in the identification of bacterial, fungal, and viral agents. A number of serological approaches are currently being considered, including the use of Enzyme Linked Immunosorbent Assay (ELISA) technology, which could be utilized during microgravity conditions. A solid phase, membrane supported ELISA for the detection of Legionella pneumophila, an expected disease agent, was developed to show a potential model system that would meet the HMF requirements and specifications for the future space station. These studies demonstrate the capability of membrane supported ELISA systems for identification of expected microbial disease agents as part of the HMF.

Current and Potential Support for Chronic Disease Management in the United States: The Perspective of Family and Friends of Chronically Ill Adults

PubMed Central

Rosland, Ann-Marie; Heisler, Michele; Janevic, Mary; Connell, Cathleen; Langa, Kenneth M.; Kerr, Eve A.; Piette, John D.

2013-01-01

Objectives Family members and friends can be an important source of self-management support for older adults with chronic diseases. We characterized the U.S. population of potential and current “disease management supporters” for people with chronic illness who are ADL-independent, the help that supporters could provide, and barriers to increasing support. Methods Nationally-representative survey of U.S. adults (N=1,722). Results 44% of respondents (representing 100 million US adults) help a family member or friend with chronic disease management; another 9% (representing 21 million US adults) are willing to start. Most are willing to assist with key tasks such as medication use and communicating with providers, although they feel constrained by privacy concerns and a lack of patient health information. Discussion The majority of U.S. adults already help or would be willing to help one of their family members or friends with chronic illness care. Supporters' specific concerns could be addressed through innovative programs. PMID:23795624

Leptospirosis in the Asia Pacific region

PubMed Central

2009-01-01

Background Leptospirosis is a worldwide zoonotic infection that has been recognized for decades, but the problem of the disease has not been fully addressed, particularly in resource-poor, developing countries, where the major burden of the disease occurs. This paper presents an overview of the current situation of leptospirosis in the region. It describes the current trends in the epidemiology of leptospirosis, the existing surveillance systems, and presents the existing prevention and control programs in the Asia Pacific region. Methods Data on leptospirosis in each member country were sought from official national organizations, international public health organizations, online articles and the scientific literature. Papers were reviewed and relevant data were extracted. Results Leptospirosis is highly prevalent in the Asia Pacific region. Infections in developed countries arise mainly from occupational exposure, travel to endemic areas, recreational activities, or importation of domestic and wild animals, whereas outbreaks in developing countries are most frequently related to normal daily activities, over-crowding, poor sanitation and climatic conditions. Conclusion In the Asia Pacific region, predominantly in developing countries, leptospirosis is largely a water-borne disease. Unless interventions to minimize exposure are aggressively implemented, the current global climate change will further aggravate the extent of the disease problem. Although trends indicate successful control of leptospirosis in some areas, there is no clear evidence that the disease has decreased in the last decade. The efficiency of surveillance systems and data collection varies significantly among the countries and areas within the region, leading to incomplete information in some instances. Thus, an accurate reflection of the true burden of the disease remains unknown. PMID:19732423

Posttraumatic Stress Disorder, Cardiovascular and Metabolic Disease: A Review of the Evidence

PubMed Central

Dedert, Eric A.; Calhoun, Patrick S.; Watkins, Lana L.; Sherwood, Andrew; Beckham, Jean C.

2011-01-01

Background Posttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease. Purpose The purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes. Methods A systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted. Results The literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers. Conclusions Although the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research. PMID:20174903

Climate change influences on marine infectious diseases: implications for management and society

USGS Publications Warehouse

Burge, Colleen A.; Eakin, C. Mark; Friedman, Carolyn S.; Froelich, Brett; Hershberger, Paul K.; Hofmann, Eileen E.; Petes, Laura E.; Prager, Katherine C.; Weil, Ernesto; Willis, Bette L.; Ford, Susan E.; Harvell, C. Drew

2014-01-01

Infectious diseases are common in marine environments, but the effects of a changing climate on marine pathogens are not well understood. Here, we focus on reviewing current knowledge about how the climate drives hostpathogen interactions and infectious disease outbreaks. Climate-related impacts on marine diseases are being documented in corals, shellfish, finfish, and humans; these impacts are less clearly linked to other organisms. Oceans and people are inextricably linked, and marine diseases can both directly and indirectly affect human health, livelihoods, and well-being. We recommend an adaptive management approach to better increase the resilience of ocean systems vulnerable to marine diseases in a changing climate. Land-based management methods of quarantining, culling, and vaccinating are not successful in the ocean; therefore, forecasting conditions that lead to outbreaks and designing tools/approaches to influence these conditions may be the best way to manage marine disease.

Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

PubMed

Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

2015-10-01

Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

The role of contrast-enhanced ultrasound in imaging carotid arterial diseases.

PubMed

Clevert, Dirk A; Paprottka, Philipp; Sommer, Wieland H; Helck, Andreas; Reiser, Maximilian F; Zengel, Pamela

2013-06-01

The standard of care for the initial diagnosis of carotid artery bifurcation diseases is carotid duplex ultrasound. Carotid abnormalities or difficult examinations may represent a diagnostic challenge in patients with clinical symptoms as well as in the follow-up after carotid endarterectomy, carotid artery stenting or other interventions. A promising new method in the diagnosis and follow-up of pathologic carotid diseases is contrast-enhanced ultrasound (CEUS). In comparison with magnetic resonance imaging or computed tomography, the contrast agents used for CEUS remain within the vascular space and hence can be used to study vascular disease and could provide additional information on carotid arterial diseases. This review describes the current carotid duplex ultrasound examination and compares the pathologic findings with CEUS. Copyright © 2013 Elsevier Inc. All rights reserved.

Asymmetrical Pedaling Patterns in Parkinson's Disease Patients

PubMed Central

Penko, Amanda L.; Hirsch, Joshua R.; Voelcker-Rehage, Claudia; Martin, Philip E.; Blackburn, Gordon; Alberts, Jay L.

2015-01-01

Background Approximately 1.5 million Americans are affected by Parkinson's disease [1] which includes the symptoms of postural instability and gait dysfunction. Currently, clinical evaluations of postural instability and gait dysfunction consist of a subjective rater assessment of gait patterns using items from the Unified Parkinson's Disease Rating Scale, and assessments can be insensitive to the effectiveness of medical interventions. Current research suggests the importance of cycling for Parkinson's disease patients, and while Parkinson's gait has been evaluated in previous studies, little is known about lower extremity control during cycling. The purpose of this study is to examine the lower extremity coordination patterns of Parkinson's patients during cycling. Methods Twenty five participants, ages 44-72, with a clinical diagnosis of idiopathic Parkinson's disease participated in an exercise test on a cycle ergometer that was equipped with pedal force measurements. Crank torque, crank angle and power produced by right and left leg were measured throughout the test to calculate Symmetry Index at three stages of exercise (20 Watt, 60 Watt, maximum performance). Findings Decreases in Symmetry Index were observed for average power output in Parkinson's patients as workload increased. Maximum power Symmetry Index showed a significant difference in symmetry between performance at both the 20 Watt and 60 Watt stage and the maximal resistance stage. Minimum power Symmetry Index did not show significant differences across the stages of the test. While lower extremity asymmetries were present in Parkinson's patients during pedaling, these asymmetries did not correlate to postural instability and gait dysfunction Unified Parkinson's Disease Rating Scale scores. Interpretation This pedaling analysis allows for a more sensitive measure of lower extremity function than the Unified Parkinson's Disease Rating Scale and may help to provide unique insight into current and future lower extremity function. PMID:25467810

Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

PubMed Central

Kim, Victor; Regan, Elizabeth; Williams, André A. A.; Santorico, Stephanie A.; Make, Barry J.; Lynch, David A.; Hokanson, John E.; Washko, George R.; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J.; Ramsdell, Joe; Han, MeiLan K.; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D.; Dransfield, Mark; Wells, J. Michael; Hersh, Craig P.; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P.; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K.; van Beek, Edwin J. R.; Wilson, Carla; Wendt, Christine; Wise, Robert A.; Curtis, Jeffrey; Kazerooni, Ella; Hanania, Nicola; Alapat, Philip; Bandi, Venkata; Guntupalli, Kalpalatha; Guy, Elizabeth; Lunn, William; Mallampalli, Antara; Trinh, Charles; Atik, Mustafa; DeMeo, Dawn; Hersh, Craig; Jacobson, Francine; Graham Barr, R.; Thomashow, Byron; Austin, John; MacIntyre, Neil; Washington, Lacey; Page McAdams, H.; Rosiello, Richard; Bresnahan, Timothy; McEvoy, Charlene; Tashjian, Joseph; Wise, Robert; Hansel, Nadia; Brown, Robert; Casaburi, Richard; Porszasz, Janos; Fischer, Hans; Budoff, Matt; Sharafkhaneh, Amir; Niewoehner, Dennis; Allen, Tadashi; Rice, Kathryn; Foreman, Marilyn; Westney, Gloria; Berkowitz, Eugene; Bowler, Russell; Friedlander, Adam; Meoni, Eleonora; Criner, Gerard; Kim, Victor; Marchetti, Nathaniel; Satti, Aditi; James Mamary, A.; Steiner, Robert; Dass, Chandra; Bailey, William; Dransfield, Mark; Gerald, Lynn; Nath, Hrudaya; Ramsdell, Joe; Ferguson, Paul; Friedman, Paul; McLennan, Geoffrey; van Beek, Edwin JR; Martinez, Fernando; Han, MeiLan; Thompson, Deborah; Kazerooni, Ella; Wendt, Christine; Allen, Tadashi; Sciurba, Frank; Weissfeld, Joel; Fuhrman, Carl; Bon, Jessica; Anzueto, Antonio; Adams, Sandra; Orozco, Carlos; Santiago Restrepo, C.; Mumbower, Amy; Crapo, James; Silverman, Edwin; Make, Barry; Regan, Elizabeth; Samet, Jonathan; Willis, Amy; Stinson, Douglas; Beaty, Terri; Klanderman, Barbara; Laird, Nan; Lange, Christoph; Ionita, Iuliana; Santorico, Stephanie; Silverman, Edwin; Lynch, David; Schroeder, Joyce; Newell, John; Reilly, John; Coxson, Harvey; Judy, Philip; Hoffman, Eric; San Jose Estepar, Raul; Washko, George; Leek, Rebecca; Zach, Jordan; Kluiber, Alex; Rodionova, Anastasia; Mann, Tanya; Crapo, Robert; Jensen, Robert; Farzadegan, Homayoon; Murphy, James; Everett, Douglas; Wilson, Carla; Hokanson, John

2014-01-01

BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George’s Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. PMID:24945159

Current advance methods for the identification of blast resistance genes in rice.

PubMed

Tanweer, Fatah A; Rafii, Mohd Y; Sijam, Kamaruzaman; Rahim, Harun A; Ahmed, Fahim; Latif, Mohammad A

2015-05-01

Rice blast caused by Magnaporthe oryzae is one of the most devastating diseases of rice around the world and crop losses due to blast are considerably high. Many blast resistant rice varieties have been developed by classical plant breeding and adopted by farmers in various rice-growing countries. However, the variability in the pathogenicity of the blast fungus according to environment made blast disease a major concern for farmers, which remains a threat to the rice industry. With the utilization of molecular techniques, plant breeders have improved rice production systems and minimized yield losses. In this article, we have summarized the current advanced molecular techniques used for controlling blast disease. With the advent of new technologies like marker-assisted selection, molecular mapping, map-based cloning, marker-assisted backcrossing and allele mining, breeders have identified more than 100 Pi loci and 350 QTL in rice genome responsible for blast disease. These Pi genes and QTLs can be introgressed into a blast-susceptible cultivar through marker-assisted backcross breeding. These molecular techniques provide timesaving, environment friendly and labour-cost-saving ways to control blast disease. The knowledge of host-plant interactions in the frame of blast disease will lead to develop resistant varieties in the future. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Added Sugars and Cardiovascular Disease Risk in Children

PubMed Central

Vos, Miriam B.; Kaar, Jill L.; Welsh, Jean A.; Van Horn, Linda V.; Feig, Daniel I.; Anderson, Cheryl A.M.; Patel, Mahesh J.; Munos, Jessica Cruz; Krebs, Nancy F.; Xanthakos, Stavra A.; Johnson, Rachel K.

2017-01-01

BACKGROUND Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. METHODS AND RESULTS For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. CONCLUSIONS Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume ≤25 g (100 cal or ≈6 teaspoons) of added sugars per day and to avoid added sugars for children <2 years of age. Although added sugars most likely can be safely consumed in low amounts as part of a healthy diet, few children achieve such levels, making this an important public health target. PMID:27550974

Advancing Cardiovascular, Neurovascular, and Renal Magnetic Resonance Imaging in Small Rodents Using Cryogenic Radiofrequency Coil Technology

PubMed Central

Niendorf, Thoralf; Pohlmann, Andreas; Reimann, Henning M.; Waiczies, Helmar; Peper, Eva; Huelnhagen, Till; Seeliger, Erdmann; Schreiber, Adrian; Kettritz, Ralph; Strobel, Klaus; Ku, Min-Chi; Waiczies, Sonia

2015-01-01

Research in pathologies of the brain, heart and kidney have gained immensely from the plethora of studies that have helped shape new methods in magnetic resonance (MR) for characterizing preclinical disease models. Methodical probing into preclinical animal models by MR is invaluable since it allows a careful interpretation and extrapolation of data derived from these models to human disease. In this review we will focus on the applications of cryogenic radiofrequency (RF) coils in small animal MR as a means of boosting image quality (e.g., by supporting MR microscopy) and making data acquisition more efficient (e.g., by reducing measuring time); both being important constituents for thorough investigational studies on animal models of disease. This review attempts to make the (bio)medical imaging, molecular medicine, and pharmaceutical communities aware of this productive ferment and its outstanding significance for anatomical and functional MR in small rodents. The goal is to inspire a more intense interdisciplinary collaboration across the fields to further advance and progress non-invasive MR methods that ultimately support thorough (patho)physiological characterization of animal disease models. In this review, current and potential future applications for the RF coil technology in cardiovascular, neurovascular, and renal disease will be discussed. PMID:26617515

Risk-based methods for fish and terrestrial animal disease surveillance.

PubMed

Oidtmann, Birgit; Peeler, Edmund; Lyngstad, Trude; Brun, Edgar; Bang Jensen, Britt; Stärk, Katharina D C

2013-10-01

Over recent years there have been considerable methodological developments in the field of animal disease surveillance. The principles of risk analysis were conceptually applied to surveillance in order to further develop approaches and tools (scenario tree modelling) to design risk-based surveillance (RBS) programmes. In the terrestrial animal context, examples of risk-based surveillance have demonstrated the substantial potential for cost saving, and a similar benefit is expected also for aquatic animals. RBS approaches are currently largely absent for aquatic animal diseases. A major constraint in developing RBS designs in the aquatic context is the lack of published data to assist in the design of RBS: this applies to data on (i) the relative risk of farm sites becoming infected due to the presence or absence of a given risk factor; (ii) the sensitivity of diagnostic tests (specificity is often addressed by follow-up investigation and re-testing and therefore less of a concern); (iii) data on the variability of prevalence of infection for fish within a holding unit, between holding units and at farm level. Another constraint is that some of the most basic data for planning surveillance are missing, e.g. data on farm location and animal movements. In Europe, registration or authorisation of fish farms has only recently become a requirement under EU Directive 2006/88. Additionally, the definition of the epidemiological unit (at site or area level) in the context of aquaculture is a challenge due to the often high level of connectedness (mainly via water) of aquaculture facilities with the aquatic environment. This paper provides a review of the principles, methods and examples of RBS in terrestrial, farmed and wild animals. It discusses the special challenges associated with surveillance for aquatic animal diseases (e.g. accessibility of animals for inspection and sampling, complexity of rearing systems) and provides an overview of current developments relevant for the design of RBS for fish diseases. Suggestions are provided on how the current constraints to applying RBS to fish diseases can be overcome. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications.

PubMed

Anderson, Kenneth C; Auclair, Daniel; Kelloff, Gary J; Sigman, Caroline C; Avet-Loiseau, Hervé; Farrell, Ann T; Gormley, Nicole J; Kumar, Shaji K; Landgren, Ola; Munshi, Nikhil C; Cavo, Michele; Davies, Faith E; Di Bacco, Alessandra; Dickey, Jennifer S; Gutman, Steven I; Higley, Howard R; Hussein, Mohamad A; Jessup, J Milburn; Kirsch, Ilan R; Little, Richard F; Loberg, Robert D; Lohr, Jens G; Mukundan, Lata; Omel, James L; Pugh, Trevor J; Reaman, Gregory H; Robbins, Michael D; Sasser, A Kate; Valente, Nancy; Zamagni, Elena

2017-08-01

Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next-generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10 -5 to 10 -6 cells. These technologies may be combined with functional imaging to detect MRD outside of bone marrow. Moreover, immune profiling methods are being developed to better understand the immune environment in myeloma and response to immunomodulatory agents while methods for molecular profiling of myeloma cells and circulating DNA in blood are also emerging. With the continued development and standardization of these methodologies, MRD has high potential for use in gaining new drug approvals in myeloma. The FDA has outlined two pathways by which MRD could be qualified as a surrogate endpoint for clinical studies directed at obtaining accelerated approval for new myeloma drugs. Most importantly, better understanding of MRD should also contribute to better treatment monitoring. Potentially, MRD status could be used as a prognostic factor for making treatment decisions and for informing timing of therapeutic interventions. Clin Cancer Res; 23(15); 3980-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Chronic Kidney Disease Screening Methods and Its Implication for Malaysia: An in Depth Review

PubMed Central

Almualm, Yasmin; Huri, Hasniza Zaman

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured. PMID:25946939

Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

PubMed

Almualm, Yasmin; Zaman Huri, Hasniza

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

RNA Extraction Methods for Real-Time PCR and Microarray Analyses of Cryptosporidium and Toxoplasma gondii Oocysts - 2nd Presentation

EPA Science Inventory

The ability of infectious oocyst forms of Toxoplasma gondii and Cryptosporidium spp. to resist disinfection treatments and cause disease may have significant public health implications. Currently, little is known about oocyst-specific factors involved during host cell invasion pr...

Label-Free Detection and Serotyping of Salmonellae by Surface Enhanced Raman Spectroscopy with Immunomagnetic Separation

USDA-ARS?s Scientific Manuscript database

Salmonella spp. are one of the leading causes of foodborne outbreaks in the United States and globally. Current detection and characterization techniques for Salmonella are time consuming and rapid methods could greatly benefit outbreak investigation, new case prevention and disease treatment. In th...

An Informatics Approach to Establishing a Sustainable Public Health Community

ERIC Educational Resources Information Center

Kriseman, Jeffrey Michael

2012-01-01

This work involved the analysis of a public health system, and the design, development and deployment of enterprise informatics architecture, and sustainable community methods to address problems with the current public health system. Specifically, assessment of the Nationally Notifiable Disease Surveillance System (NNDSS) was instrumental in…

RNA Extraction Methods for Reverse Transcriptase Real-Time PCR and Microarray Analysis of Cryptosporidium and Toxoplasma gondii Oocysts

EPA Science Inventory

The ability of infectious oocyst forms of Toxoplasma gondii and Cryptosporidium spp. to resist disinfection treatments and cause disease may have significant public health implications. Currently, little is known about oocyst-specific factors involved during host cell invasion p...

Employees on the Move!

ERIC Educational Resources Information Center

Levin, Sarah

This paper describes a method for designing, implementing, and evaluating a work-site physical activity campaign aimed at employees who are currently sedentary in their leisure time. Inactivity is a major but modifiable risk factor for coronary heart disease. Increasing the activity levels of underactive adults would have a positive impact on…

42 CFR 37.52 - Method of obtaining definitive interpretations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... other diseases must be demonstrated by those physicians who desire to be B Readers by taking and passing... specified by NIOSH. Each physician who desires to take the digital version of the examination will be provided a complete set of the current NIOSH-approved standard reference digital radiographs. Physicians...

Antibody Responses of Cervids (Cervus elaphus) following Experimental Mycobacterium bovis Infection and the Implications for Immunodiagnosis

USDA-ARS?s Scientific Manuscript database

Captive and free-ranging wildlife are implicated in the maintenance and transmission of bovine tuberculosis (TB) and therefore pose a significant obstacle to eradication of the disease from domestic livestock. The current ante-mortem diagnostic method, the intradermal tuberculin skin test, has seri...

Simultaneous detection and serotyping of Salmonellae by immunomagnetic separation and label-free surface enhanced Raman spectroscopy

USDA-ARS?s Scientific Manuscript database

Salmonella spp. are one of the leading causes of foodborne outbreaks in the United States and globally. Current detection and characterization techniques for Salmonellae are time consuming and costly, and rapid methods could greatly benefit outbreak investigation, new case prevention and disease tre...

ECONOMIC AND PUBLIC HEALTH IMPACTS OF POLICIES RESTRICTING ACCESS TO HEPATITIS C TREATMENT FOR MEDICAID PATIENTS

PubMed Central

Chidi, Alexis P.; Bryce, Cindy L.; Donohue, Julie; Fine, Michael J.; Landsittel, Doug; Myaskovsky, Larissa; Rogal, Shari; Switzer, Galen; Tsung, Allan; Smith, Kenneth

2016-01-01

INTRODUCTION Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown. METHODS Using a Markov model, we compared two strategies for 45–55 year old Medicaid beneficiaries: (1) Current Practice - only advanced disease is treated before Medicare eligibility; and (2) Full Access – both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare and Medicaid Services (CMS) perspective. We varied model inputs in one-way and probabilistic sensitivity analyses. RESULTS Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost from $5,369–$11,960 and in effectiveness from 0.82–3.01 quality adjusted life-years). In a probabilistic sensitivity analysis, Full Access was cost saving in 93% of model iterations. Compared to Current Practice, Full Access averted 5,994 hepatocellular carcinoma cases and 121 liver transplants per 100,000 patients. CONCLUSIONS Current Medicaid policies restricting hepatitis C treatment to patients with advanced disease are more costly and less effective than unrestricted, full access strategies. Collaboration between state and federal payers may be needed to realize the full public health impact of recent innovations in hepatitis C treatment. PMID:27325324

Label-Free Immuno-Sensors for the Fast Detection of Listeria in Food.

PubMed

Morlay, Alexandra; Roux, Agnès; Templier, Vincent; Piat, Félix; Roupioz, Yoann

2017-01-01

Foodborne diseases are a major concern for both food industry and health organizations due to the economic costs and potential threats for human lives. For these reasons, specific regulations impose the research of pathogenic bacteria in food products. Nevertheless, current methods, references and alternatives, take up to several days and require many handling steps. In order to improve pathogen detection in food, we developed an immune-sensor, based on Surface Plasmon Resonance imaging (SPRi) and bacterial growth which allows the detection of a very low number of Listeria monocytogenes in food sample in one day. Adequate sensitivity is achieved by the deposition of several antibodies in a micro-array format allowing real-time detection. This label-free method thus reduces handling and time to result compared with current methods.

Republished review: Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-07-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

The Genetic Structure of an Invasive Pest, the Asian Citrus Psyllid Diaphorina citri (Hemiptera: Liviidae)

PubMed Central

Guidolin, Aline S.; Fresia, Pablo; Cônsoli, Fernando L.

2014-01-01

The Asian citrus psyllid Diaphorina citri is currently the major threat to the citrus industry as it is the vector of Candidatus Liberibacter, the causal agent of huanglongbing disease (HLB). D. citri is native to Asia and now colonizes the Americas. Although it has been known in some countries for a long time, invasion routes remain undetermined. There are no efficient control methods for the HLB despite the intensive management tools currently in use. We investigated the genetic variability and structure of populations of D. citri to aid in the decision making processes toward sustainable management of this species/disease. We employed different methods to quantify and compare the genetic diversity and structure of D. citri populations among 36 localities in Brazil, using an almost complete sequence of the cytochrome oxidase I (COI) gene. Our analyses led to the identification of two geographically and genetically structured groups. The indices of molecular diversity pointed to a recent population expansion, and we discuss the role of multiple invasion events in this scenario. We also argue that such genetic diversity and population structure may have implications for the best management strategies to be adopted for controlling this psyllid and/or the disease it vectors in Brazil. PMID:25545788

The genetic structure of an invasive pest, the Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae).

PubMed

Guidolin, Aline S; Fresia, Pablo; Cônsoli, Fernando L

2014-01-01

The Asian citrus psyllid Diaphorina citri is currently the major threat to the citrus industry as it is the vector of Candidatus Liberibacter, the causal agent of huanglongbing disease (HLB). D. citri is native to Asia and now colonizes the Americas. Although it has been known in some countries for a long time, invasion routes remain undetermined. There are no efficient control methods for the HLB despite the intensive management tools currently in use. We investigated the genetic variability and structure of populations of D. citri to aid in the decision making processes toward sustainable management of this species/disease. We employed different methods to quantify and compare the genetic diversity and structure of D. citri populations among 36 localities in Brazil, using an almost complete sequence of the cytochrome oxidase I (COI) gene. Our analyses led to the identification of two geographically and genetically structured groups. The indices of molecular diversity pointed to a recent population expansion, and we discuss the role of multiple invasion events in this scenario. We also argue that such genetic diversity and population structure may have implications for the best management strategies to be adopted for controlling this psyllid and/or the disease it vectors in Brazil.

To Control False Positives in Gene-Gene Interaction Analysis: Two Novel Conditional Entropy-Based Approaches

PubMed Central

Lin, Meihua; Li, Haoli; Zhao, Xiaolei; Qin, Jiheng

2013-01-01

Genome-wide analysis of gene-gene interactions has been recognized as a powerful avenue to identify the missing genetic components that can not be detected by using current single-point association analysis. Recently, several model-free methods (e.g. the commonly used information based metrics and several logistic regression-based metrics) were developed for detecting non-linear dependence between genetic loci, but they are potentially at the risk of inflated false positive error, in particular when the main effects at one or both loci are salient. In this study, we proposed two conditional entropy-based metrics to challenge this limitation. Extensive simulations demonstrated that the two proposed metrics, provided the disease is rare, could maintain consistently correct false positive rate. In the scenarios for a common disease, our proposed metrics achieved better or comparable control of false positive error, compared to four previously proposed model-free metrics. In terms of power, our methods outperformed several competing metrics in a range of common disease models. Furthermore, in real data analyses, both metrics succeeded in detecting interactions and were competitive with the originally reported results or the logistic regression approaches. In conclusion, the proposed conditional entropy-based metrics are promising as alternatives to current model-based approaches for detecting genuine epistatic effects. PMID:24339984

Highlights of the Biology and Disease-driven Human Proteome Project, 2015-2016.

PubMed

Van Eyk, Jennifer E; Corrales, Fernando J; Aebersold, Ruedi; Cerciello, Ferdinando; Deutsch, Eric W; Roncada, Paola; Sanchez, Jean-Charles; Yamamoto, Tadashi; Yang, Pengyuan; Zhang, Hui; Omenn, Gilbert S

2016-11-04

The Biology and Disease-driven Human Proteome Project (B/D-HPP) is aimed at supporting and enhancing the broad use of state-of-the-art proteomic methods to characterize and quantify proteins for in-depth understanding of the molecular mechanisms of biological processes and human disease. Based on a foundation of the pre-existing HUPO initiatives begun in 2002, the B/D-HPP is designed to provide standardized methods and resources for mass spectrometry and specific protein affinity reagents and facilitate accessibility of these resources to the broader life sciences research and clinical communities. Currently there are 22 B/D-HPP initiatives and 3 closely related HPP resource pillars. The B/D-HPP groups are working to define sets of protein targets that are highly relevant to each particular field to deliver relevant assays for the measurement of these selected targets and to disseminate and make publicly accessible the information and tools generated. Major developments are the 2016 publications of the Human SRM Atlas and of "popular protein sets" for six organ systems. Here we present the current activities and plans of the BD-HPP initiatives as highlighted in numerous B/D-HPP workshops at the 14th annual HUPO 2015 World Congress of Proteomics in Vancouver, Canada.

A novel method to identify herds with an increased probability of disease introduction due to animal trade.

PubMed

Frössling, Jenny; Nusinovici, Simon; Nöremark, Maria; Widgren, Stefan; Lindberg, Ann

2014-11-15

In the design of surveillance, there is often a desire to target high risk herds. Such risk-based approaches result in better allocation of resources and improve the performance of surveillance activities. For many contagious animal diseases, movement of live animals is a main route of transmission, and because of this, herds that purchase many live animals or have a large contact network due to trade can be seen as a high risk stratum of the population. This paper presents a new method to assess herd disease risk in animal movement networks. It is an improvement to current network measures that takes direction, temporal order, and also movement size and probability of disease into account. In the study, the method was used to calculate a probability of disease ratio (PDR) of herds in simulated datasets, and of real herds based on animal movement data from dairy herds included in a bulk milk survey for Coxiella burnetii. Known differences in probability of disease are easily incorporated in the calculations and the PDR was calculated while accounting for regional differences in probability of disease, and also by applying equal probability of disease throughout the population. Each herd's increased probability of disease due to purchase of animals was compared to both the average herd and herds within the same risk stratum. The results show that the PDR is able to capture the different circumstances related to disease prevalence and animal trade contact patterns. Comparison of results based on inclusion or exclusion of differences in risk also highlights how ignoring such differences can influence the ability to correctly identify high risk herds. The method shows a potential to be useful for risk-based surveillance, in the classification of herds in control programmes or to represent influential contacts in risk factor studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Aggressive periodontitis: case definition and diagnostic criteria.

PubMed

Albandar, Jasim M

2014-06-01

Aggressive periodontitis is a destructive disease characterized by the following: the involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases. In some patients periodontal tissue loss may commence before puberty, whereas in most patients the age of onset is during or somewhat after the circumpubertal period. Besides infection with specific microorganisms, a host predisposition seems to play a key role in the pathogenesis of aggressive periodontitis, as evidenced by the familial aggregation of the disease. In this article we review the historical background of the diagnostic criteria of aggressive periodontitis, present a contemporary case definition and describe the clinical parameters of the disease. At present, the diagnosis of aggressive periodontitis is achieved using case history, clinical examination and radiographic evaluation. The data gathered using these methods are prone to relatively high measurement errors. Besides, this diagnostic approach measures past disease history and may not reliably measure existing disease activity or accurately predict future tissue loss. A diagnosis is often made years after the onset of the disease, partly because current assessment methods detect established disease more readily and reliably than they detect incipient or initial lesions where the tissue loss is minimal and usually below the detection threshold of present examination methods. Future advancements in understanding the pathogenesis of this disease may contribute to an earlier diagnosis. Insofar, future case definitions may involve the identification of key etiologic and risk factors, combined with high-precision methodologies that enable the early detection of initial lesions. This may significantly enhance the predictive value of these tests and detect cases of aggressive periodontitis before significant tissue loss develops. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cardioproteomics: advancing the discovery of signaling mechanisms involved in cardiovascular diseases

PubMed Central

Cui, Ziyou; Dewey, Shannamar; Gomes, Aldrin V

2011-01-01

Cardioproteomics (Cardiovascular proteomics) is fast becoming an indispensible technique in deciphering changes in signaling pathways that occur in cardiovascular diseases (CVDs). The quality and availability of the instruments and bioinformatics software used for cardioproteomics continues to improve, and these techniques are now available to most cardiovascular researchers either directly or indirectly via university core centers. The heart and aorta are specialized tissues which present unique challenges to investigate. Currently, the diverse range of proteomic techniques available for cardiovascular research makes the choice of the best method or best combination of methods for the disease parameter(s) being investigated as important as the equipment used. This review focuses on proteomic techniques and their applications which have advanced our understanding of the signaling mechanisms involved in CVDs at the levels of protein complex/protein-protein interaction, post-translational modifications and signaling induced protein changes. PMID:22254205

Predicting disease progression from short biomarker series using expert advice algorithm

NASA Astrophysics Data System (ADS)

Morino, Kai; Hirata, Yoshito; Tomioka, Ryota; Kashima, Hisashi; Yamanishi, Kenji; Hayashi, Norihiro; Egawa, Shin; Aihara, Kazuyuki

2015-05-01

Well-trained clinicians may be able to provide diagnosis and prognosis from very short biomarker series using information and experience gained from previous patients. Although mathematical methods can potentially help clinicians to predict the progression of diseases, there is no method so far that estimates the patient state from very short time-series of a biomarker for making diagnosis and/or prognosis by employing the information of previous patients. Here, we propose a mathematical framework for integrating other patients' datasets to infer and predict the state of the disease in the current patient based on their short history. We extend a machine-learning framework of ``prediction with expert advice'' to deal with unstable dynamics. We construct this mathematical framework by combining expert advice with a mathematical model of prostate cancer. Our model predicted well the individual biomarker series of patients with prostate cancer that are used as clinical samples.

Tibetan medicine "RNSP" in treatment of Alzheimer disease.

PubMed

Shi, Jing-Ming; He, Xue; Lian, Hui-Juan; Yuan, Dong-Ya; Hu, Qun-Ying; Sun, Zheng-Qi; Li, Yan-Song; Zeng, Yu-Wen

2015-01-01

Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD.

The touchscreen operant platform for testing learning and memory in rats and mice

PubMed Central

Horner, Alexa E.; Heath, Christopher J.; Hvoslef-Eide, Martha; Kent, Brianne A.; Kim, Chi Hun; Nilsson, Simon R. O.; Alsiö, Johan; Oomen, Charlotte A.; Holmes, Andrew; Saksida, Lisa M.; Bussey, Timothy J.

2014-01-01

Summary An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive, rather than aversive reinforcement), has high translational potential, and lends itself to a high degree of standardisation and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer’s disease, schizophrenia, Huntington’s disease, frontotemporal dementia), and characterisation of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: Visual Discrimination, Object-Location Paired-Associates Learning, Visuomotor Conditional Learning and Autoshaping. It is accompanied by two further protocols using the touchscreen platform to assess executive function, working memory and pattern separation. PMID:24051959

Predicting disease progression from short biomarker series using expert advice algorithm.

PubMed

Morino, Kai; Hirata, Yoshito; Tomioka, Ryota; Kashima, Hisashi; Yamanishi, Kenji; Hayashi, Norihiro; Egawa, Shin; Aihara, Kazuyuki

2015-05-20

Well-trained clinicians may be able to provide diagnosis and prognosis from very short biomarker series using information and experience gained from previous patients. Although mathematical methods can potentially help clinicians to predict the progression of diseases, there is no method so far that estimates the patient state from very short time-series of a biomarker for making diagnosis and/or prognosis by employing the information of previous patients. Here, we propose a mathematical framework for integrating other patients' datasets to infer and predict the state of the disease in the current patient based on their short history. We extend a machine-learning framework of "prediction with expert advice" to deal with unstable dynamics. We construct this mathematical framework by combining expert advice with a mathematical model of prostate cancer. Our model predicted well the individual biomarker series of patients with prostate cancer that are used as clinical samples.

[Laboratory diagnosis of mucormycosis].

PubMed

Garcia-Hermoso, Dea

2013-03-01

Mucormycosis are deep infections caused by ubiquitous filamentous fungi of the order of Mucorales. The disease occurs mostly in immunocompromised, diabetic or solid organ transplant recipients. There are currently no specific diagnostic guidelines for mucormycosis. The histological examination and culture of the clinical sample remain the most useful approaches for diagnosis. Furthermore, alternative methods to the fungal culture are yet to be standardized. Here we review the current microbiological approaches used for the diagnosis and identification of Mucorales. © 2013 médecine/sciences – Inserm / SRMS.

Detecting Disease Specific Pathway Substructures through an Integrated Systems Biology Approach

PubMed Central

Alaimo, Salvatore; Marceca, Gioacchino Paolo; Ferro, Alfredo; Pulvirenti, Alfredo

2017-01-01

In the era of network medicine, pathway analysis methods play a central role in the prediction of phenotype from high throughput experiments. In this paper, we present a network-based systems biology approach capable of extracting disease-perturbed subpathways within pathway networks in connection with expression data taken from The Cancer Genome Atlas (TCGA). Our system extends pathways with missing regulatory elements, such as microRNAs, and their interactions with genes. The framework enables the extraction, visualization, and analysis of statistically significant disease-specific subpathways through an easy to use web interface. Our analysis shows that the methodology is able to fill the gap in current techniques, allowing a more comprehensive analysis of the phenomena underlying disease states. PMID:29657291

(GERD)].

PubMed

Olmos, Jorge A; Piskorz, María Marta; Vela, Marcelo F

2016-06-01

GERD is a highly prevalent disease in our country. It has a deep impact in patient´s quality of life, representing extremely high costs regarding health. The correct understanding of its pathophysiology is crucial for the rational use of diagnoses methods and the implementation of appropriate treatment adjusted to each individual case. In this review we evaluate this disorder based on the best available evidence, focusing in pathophysiological mechanisms, its epidemiology, modern diagnosis methods and current management standards.

Preventing the transmission of pathogenic mitochondrial DNA mutations: can we achieve long-term benefits from germ-line gene transfer?

PubMed Central

Samuels, David C.; Wonnapinij, Passorn; Chinnery, Patrick F.

2013-01-01

Mitochondrial medicine is one of the few areas of genetic disease where germ-line transfer is being actively pursued as a treatment option. All of the germ-line transfer methods currently under development involve some carry-over of the maternal mitochondrial DNA (mtDNA) heteroplasmy, potentially delivering the pathogenic mutation to the offspring. Rapid changes in mtDNA heteroplasmy have been observed within a single generation, and so any ‘leakage’ of mutant mtDNA could lead to mtDNA disease in future generations, compromising the reproductive health of the first generation, and leading to repeated interventions in subsequent generations. To determine whether this is a real concern, we developed a model of mtDNA heteroplasmy inheritance by studying 87 mother–child pairs, and predicted the likely outcome of different levels of ‘mutant mtDNA leakage’ on subsequent maternal generations. This showed that, for a clinical threshold of 60%, reducing the proportion of mutant mtDNA to <5% dramatically reduces the chance of disease recurrence in subsequent generations, but transmitting >5% mutant mtDNA was associated with a significant chance of disease recurrence. Mutations with a lower clinical threshold were associated with a higher risk of recurrence. Our findings provide reassurance that, at least from an mtDNA perspective, methods currently under development have the potential to effectively eradicate pathogenic mtDNA mutations from subsequent generations. PMID:23297368

Biological Control of Mosquito Vectors: Past, Present, and Future

PubMed Central

Benelli, Giovanni; Jeffries, Claire L.; Walker, Thomas

2016-01-01

Mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs) is available for most of these diseases and vector control is still the main form of prevention. The limitations of traditional insecticide-based strategies, particularly the development of insecticide resistance, have resulted in significant efforts to develop alternative eco-friendly methods. Biocontrol strategies aim to be sustainable and target a range of different mosquito species to reduce the current reliance on insecticide-based mosquito control. In this review, we outline non-insecticide based strategies that have been implemented or are currently being tested. We also highlight the use of mosquito behavioural knowledge that can be exploited for control strategies. PMID:27706105

Natural history and clinical detection of undiagnosed coeliac disease in a North American community.

PubMed

Hujoel, I A; Van Dyke, C T; Brantner, T; Larson, J; King, K S; Sharma, A; Murray, J A; Rubio-Tapia, A

2018-05-01

Coeliac disease is a substantially underdiagnosed disorder, with clinical testing currently guided by case finding. To determine the presence of indications for diagnostic testing and frequency of clinical testing in undiagnosed coeliac disease. This was a case-control study of adults without prior diagnosis of coeliac disease. Undiagnosed cases were identified through sequential serology, and unaffected age- and gender-matched controls were selected. Medical records were systematically reviewed for indications for and evidence of clinical testing. Of 47 557 adults, 408 cases of undiagnosed coeliac disease were identified. 408 serology negative matched controls were selected. Eight-matched pairs were excluded, leading to 800 included individuals (61% female; median age 44.2 years). The odds of any indication for clinical testing were similar among undiagnosed coeliac disease and controls (odds ratio (OR) 1.18; 95% CI: 0.85-1.63, P = 0.32). Most individual indications were not associated with serologic status. Exceptions to this include hypothyroidism, which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease were more likely to develop osteoporosis (P = 0.005), dermatitis herpetiformis (P = 0.006), chronic fatigue (P = 0.033), thyroiditis (P = 0.003), autoimmune diseases (P = 0.008), and have a family member diagnosed with coeliac disease (P = 0.001). This study strongly suggests that current case finding is not effective in detecting undiagnosed coeliac disease. Individuals with undiagnosed coeliac disease were more likely than controls to develop indications for testing overtime. A more effective method for detection of coeliac disease is needed. © 2018 John Wiley & Sons Ltd and Mayo Foundation.

Single nucleotide variations: Biological impact and theoretical interpretation

PubMed Central

Katsonis, Panagiotis; Koire, Amanda; Wilson, Stephen Joseph; Hsu, Teng-Kuei; Lua, Rhonald C; Wilkins, Angela Dawn; Lichtarge, Olivier

2014-01-01

Genome-wide association studies (GWAS) and whole-exome sequencing (WES) generate massive amounts of genomic variant information, and a major challenge is to identify which variations drive disease or contribute to phenotypic traits. Because the majority of known disease-causing mutations are exonic non-synonymous single nucleotide variations (nsSNVs), most studies focus on whether these nsSNVs affect protein function. Computational studies show that the impact of nsSNVs on protein function reflects sequence homology and structural information and predict the impact through statistical methods, machine learning techniques, or models of protein evolution. Here, we review impact prediction methods and discuss their underlying principles, their advantages and limitations, and how they compare to and complement one another. Finally, we present current applications and future directions for these methods in biological research and medical genetics. PMID:25234433

Influence of environmental tobacco smoke on morphology and functions of cardiovascular system assessed using diagnostic imaging.

PubMed

Gać, Paweł; Poręba, Małgorzata; Pawlas, Krystyna; Sobieszczańska, Małgorzata; Poręba, Rafał

Exposure to tobacco smoke is a significant problem of environmental medicine. Tobacco smoke contains over one thousand identified chemicals including numerous toxicants. Cardiovascular system diseases are the major cause of general mortality. The recent development of diagnostic imaging provided methods which enable faster and more precise diagnosis of numerous diseases, also those of cardiovascular system. This paper reviews the most significant scientific research concerning relationship between environmental exposure to tobacco smoke and the morphology and function of cardiovascular system carried out using diagnostic imaging methods, i.e. ultrasonography, angiography, computed tomography and magnetic resonance imaging. In the forthcoming future, the studies using current diagnostic imaging methods should contribute to the reliable documentation, followed by the wide-spreading knowledge of the harmful impact of the environmental tobacco smoke exposure on the cardiovascular system.

Dynamic Measurement of Disease Activity in Acute Pancreatitis: The Pancreatitis Activity Scoring System

PubMed Central

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

Proteus: a random forest classifier to predict disorder-to-order transitioning binding regions in intrinsically disordered proteins

NASA Astrophysics Data System (ADS)

Basu, Sankar; Söderquist, Fredrik; Wallner, Björn

2017-05-01

The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs/IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules. Also, their involvement in several deadly human diseases (e.g. cancer, cardiovascular and neurodegenerative diseases) makes them attractive drug targets, and important for a biochemical understanding of the disease(s). The study of the structural ensemble of IDPs is rather difficult, in particular for transient interactions. When bound to a structured partner, an IDPR adapts an ordered conformation in the complex. The residues that undergo this disorder-to-order transition are called protean residues, generally found in short contiguous stretches and the first step in understanding the modus operandi of an IDP/IDPR would be to predict these residues. There are a few available methods which predict these protean segments from their amino acid sequences; however, their performance reported in the literature leaves clear room for improvement. With this background, the current study presents `Proteus', a random forest classifier that predicts the likelihood of a residue undergoing a disorder-to-order transition upon binding to a potential partner protein. The prediction is based on features that can be calculated using the amino acid sequence alone. Proteus compares favorably with existing methods predicting twice as many true positives as the second best method (55 vs. 27%) with a much higher precision on an independent data set. The current study also sheds some light on a possible `disorder-to-order' transitioning consensus, untangled, yet embedded in the amino acid sequence of IDPs. Some guidelines have also been suggested for proceeding with a real-life structural modeling involving an IDPR using Proteus.

Simulation-based planning of surgical interventions in pediatric cardiology

NASA Astrophysics Data System (ADS)

Marsden, Alison

2012-11-01

Hemodynamics plays an essential role in the progression and treatment of cardiovascular disease. This is particularly true in pediatric cardiology, due to the wide variation in anatomy observed in congenital heart disease patients. While medical imaging provides increasingly detailed anatomical information, clinicians currently have limited knowledge of important fluid mechanical parameters. Treatment decisions are therefore often made using anatomical information alone, despite the known links between fluid mechanics and disease progression. Patient-specific simulations now offer the means to provide this missing information, and, more importantly, to perform in-silico testing of new surgical designs at no risk to the patient. In this talk, we will outline the current state of the art in methods for cardiovascular blood flow simulation and virtual surgery. We will then present new methodology for coupling optimization with simulation and uncertainty quantification to customize treatments for individual patients. Finally, we will present examples in pediatric cardiology that illustrate the potential impact of these tools in the clinical setting.

Expansion of space station diagnostic capability to include serological identification of viral and bacterial infections

NASA Technical Reports Server (NTRS)

Hejtmancik, Kelly E.

1987-01-01

It is necessary that an adequate microbiology capability be provided as part of the Health Maintenance Facility (HMF) to support expected microbial disease events during long periods of space flight. The applications of morphological and biochemical studies to confirm the presence of certain bacterial and fungal disease agents are currently available and under consideration. This confirmation would be greatly facilitated through employment of serological methods to aid in the identification for not only bacterial and fungal agents, but viruses as well. A number of serological approached were considered, particularly the use of Enzyme Linked Immunosorbent Assays (ELISAs), which could be utilized during space flight conditions. A solid phase, membrane supported ELISA for the detection of Bordetella pertussis was developed to show a potential model system that would meet the HMF requirements and specifications for the future space station. A second model system for the detection of Legionella pneumophilia, an expected bacterial disease agent, is currently under investigation.

[Status and progress of stimulating parameters in acupuncture treatment of ischemic cerebrovascular disease].

PubMed

Wei, Yuan-yuan; Fan, Xiao-nong; Wang, Shu; Shi, Xue-min

2008-08-01

Acute ischemic cerebrovascular disease is one of the critical diseases seriously endangering human health. Acupuncture therapy, an effective treatment method for many types of disorders has been generally acknowledged. In recent years, many scientific researchers have studied the relationship between the effects of acupuncture in relieving cerebral ischemia-induced sequelae and the stimulating parameters. The acupuncture stimulating parameter includes the frequency of electroacupuncture (EA), the frequency of acupuncture treatment, and the acquired quantity of stimulation, etc for clinical patients and experimental animals. It was found that different stimulating parameters may have different efficacies. Current research results provide a good basis not only for analysis of the factors of acupuncture-produced effects, but also for determination of the optimal combination of stimulating parameters. However, acupuncture therapeutic effect involves multiple factors and multiple levels, and current quantitative acupuncture parameter researches have been mainly restricted to animal experiments. Hence, more researches in which statistics specialists take part are definitely needed.

Employment among Patients with Multiple Sclerosis-A Population Study

PubMed Central

Bøe Lunde, Hanne Marie; Telstad, Wenche; Grytten, Nina; Kyte, Lars; Aarseth, Jan; Myhr, Kjell-Morten; Bø, Lars

2014-01-01

Objective To investigate demographic and clinical factors associated with employment in MS. Methods The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. Results After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing –remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Conclusions Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual ’s needs in order to improve working ability among MS patients. PMID:25054972

Multiprotocol MR image segmentation in multiple sclerosis: experience with over 1000 studies

NASA Astrophysics Data System (ADS)

Udupa, Jayaram K.; Nyul, Laszlo G.; Ge, Yulin; Grossman, Robert I.

2000-06-01

Multiple Sclerosis (MS) is an acquired disease of the central nervous system. Subjective cognitive and ambulatory test scores on a scale called EDSS are currently utilized to assess the disease severity. Various MRI protocols are being investigated to study the disease based on how it manifests itself in the images. In an attempt to eventually replace EDSS by an objective measure to assess the natural course of the disease and its response to therapy, we have developed image segmentation methods based on fuzzy connectedness to quantify various objects in multiprotocol MRI. These include the macroscopic objects such as lesions, the gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and brain parenchyma as well as the microscopic aspects of the diseased WM. Over 1000 studies have been processed to date. By far the strongest correlations with the clinical measures were demonstrated by the Magnetization Transfer Ratio (MTR) histogram parameters obtained for the various segmented tissue regions emphasizing the importance of considering the microscopic/diffused nature of the disease in the individual tissue regions. Brain parenchymal volume also demonstrated a strong correlation with the clinical measures indicating that brain atrophy is an important indicator of the disease. Fuzzy connectedness is a viable segmentation method for studying MS.

Using the H-index to assess disease priorities for salmon aquaculture.

PubMed

Murray, Alexander G; Wardeh, Maya; McIntyre, K Marie

2016-04-01

Atlantic salmon's (Salmo salar) annual aquaculture production exceeds 2M tonnes globally, and for the UK forms the largest single food export. However, aquaculture production is negatively affected by a range of different diseases and parasites. Effort to control pathogens should be focused on those which are most "important" to aquaculture. It is difficult to specify what makes a pathogen important; this is particularly true in the aquatic sector where data capture systems are less developed than for human or terrestrial animal diseases. Mortality levels might be one indicator, but these can cause a range of different problems such as persistent endemic losses, occasional large epidemics or control/treatment costs. Economic and multi-criteria decision methods can incorporate this range of impacts, however these have not been consistently applied to aquaculture and the quantity and quality of data required is large, so their potential for comparing aquatic pathogens is currently limited. A method that has been developed and applied to both human and terrestrial animal diseases is the analysis of published scientific literature using the H-index method. We applied this method to salmon pathogens using Web of Science searches for 23 pathogens. The top 3 H-indices were obtained for: sea lice, furunculosis, and infectious salmon anaemia; post 2000, Amoebic Gill Disease (AGD) replaced furunculosis. The number of publications per year describing bacterial disease declined significantly, while those for viruses and sea lice increased significantly. This reflects effective bacterial control by vaccination, while problems related to viruses and sea lice have increased. H-indices by country reflected different national concerns (e.g. AGD ranked top for Australia). Averaged national H-indices for salmon diseases tend to increase with log of salmon production; countries with H-Indices significantly below the trend line have suffered particularly large disease losses. The H-index method, supported by other literature analyses, is consistent with the nature and history of salmon diseases and so provides a useful quantitative measure for comparing different diseases in the absence of other measures. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Mapping Health Data: Improved Privacy Protection With Donut Method Geomasking

PubMed Central

Hampton, Kristen H.; Fitch, Molly K.; Allshouse, William B.; Doherty, Irene A.; Gesink, Dionne C.; Leone, Peter A.; Serre, Marc L.; Miller, William C.

2010-01-01

A major challenge in mapping health data is protecting patient privacy while maintaining the spatial resolution necessary for spatial surveillance and outbreak identification. A new adaptive geomasking technique, referred to as the donut method, extends current methods of random displacement by ensuring a user-defined minimum level of geoprivacy. In donut method geomasking, each geocoded address is relocated in a random direction by at least a minimum distance, but less than a maximum distance. The authors compared the donut method with current methods of random perturbation and aggregation regarding measures of privacy protection and cluster detection performance by masking multiple disease field simulations under a range of parameters. Both the donut method and random perturbation performed better than aggregation in cluster detection measures. The performance of the donut method in geoprivacy measures was at least 42.7% higher and in cluster detection measures was less than 4.8% lower than that of random perturbation. Results show that the donut method provides a consistently higher level of privacy protection with a minimal decrease in cluster detection performance, especially in areas where the risk to individual geoprivacy is greatest. PMID:20817785

Mapping health data: improved privacy protection with donut method geomasking.

PubMed

Hampton, Kristen H; Fitch, Molly K; Allshouse, William B; Doherty, Irene A; Gesink, Dionne C; Leone, Peter A; Serre, Marc L; Miller, William C

2010-11-01

A major challenge in mapping health data is protecting patient privacy while maintaining the spatial resolution necessary for spatial surveillance and outbreak identification. A new adaptive geomasking technique, referred to as the donut method, extends current methods of random displacement by ensuring a user-defined minimum level of geoprivacy. In donut method geomasking, each geocoded address is relocated in a random direction by at least a minimum distance, but less than a maximum distance. The authors compared the donut method with current methods of random perturbation and aggregation regarding measures of privacy protection and cluster detection performance by masking multiple disease field simulations under a range of parameters. Both the donut method and random perturbation performed better than aggregation in cluster detection measures. The performance of the donut method in geoprivacy measures was at least 42.7% higher and in cluster detection measures was less than 4.8% lower than that of random perturbation. Results show that the donut method provides a consistently higher level of privacy protection with a minimal decrease in cluster detection performance, especially in areas where the risk to individual geoprivacy is greatest.

Hepatic steatosis and fibrosis: Non-invasive assessment

PubMed Central

Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D

2016-01-01

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096

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

PubMed

Mezlini, Aziz M; Goldenberg, Anna

2017-10-01

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

Quantifying trends in disease impact to produce a consistent and reproducible definition of an emerging infectious disease.

PubMed

Funk, Sebastian; Bogich, Tiffany L; Jones, Kate E; Kilpatrick, A Marm; Daszak, Peter

2013-01-01

The proper allocation of public health resources for research and control requires quantification of both a disease's current burden and the trend in its impact. Infectious diseases that have been labeled as "emerging infectious diseases" (EIDs) have received heightened scientific and public attention and resources. However, the label 'emerging' is rarely backed by quantitative analysis and is often used subjectively. This can lead to over-allocation of resources to diseases that are incorrectly labelled "emerging," and insufficient allocation of resources to diseases for which evidence of an increasing or high sustained impact is strong. We suggest a simple quantitative approach, segmented regression, to characterize the trends and emergence of diseases. Segmented regression identifies one or more trends in a time series and determines the most statistically parsimonious split(s) (or joinpoints) in the time series. These joinpoints in the time series indicate time points when a change in trend occurred and may identify periods in which drivers of disease impact change. We illustrate the method by analyzing temporal patterns in incidence data for twelve diseases. This approach provides a way to classify a disease as currently emerging, re-emerging, receding, or stable based on temporal trends, as well as to pinpoint the time when the change in these trends happened. We argue that quantitative approaches to defining emergence based on the trend in impact of a disease can, with appropriate context, be used to prioritize resources for research and control. Implementing this more rigorous definition of an EID will require buy-in and enforcement from scientists, policy makers, peer reviewers and journal editors, but has the potential to improve resource allocation for global health.

Efficient Manufacturing of Therapeutic Mesenchymal Stromal Cells Using the Quantum Cell Expansion System

PubMed Central

Hanley, Patrick J.; Mei, Zhuyong; Durett, April G.; Cabreira-Harrison, Marie da Graca; Klis, Mariola; Li, Wei; Zhao, Yali; Yang, Bing; Parsha, Kaushik; Mir, Osman; Vahidy, Farhaan; Bloom, Debra; Rice, R. Brent; Hematti, Peiman; Savitz, Sean I; Gee, Adrian P.

2014-01-01

Background The use of bone marrow-derived mesenchymal stromal cells (MSCs) as a cellular therapy for various diseases, such as graft-versus-host-disease, diabetes, ischemic cardiomyopathy, and Crohn's disease has produced promising results in early-phase clinical trials. However, for widespread application and use in later phase studies, manufacture of these cells needs to be cost effective, safe, and reproducible. Current methods of manufacturing in flasks or cell factories are labor-intensive, involve a large number of open procedures, and require prolonged culture times. Methods We evaluated the Quantum Cell Expansion system for the expansion of large numbers of MSCs from unprocessed bone marrow in a functionally closed system and compared the results to a flask-based method currently in clinical trials. Results After only two passages, we were able to expand a mean of 6.6×108 MSCs from 25 mL of bone marrow reproducibly. The mean expansion time was 21 days, and cells obtained were able to differentiate into all three lineages: chondrocytes, osteoblasts, and adipocytes. The Quantum was able to generate the target cell number of 2.0×108 cells in an average of 9-fewer days and in half the number of passages required during flask-based expansion. We estimated the Quantum would involve 133 open procedures versus 54,400 in flasks when manufacturing for a clinical trial. Quantum-expanded MSCs infused into an ischemic stroke rat model were therapeutically active. Discussion The Quantum is a novel method of generating high numbers of MSCs in less time and at lower passages when compared to flasks. In the Quantum, the risk of contamination is substantially reduced due to the substantial decrease in open procedures. PMID:24726657

Helicobacter pylori Detection and Antimicrobial Susceptibility Testing

PubMed Central

Mégraud, Francis; Lehours, Philippe

2007-01-01

The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed. PMID:17428887

The use of a gas chromatograph coupled to a metal oxide sensor for rapid assessment of stool samples from irritable bowel syndrome and inflammatory bowel disease patients

PubMed Central

Shepherd, S F; McGuire, N D; de Lacy Costello, B P J; Ewen, R J; Jayasena, D H; Vaughan, K; Ahmed, I; Probert, C S; Ratcliffe, N M

2016-01-01

There is much clinical interest in the development of a low cost and reliable test for diagnosing inflammatory bowel disease and irritable bowel syndrome, two very distinct diseases that can present with similar symptoms. The assessment of stool samples for the diagnosis of gastro-intestinal diseases is in principle an ideal non-invasive testing method. This paper presents an approach to stool analysis using headspace gas chromatography and a single metal oxide sensor coupled to artificial neural network (ANN) software. Currently the system is able to distinguish samples from patients with irritable bowel syndrome (IBS) from patients with inflammatory bowel disease (IBD) with a sensitivity and specificity of 76% and 88% respectively, with an overall mean predictive accuracy of 76%. PMID:24674940

3D temporal subtraction on multislice CT images using nonlinear warping technique

NASA Astrophysics Data System (ADS)

Ishida, Takayuki; Katsuragawa, Shigehiko; Kawashita, Ikuo; Kim, Hyounseop; Itai, Yoshinori; Awai, Kazuo; Li, Qiang; Doi, Kunio

2007-03-01

The detection of very subtle lesions and/or lesions overlapped with vessels on CT images is a time consuming and difficult task for radiologists. In this study, we have developed a 3D temporal subtraction method to enhance interval changes between previous and current multislice CT images based on a nonlinear image warping technique. Our method provides a subtraction CT image which is obtained by subtraction of a previous CT image from a current CT image. Reduction of misregistration artifacts is important in the temporal subtraction method. Therefore, our computerized method includes global and local image matching techniques for accurate registration of current and previous CT images. For global image matching, we selected the corresponding previous section image for each current section image by using 2D cross-correlation between a blurred low-resolution current CT image and a blurred previous CT image. For local image matching, we applied the 3D template matching technique with translation and rotation of volumes of interests (VOIs) which were selected in the current and the previous CT images. The local shift vector for each VOI pair was determined when the cross-correlation value became the maximum in the 3D template matching. The local shift vectors at all voxels were determined by interpolation of shift vectors of VOIs, and then the previous CT image was nonlinearly warped according to the shift vector for each voxel. Finally, the warped previous CT image was subtracted from the current CT image. The 3D temporal subtraction method was applied to 19 clinical cases. The normal background structures such as vessels, ribs, and heart were removed without large misregistration artifacts. Thus, interval changes due to lung diseases were clearly enhanced as white shadows on subtraction CT images.

Optimization model using Markowitz model approach for reducing the number of dengue cases in Bandung

NASA Astrophysics Data System (ADS)

Yong, Benny; Chin, Liem

2017-05-01

Dengue fever is one of the most serious diseases and this disease can cause death. Currently, Indonesia is a country with the highest cases of dengue disease in Southeast Asia. Bandung is one of the cities in Indonesia that is vulnerable to dengue disease. The sub-districts in Bandung had different levels of relative risk of dengue disease. Dengue disease is transmitted to people by the bite of an Aedesaegypti mosquito that is infected with a dengue virus. Prevention of dengue disease is by controlling the vector mosquito. It can be done by various methods, one of the methods is fogging. The efforts made by the Health Department of Bandung through fogging had constraints in terms of limited funds. This problem causes Health Department selective in fogging, which is only done for certain locations. As a result, many sub-districts are not handled properly by the Health Department because of the unequal distribution of activities to prevent the spread of dengue disease. Thus, it needs the proper allocation of funds to each sub-district in Bandung for preventing dengue transmission optimally. In this research, the optimization model using Markowitz model approach will be applied to determine the allocation of funds should be given to each sub-district in Bandung. Some constraints will be added to this model and the numerical solution will be solved with generalized reduced gradient method using Solver software. The expected result of this research is the proportion of funds given to each sub-district in Bandung correspond to the level of risk of dengue disease in each sub-district in Bandung so that the number of dengue cases in this city can be reduced significantly.

Detection of motion artifact patterns in photoplethysmographic signals based on time and period domain analysis.

PubMed

Couceiro, R; Carvalho, P; Paiva, R P; Henriques, J; Muehlsteff, J

2014-12-01

The presence of motion artifacts in photoplethysmographic (PPG) signals is one of the major obstacles in the extraction of reliable cardiovascular parameters in continuous monitoring applications. In the current paper we present an algorithm for motion artifact detection based on the analysis of the variations in the time and the period domain characteristics of the PPG signal. The extracted features are ranked using a normalized mutual information feature selection algorithm and the best features are used in a support vector machine classification model to distinguish between clean and corrupted sections of the PPG signal. The proposed method has been tested in healthy and cardiovascular diseased volunteers, considering 11 different motion artifact sources. The results achieved by the current algorithm (sensitivity--SE: 84.3%, specificity--SP: 91.5% and accuracy--ACC: 88.5%) show that the current methodology is able to identify both corrupted and clean PPG sections with high accuracy in both healthy (ACC: 87.5%) and cardiovascular diseases (ACC: 89.5%) context.

Joint Estimation of Effective Brain Wave Activation Modes Using EEG/MEG Sensor Arrays and Multimodal MRI Volumes.

PubMed

Galinsky, Vitaly L; Martinez, Antigona; Paulus, Martin P; Frank, Lawrence R

2018-04-13

In this letter, we present a new method for integration of sensor-based multifrequency bands of electroencephalography and magnetoencephalography data sets into a voxel-based structural-temporal magnetic resonance imaging analysis by utilizing the general joint estimation using entropy regularization (JESTER) framework. This allows enhancement of the spatial-temporal localization of brain function and the ability to relate it to morphological features and structural connectivity. This method has broad implications for both basic neuroscience research and clinical neuroscience focused on identifying disease-relevant biomarkers by enhancing the spatial-temporal resolution of the estimates derived from current neuroimaging modalities, thereby providing a better picture of the normal human brain in basic neuroimaging experiments and variations associated with disease states.

An Evidence-Based Systematic Review on Cognitive Interventions for Individuals with Dementia

ERIC Educational Resources Information Center

Hopper, Tammy; Bourgeois, Michelle; Pimentel, Jane; Qualls, Constance Dean; Hickey, Ellen; Frymark, Tobi; Schooling, Tracy

2013-01-01

Purpose: To evaluate the current state of research evidence related to cognitive interventions for individuals with Alzheimer's disease or related dementias. Method: A systematic search of the literature was conducted across 27 electronic databases based on a set of a priori questions, inclusion/exclusion criteria, and search parameters. Studies…

Highly Accurate Antibody Assays for Early and Rapid Detection of Tuberculosis in African and Asian Elephants

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB) in elephants is a re-emerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current methods for screening and diagnosis rely on trunk wash culture, which has serious limitations due to low test sensitivity, slow turn-around time, and variable sample quality. Inn...

A Structured Peer-Mentoring Method for Physical Activity Behavior Change among Adolescents

ERIC Educational Resources Information Center

Smith, Laureen H.; Petosa, Rick L.

2016-01-01

Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be…

The Anopheles gambiae transcriptome - a turning point for malaria control.

PubMed

Domingos, A; Pinheiro-Silva, R; Couto, J; do Rosário, V; de la Fuente, J

2017-04-01

Mosquitoes are important vectors of several pathogens and thereby contribute to the spread of diseases, with social, economic and public health impacts. Amongst the approximately 450 species of Anopheles, about 60 are recognized as vectors of human malaria, the most important parasitic disease. In Africa, Anopheles gambiae is the main malaria vector mosquito. Current malaria control strategies are largely focused on drugs and vector control measures such as insecticides and bed-nets. Improvement of current, and the development of new, mosquito-targeted malaria control methods rely on a better understanding of mosquito vector biology. An organism's transcriptome is a reflection of its physiological state and transcriptomic analyses of different conditions that are relevant to mosquito vector competence can therefore yield important information. Transcriptomic analyses have contributed significant information on processes such as blood-feeding parasite-vector interaction, insecticide resistance, and tissue- and stage-specific gene regulation, thereby facilitating the path towards the development of new malaria control methods. Here, we discuss the main applications of transcriptomic analyses in An. gambiae that have led to a better understanding of mosquito vector competence. © 2017 The Royal Entomological Society.

Current methods of laboratory diagnosis of Chlamydia trachomatis infections.

PubMed Central

Black, C M

1997-01-01

Infections caused by Chlamydia trachomatis are probably the most common sexually transmitted diseases in the United States. Commonly unrecognized and often inadequately treated, chlamydial infections can ascend the reproductive tract and cause pelvic inflammatory disease, which often results in the devastating consequences of infertility, ectopic pregnancy, or chronic pelvic pain. C. trachomatis infections are also known to increase the risk for human immunodeficiency virus infection. The obligate intracellular life cycle of C. trachomatis has traditionally required laboratory diagnostic tests that are technically demanding, labor-intensive, expensive, and difficult to access. In spite of these historical challenges, however, laboratory diagnosis of C. trachomatis has been a rapidly advancing area in which there is presently a wide array of commercial diagnostic technologies, costs, manufacturers. This review describes and compares the diagnostic methods for C. trachomatis infection that are currently approved for use in the United States, including the newest DNA amplification technologies which are yet to be licensed for commercial use. Issues to consider in selecting a test for purposes of screening versus diagnosis based on prevalence, performance, legal, social, and cost issues are also discussed. PMID:8993862

Image Processing Diagnostics: Emphysema

NASA Astrophysics Data System (ADS)

McKenzie, Alex

2009-10-01

Currently the computerized tomography (CT) scan can detect emphysema sooner than traditional x-rays, but other tests are required to measure more accurately the amount of affected lung. CT scan images show clearly if a patient has emphysema, but is unable by visual scan alone, to quantify the degree of the disease, as it appears merely as subtle, barely distinct, dark spots on the lung. Our goal is to create a software plug-in to interface with existing open source medical imaging software, to automate the process of accurately diagnosing and determining emphysema severity levels in patients. This will be accomplished by performing a number of statistical calculations using data taken from CT scan images of several patients representing a wide range of severity of the disease. These analyses include an examination of the deviation from a normal distribution curve to determine skewness, a commonly used statistical parameter. Our preliminary results show that this method of assessment appears to be more accurate and robust than currently utilized methods which involve looking at percentages of radiodensities in air passages of the lung.

Prediction of cancer proteins by integrating protein interaction, domain frequency, and domain interaction data using machine learning algorithms.

PubMed

Huang, Chien-Hung; Peng, Huai-Shun; Ng, Ka-Lok

2015-01-01

Many proteins are known to be associated with cancer diseases. It is quite often that their precise functional role in disease pathogenesis remains unclear. A strategy to gain a better understanding of the function of these proteins is to make use of a combination of different aspects of proteomics data types. In this study, we extended Aragues's method by employing the protein-protein interaction (PPI) data, domain-domain interaction (DDI) data, weighted domain frequency score (DFS), and cancer linker degree (CLD) data to predict cancer proteins. Performances were benchmarked based on three kinds of experiments as follows: (I) using individual algorithm, (II) combining algorithms, and (III) combining the same classification types of algorithms. When compared with Aragues's method, our proposed methods, that is, machine learning algorithm and voting with the majority, are significantly superior in all seven performance measures. We demonstrated the accuracy of the proposed method on two independent datasets. The best algorithm can achieve a hit ratio of 89.4% and 72.8% for lung cancer dataset and lung cancer microarray study, respectively. It is anticipated that the current research could help understand disease mechanisms and diagnosis.

Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis

PubMed Central

Nishikawa, Hiroki; Osaki, Yukio

2015-01-01

The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes. PMID:26494949

Prediction of Cancer Proteins by Integrating Protein Interaction, Domain Frequency, and Domain Interaction Data Using Machine Learning Algorithms

PubMed Central

2015-01-01

Many proteins are known to be associated with cancer diseases. It is quite often that their precise functional role in disease pathogenesis remains unclear. A strategy to gain a better understanding of the function of these proteins is to make use of a combination of different aspects of proteomics data types. In this study, we extended Aragues's method by employing the protein-protein interaction (PPI) data, domain-domain interaction (DDI) data, weighted domain frequency score (DFS), and cancer linker degree (CLD) data to predict cancer proteins. Performances were benchmarked based on three kinds of experiments as follows: (I) using individual algorithm, (II) combining algorithms, and (III) combining the same classification types of algorithms. When compared with Aragues's method, our proposed methods, that is, machine learning algorithm and voting with the majority, are significantly superior in all seven performance measures. We demonstrated the accuracy of the proposed method on two independent datasets. The best algorithm can achieve a hit ratio of 89.4% and 72.8% for lung cancer dataset and lung cancer microarray study, respectively. It is anticipated that the current research could help understand disease mechanisms and diagnosis. PMID:25866773

Towards a resource-based habitat approach for spatial modelling of vector-borne disease risks.

PubMed

Hartemink, Nienke; Vanwambeke, Sophie O; Purse, Bethan V; Gilbert, Marius; Van Dyck, Hans

2015-11-01

Given the veterinary and public health impact of vector-borne diseases, there is a clear need to assess the suitability of landscapes for the emergence and spread of these diseases. Current approaches for predicting disease risks neglect key features of the landscape as components of the functional habitat of vectors or hosts, and hence of the pathogen. Empirical-statistical methods do not explicitly incorporate biological mechanisms, whereas current mechanistic models are rarely spatially explicit; both methods ignore the way animals use the landscape (i.e. movement ecology). We argue that applying a functional concept for habitat, i.e. the resource-based habitat concept (RBHC), can solve these issues. The RBHC offers a framework to identify systematically the different ecological resources that are necessary for the completion of the transmission cycle and to relate these resources to (combinations of) landscape features and other environmental factors. The potential of the RBHC as a framework for identifying suitable habitats for vector-borne pathogens is explored and illustrated with the case of bluetongue virus, a midge-transmitted virus affecting ruminants. The concept facilitates the study of functional habitats of the interacting species (vectors as well as hosts) and provides new insight into spatial and temporal variation in transmission opportunities and exposure that ultimately determine disease risks. It may help to identify knowledge gaps and control options arising from changes in the spatial configuration of key resources across the landscape. The RBHC framework may act as a bridge between existing mechanistic and statistical modelling approaches. © 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

Microstates in resting-state EEG: current status and future directions.

PubMed

Khanna, Arjun; Pascual-Leone, Alvaro; Michel, Christoph M; Farzan, Faranak

2015-02-01

Electroencephalography (EEG) is a powerful method of studying the electrophysiology of the brain with high temporal resolution. Several analytical approaches to extract information from the EEG signal have been proposed. One method, termed microstate analysis, considers the multichannel EEG recording as a series of quasi-stable "microstates" that are each characterized by a unique topography of electric potentials over the entire channel array. Because this technique simultaneously considers signals recorded from all areas of the cortex, it is capable of assessing the function of large-scale brain networks whose disruption is associated with several neuropsychiatric disorders. In this review, we first introduce the method of EEG microstate analysis. We then review studies that have discovered significant changes in the resting-state microstate series in a variety of neuropsychiatric disorders and behavioral states. We discuss the potential utility of this method in detecting neurophysiological impairments in disease and monitoring neurophysiological changes in response to an intervention. Finally, we discuss how the resting-state microstate series may reflect rapid switching among neural networks while the brain is at rest, which could represent activity of resting-state networks described by other neuroimaging modalities. We conclude by commenting on the current and future status of microstate analysis, and suggest that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microstates in Resting-State EEG: Current Status and Future Directions

PubMed Central

Khanna, Arjun; Pascual-Leone, Alvaro; Michel, Christoph M.; Farzan, Faranak

2015-01-01

Electroencephalography (EEG) is a powerful method of studying the electrophysiology of the brain with high temporal resolution. Several analytical approaches to extract information from the EEG signal have been proposed. One method, termed microstate analysis, considers the multichannel EEG recording as a series of quasi-stable “microstates” that are each characterized by a unique topography of electric potentials over the entire channel array. Because this technique simultaneously considers signals recorded from all areas of the cortex, it is capable of assessing the function of large-scale brain networks whose disruption is associated with several neuropsychiatric disorders. In this review, we first introduce the method of EEG microstate analysis. We then review studies that have discovered significant changes in the resting-state microstate series in a variety of neuropsychiatric disorders and behavioral states. We discuss the potential utility of this method in detecting neurophysiological impairments in disease and monitoring neurophysiological changes in response to an intervention. Finally, we discuss how the resting-state microstate series may reflect rapid switching among neural networks while the brain is at rest, which could represent activity of resting-state networks described by other neuroimaging modalities. We conclude by commenting on the current and future status of microstate analysis, and suggest that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease. PMID:25526823

Circulating Tumor Cells: A Review of Non-EpCAM-Based Approaches for Cell Enrichment and Isolation.

PubMed

Gabriel, Marta Tellez; Calleja, Lidia Rodriguez; Chalopin, Antoine; Ory, Benjamin; Heymann, Dominique

2016-04-01

Circulating tumor cells (CTCs) are biomarkers for noninvasively measuring the evolution of tumor genotypes during treatment and disease progression. Recent technical progress has made it possible to detect and characterize CTCs at the single-cell level in blood. Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection because it fails to detect both carcinoma cells that undergo epithelial-mesenchymal transition (EMT) and CTCs of mesenchymal origin. Moreover, EpCAM expression has been found in patients with benign diseases. A large proportion of the current studies and reviews about CTCs describe EpCAM-based methods, but there is evidence that not all tumor cells can be detected using this marker. Here we describe the most recent EpCAM-independent methods for enriching, isolating, and characterizing CTCs on the basis of physical and biological characteristics and point out the main advantages and disadvantages of these methods. CTCs offer an opportunity to obtain key biological information required for the development of personalized medicine. However, there is no universal marker of these cells. To strengthen the clinical utility of CTCs, it is important to improve existing technologies and develop new, non-EpCAM-based systems to enrich and isolate CTCs. © 2016 American Association for Clinical Chemistry.

Design of fuzzy classifier for diabetes disease using Modified Artificial Bee Colony algorithm.

PubMed

Beloufa, Fayssal; Chikh, M A

2013-10-01

In this study, diagnosis of diabetes disease, which is one of the most important diseases, is conducted with artificial intelligence techniques. We have proposed a novel Artificial Bee Colony (ABC) algorithm in which a mutation operator is added to an Artificial Bee Colony for improving its performance. When the current best solution cannot be updated, a blended crossover operator (BLX-α) of genetic algorithm is applied, in order to enhance the diversity of ABC, without compromising with the solution quality. This modified version of ABC is used as a new tool to create and optimize automatically the membership functions and rules base directly from data. We take the diabetes dataset used in our work from the UCI machine learning repository. The performances of the proposed method are evaluated through classification rate, sensitivity and specificity values using 10-fold cross-validation method. The obtained classification rate of our method is 84.21% and it is very promising when compared with the previous research in the literature for the same problem. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Direct Isolation, Culture and Transplant of Mouse Skeletal Muscle Derived Endothelial Cells with Angiogenic Potential

PubMed Central

Ieronimakis, Nicholas; Balasundaram, Gayathri; Reyes, Morayma

2008-01-01

Background Although diseases associated with microvascular endothelial dysfunction are among the most prevalent illnesses to date, currently no method exists to isolate pure endothelial cells (EC) from skeletal muscle for in vivo or in vitro study. Methodology By utilizing multicolor fluorescent-activated cell sorting (FACS), we have isolated a distinct population of Sca-1+, CD31+, CD34dim and CD45− cells from skeletal muscles of C57BL6 mice. Characterization of this population revealed these cells are functional EC that can be expanded several times in culture without losing their phenotype or capabilities to uptake acetylated low-density lipoprotein (ac-LDL), produce nitric oxide (NO) and form vascular tubes. When transplanted subcutaneously or intramuscularly into the tibialis anterior muscle, EC formed microvessels and integrated with existing vasculature. Conclusion This method, which is highly reproducible, can be used to study the biology and role of EC in diseases such as peripheral vascular disease. In addition this method allows us to isolate large quantities of skeletal muscle derived EC with potential for therapeutic angiogenic applications. PMID:18335025

Diagnosis of Hirschsprung's disease with particular emphasis on histopathology. A systematic review of current literature

PubMed Central

Szylberg, Łukasz

2014-01-01

Hirschsprung's disease (HD) is a disorder that involves several medical specialties such as paediatric gastroenterology, paediatric surgery, and pathology. Hirschsprung's disease is a congenital bowel innervation disorder characterised by the absence of ganglion cells in myenteric (Auerbach) and submucosal (Meissner) plexus in the distal colon in its classical form. Rapid and accurate diagnosis of HD is a key element in further treatment patterns. The efficiency of different diagnostic methods used in HD patients may vary. Using one limited diagnostic procedure can lead to as much as a few per cent of overlooked cases. In recent years, rectal biopsy was recognised as an important diagnostic tool that allows for a definitive HD diagnosis with an accuracy of 95% of cases. A correct diagnosis depends on the localisation of the biopsied sample, its representativeness, the number of specimens, and proper interpretation of microscopic studies supported by histochemical and immunohistochemical methods. When several methods are used and all diagnostic criteria are used, the diagnostic sensitivity can almost eliminate cases of undiagnosed patients. PMID:25395999

Regenerative Medicine Strategies for Esophageal Repair

PubMed Central

Londono, Ricardo

2015-01-01

Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

Current practice in laboratory diagnostics of autoimmune diseases in Croatia. 
Survey of the Working group for laboratory diagnostics of autoimmune diseases of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

PubMed

Kuna, Andrea Tešija; Đerek, Lovorka; Kozmar, Ana; Drvar, Vedrana

2016-10-15

With the trend of increasing incidence of autoimmune diseases, laboratories are faced with exponential growth of the requests for tests relating the diagnosis of these diseases. Unfortunately, the lack of laboratory personnel experienced in this specific discipline of laboratory diagnostic, as well as an unawareness of a method limitation often results in confusion for clinicians. The aim was to gain insight into number and type of Croatian laboratories that perform humoral diagnostics with the final goal to improve and harmonize laboratory diagnostics of autoimmune diseases in Croatia. In order to get insight into current laboratory practice two questionnaires, consisting of 42 questions in total, were created. Surveys were conducted using SurveyMonkey application and were sent to 88 medical biochemistry laboratories in Croatia for the first survey. Out of 33 laboratories that declared to perform diagnostic from the scope, 19 were selected for the second survey based on the tests they pleaded to perform. The survey comprised questions regarding autoantibody hallmarks of systemic autoimmune diseases while regarding organ-specific autoimmune diseases was limited to diseases of liver, gastrointestinal and nervous system. Response rate was high with 80 / 88 (91%) laboratories which answered the first questionnaire, and 19 / 19 (1.0) for the second questionnaire. Obtained results of surveys indicate high heterogeneity in the performance of autoantibody testing among laboratories in Croatia. Results indicate the need of creating recommendations and algorithms in order to harmonize the approach to laboratory diagnostics of autoimmune diseases in Croatia.

Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.

PubMed

Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan

2016-01-01

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.

Measurement of ciliary beat frequency using ultra-high resolution optical coherence tomography

NASA Astrophysics Data System (ADS)

Chen, Jason J.; Jing, Joseph C.; Su, Erica; Badger, Christopher; Coughlan, Carolyn A.; Chen, Zhongping; Wong, Brian J. F.

2016-02-01

Ciliated epithelial cells populate up to 80% of the surface area of the human airway and are responsible for mucociliary transport, which is the key protective mechanism that provides the first line of defense in the respiratory tract. Cilia beat in a rhythmic pattern and may be easily affected by allergens, pollutants, and pathogens, altering ciliary beat frequency (CBF) subsequently. Diseases including cystic fibrosis, chronic obstructive pulmonary disease, and primary ciliary dyskinesia may also decrease CBF. CBF is therefore a critical component of respiratory health. The current clinical method of measuring CBF is phase-contrast microscopy, which involves a tissue biopsy obtained via brushing of the nasal cavity. While this method is minimally invasive, the tissue sample must be oriented to display its profile view, making the visualization of a single layer of cilia challenging. In addition, the conventional method requires subjective analysis of CBF, e.g., manually counting by visual inspection. On the contrary, optical coherence tomography (OCT) has been used to study the retina in ophthalmology as well as vasculature in cardiology, and offers higher resolution than conventional computed tomography and magnetic resonance imaging. Based on this technology, our lab specifically developed an ultra-high resolution OCT system to image the microstructure of the ciliated epithelial cells. Doppler analysis was also performed to determine CBF. Lastly, we also developed a program that utilizes fast Fourier transform to determine CBF under phase-contrast microscopy, providing a more objective method compared to the current method.

Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Kanzaki, Sayaka; Maruyama, Koutatsu; Tanaka, Keiko; Ueda, Teruhisa; Senba, Hidenori; Torisu, Masamoto; Minami, Hisaka; Onji, Morikazu; Tanigawa, Takeshi; Matsuura, Bunzo; Hiasa, Yoichi; Miyake, Yoshihiro

2017-01-01

Objective Macrovascular diseases and urgency incontinence are common among Japanese patients with type 2 diabetes mellitus. However, little evidence exists regarding the association between stroke and urgency incontinence among patients with type 2 diabetes mellitus. We examined the associations between macrovascular complications and urgency incontinence among Japanese patients with type 2 diabetes mellitus. Methods The study subjects were 818 Japanese patients with type 2 diabetes mellitus. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate?" We adjusted our analyses for sex, age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was independently positively associated with urgency incontinence, with an adjusted odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between ischemic heart disease or peripheral artery disease and the prevalence of urgency incontinence were not significant. Conclusion In Japanese patients with type 2 diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery disease, was independently positively associated with urgency incontinence.

Thyroid Hormones and Thyroid Disease in Relation to Perchlorate Dose and Residence Near a Superfund Site

PubMed Central

Gold, Ellen B.; Blount, Benjamin C.; Rasor, Marianne O’Neill; Lee, Jennifer S.; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-01-01

Background Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. Objectives In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Methods Residential blocks were randomly selected from areas: 1) with potential perchlorate exposure via drinking water; 2) with potential exposure to environmental contaminants; and 3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20–50 years during 1988–1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone [TSH] and free thyroxine [fT4]) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Results Residential location and current perchlorate dose were not associated with thyroid function or disease. Conclusions No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped. PMID:22968349

Physicians’ perceptions of capacity building for managing chronic disease in seniors using integrated interprofessional care models

PubMed Central

Lee, Linda; Heckman, George; McKelvie, Robert; Jong, Philip; D’Elia, Teresa; Hillier, Loretta M.

2015-01-01

Abstract Objective To explore the barriers to and facilitators of adapting and expanding a primary care memory clinic model to integrate care of additional complex chronic geriatric conditions (heart failure, falls, chronic obstructive pulmonary disease, and frailty) into care processes with the goal of improving outcomes for seniors. Design Mixed-methods study using quantitative (questionnaires) and qualitative (interviews) methods. Setting Ontario. Participants Family physicians currently working in primary care memory clinic teams and supporting geriatric specialists. Methods Family physicians currently working in memory clinic teams (n = 29) and supporting geriatric specialists (n = 9) were recruited as survey participants. Interviews were conducted with memory clinic lead physicians (n = 16). Statistical analysis was done to assess differences between family physician ratings and geriatric specialist ratings related to the capacity for managing complex chronic geriatric conditions, the role of interprofessional collaboration within primary care, and funding and staffing to support geriatric care. Results from both study methods were compared to identify common findings. Main findings Results indicate overall support for expanding the memory clinic model to integrate care for other complex conditions. However, the current primary care structure is challenged to support optimal management of patients with multiple comorbidities, particularly as related to limited funding and staffing resources. Structured training, interprofessional teams, and an active role of geriatric specialists within primary care were identified as important facilitators. Conclusion The memory clinic model, as applied to other complex chronic geriatric conditions, has the potential to build capacity for high-quality primary care, improve health outcomes, promote efficient use of health care resources, and reduce health care costs. PMID:25932482

A multi-layer MRI description of Parkinson's disease

NASA Astrophysics Data System (ADS)

La Rocca, M.; Amoroso, N.; Lella, E.; Bellotti, R.; Tangaro, S.

2017-09-01

Magnetic resonance imaging (MRI) along with complex network is currently one of the most widely adopted techniques for detection of structural changes in neurological diseases, such as Parkinson's Disease (PD). In this paper, we present a digital image processing study, within the multi-layer network framework, combining more classifiers to evaluate the informative power of the MRI features, for the discrimination of normal controls (NC) and PD subjects. We define a network for each MRI scan; the nodes are the sub-volumes (patches) the images are divided into and the links are defined using the Pearson's pairwise correlation between patches. We obtain a multi-layer network whose important network features, obtained with different feature selection methods, are used to feed a supervised multi-level random forest classifier which exploits this base of knowledge for accurate classification. Method evaluation has been carried out using T1 MRI scans of 354 individuals, including 177 PD subjects and 177 NC from the Parkinson's Progression Markers Initiative (PPMI) database. The experimental results demonstrate that the features obtained from multiplex networks are able to accurately describe PD patterns. Besides, also if a privileged scale for studying PD disease exists, exploring the informative content of more scales leads to a significant improvement of the performances in the discrimination between disease and healthy subjects. In particular, this method gives a comprehensive overview of brain regions statistically affected by the disease, an additional value to the presented study.

Noise detection in heart sound recordings.

PubMed

Zia, Mohammad K; Griffel, Benjamin; Fridman, Vladimir; Saponieri, Cesare; Semmlow, John L

2011-01-01

Coronary artery disease (CAD) is the leading cause of death in the United States. Although progression of CAD can be controlled using drugs and diet, it is usually detected in advanced stages when invasive treatment is required. Current methods to detect CAD are invasive and/or costly, hence not suitable as a regular screening tool to detect CAD in early stages. Currently, we are developing a noninvasive and cost-effective system to detect CAD using the acoustic approach. This method identifies sounds generated by turbulent flow through partially narrowed coronary arteries to detect CAD. The limiting factor of this method is sensitivity to noises commonly encountered in the clinical setting. Because the CAD sounds are faint, these noises can easily obscure the CAD sounds and make detection impossible. In this paper, we propose a method to detect and eliminate noise encountered in the clinical setting using a reference channel. We show that our method is effective in detecting noise, which is essential to the success of the acoustic approach.

Automatic Cone Photoreceptor Localisation in Healthy and Stargardt Afflicted Retinas Using Deep Learning.

PubMed

Davidson, Benjamin; Kalitzeos, Angelos; Carroll, Joseph; Dubra, Alfredo; Ourselin, Sebastien; Michaelides, Michel; Bergeles, Christos

2018-05-21

We present a robust deep learning framework for the automatic localisation of cone photoreceptor cells in Adaptive Optics Scanning Light Ophthalmoscope (AOSLO) split-detection images. Monitoring cone photoreceptors with AOSLO imaging grants an excellent view into retinal structure and health, provides new perspectives into well known pathologies, and allows clinicians to monitor the effectiveness of experimental treatments. The MultiDimensional Recurrent Neural Network (MDRNN) approach developed in this paper is the first method capable of reliably and automatically identifying cones in both healthy retinas and retinas afflicted with Stargardt disease. Therefore, it represents a leap forward in the computational image processing of AOSLO images, and can provide clinical support in on-going longitudinal studies of disease progression and therapy. We validate our method using images from healthy subjects and subjects with the inherited retinal pathology Stargardt disease, which significantly alters image quality and cone density. We conduct a thorough comparison of our method with current state-of-the-art methods, and demonstrate that the proposed approach is both more accurate and appreciably faster in localizing cones. As further validation to the method's robustness, we demonstrate it can be successfully applied to images of retinas with pathologies not present in the training data: achromatopsia, and retinitis pigmentosa.

Advancing current approaches to disease management evaluation: capitalizing on heterogeneity to understand what works and for whom.

PubMed

Elissen, Arianne M J; Adams, John L; Spreeuwenberg, Marieke; Duimel-Peeters, Inge G P; Spreeuwenberg, Cor; Linden, Ariel; Vrijhoef, Hubertus J M

2013-03-14

Evaluating large-scale disease management interventions implemented in actual health care settings is a complex undertaking for which universally accepted methods do not exist. Fundamental issues, such as a lack of control patients and limited generalizability, hamper the use of the 'gold-standard' randomized controlled trial, while methodological shortcomings restrict the value of observational designs. Advancing methods for disease management evaluation in practice is pivotal to learn more about the impact of population-wide approaches. Methods must account for the presence of heterogeneity in effects, which necessitates a more granular assessment of outcomes. This paper introduces multilevel regression methods as valuable techniques to evaluate 'real-world' disease management approaches in a manner that produces meaningful findings for everyday practice. In a worked example, these methods are applied to retrospectively gathered routine health care data covering a cohort of 105,056 diabetes patients who receive disease management for type 2 diabetes mellitus in the Netherlands. Multivariable, multilevel regression models are fitted to identify trends in clinical outcomes and correct for differences in characteristics of patients (age, disease duration, health status, diabetes complications, smoking status) and the intervention (measurement frequency and range, length of follow-up). After a median one year follow-up, the Dutch disease management approach was associated with small average improvements in systolic blood pressure and low-density lipoprotein, while a slight deterioration occurred in glycated hemoglobin. Differential findings suggest that patients with poorly controlled diabetes tend to benefit most from disease management in terms of improved clinical measures. Additionally, a greater measurement frequency was associated with better outcomes, while longer length of follow-up was accompanied by less positive results. Despite concerted efforts to adjust for potential sources of confounding and bias, there ultimately are limits to the validity and reliability of findings from uncontrolled research based on routine intervention data. While our findings are supported by previous randomized research in other settings, the trends in outcome measures presented here may have alternative explanations. Further practice-based research, perhaps using historical data to retrospectively construct a control group, is necessary to confirm results and learn more about the impact of population-wide disease management.

Effects of past and recent blood pressure and cholesterol level on coronary heart disease and stroke mortality, accounting for measurement error.

PubMed

Boshuizen, Hendriek C; Lanti, Mariapaola; Menotti, Alessandro; Moschandreas, Joanna; Tolonen, Hanna; Nissinen, Aulikki; Nedeljkovic, Srecko; Kafatos, Anthony; Kromhout, Daan

2007-02-15

The authors aimed to quantify the effects of current systolic blood pressure (SBP) and serum total cholesterol on the risk of mortality in comparison with SBP or serum cholesterol 25 years previously, taking measurement error into account. The authors reanalyzed 35-year follow-up data on mortality due to coronary heart disease and stroke among subjects aged 65 years or more from nine cohorts of the Seven Countries Study. The two-step method of Tsiatis et al. (J Am Stat Assoc 1995;90:27-37) was used to adjust for regression dilution bias, and results were compared with those obtained using more commonly applied methods of adjustment for regression dilution bias. It was found that the commonly used univariate adjustment for regression dilution bias overestimates the effects of both SBP and cholesterol compared with multivariate methods. Also, the two-step method makes better use of the information available, resulting in smaller confidence intervals. Results comparing recent and past exposure indicated that past SBP is more important than recent SBP in terms of its effect on coronary heart disease mortality, while both recent and past values seem to be important for effects of cholesterol on coronary heart disease mortality and effects of SBP on stroke mortality. Associations between serum cholesterol concentration and risk of stroke mortality are weak.

Predictors of health-related quality of life in children with chronic heart disease.

PubMed

Niemitz, Mandy; Gunst, Diana C M; Hövels-Gürich, Hedwig H; Hofbeck, Michael; Kaulitz, Renate; Galm, Christoph; Berger, Felix; Nagdyman, Nicole; Stiller, Brigitte; Borth-Bruhns, Thomas; Konzag, Ines; Balmer, Christian; Goldbeck, Lutz

2017-10-01

Chronic paediatric heart disease is often associated with residual symptoms, persisting functional restrictions, and late sequelae for psychosocial development. It is, therefore, increasingly important to evaluate the health-related quality of life of children and adolescents with chronic heart disease. The aim of this study was to determine medical and socio-demographic variables affecting health-related quality of life in school-aged children and adolescents with chronic heart disease. Patients and methods The Pediatric Cardiac Quality of Life Inventory was administered to 375 children and adolescents and 386 parental caregivers. Medical information was obtained from the charts. The socio-demographic information was provided by the patients and caregivers. Greater disease severity, low school attendance, current cardiac medication, current parental employment, uncertain or limited prognosis, history of connection to a heart-lung machine, number of nights spent in a hospital, and need for treatment in a paediatric aftercare clinic independently contributed to lower health-related quality of life (self-report: R2=0.41; proxy-report: R2=0.46). High correlations between self-reports and parent-proxy reports indicated concordance regarding the evaluation of a child's health-related quality of life. Beyond medical treatment, integration into school is important to increase health-related quality of life in children and adolescents surviving with chronic heart disease. Regular screening of health-related quality of life is recommended to identify patients with special needs.

Studying infrared light therapy for treating Alzheimer's disease

NASA Astrophysics Data System (ADS)

Han, Mengmeng; Wang, Qiyan; Zeng, Yuhui; Meng, Qingqiang; Zhang, Jun; Wei, Xunbin

2016-03-01

Alzheimer's disease (AD) is an extensive neurodegenerative disease. It is generally believed that there are some connections between AD and amyloid protein plaques in the brain. AD is a chronic disease that usually starts slowly and gets worse over time. The typical symptoms are memory loss, language disorders, mood swings and behavioral issues. Gradual losses of somatic functions eventually lead patients to death. Currently, the main therapeutic method is pharmacotherapy, which may temporarily reduce symptoms, but has many side effects. No current treatment can reverse AD's deterioration. Infrared (IR) light therapy has been studied in a range of single and multiple irradiation protocols in previous studies and was found beneficial for neuropathology. In our research, we have verified the effect of infrared light on AD through Alzheimer's disease mouse model. This transgenic mouse model is made by co-injecting two vectors encoding mutant amyloid precursor protein (APP) and mutant presenilin-1 (PSEN1). We designed an experimental apparatus for treating mice, which primarily includes a therapeutic box and a LED array, which emits infrared light. After the treatment, we assessed the effects of infrared light by testing cognitive performance of the mice in Morris water maze. Our results show that infra-red therapy is able to improve cognitive performance in the mouse model. It might provide a novel and safe way to treat Alzheimer's disease.

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

PubMed

Conklin, Annalijn; Nolte, Ellen

2011-01-01

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

Comparative biology of cystic fibrosis animal models.

PubMed

Fisher, John T; Zhang, Yulong; Engelhardt, John F

2011-01-01

Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

Economic Burden of Hepatitis C Virus Infection in Different Stages of Disease: A Report From Southern Iran

PubMed Central

Zare, Fatemeh; Fattahi, Mohammad Reza; Sepehrimanesh, Masood; Safarpour, Ali Reza

2016-01-01

Background Hepatitis C virus (HCV) infection is a major blood-borne infection which imposes high economic cost on the patients. Objectives The current study aimed to evaluate the total annual cost due to chronic HCV related diseases imposed on each patient and their family in Southern Iran. Patients and Methods Economic burden of chronic hepatitis C-related liver diseases (chronic hepatitis C, cirrhosis and hepatocellular carcinoma) were examined. The current retrospective study evaluated 200 Iranian patients for their socioeconomic status, utilization (direct and indirect costs) and treatment costs and work days lost due to illness by a structured questionnaire in 2015. Costs of hospital admissions were extracted from databases of Nemazee hospital, Shiraz, Iran. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients; while the inpatient costs were calculated through annual rate of hospital admissions and average expenditure. Self-medication and direct non-medical costs were also reported. The human capital approach was used to measure the work loss cost. Results The total annual cost per patient for chronic hepatitis C, cirrhosis and hepatocellular carcinoma (HCC) based on purchasing power parity (PPP) were USD 1625.50, USD 6117.2, and USD 11047.2 in 2015, respectively. Conclusions Chronic hepatitis C-related liver diseases impose a substantial economic burden on patients, families and the society. The current study provides useful information on cost of treatment and work loss for different disease states, which can be further used in cost-effectiveness evaluations. PMID:27257424

Breath Tests in Respiratory and Critical Care Medicine: From Research to Practice in Current Perspectives

PubMed Central

Cheepsattayakorn, Attapon; Cheepsattayakorn, Ruangrong

2013-01-01

Today, exhaled nitric oxide has been studied the most, and most researches have now focusd on asthma. More than a thousand different volatile organic compounds have been observed in low concentrations in normal human breath. Alkanes and methylalkanes, the majority of breath volatile organic compounds, have been increasingly used by physicians as a novel method to diagnose many diseases without discomforts of invasive procedures. None of the individual exhaled volatile organic compound alone is specific for disease. Exhaled breath analysis techniques may be available to diagnose and monitor the diseases in home setting when their sensitivity and specificity are improved in the future. PMID:24151617

Cattle trypanosomosis: the diversity of trypanosomes and implications for disease epidemiology and control.

PubMed

Auty, H; Torr, S J; Michoel, T; Jayaraman, S; Morrison, L J

2015-08-01

Trypanosomosis is one of the most significant infectious threats to cattle in sub-Saharan Africa, and one form has also spread to Asia and South America. The disease is caused by a complex of trypanosome species, and the species and strain of parasite can have a profound influence upon the epidemiology of the host-parasite-vector relationships, the severity and course of infection, and, consequently, the implementation and development of control methods. This review will summarise our current knowledge of the relationship between trypanosome species/genotype and the phenotype of disease in cattle, and the implications that this has for ongoing efforts to develop diagnostics, drugs and vaccines for the control of cattle trypanosomosis.

Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry

PubMed Central

Soh, Kah Teong; Tario, Joseph D.; Wallace, Paul K.

2018-01-01

Synopsis Plasma cell dyscrasia (PCD) is a heterogeneous disease which has seen a tremendous change in outcomes due to improved therapies. Over the last few decades, multiparametric flow cytometry has played an important role in the detection and monitoring of PCDs. Flow cytometry is a high sensitivity assay for early detection of minimal residual disease (MRD) that correlates well with progression-free survival and overall survival. Before flow cytometry can be effectively implemented in the clinical setting sample preparation, panel configuration, analysis, and gating strategies must be optimized to ensure accurate results. Current consensus methods and reporting guidelines for MRD testing are discussed. PMID:29128071

Applying phylogenetic analysis to viral livestock diseases: moving beyond molecular typing.

PubMed

Olvera, Alex; Busquets, Núria; Cortey, Marti; de Deus, Nilsa; Ganges, Llilianne; Núñez, José Ignacio; Peralta, Bibiana; Toskano, Jennifer; Dolz, Roser

2010-05-01

Changes in livestock production systems in recent years have altered the presentation of many diseases resulting in the need for more sophisticated control measures. At the same time, new molecular assays have been developed to support the diagnosis of animal viral disease. Nucleotide sequences generated by these diagnostic techniques can be used in phylogenetic analysis to infer phenotypes by sequence homology and to perform molecular epidemiology studies. In this review, some key elements of phylogenetic analysis are highlighted, such as the selection of the appropriate neutral phylogenetic marker, the proper phylogenetic method and different techniques to test the reliability of the resulting tree. Examples are given of current and future applications of phylogenetic reconstructions in viral livestock diseases. Copyright 2009 Elsevier Ltd. All rights reserved.

The role of fungi in diseases of the nose and sinuses

PubMed Central

Schlosser, Rodney J.

2012-01-01

Background: Human exposure to fungal elements is inevitable, with normal respiration routinely depositing fungal hyphae within the nose and paranasal sinuses. Fungal species can cause sinonasal disease, with clinical outcomes ranging from mild symptoms to intracranial invasion and death. There has been much debate regarding the precise role fungal species play in sinonasal disease and optimal treatment strategies. Methods: A literature review of fungal diseases of the nose and sinuses was conducted. Results: Presentation, diagnosis, and current management strategies of each recognized form of fungal rhinosinusitis was reviewed. Conclusion: Each form of fungal rhinosinusitis has a characteristic presentation and clinical course, with the immune status of the host playing a critical pathophysiological role. Accurate diagnosis and targeted treatment strategies are necessary to achieve optimal outcomes. PMID:23168148

Infectious Disease Transmission during Organ and Tissue Transplantation

PubMed Central

Kuehnert, Matthew J.; Fishman, Jay A.

2012-01-01

Infectious disease transmission through organ and tissue transplantation has been associated with severe complications in recipients. Determination of donor-derived infectious risk associated with organ and tissue transplantation is challenging and limited by availability and performance characteristics of current donor epidemiologic screening (e.g., questionnaire) and laboratory testing tools. Common methods and standards for evaluating potential donors of organs and tissues are needed to facilitate effective data collection for assessing the risk for infectious disease transmission. Research programs can use advanced microbiological technologies to define infectious risks posed by pathogens that are known to be transplant transmissible and provide insights into transmission potential of emerging infectious diseases for which transmission characteristics are unknown. Key research needs are explored. Stakeholder collaboration for surveillance and research infrastructure is required to enhance transplant safety. PMID:22840823

Legionnaire's Disease and Acute Renal Failure: A Case Report and Literature Review

PubMed Central

Boucree, Michael C.

1988-01-01

A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad. PMID:3074172

Legionnaire's disease and acute renal failure: a case report and literature review.

PubMed

Boucree, M C

1988-10-01

A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad.

Potential Impact and Study Considerations of Metabolomics in Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association.

PubMed

Cheng, Susan; Shah, Svati H; Corwin, Elizabeth J; Fiehn, Oliver; Fitzgerald, Robert L; Gerszten, Robert E; Illig, Thomas; Rhee, Eugene P; Srinivas, Pothur R; Wang, Thomas J; Jain, Mohit

2017-04-01

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine- N -oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine. © 2017 American Heart Association, Inc.

Paper-based microfluidic sensing device for label-free immunoassay demonstrated by biotin-avidin binding interaction.

PubMed

Lei, Kin Fong; Yang, Shih-I; Tsai, Shiao-Wen; Hsu, Hsiao-Ting

2015-03-01

Efficient diagnosis is very important for the prevention and treatment of diseases. Rapid disease screening in ambulatory environment is one of the most pressing needs for disease control. Despite there are many methods to detect the results of immunoassays, quantitative measurement for rapid disease screening is still a great challenge for point-of-care applications. In this study, a fabrication method for depositing carbon nanotube bundles has been successfully developed for realization of functional paper-based microfluidic sensing device. Quantitative detection of label-free immunoassay, i.e., biotin-avidin binding interaction, was demonstrated by direct measurement of the current change of the biosensor after single application of the target analyte. Sensitivity of 0.33 μA/ng mL(-1) and minimal detectable analyte concentration of 25 ng/mL were achieved. The time necessary for the detection was 500 s which is a large reduction compared with the conventional immunoassay. Such paper-based biosensor has the benefits of portability, fast response, simple operation, and low cost and has the potential for the development of rapid disease screening devices. Copyright © 2014 Elsevier B.V. All rights reserved.

Adult asthma disease management: an analysis of studies, approaches, outcomes, and methods.

PubMed

Maciejewski, Matthew L; Chen, Shih-Yin; Au, David H

2009-07-01

Disease management has been implemented for patients with asthma in various ways. We describe the approaches to and components of adult asthma disease-management interventions, examine the outcomes evaluated, and assess the quality of published studies. We searched the MEDLINE, EMBASE, CINAHL, PsychInfo, and Cochrane databases for studies published in 1986 through 2008, on adult asthma management. With the studies that met our inclusion criteria, we examined the clinical, process, medication, economic, and patient-reported outcomes reported, and the study designs, provider collaboration during the studies, and statistical methods. Twenty-nine articles describing 27 studies satisfied our inclusion criteria. There was great variation in the content, extent of collaboration between physician and non-physician providers responsible for intervention delivery, and outcomes examined across the 27 studies. Because of limitations in the design of 22 of the 27 studies, the differences in outcomes assessed, and the lack of rigorous statistical adjustment, we could not draw definitive conclusions about the effectiveness or cost-effectiveness of the asthma disease-management programs or which approach was most effective. Few well-designed studies with rigorous evaluations have been conducted to evaluate disease-management interventions for adults with asthma. Current evidence is insufficient to recommend any particular intervention.

Techniques for the diagnosis of Fasciola infections in animals: room for improvement.

PubMed

Alvarez Rojas, Cristian A; Jex, Aaron R; Gasser, Robin B; Scheerlinck, Jean-Pierre Y

2014-01-01

The common liver fluke, Fasciola hepatica, causes fascioliasis, a significant disease in mammals, including livestock, wildlife and humans, with a major socioeconomic impact worldwide. In spite of its impact, and some advances towards the development of vaccines and new therapeutic agents, limited attention has been paid to the need for practical and reliable methods for the diagnosis of infection or disease. Accurate diagnosis is central to effective control, particularly given an emerging problem with drug resistance in F. hepatica. Traditional coprological techniques have been widely used, but are often unreliable. Although there have been some advances in establishing immunologic techniques, these tools can suffer from a lack of diagnostic specificity and/or sensitivity. Nonetheless, antigen detection tests seem to have considerable potential, but have not yet been adequately evaluated in the field. Moreover, advanced nucleic acid-based methods appear to offer the most promise for the diagnosis of current infection. This chapter (i) provides a brief account of the biology and significance of F. hepatica/fascioliasis, (ii) describes key techniques currently in use, (iii) compares their advantages/disadvantages and (iv) reviews polymerase chain reaction-based methods for specific diagnosis and/or the genetic characterization of Fasciola species. © 2014 Elsevier Ltd. All rights reserved.

Rapid detection of Ganoderma-infected oil palms by microwave ergosterol extraction with HPLC and TLC.

PubMed

Muniroh, M S; Sariah, M; Zainal Abidin, M A; Lima, N; Paterson, R R M

2014-05-01

Detection of basal stem rot (BSR) by Ganoderma of oil palms was based on foliar symptoms and production of basidiomata. Enzyme-Linked Immunosorbent Assays-Polyclonal Antibody (ELISA-PAB) and PCR have been proposed as early detection methods for the disease. These techniques are complex, time consuming and have accuracy limitations. An ergosterol method was developed which correlated well with the degree of infection in oil palms, including samples growing in plantations. However, the method was capable of being optimised. This current study was designed to develop a simpler, more rapid and efficient ergosterol method with utility in the field that involved the use of microwave extraction. The optimised procedure involved extracting a small amount of Ganoderma, or Ganoderma-infected oil palm suspended in low volumes of solvent followed by irradiation in a conventional microwave oven at 70°C and medium high power for 30s, resulting in simultaneous extraction and saponification. Ergosterol was detected by thin layer chromatography (TLC) and quantified using high performance liquid chromatography with diode array detection. The TLC method was novel and provided a simple, inexpensive method with utility in the field. The new method was particularly effective at extracting high yields of ergosterol from infected oil palm and enables rapid analysis of field samples on site, allowing infected oil palms to be treated or culled very rapidly. Some limitations of the method are discussed herein. The procedures lend themselves to controlling the disease more effectively and allowing more effective use of land currently employed to grow oil palms, thereby reducing pressure to develop new plantations. Copyright © 2014 Elsevier B.V. All rights reserved.

Computer-aided diagnosis of psoriasis skin images with HOS, texture and color features: A first comparative study of its kind.

PubMed

Shrivastava, Vimal K; Londhe, Narendra D; Sonawane, Rajendra S; Suri, Jasjit S

2016-04-01

Psoriasis is an autoimmune skin disease with red and scaly plaques on skin and affecting about 125 million people worldwide. Currently, dermatologist use visual and haptic methods for diagnosis the disease severity. This does not help them in stratification and risk assessment of the lesion stage and grade. Further, current methods add complexity during monitoring and follow-up phase. The current diagnostic tools lead to subjectivity in decision making and are unreliable and laborious. This paper presents a first comparative performance study of its kind using principal component analysis (PCA) based CADx system for psoriasis risk stratification and image classification utilizing: (i) 11 higher order spectra (HOS) features, (ii) 60 texture features, and (iii) 86 color feature sets and their seven combinations. Aggregate 540 image samples (270 healthy and 270 diseased) from 30 psoriasis patients of Indian ethnic origin are used in our database. Machine learning using PCA is used for dominant feature selection which is then fed to support vector machine classifier (SVM) to obtain optimized performance. Three different protocols are implemented using three kinds of feature sets. Reliability index of the CADx is computed. Among all feature combinations, the CADx system shows optimal performance of 100% accuracy, 100% sensitivity and specificity, when all three sets of feature are combined. Further, our experimental result with increasing data size shows that all feature combinations yield high reliability index throughout the PCA-cutoffs except color feature set and combination of color and texture feature sets. HOS features are powerful in psoriasis disease classification and stratification. Even though, independently, all three set of features HOS, texture, and color perform competitively, but when combined, the machine learning system performs the best. The system is fully automated, reliable and accurate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A literature review of economic evaluations for a neglected tropical disease: human African trypanosomiasis ("sleeping sickness").

PubMed

Sutherland, C Simone; Yukich, Joshua; Goeree, Ron; Tediosi, Fabrizio

2015-02-01

Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020.

Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology.

PubMed

Sibley, Christopher D; Peirano, Gisele; Church, Deirdre L

2012-04-01

Clinical microbiology laboratories worldwide have historically relied on phenotypic methods (i.e., culture and biochemical tests) for detection, identification and characterization of virulence traits (e.g., antibiotic resistance genes, toxins) of human pathogens. However, limitations to implementation of molecular methods for human infectious diseases testing are being rapidly overcome allowing for the clinical evaluation and implementation of diverse technologies with expanding diagnostic capabilities. The advantages and limitation of molecular techniques including real-time polymerase chain reaction, partial or whole genome sequencing, molecular typing, microarrays, broad-range PCR and multiplexing will be discussed. Finally, terminal restriction fragment length polymorphism (T-RFLP) and deep sequencing are introduced as technologies at the clinical interface with the potential to dramatically enhance our ability to diagnose infectious diseases and better define the epidemiology and microbial ecology of a wide range of complex infections. Copyright © 2012 Elsevier B.V. All rights reserved.

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

NASA Astrophysics Data System (ADS)

Song, Yong-Ak; Melik, Rohat; Rabie, Amr N.; Ibrahim, Ahmed M. S.; Moses, David; Tan, Ara; Han, Jongyoon; Lin, Samuel J.

2011-12-01

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

Increasing conclusiveness of clinical breath analysis by improved baseline correction of multi capillary column - ion mobility spectrometry (MCC-IMS) data.

PubMed

Szymańska, Ewa; Tinnevelt, Gerjen H; Brodrick, Emma; Williams, Mark; Davies, Antony N; van Manen, Henk-Jan; Buydens, Lutgarde M C

2016-08-05

Current challenges of clinical breath analysis include large data size and non-clinically relevant variations observed in exhaled breath measurements, which should be urgently addressed with competent scientific data tools. In this study, three different baseline correction methods are evaluated within a previously developed data size reduction strategy for multi capillary column - ion mobility spectrometry (MCC-IMS) datasets. Introduced for the first time in breath data analysis, the Top-hat method is presented as the optimum baseline correction method. A refined data size reduction strategy is employed in the analysis of a large breathomic dataset on a healthy and respiratory disease population. New insights into MCC-IMS spectra differences associated with respiratory diseases are provided, demonstrating the additional value of the refined data analysis strategy in clinical breath analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Contraception for the older woman.

PubMed

Glasier, A; Gebbie, A

1996-04-01

Contraception presents particular problems for women over the age of 40. Although fertility is declining and the risk of pregnancy may be small, the consequences of an unplanned pregnancy may be socially devastating and medically ill-advised. Menstrual dysfunction and psychosexual difficulties increase with age and may exacerbate the side-effects of some methods of contraception. The long-term risks of combined hormonal contraception, particularly cardiovascular disease, become more pertinent to women whose natural risk of disease increases with age. Patterns of sexual activity and contraceptive use change with age. The advantages and disadvantages of currently available methods of contraception are difficult to quantify, and the choice of method is very much a matter for individual concern. The increasing prevalence of HRT may complicate matters for some women who are unsure for how long to continue using contraception. Contraceptives of the future may be designed to improve the reproductive health of all women, particularly those approaching the menopause.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease

PubMed Central

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P.; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C.; Goate, Alison

2017-01-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. PMID:29091718

The Immunological Challenges of Cell Transplantation for the Treatment of Parkinson’s Disease

PubMed Central

Piquet, Amanda L.; Venkiteswaran, Kala; Marupudi, Neena I.; Berk, Matthew; Subramanian, Thyagarajan

2012-01-01

Dopaminergic cell transplantation is an experimental therapy for Parkinson’s disease (PD). It has many potential theoretical advantages over current treatment strategies such as providing continuous local dopaminergic replenishment, eliminating motor fluctuations and medication-induced dyskinesias, slowing down disease progression or even reversing disease pathology in the host. Recent studies also show that dopaminergic cell transplants provide long-term neuromodulation in the basal ganglia that simulates the combined effects of oral dopaminergic therapy and surgical therapies like deep brain stimulation, the contemporary therapeutic approach to advanced PD. However, dopaminergic cell transplantation in PD as not been optimized and current experimental techniques have many drawbacks. In published experiments to date of attempted dopaminergic grafting in PD, the major challenges are unacceptable graft-induced dyskinesias or failure of such grafts to exceed the benefits afforded by sham surgery. A deleterious host immune response to the transplant has been implicated as a major putative cause for these adverse outcomes. This article focuses on recent advances in understanding the immunology of the transplantation in PD and possible methods to overcome adverse events such that we could translate cell replacement strategies into viable clinical treatments in the future. PMID:22521427

Prevalence of Periodontal Diseases in a Multicenter Cohort of Perinatally HIV-Infected and HIV-exposed and Uninfected Youth

PubMed Central

Ryder, Mark I.; Yao, Tzy-Jyun; Russell, Jonathan S.; Moscicki, Anna-Barbara; Shiboski, Caroline H.

2016-01-01

Aims To compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol (AMP) study of the Pediatric HIV/AIDS cohort study (PHACS) network. Methods Several analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing threshold, and analyses based on more detailed whole mouth, intraoral regionally, site-based, and tooth-based criteria of bleeding on probing, plaque levels, pockets depths and clinical attachment levels. Results After adjusting for plaque control habits, and behavioral and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria. For PHIV youth, there was no significant association between parameters of periodontal disease and current HIV status. Conclusions While no significant differences in periodontal parameters were noted between the PHIV and PHEU youth, the influence of antiretroviral therapy on merits further exploration in this cohort in a longitudinal study. PMID:27801947

The immunological challenges of cell transplantation for the treatment of Parkinson's disease.

PubMed

Piquet, Amanda L; Venkiteswaran, Kala; Marupudi, Neena I; Berk, Matthew; Subramanian, Thyagarajan

2012-07-01

Dopaminergic cell transplantation is an experimental therapy for Parkinson's disease (PD). It has many potential theoretical advantages over current treatment strategies such as providing continuous local dopaminergic replenishment, eliminating motor fluctuations and medication-induced dyskinesias, slowing down disease progression or even reversing disease pathology in the host. Recent studies also show that dopaminergic cell transplants provide long-term neuromodulation in the basal ganglia that simulates the combined effects of oral dopaminergic therapy and surgical therapies like deep brain stimulation, the contemporary therapeutic approach to advanced PD. However, dopaminergic cell transplantation in PD as not been optimized and current experimental techniques have many drawbacks. In published experiments to date of attempted dopaminergic grafting in PD, the major challenges are unacceptable graft-induced dyskinesias or failure of such grafts to exceed the benefits afforded by sham surgery. A deleterious host immune response to the transplant has been implicated as a major putative cause for these adverse outcomes. This article focuses on recent advances in understanding the immunology of the transplantation in PD and possible methods to overcome adverse events such that we could translate cell replacement strategies into viable clinical treatments in the future. Copyright © 2012 Elsevier Inc. All rights reserved.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

PubMed

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Deming, Yuetiva; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C; Goate, Alison; Cruchaga, Carlos

2017-11-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

Automated segmentation of pulmonary structures in thoracic computed tomography scans: a review

NASA Astrophysics Data System (ADS)

van Rikxoort, Eva M.; van Ginneken, Bram

2013-09-01

Computed tomography (CT) is the modality of choice for imaging the lungs in vivo. Sub-millimeter isotropic images of the lungs can be obtained within seconds, allowing the detection of small lesions and detailed analysis of disease processes. The high resolution of thoracic CT and the high prevalence of lung diseases require a high degree of automation in the analysis pipeline. The automated segmentation of pulmonary structures in thoracic CT has been an important research topic for over a decade now. This systematic review provides an overview of current literature. We discuss segmentation methods for the lungs, the pulmonary vasculature, the airways, including airway tree construction and airway wall segmentation, the fissures, the lobes and the pulmonary segments. For each topic, the current state of the art is summarized, and topics for future research are identified.

Chromoendoscopy and Advanced Imaging Technologies for Surveillance of Patients with IBD

PubMed Central

Barkin, Jodie A.; Abreu, Maria T.

2012-01-01

Inflammatory bowel disease patients with long-standing colitis have an increased risk of colorectal cancer. The high rate of interval colitis-associated cancers among patients who adhere to a nontargeted, random biopsy surveillance strategy underlies the need for improved methods of early dysplasia detection. Compelling evidence supports the efficacy of chromoendoscopy for increasing the detection rate of dysplasia; however, this technology is currently underutilized in the clinical setting. Other contrast-based technologies—including confocal laser endomicroscopy (Pentax), endocytoscopy, multiband imaging, i-scan (Pentax), and molecular-targeted techniques—show promise in the detection of dysplasia in patients with inflammatory bowel disease. The strategies currently available for identifying patients with dysplasia or colitis-associated cancers remain inadequate and need to demonstrate both cost and time efficiency before they can be adopted in community-based practices. PMID:24693269

NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

PubMed

Sun, Duanchen; Liu, Yinliang; Zhang, Xiang-Sun; Wu, Ling-Yun

2017-09-21

High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies. The GO terms identified via current functional enrichment analysis tools often contain direct parent or descendant terms in the GO hierarchical structure. Highly redundant terms make users difficult to analyze the underlying biological processes. In this paper, a novel network-based probabilistic generative model, NetGen, was proposed to perform the functional enrichment analysis. An additional protein-protein interaction (PPI) network was explicitly used to assist the identification of significantly enriched GO terms. NetGen achieved a superior performance than the existing methods in the simulation studies. The effectiveness of NetGen was explored further on four real datasets. Notably, several GO terms which were not directly linked with the active gene list for each disease were identified. These terms were closely related to the corresponding diseases when accessed to the curated literatures. NetGen has been implemented in the R package CopTea publicly available at GitHub ( http://github.com/wulingyun/CopTea/ ). Our procedure leads to a more reasonable and interpretable result of the functional enrichment analysis. As a novel term combination-based functional enrichment analysis method, NetGen is complementary to current individual term-based methods, and can help to explore the underlying pathogenesis of complex diseases.

Revisiting the Posttherapeutic Cure Criterion in Chagas Disease: Time for New Methods, More Questions, Doubts, and Polemics or Time to Change Old Concepts?

PubMed Central

de Lana, Marta; Martins-Filho, Olindo Assis

2015-01-01

One of the most relevant issues beyond the effectiveness of etiological treatment of Chagas disease is the lack of consensual/feasible tools to identify and certify the definitive parasitological cure. Several methods of distinct natures (parasitological, serological, and molecular) have been continuously proposed and novel perspectives are currently under investigation. Although the simultaneous use of distinct tests may offer better contributions and advances, it also leads to controversies of interpretation, with lack of mutual consent of cure criterion amongst researchers and physicians. In fact, when distinct host compartments (blood/tissues) are evaluated and explored, novel questions may arise due to the nature and sensitivity limit of each test. This short analytical review intends to present a chronological and critical overview and discuss the state-of-the-art distinct devices available for posttherapeutic cure assessment in Chagas disease, their contributions, meanings, and interpretation, aiming to point out the major gaps and propose novel insight for future perspectives of posttherapeutic management of Chagas disease patients. PMID:26583124

Cleft lift procedure for pilonidal disease: technique and perioperative management.

PubMed

Favuzza, J; Brand, M; Francescatti, A; Orkin, B

2015-08-01

Pilonidal disease is a common condition affecting young patients. It is often disruptive to their lifestyle due to recurrent abscesses or chronic wound drainage. The most common surgical treatment, "cystectomy," removes useful tissue unnecessarily and does not address the etiology of the condition. Herein, we describe the etiology of pilonidal disease and our technique for definitive management of pilonidal disease using the cleft lift procedure. In this paper, we present our method of performing the cleft lift procedure for pilonidal disease including perioperative management and surgical technique. We have used the cleft lift procedure in nearly 200 patients with pilonidal disease, in both primary and salvage procedures settings. It has been equally successful in both settings with a high rate of success. It results in a closed wound with relatively minimal discomfort and straightforward wound care. We have described our current approach to recurrent and complex pilonidal disease using the cleft lift procedure. Once learned, the cleft lift procedure is a straightforward and highly successful solution to a chronic and challenging condition.

Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research

PubMed Central

Wangler, Michael F.; Yamamoto, Shinya; Chao, Hsiao-Tuan; Posey, Jennifer E.; Westerfield, Monte; Postlethwait, John; Hieter, Philip; Boycott, Kym M.; Campeau, Philippe M.; Bellen, Hugo J.

2017-01-01

Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functions. Here, we review the current state of research into undiagnosed diseases, highlighting large efforts in North America and internationally, including the Undiagnosed Diseases Network (UDN) (Supplemental Material, File S1) and UDN International (UDNI), the Centers for Mendelian Genomics (CMG), and the Canadian Rare Diseases Models and Mechanisms Network (RDMM). We discuss how merging human genetics with model organism research guides experimental studies to solve these medical mysteries, gain new insights into disease pathogenesis, and uncover new therapeutic strategies. PMID:28874452

Will Culling White-Tailed Deer Prevent Lyme Disease?

PubMed

Kugeler, K J; Jordan, R A; Schulze, T L; Griffith, K S; Mead, P S

2016-08-01

White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances. © 2015 Blackwell Verlag GmbH.

Will Culling White-Tailed Deer Prevent Lyme Disease?

PubMed Central

Kugeler, K. J.; Jordan, R. A.; Schulze, T. L.; Griffith, K. S.; Mead, P. S.

2015-01-01

Summary White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances. PMID:26684932

Health utility of patients with Crohn's disease and ulcerative colitis: a systematic review and meta-analysis.

PubMed

Malinowski, Krzysztof Piotr; Kawalec, Paweł

2016-08-01

The aim of this systematic review was to collect and summarize the current data on the utilities of patients with Crohn's disease (CD) and ulcerative colitis (UC). A meta-analysis of the obtained utilities was performed using a random-effects model and meta-regression by the disease type and severity. A bootstrap analysis was performed as it does not require assumption on distribution of the data. The highest utility among patients with CD and UC was observed when the diseases were in remission. The meta-regression analysis showed that both disease severity and an instrument/method/questionnaire used to obtain utilities were significant predictors of utility. Utility was the lowest for severe disease and the highest for disease in remission, the association was more notable in patients with CD compared with UC. Expert commentary: The issue of patients' utility is important for healthcare decision makers but it has not been fully investigated and requires further study.

Estimating the NIH Efficient Frontier

PubMed Central

2012-01-01

Background The National Institutes of Health (NIH) is among the world’s largest investors in biomedical research, with a mandate to: “…lengthen life, and reduce the burdens of illness and disability.” Its funding decisions have been criticized as insufficiently focused on disease burden. We hypothesize that modern portfolio theory can create a closer link between basic research and outcome, and offer insight into basic-science related improvements in public health. We propose portfolio theory as a systematic framework for making biomedical funding allocation decisions–one that is directly tied to the risk/reward trade-off of burden-of-disease outcomes. Methods and Findings Using data from 1965 to 2007, we provide estimates of the NIH “efficient frontier”, the set of funding allocations across 7 groups of disease-oriented NIH institutes that yield the greatest expected return on investment for a given level of risk, where return on investment is measured by subsequent impact on U.S. years of life lost (YLL). The results suggest that NIH may be actively managing its research risk, given that the volatility of its current allocation is 17% less than that of an equal-allocation portfolio with similar expected returns. The estimated efficient frontier suggests that further improvements in expected return (89% to 119% vs. current) or reduction in risk (22% to 35% vs. current) are available holding risk or expected return, respectively, constant, and that 28% to 89% greater decrease in average years-of-life-lost per unit risk may be achievable. However, these results also reflect the imprecision of YLL as a measure of disease burden, the noisy statistical link between basic research and YLL, and other known limitations of portfolio theory itself. Conclusions Our analysis is intended to serve as a proof-of-concept and starting point for applying quantitative methods to allocating biomedical research funding that are objective, systematic, transparent, repeatable, and expressly designed to reduce the burden of disease. By approaching funding decisions in a more analytical fashion, it may be possible to improve their ultimate outcomes while reducing unintended consequences. PMID:22567087

Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy.

PubMed

Rae, Caroline D; Williams, Stephen R

2017-07-15

We review the transport, synthesis and catabolism of glutathione in the brain as well as its compartmentation and biochemistry in different brain cells. The major reactions involving glutathione are reviewed and the factors limiting its availability in brain cells are discussed. We also describe and critique current methods for measuring glutathione in the human brain using magnetic resonance spectroscopy, and review the literature on glutathione measurements in healthy brains and in neurological, psychiatric, neurodegenerative and neurodevelopmental conditions In summary: Healthy human brain glutathione concentration is ∼1-2 mM, but it varies by brain region, with evidence of gender differences and age effects; in neurological disease glutathione appears reduced in multiple sclerosis, motor neurone disease and epilepsy, while being increased in meningiomas; in psychiatric disease the picture is complex and confounded by methodological differences, regional effects, length of disease and drug-treatment. Both increases and decreases in glutathione have been reported in depression and schizophrenia. In Alzheimer's disease and mild cognitive impairment there is evidence for a decrease in glutathione compared to age-matched healthy controls. Improved methods to measure glutathione in vivo will provide better precision in glutathione determination and help resolve the complex biochemistry of this molecule in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing the risk zones of Chagas' disease in Chile, in a world marked by global climatic change

PubMed Central

Tapia-Garay, Valentina; Figueroa, Daniela P; Maldonado, Ana; Frías-Laserre, Daniel; Gonzalez, Christian R; Parra, Alonso; Canals, Lucia; Apt, Werner; Alvarado, Sergio; Cáceres, Dante; Canals, Mauricio

2018-01-01

BACKGROUND Vector transmission of Trypanosoma cruzi appears to be interrupted in Chile; however, data show increasing incidence of Chagas' disease, raising concerns that there may be a reemerging problem. OBJECTIVE To estimate the actual risk in a changing world it is necessary to consider the historical vector distribution and correlate this distribution with the presence of cases and climate change. METHODS Potential distribution models of Triatoma infestans and Chagas disease were performed using Maxent, a machine-learning method. FINDINGS Climate change appears to play a major role in the reemergence of Chagas' disease and T. infestans in Chile. The distribution of both T. infestans and Chagas' disease correlated with maximum temperature, and the precipitation during the driest month. The overlap of Chagas' disease and T. infestans distribution areas was high. The distribution of T. infestans, under two global change scenarios, showed a minimal reduction tendency in suitable areas. MAIN CONCLUSION The impact of temperature and precipitation on the distribution of T. infestans, as shown by the models, indicates the need for aggressive control efforts; the current control measures, including T. infestans control campaigns, should be maintained with the same intensity as they have at present, avoiding sylvatic foci, intrusions, and recolonisation of human dwellings. PMID:29211105

A weighted U statistic for association analyses considering genetic heterogeneity.

PubMed

Wei, Changshuai; Elston, Robert C; Lu, Qing

2016-07-20

Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Correlation between smoking habit and surgical outcomes on viral-associated hepatocellular carcinomas

PubMed Central

Kai, Keita; Komukai, Sho; Koga, Hiroki; Yamaji, Koutaro; Ide, Takao; Kawaguchi, Atsushi; Aishima, Shinichi; Noshiro, Hirokazu

2018-01-01

AIM To investigate the association between smoking habits and surgical outcomes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological features associated with smoking status in B-HCC and C-HCC patients. METHODS We retrospectively examined the cases of the 341 consecutive patients with viral-associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for their primary lesion. We categorized smoking status at the time of surgery into never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups’ clinicopathological features and surgical outcomes, i.e., disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. We also performed subset analyses in both patient groups comparing the current smokers to the other patients. RESULTS The multivariate analysis in the C-HCC group revealed that current-smoker status was significantly correlated with both OS (P = 0.0039) and DSS (P = 0.0416). In the B-HCC patients, no significant correlation was observed between current-smoker status and DFS, OS, or DSS in the univariate or multivariate analyses. The subset analyses comparing the current smokers to the other patients in both the C-HCC and B-HCC groups revealed that the current smokers developed HCC at significantly younger ages than the other patients irrespective of viral infection status. CONCLUSION A smoking habit is significantly correlated with the overall and disease-specific survivals of patients with C-HCC. In contrast, the B-HCC patients showed a weak association between smoking status and surgical outcomes. PMID:29358882

Interactogeneous: Disease Gene Prioritization Using Heterogeneous Networks and Full Topology Scores

PubMed Central

Gonçalves, Joana P.; Francisco, Alexandre P.; Moreau, Yves; Madeira, Sara C.

2012-01-01

Disease gene prioritization aims to suggest potential implications of genes in disease susceptibility. Often accomplished in a guilt-by-association scheme, promising candidates are sorted according to their relatedness to known disease genes. Network-based methods have been successfully exploiting this concept by capturing the interaction of genes or proteins into a score. Nonetheless, most current approaches yield at least some of the following limitations: (1) networks comprise only curated physical interactions leading to poor genome coverage and density, and bias toward a particular source; (2) scores focus on adjacencies (direct links) or the most direct paths (shortest paths) within a constrained neighborhood around the disease genes, ignoring potentially informative indirect paths; (3) global clustering is widely applied to partition the network in an unsupervised manner, attributing little importance to prior knowledge; (4) confidence weights and their contribution to edge differentiation and ranking reliability are often disregarded. We hypothesize that network-based prioritization related to local clustering on graphs and considering full topology of weighted gene association networks integrating heterogeneous sources should overcome the above challenges. We term such a strategy Interactogeneous. We conducted cross-validation tests to assess the impact of network sources, alternative path inclusion and confidence weights on the prioritization of putative genes for 29 diseases. Heat diffusion ranking proved the best prioritization method overall, increasing the gap to neighborhood and shortest paths scores mostly on single source networks. Heterogeneous associations consistently delivered superior performance over single source data across the majority of methods. Results on the contribution of confidence weights were inconclusive. Finally, the best Interactogeneous strategy, heat diffusion ranking and associations from the STRING database, was used to prioritize genes for Parkinson’s disease. This method effectively recovered known genes and uncovered interesting candidates which could be linked to pathogenic mechanisms of the disease. PMID:23185389

Pathway activity inference for multiclass disease classification through a mathematical programming optimisation framework.

PubMed

Yang, Lingjian; Ainali, Chrysanthi; Tsoka, Sophia; Papageorgiou, Lazaros G

2014-12-05

Applying machine learning methods on microarray gene expression profiles for disease classification problems is a popular method to derive biomarkers, i.e. sets of genes that can predict disease state or outcome. Traditional approaches where expression of genes were treated independently suffer from low prediction accuracy and difficulty of biological interpretation. Current research efforts focus on integrating information on protein interactions through biochemical pathway datasets with expression profiles to propose pathway-based classifiers that can enhance disease diagnosis and prognosis. As most of the pathway activity inference methods in literature are either unsupervised or applied on two-class datasets, there is good scope to address such limitations by proposing novel methodologies. A supervised multiclass pathway activity inference method using optimisation techniques is reported. For each pathway expression dataset, patterns of its constituent genes are summarised into one composite feature, termed pathway activity, and a novel mathematical programming model is proposed to infer this feature as a weighted linear summation of expression of its constituent genes. Gene weights are determined by the optimisation model, in a way that the resulting pathway activity has the optimal discriminative power with regards to disease phenotypes. Classification is then performed on the resulting low-dimensional pathway activity profile. The model was evaluated through a variety of published gene expression profiles that cover different types of disease. We show that not only does it improve classification accuracy, but it can also perform well in multiclass disease datasets, a limitation of other approaches from the literature. Desirable features of the model include the ability to control the maximum number of genes that may participate in determining pathway activity, which may be pre-specified by the user. Overall, this work highlights the potential of building pathway-based multi-phenotype classifiers for accurate disease diagnosis and prognosis problems.

Optical biosensor system for the quick and reliable detection of virus infections: VIROSENS

NASA Astrophysics Data System (ADS)

Proll, Günther; Hartjes, Anja; Sinclair, Alexander; Markovic, Goran; Pröll, Florian; Patel, Pranav; Niedrig, Matthias

2014-10-01

Viral infections are of special threat because they can induce severe courses of disease but only few medical treatments are available. Because of socio-economic and climate changes, increased worldwide mobility and population growth, the risk of newly occurring and quickly spreading viral pathogens has increased. A diagnosis of these diseases at an early stage is essential for a quick risk assessment and a proper health management as well as patient's treatment in an optimal way. Currently, the diagnosis of such diseases is based on time consuming and costly detection methods that can only be performed by specially trained personnel in laboratories at specific security levels. Aim of the project VIROSENS is the development of a biosensor platform that can specifically detect virus particles as well as virus-specific antibodies out of biological matrices like blood, serum, plasma and other body fluids. For this purpose, a disposable cartridge for such antibody- and virus-arrays is designed and developed within the project. The optical detection of viruses is performed with a portable device that will be benchmarked and evaluated concerning currently used standard detection methods in terms of its analytical performance. Within this project, a novel combination of serological tests and direct detection of virus particles will be developed, which will provide faster and more reliable results than presently available and used test systems.

The applications of nanotechnology in food industry.

PubMed

Rashidi, Ladan; Khosravi-Darani, Kianoush

2011-09-01

Nanotechnology has the potential of application in the food industry and processing as new tools for pathogen detection, disease treatment delivery systems, food packaging, and delivery of bioactive compounds to target sites. The application of nanotechnology in food systems will provide new methods to improve safety and the nutritional value of food products. This article will review the current advances of applications of nanotechnology in food science and technology. Also, it describes new current food laws for nanofood and novel articles in the field of risk assessment of using nanotechnology in the food industry.

Implementation of MP3 player for music therapy on hypertension.

PubMed

Yu, J Y; Huang, D F; Li, Y; Zhang, Y T

2009-01-01

Hypertension is a common clinical disease and a major risk to human health. Many clinical findings indicate that certain types of music can reduce blood pressure (BP), and music therapy is considered as an important part of anti-hypertension treatment. We integrate our former related research achievement into the new MP3 player, which can also detect the current BP value with a cuffless measurement method. According to the current BP value, the MP3 player selects certain types of music for playing in order to alleviate the hypertension of patients.

Methods for Estimating Kidney Disease Stage Transition Probabilities Using Electronic Medical Records

PubMed Central

Luo, Lola; Small, Dylan; Stewart, Walter F.; Roy, Jason A.

2013-01-01

Chronic diseases are often described by stages of severity. Clinical decisions about what to do are influenced by the stage, whether a patient is progressing, and the rate of progression. For chronic kidney disease (CKD), relatively little is known about the transition rates between stages. To address this, we used electronic health records (EHR) data on a large primary care population, which should have the advantage of having both sufficient follow-up time and sample size to reliably estimate transition rates for CKD. However, EHR data have some features that threaten the validity of any analysis. In particular, the timing and frequency of laboratory values and clinical measurements are not determined a priori by research investigators, but rather, depend on many factors, including the current health of the patient. We developed an approach for estimating CKD stage transition rates using hidden Markov models (HMMs), when the level of information and observation time vary among individuals. To estimate the HMMs in a computationally manageable way, we used a “discretization” method to transform daily data into intervals of 30 days, 90 days, or 180 days. We assessed the accuracy and computation time of this method via simulation studies. We also used simulations to study the effect of informative observation times on the estimated transition rates. Our simulation results showed good performance of the method, even when missing data are non-ignorable. We applied the methods to EHR data from over 60,000 primary care patients who have chronic kidney disease (stage 2 and above). We estimated transition rates between six underlying disease states. The results were similar for men and women. PMID:25848580

A Network-Based Kernel Machine Test for the Identification of Risk Pathways in Genome-Wide Association Studies

PubMed Central

Freytag, Saskia; Manitz, Juliane; Schlather, Martin; Kneib, Thomas; Amos, Christopher I.; Risch, Angela; Chang-Claude, Jenny; Heinrich, Joachim; Bickeböller, Heike

2014-01-01

Biological pathways provide rich information and biological context on the genetic causes of complex diseases. The logistic kernel machine test integrates prior knowledge on pathways in order to analyze data from genome-wide association studies (GWAS). Here, the kernel converts genomic information of two individuals to a quantitative value reflecting their genetic similarity. With the selection of the kernel one implicitly chooses a genetic effect model. Like many other pathway methods, none of the available kernels accounts for topological structure of the pathway or gene-gene interaction types. However, evidence indicates that connectivity and neighborhood of genes are crucial in the context of GWAS, because genes associated with a disease often interact. Thus, we propose a novel kernel that incorporates the topology of pathways and information on interactions. Using simulation studies, we demonstrate that the proposed method maintains the type I error correctly and can be more effective in the identification of pathways associated with a disease than non-network-based methods. We apply our approach to genome-wide association case control data on lung cancer and rheumatoid arthritis. We identify some promising new pathways associated with these diseases, which may improve our current understanding of the genetic mechanisms. PMID:24434848

Association between physical fitness, cardiovascular risk factors, and Parkinson's disease.

PubMed

Müller, Jan; Myers, Jonathan

2018-01-01

Objective Exercise is a cornerstone of therapy for Parkinson's disease. This study addressed the association between physical fitness and the onset of Parkinson's disease and association with cardiovascular risk factors. Patients and methods Male veterans ( N = 7347, 59.0 ± 11.2 years) from the Veterans Exercise Testing Study cohort were evaluated. Physical fitness was measured objectively by maximal exercise testing. Onset of Parkinson's disease was abstracted from the Veterans Affairs computerized patient records system. Results After a mean follow-up of 12.5 ± 6.3 years, a total of 94 (1.3%) developed Parkinson's disease. Incidence was 86 cases per 100,000 person-years. The strongest multivariate factors associated with incidence of Parkinson's disease were higher age (hazard ratio: 1.067, 95% confidence interval (CI): 1.043-1.093, p < .001), current smoking (hazard ratio: 0.511, 95% CI: 0.274-0.953, p = .035) and physical fitness (high vs. low: hazard ratio: 0.239, 95% CI: 0.079-0.725, p = .011). Compared with patients with no or only one of these risk factors, patients with two risk factors had a 3.7-fold ( p < .001) increased risk for incidence of Parkinson's disease; those with all three risk factors had a 7.8-fold ( p < .001) higher risk. Conclusions High physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson's disease. These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson's disease. Together, these observations provide strong support for recommending physical activity to diminish risk of Parkinson's disease.

A Systematic Bayesian Integration of Epidemiological and Genetic Data

PubMed Central

Lau, Max S. Y.; Marion, Glenn; Streftaris, George; Gibson, Gavin

2015-01-01

Genetic sequence data on pathogens have great potential to inform inference of their transmission dynamics ultimately leading to better disease control. Where genetic change and disease transmission occur on comparable timescales additional information can be inferred via the joint analysis of such genetic sequence data and epidemiological observations based on clinical symptoms and diagnostic tests. Although recently introduced approaches represent substantial progress, for computational reasons they approximate genuine joint inference of disease dynamics and genetic change in the pathogen population, capturing partially the joint epidemiological-evolutionary dynamics. Improved methods are needed to fully integrate such genetic data with epidemiological observations, for achieving a more robust inference of the transmission tree and other key epidemiological parameters such as latent periods. Here, building on current literature, a novel Bayesian framework is proposed that infers simultaneously and explicitly the transmission tree and unobserved transmitted pathogen sequences. Our framework facilitates the use of realistic likelihood functions and enables systematic and genuine joint inference of the epidemiological-evolutionary process from partially observed outbreaks. Using simulated data it is shown that this approach is able to infer accurately joint epidemiological-evolutionary dynamics, even when pathogen sequences and epidemiological data are incomplete, and when sequences are available for only a fraction of exposures. These results also characterise and quantify the value of incomplete and partial sequence data, which has important implications for sampling design, and demonstrate the abilities of the introduced method to identify multiple clusters within an outbreak. The framework is used to analyse an outbreak of foot-and-mouth disease in the UK, enhancing current understanding of its transmission dynamics and evolutionary process. PMID:26599399

Network-based ranking methods for prediction of novel disease associated microRNAs.

PubMed

Le, Duc-Hau

2015-10-01

Many studies have shown roles of microRNAs on human disease and a number of computational methods have been proposed to predict such associations by ranking candidate microRNAs according to their relevance to a disease. Among them, machine learning-based methods usually have a limitation in specifying non-disease microRNAs as negative training samples. Meanwhile, network-based methods are becoming dominant since they well exploit a "disease module" principle in microRNA functional similarity networks. Of which, random walk with restart (RWR) algorithm-based method is currently state-of-the-art. The use of this algorithm was inspired from its success in predicting disease gene because the "disease module" principle also exists in protein interaction networks. Besides, many algorithms designed for webpage ranking have been successfully applied in ranking disease candidate genes because web networks share topological properties with protein interaction networks. However, these algorithms have not yet been utilized for disease microRNA prediction. We constructed microRNA functional similarity networks based on shared targets of microRNAs, and then we integrated them with a microRNA functional synergistic network, which was recently identified. After analyzing topological properties of these networks, in addition to RWR, we assessed the performance of (i) PRINCE (PRIoritizatioN and Complex Elucidation), which was proposed for disease gene prediction; (ii) PageRank with Priors (PRP) and K-Step Markov (KSM), which were used for studying web networks; and (iii) a neighborhood-based algorithm. Analyses on topological properties showed that all microRNA functional similarity networks are small-worldness and scale-free. The performance of each algorithm was assessed based on average AUC values on 35 disease phenotypes and average rankings of newly discovered disease microRNAs. As a result, the performance on the integrated network was better than that on individual ones. In addition, the performance of PRINCE, PRP and KSM was comparable with that of RWR, whereas it was worst for the neighborhood-based algorithm. Moreover, all the algorithms were stable with the change of parameters. Final, using the integrated network, we predicted six novel miRNAs (i.e., hsa-miR-101, hsa-miR-181d, hsa-miR-192, hsa-miR-423-3p, hsa-miR-484 and hsa-miR-98) associated with breast cancer. Network-based ranking algorithms, which were successfully applied for either disease gene prediction or for studying social/web networks, can be also used effectively for disease microRNA prediction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rheumatoid cachexia and other nutritional alterations in rheumatologic diseases.

PubMed

Hurtado-Torres, Gilberto Fabián; González-Baranda, Lourdes Larisa; Abud-Mendoza, Carlos

2015-01-01

The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Computational intelligence in bioinformatics: SNP/haplotype data in genetic association study for common diseases.

PubMed

Kelemen, Arpad; Vasilakos, Athanasios V; Liang, Yulan

2009-09-01

Comprehensive evaluation of common genetic variations through association of single-nucleotide polymorphism (SNP) structure with common complex disease in the genome-wide scale is currently a hot area in human genome research due to the recent development of the Human Genome Project and HapMap Project. Computational science, which includes computational intelligence (CI), has recently become the third method of scientific enquiry besides theory and experimentation. There have been fast growing interests in developing and applying CI in disease mapping using SNP and haplotype data. Some of the recent studies have demonstrated the promise and importance of CI for common complex diseases in genomic association study using SNP/haplotype data, especially for tackling challenges, such as gene-gene and gene-environment interactions, and the notorious "curse of dimensionality" problem. This review provides coverage of recent developments of CI approaches for complex diseases in genetic association study with SNP/haplotype data.

Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

PubMed Central

Parkash, Om; Hanim Shueb, Rafidah

2015-01-01

Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. PMID:26492265

Relationship between Calcium Score and Myocardial Scintigraphy in the Diagnosis of Coronary Disease

PubMed Central

Siqueira, Fabio Paiva Rossini; Mesquita, Claudio Tinoco; dos Santos, Alair Augusto Sarmet M. Damas; Nacif, Marcelo Souto

2016-01-01

Half the patients with coronary artery disease present with sudden death - or acute infarction as first symptom, making early diagnosis pivotal. Myocardial perfusion scintigraphy is frequently used in the assessment of these patients, but it does not detect the disease without flow restriction, exposes the patient to high levels of radiation and is costly. On the other hand, with less radiological exposure, calcium score is directly correlated to the presence and extension of coronary atherosclerosis, and also to the risk of cardiovascular events. Even though calcium score is a tried-and-true method for stratification of asymptomatic patients, its use is still reduced in this context, since current guidelines are contradictory to its use on symptomatic diseases. The aim of this review is to identify, on patients under investigation for coronary artery disease, the main evidence of the use of calcium score associated with functional evaluation and scintigraphy. PMID:27437867

The Vascular Wall: a Plastic Hub of Activity in Cardiovascular Homeostasis and Disease.

PubMed

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.

A nurse-led model of chronic disease management in general practice: Patients' perspectives.

PubMed

Young, Jacqueline; Eley, Diann; Patterson, Elizabeth; Turner, Catherine

2016-12-01

Evidence suggests that current models of chronic disease management within general practice are not effective in meeting the needs of the community. The objective of this article is to examine patients' perceptions of a nurse-led collaborative model of care trialled in three general practices in Australia. This article reports on the second phase of a mixed-methods study in which semi-structured interviews with purposively selected patients were conducted to elicit information about their perceptions of nurse-led care. Three themes emerged from the data - time, ambiance and dimensions of the nurse role. The results suggest that general practice nurses had a positive impact on patients' ability to manage their chronic disease. This infers that there is scope for general practice nurses to expand their role in chronic disease management to assist patients to better self-manage their chronic diseases.

Workgroup Report: Public Health Strategies for Reducing Aflatoxin Exposure in Developing Countries

PubMed Central

Strosnider, Heather; Azziz-Baumgartner, Eduardo; Banziger, Marianne; Bhat, Ramesh V.; Breiman, Robert; Brune, Marie-Noel; DeCock, Kevin; Dilley, Abby; Groopman, John; Hell, Kerstin; Henry, Sara H.; Jeffers, Daniel; Jolly, Curtis; Jolly, Pauline; Kibata, Gilbert N.; Lewis, Lauren; Liu, Xiumei; Luber, George; McCoy, Leslie; Mensah, Patience; Miraglia, Marina; Misore, Ambrose; Njapau, Henry; Ong, Choon-Nam; Onsongo, Mary T.K.; Page, Samuel W.; Park, Douglas; Patel, Manish; Phillips, Timothy; Pineiro, Maya; Pronczuk, Jenny; Rogers, Helen Schurz; Rubin, Carol; Sabino, Myrna; Schaafsma, Arthur; Shephard, Gordon; Stroka, Joerg; Wild, Christopher; Williams, Jonathan T.; Wilson, David

2006-01-01

Consecutive outbreaks of acute aflatoxicosis in Kenya in 2004 and 2005 caused > 150 deaths. In response, the Centers for Disease Control and Prevention and the World Health Organization convened a workgroup of international experts and health officials in Geneva, Switzerland, in July 2005. After discussions concerning what is known about aflatoxins, the workgroup identified gaps in current knowledge about acute and chronic human health effects of aflatoxins, surveillance and food monitoring, analytic methods, and the efficacy of intervention strategies. The workgroup also identified public health strategies that could be integrated with current agricultural approaches to resolve gaps in current knowledge and ultimately reduce morbidity and mortality associated with the consumption of aflatoxin-contaminated food in the developing world. Four issues that warrant immediate attention were identified: a) quantify the human health impacts and the burden of disease due to aflatoxin exposure; b) compile an inventory, evaluate the efficacy, and disseminate results of ongoing intervention strategies; c) develop and augment the disease surveillance, food monitoring, laboratory, and public health response capacity of affected regions; and d) develop a response protocol that can be used in the event of an outbreak of acute aflatoxicosis. This report expands on the workgroup’s discussions concerning aflatoxin in developing countries and summarizes the findings. PMID:17185282

Development of a Metabolic Biosignature for Detection of Early Lyme Disease

PubMed Central

Molins, Claudia R.; Ashton, Laura V.; Wormser, Gary P.; Hess, Ann M.; Delorey, Mark J.; Mahapatra, Sebabrata; Schriefer, Martin E.; Belisle, John T.

2015-01-01

Background. Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%–40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Methods. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Results. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%–95%), and a specificity of 95% (90%–100%). Importantly, the metabolic biosignature correctly classified 77%–95% of the of serology negative Lyme disease patients. Conclusions. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining high specificity. PMID:25761869

Adapting biomarker technologies to adverse outcome pathways (AOPs) research: current thoughts on using in vivo discovery for developing in vitro target methods

EPA Science Inventory

Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, the...

The Diagnosis and Understanding of Apraxia of Speech: Why Including Neurodegenerative Etiologies May Be Important

ERIC Educational Resources Information Center

Duffy, Joseph R.; Josephs, Keith A.

2012-01-01

Purpose: To discuss apraxia of speech (AOS) as it occurs in neurodegenerative disease (progressive AOS [PAOS]) and how its careful study may contribute to general concepts of AOS and help refine its diagnostic criteria. Method: The article summarizes our current understanding of the clinical features and neuroanatomical and pathologic correlates…

Identification of alleles conferring resistance to gray leaf spot in maize derived from its wild progenitor species teosinte (Zea mays ssp. parviglumis)

USDA-ARS?s Scientific Manuscript database

Gray Leaf Spot [(GLS), causal agent Cercospora zeae-maydis and Cercospora zeina] is an important maize disease in the United States. Current control methods for GLS include using resistant cultivars, crop rotation, chemical applications, and conventional tillage to reduce inoculum levels. Teosinte ...

The various aspects of genetic and epigenetic toxicology: testing methods and clinical applications.

PubMed

Ren, Ning; Atyah, Manar; Chen, Wan-Yong; Zhou, Chen-Hao

2017-05-22

Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells.

[The current status and outlook for molecular genetic methods in solving the tasks of medical microbiology].

PubMed

Gintsburg, A L; Zigangirova, N A; Romanova, Iu M

1999-01-01

The article deals with modern methods, viz. PCR, molecular display and genotherapy, which permit the new approach to the solution of problems connected with the identification of infective agents, the study of the mechanisms of the pathogenesis of infectious diseases and their treatment. In this article concrete examples, clearly demonstrating how each of the above-mentioned technologies makes it possible to broaden the circle of problems solved in infectious pathology of man, are presented.

[Automated procedure for volumetric measurement of metastases: estimation of tumor burden].

PubMed

Fabel, M; Bolte, H

2008-09-01

Cancer is a common and increasing disease worldwide. Therapy monitoring in oncologic patient care requires accurate and reliable measurement methods for evaluation of the tumor burden. RECIST (response evaluation criteria in solid tumors) and WHO criteria are still the current standards for therapy response evaluation with inherent disadvantages due to considerable interobserver variation of the manual diameter estimations. Volumetric analysis of e.g. lung, liver and lymph node metastases, promises to be a more accurate, precise and objective method for tumor burden estimation.

Advancing current approaches to disease management evaluation: capitalizing on heterogeneity to understand what works and for whom

PubMed Central

2013-01-01

Background Evaluating large-scale disease management interventions implemented in actual health care settings is a complex undertaking for which universally accepted methods do not exist. Fundamental issues, such as a lack of control patients and limited generalizability, hamper the use of the ‘gold-standard’ randomized controlled trial, while methodological shortcomings restrict the value of observational designs. Advancing methods for disease management evaluation in practice is pivotal to learn more about the impact of population-wide approaches. Methods must account for the presence of heterogeneity in effects, which necessitates a more granular assessment of outcomes. Methods This paper introduces multilevel regression methods as valuable techniques to evaluate ‘real-world’ disease management approaches in a manner that produces meaningful findings for everyday practice. In a worked example, these methods are applied to retrospectively gathered routine health care data covering a cohort of 105,056 diabetes patients who receive disease management for type 2 diabetes mellitus in the Netherlands. Multivariable, multilevel regression models are fitted to identify trends in clinical outcomes and correct for differences in characteristics of patients (age, disease duration, health status, diabetes complications, smoking status) and the intervention (measurement frequency and range, length of follow-up). Results After a median one year follow-up, the Dutch disease management approach was associated with small average improvements in systolic blood pressure and low-density lipoprotein, while a slight deterioration occurred in glycated hemoglobin. Differential findings suggest that patients with poorly controlled diabetes tend to benefit most from disease management in terms of improved clinical measures. Additionally, a greater measurement frequency was associated with better outcomes, while longer length of follow-up was accompanied by less positive results. Conclusions Despite concerted efforts to adjust for potential sources of confounding and bias, there ultimately are limits to the validity and reliability of findings from uncontrolled research based on routine intervention data. While our findings are supported by previous randomized research in other settings, the trends in outcome measures presented here may have alternative explanations. Further practice-based research, perhaps using historical data to retrospectively construct a control group, is necessary to confirm results and learn more about the impact of population-wide disease management. PMID:23497125

Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.

PubMed

Monsuur, Alienke J; de Bakker, Paul I W; Zhernakova, Alexandra; Pinto, Dalila; Verduijn, Willem; Romanos, Jihane; Auricchio, Renata; Lopez, Ana; van Heel, David A; Crusius, J Bart A; Wijmenga, Cisca

2008-05-28

The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.

Bayesian approach to transforming public gene expression repositories into disease diagnosis databases.

PubMed

Huang, Haiyan; Liu, Chun-Chi; Zhou, Xianghong Jasmine

2010-04-13

The rapid accumulation of gene expression data has offered unprecedented opportunities to study human diseases. The National Center for Biotechnology Information Gene Expression Omnibus is currently the largest database that systematically documents the genome-wide molecular basis of diseases. However, thus far, this resource has been far from fully utilized. This paper describes the first study to transform public gene expression repositories into an automated disease diagnosis database. Particularly, we have developed a systematic framework, including a two-stage Bayesian learning approach, to achieve the diagnosis of one or multiple diseases for a query expression profile along a hierarchical disease taxonomy. Our approach, including standardizing cross-platform gene expression data and heterogeneous disease annotations, allows analyzing both sources of information in a unified probabilistic system. A high level of overall diagnostic accuracy was shown by cross validation. It was also demonstrated that the power of our method can increase significantly with the continued growth of public gene expression repositories. Finally, we showed how our disease diagnosis system can be used to characterize complex phenotypes and to construct a disease-drug connectivity map.

Development and evaluation of tailored specific real-time RT-PCR assays for detection of foot-and-mouth disease virus serotypes circulating in East Africa.

PubMed

Bachanek-Bankowska, Katarzyna; Mero, Herieth R; Wadsworth, Jemma; Mioulet, Valerie; Sallu, Raphael; Belsham, Graham J; Kasanga, Christopher J; Knowles, Nick J; King, Donald P

2016-11-01

Rapid, reliable and accurate diagnostic methods provide essential support to programmes that monitor and control foot-and-mouth disease (FMD). While pan-specific molecular tests for FMD virus (FMDV) detection are well established and widely used in endemic and FMD-free countries, current serotyping methods mainly rely either on antigen detection ELISAs or nucleotide sequencing approaches. This report describes the development of a panel of serotype-specific real-time RT-PCR assays (rRT-PCR) tailored to detect FMDV lineages currently circulating in East Africa. These assays target sequences within the VP1-coding region that share high intra-lineage identity, but do not cross-react with FMD viruses from other serotypes that circulate in the region. These serotype-specific assays operate with the same thermal profile as the pan-diagnostic tests making it possible to run them in parallel to produce C T values comparable to the pan-diagnostic test detecting the 3D-coding region. These assays were evaluated alongside the established pan-specific molecular test using field samples and virus isolates collected from Tanzania, Kenya and Ethiopia that had been previously characterised by nucleotide sequencing. Samples (n=71) representing serotype A (topotype AFRICA, lineage G-I), serotype O (topotypes EA-2 and EA-4), serotype SAT 1 (topotype I (NWZ)) and serotype SAT2 (topotype IV) were correctly identified with these rRT-PCR assays. Furthermore, FMDV RNA from samples that did not contain infectious virus could still be serotyped using these assays. These serotype-specific real-time RT-PCR assays can detect and characterise FMDVs currently circulating in East Africa and hence improve disease control in this region. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Physicians' perceptions of capacity building for managing chronic disease in seniors using integrated interprofessional care models.

PubMed

Lee, Linda; Heckman, George; McKelvie, Robert; Jong, Philip; D'Elia, Teresa; Hillier, Loretta M

2015-03-01

To explore the barriers to and facilitators of adapting and expanding a primary care memory clinic model to integrate care of additional complex chronic geriatric conditions (heart failure, falls, chronic obstructive pulmonary disease, and frailty) into care processes with the goal of improving outcomes for seniors. Mixed-methods study using quantitative (questionnaires) and qualitative (interviews) methods. Ontario. Family physicians currently working in primary care memory clinic teams and supporting geriatric specialists. Family physicians currently working in memory clinic teams (n = 29) and supporting geriatric specialists(n = 9) were recruited as survey participants. Interviews were conducted with memory clinic lead physicians (n = 16).Statistical analysis was done to assess differences between family physician ratings and geriatric specialist ratings related to the capacity for managing complex chronic geriatric conditions, the role of interprofessional collaboration within primary care, and funding and staffing to support geriatric care. Results from both study methods were compared to identify common findings. Results indicate overall support for expanding the memory clinic model to integrate care for other complex conditions. However, the current primary care structure is challenged to support optimal management of patients with multiple comorbidities, particularly as related to limited funding and staffing resources. Structured training, interprofessional teams, and an active role of geriatric specialists within primary care were identified as important facilitators. The memory clinic model, as applied to other complex chronic geriatric conditions, has the potential to build capacity for high-quality primary care, improve health outcomes,promote efficient use of health care resources, and reduce healthcare costs.

Rethinking blood shield statutes in view of the hepatitis C pandemic and other emerging threats to the blood supply.

PubMed

Rueda, A

2001-01-01

Researchers have identified at least twenty-five pathogens that can be transmitted through blood transfusions. Four percent of patients who receive the average amount of blood during a transfusion are at risk of being infected with a contaminated unit, and exposed to the danger of serious adverse reactions, including future debilitating conditions. Victims of transfusion-related diseases, however, generally have been unsuccessful when making claims against the purveyors of blood products because of blood shield statutes that were initially enacted in response to unknown pathogens that made the blood an "unavoidably unsafe" product. Today, blood purveyors are aware of the possibility of epidemics from unsafe blood and have continued to research and supervise the blood supply to create mechanisms that detect and inactivate various blood-borne pathogens. In response to the current and advancing methods of blood purification, this Article suggests that a hybrid strict liability/negligence standard be implemented to ensure advancements in safety of blood transfusions. A strict liability standard should attach for infections that can be detected and eliminated through current testing and inactivation methods. A negligence standard should govern infections for which no current test or inactivating method is available. Under this approach, blood purveyors would be compelled to take account of the risks of any manufacturing decisions that they make, and they would not enjoy the freedom from liability that the blood shield statutes now provide. The costs necessary to ensure compliance with this hybrid structure are small in comparison to the social and economic costs exacted by thousands of transfusion-related diseases.

Risk Factors Associated with Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-infected Cohort

PubMed Central

Leader, Joseph K.; Crothers, Kristina; Huang, Laurence; King, Mark A.; Morris, Alison; Thompson, Bruce W.; Flores, Sonia C.; Drummond, M. Bradley; Rom, William N.; Diaz, Philip T.

2015-01-01

Introduction The disease spectrum for HIV-infected individuals has shifted towards co-morbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. Objectives To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. Methods A cross-sectional analysis of 510 HIV-infected participants in the multi-center Lung-HIV study was performed. Data collected included: demographics, biological markers of HIV, pulmonary function testing, and chest CT examinations. Emphysema and fibrosis-like changes were quantified on CT images based on threshold approaches. Results In our cohort: 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells/μL, 39% had an HIV viral load greater than 500 copies/mL, 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210, p<0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107, P = 0.03). Conclusion A higher HIV viral load was significantly associated with fibrosis-like changes possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load. PMID:26914911

The role of robotic surgical system in the management of vascular disease.

PubMed

Lin, Judith C

2013-10-01

The evolution of minimally invasive treatment for aneurysms and occlusive disease has led to the development of endovascular, laparoscopic, and robot-assisted techniques. This article reviews the current literature on the clinical use of robotic surgical systems in the treatment of patients with aneurysms and occlusive disease. A MEDLINE search was performed using the keywords "robotic, vascular, AND surgery." All pertinent articles concerning the use of the robotic surgical system on aneurysms and occlusive disease were reviewed. The author's personal experience consisted of a retrospective review of a prospectively maintained confidential database on all procedures performed with the da Vinci(®) surgical system. Several robot-assisted laparoscopic series on the treatment of aortic disease were identified, including review articles of potential clinical applications in hybrid, laparoscopic vascular, and endovascular treatments for vascular patients using robotic technology. The use of computer-enhanced or robotic technology as a sole modality for bypass of occlusive disease and repair of abdominal aortic, splenic, and renal aneurysms was described in case series with satisfactory patient outcomes. Current robotic endovascular technology was also described. Minimally invasive techniques using endovascular, laparoscopic, or robot-assisted technology have revolutionized the treatment of aortoiliac, splanchnic, and renal aneurysms and occlusive disease. However, robot-assisted techniques for aortic disease may involve a learning curve and increased operating times. Although endovascular therapy is preferred because of faster recovery, this preference for improved short-term outcomes will be balanced with the superiority and durability of robot-assisted endoscopic methods as comparable to open surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of clinical questionnaires in optimizing everyday care of chronic obstructive pulmonary disease

PubMed Central

Jones, Paul W; Price, David; van der Molen, Thys

2011-01-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability in all its stages, and death in patients with moderate or severe obstruction. At present, COPD is suboptimally managed; current health is often not measured properly and hardly taken into account in management plans, and the future risk for patients with regard to health status and quality of life is not being evaluated. This review addresses the effect of COPD on the lives of patients and examines ways in which existing assessment tools meet physicians’ needs for a standardized, simple method to measure consistently the full impact of COPD on patients in routine clinical practice. Current assessment of COPD severity tends to focus on airflow limitation, but this does not capture the full impact of the disease and is not well correlated with patient perception of symptoms and health-related quality of life. Qualitative studies have demonstrated that patients usually consider COPD impact in terms of frequency and severity of symptoms, and physical and emotional wellbeing. However, patients often have difficulty expressing their disease burden and physicians generally have insufficient time to collect this information. Therefore, it is important that methods are implemented to help generate a more complete understanding of the impact of COPD. This can be achieved most efficiently using a quick, reliable, and standardized measure of disease impact, such as a short questionnaire that can be applied in daily clinical practice. Questionnaires are precision instruments that contribute sensitive and specific information, and can potentially help physicians provide optimal care for patients with COPD. Two short, easy-to-use, specific measures, ie, the COPD Assessment Test and the Clinical COPD Questionnaire, enable physicians to assess patients’ health status accurately and improve disease management. Such questionnaires provide important measurements that can assist primary care physicians to capture the impact of COPD on patients’ daily lives and wellbeing, and improve long-term COPD management. PMID:21697993

Control and management of congenital Chagas disease in Europe and other non-endemic countries: current policies and practices.

PubMed

Soriano-Arandes, Antoni; Angheben, Andrea; Serre-Delcor, Nuria; Treviño-Maruri, Begoña; Gómez I Prat, Jordi; Jackson, Yves

2016-05-01

Identifying pregnant women infected with Trypanosoma cruzi is one of the major challenges for preventing and controlling Chagas disease (CD) in non-endemic countries. The aim of this paper was to perform a policy evaluation of the current practices of congenital Chagas disease (CCD) control in non-endemic countries and to propose specific targets for enhanced interventions to tackle this emerging health problem outside the endemic areas of Latin America. We conducted a mixed method review of CCD policy strategies by searching the literature in the PubMed, Google Scholar and the World Health Organization (WHO) databases using the key terms 'CCD', 'paediatric Chagas disease' and 'non-endemic countries'; as free text and combined as one phrase to increase the search sensitivity. Reviews, recommendations, guidelines and control/surveillance programme reports were included. Of 427 CCD papers identified in non-endemic countries, 44 matched the inclusion. Although local programmes were launched in different countries with large numbers of Latin American immigrants, there were considerable disparities in terms of the programmes' distribution, delivery, integration and appropriated CCD control strategies. Moreover, Catalonia, Spain is the only region/country with an established systematic monitoring of CCD in pregnant women from Latin American countries. Given the worldwide dissemination of CD, the nature of its vertical transmission, and the gaps of the current strategies in non-endemic countries, there is an urgent need to standardise, expand and reinforce the control measures against CCD transmission. © 2016 John Wiley & Sons Ltd.

A cross-species analysis method to analyze animal models' similarity to human's disease state

PubMed Central

2012-01-01

Background Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. Results We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. Conclusions We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology. PMID:23282076

A cross-species analysis method to analyze animal models' similarity to human's disease state.

PubMed

Yu, Shuhao; Zheng, Lulu; Li, Yun; Li, Chunyan; Ma, Chenchen; Li, Yixue; Li, Xuan; Hao, Pei

2012-01-01

Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology.

PHENOstruct: Prediction of human phenotype ontology terms using heterogeneous data sources.

PubMed

Kahanda, Indika; Funk, Christopher; Verspoor, Karin; Ben-Hur, Asa

2015-01-01

The human phenotype ontology (HPO) was recently developed as a standardized vocabulary for describing the phenotype abnormalities associated with human diseases. At present, only a small fraction of human protein coding genes have HPO annotations. But, researchers believe that a large portion of currently unannotated genes are related to disease phenotypes. Therefore, it is important to predict gene-HPO term associations using accurate computational methods. In this work we demonstrate the performance advantage of the structured SVM approach which was shown to be highly effective for Gene Ontology term prediction in comparison to several baseline methods. Furthermore, we highlight a collection of informative data sources suitable for the problem of predicting gene-HPO associations, including large scale literature mining data.

Biomarker detection for disease diagnosis using cost-effective microfluidic platforms.

PubMed

Sanjay, Sharma T; Fu, Guanglei; Dou, Maowei; Xu, Feng; Liu, Rutao; Qi, Hao; Li, XiuJun

2015-11-07

Early and timely detection of disease biomarkers can prevent the spread of infectious diseases, and drastically decrease the death rate of people suffering from different diseases such as cancer and infectious diseases. Because conventional diagnostic methods have limited application in low-resource settings due to the use of bulky and expensive instrumentation, simple and low-cost point-of-care diagnostic devices for timely and early biomarker diagnosis is the need of the hour, especially in rural areas and developing nations. The microfluidics technology possesses remarkable features for simple, low-cost, and rapid disease diagnosis. There have been significant advances in the development of microfluidic platforms for biomarker detection of diseases. This article reviews recent advances in biomarker detection using cost-effective microfluidic devices for disease diagnosis, with the emphasis on infectious disease and cancer diagnosis in low-resource settings. This review first introduces different microfluidic platforms (e.g. polymer and paper-based microfluidics) used for disease diagnosis, with a brief description of their common fabrication techniques. Then, it highlights various detection strategies for disease biomarker detection using microfluidic platforms, including colorimetric, fluorescence, chemiluminescence, electrochemiluminescence (ECL), and electrochemical detection. Finally, it discusses the current limitations of microfluidic devices for disease biomarker detection and future prospects.

Current devices of respiratory physiotherapy

PubMed Central

Hristara-Papadopoulou, A; Tsanakas, J; Diomou, G; Papadopoulou, O

2008-01-01

In recent years patients with respiratory diseases use various devices, which help the removal of mucus from the airways and the improvement of pulmonary function. The aim of the present study is to determine the effectiveness of the current devices of respiratory physiotherapy, as it comes from the review of literature. The current devices of physiotherapy for patients with respiratory diseases, are presented as an alternative therapy method or a supplemental therapy and they can motivate patients to apply therapy by themselves. These devices seem to increase patients' compliance to daily treatment, because they present many benefits, as independent application, full control of therapy and easy use. These devices are the Positive Expiratory Pressure, the High Frequency Chest Wall Oscillation, the Oral High Frequency Oscillation, the Intrapulmonary Percussive Ventilation, the Incentive Spirometry the Flutter and the Acapella and the Cornet. Current devices seem to be effective in terms of mucus expectoration and pulmonary function improvement, as it is shown by published studies. The choice of the suitable device for each patient is a challenge for the physiotherapist in order to achieve better compliance in daily treatment. More controlled studies are needed due to the fact that the number of published studies is limited. PMID:19158964

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Leptospirosis disease mapping with standardized morbidity ratio and Poisson-Gamma model: An analysis of Leptospirosis disease in Kelantan, Malaysia

NASA Astrophysics Data System (ADS)

Che Awang, Aznida; Azah Samat, Nor

2017-09-01

Leptospirosis is a disease caused by the infection of pathogenic species from the genus of Leptospira. Human can be infected by the leptospirosis from direct or indirect exposure to the urine of infected animals. The excretion of urine from the animal host that carries pathogenic Leptospira causes the soil or water to be contaminated. Therefore, people can become infected when they are exposed to contaminated soil and water by cut on the skin as well as open wound. It also can enter the human body by mucous membrane such nose, eyes and mouth, for example by splashing contaminated water or urine into the eyes or swallowing contaminated water or food. Currently, there is no vaccine available for the prevention or treatment of leptospirosis disease but this disease can be treated if it is diagnosed early to avoid any complication. The disease risk mapping is important in a way to control and prevention of disease. Using a good choice of statistical model will produce a good disease risk map. Therefore, the aim of this study is to estimate the relative risk for leptospirosis disease based initially on the most common statistic used in disease mapping called Standardized Morbidity Ratio (SMR) and Poisson-gamma model. This paper begins by providing a review of the SMR method and Poisson-gamma model, which we then applied to leptospirosis data of Kelantan, Malaysia. Both results are displayed and compared using graph, tables and maps. The result shows that the second method Poisson-gamma model produces better relative risk estimates compared to the SMR method. This is because the Poisson-gamma model can overcome the drawback of SMR where the relative risk will become zero when there is no observed leptospirosis case in certain regions. However, the Poisson-gamma model also faced problems where the covariate adjustment for this model is difficult and no possibility for allowing spatial correlation between risks in neighbouring areas. The problems of this model have motivated many researchers to introduce other alternative methods for estimating the risk.

Preeclampsia and long-term risk of cardiovascular disease: what do obstetrician-gynecologists know?

PubMed Central

2013-01-01

Background Preeclampsia (PE), a hypertensive disorder of pregnancy affects 2-8% of women and is associated with increased cardiovascular disease (CVD) risk later in life. There is little information about the knowledge of obstetrician-gynecologists in German outpatient care setting regarding the future health risk of PE and knowledge of the current guidelines on treatment and counseling patients post PE. This study aimed to assess whether obstetrician-gynecologists are aware of PE’s association with maternal long-term adverse outcomes and providing appropriate counseling. Methods A random sample of 500 obstetrician-gynecologists in the federal state of Lower Saxony was mailed a survey and a reminder with a second copy of the survey. The questionnaire elicited both personal information, and knowledge on future disease risks, e.g. cardiovascular disease (CVD) and current guidelines as well as on counseling practice. Descriptive analysis was used to analyze the responses. Results A total of 212 obstetrician-gynecologists (42.4%) responded to the questionnaire. A large proportion of physicians stated that PE was associated with a higher risk for the development for hypertension (86.6%), stroke (78.5%) and kidney disease (78.0%). Of the participants 75.8% reported that women after PE have a shorter life expectancy. Respondents with knowledge of the current guidelines of the German Association of Obstetrics and Gynecology concerning follow up and risk management of PE (45.2%) were more often aware of the development of CVD and stroke and counseled patients on self -blood-pressure measurement, meaning and long-term-risks of PE and attached importance to family history of PE compared to physicians with no knowledge of the guidelines. Conclusion Although the majority of obstetrician-gynecologists were aware of higher CVD risk after PE, weaknesses exist in the follow up care and counseling of these patients. These deficiencies would be amendable to directed educational activities to improve the implementation of current guidelines. PMID:23497157

A Structured Peer-Mentoring Method for Physical Activity Behavior Change Among Adolescents.

PubMed

Smith, Laureen H; Petosa, Rick L

2016-10-01

Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be reversed without a strong contribution from local schools. This article describes how a structured peer-mentoring method provides a feasible, flexible, and tailored means to meet the current guidelines for best practice in a school setting. Structured peer mentoring using trained high school mentors to support behavior change in younger peers is an innovative method to meeting the School Health Guidelines to Promote Healthy Eating and Physical Activity Through structured peer mentoring, adolescents are provided consistent social support in a caring and personalized manner. This support builds skills and competencies enhancing self-efficacy to sustain a lifetime of physical activity behavior. © The Author(s) 2016.

A Structured Peer-Mentoring Method for Physical Activity Behavior Change Among Adolescents

PubMed Central

Smith, Laureen H.; Petosa, Rick L.

2016-01-01

Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be reversed without a strong contribution from local schools. This article describes how a structured peer-mentoring method provides a feasible, flexible, and tailored means to meet the current guidelines for best practice in a school setting. Structured peer mentoring using trained high school mentors to support behavior change in younger peers is an innovative method to meeting the School Health Guidelines to Promote Healthy Eating and Physical Activity. Through structured peer mentoring, adolescents are provided consistent social support in a caring and personalized manner. This support builds skills and competencies enhancing self-efficacy to sustain a lifetime of physical activity behavior. PMID:27257081

The touchscreen operant platform for testing learning and memory in rats and mice.

PubMed

Horner, Alexa E; Heath, Christopher J; Hvoslef-Eide, Martha; Kent, Brianne A; Kim, Chi Hun; Nilsson, Simon R O; Alsiö, Johan; Oomen, Charlotte A; Holmes, Andrew; Saksida, Lisa M; Bussey, Timothy J

2013-10-01

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, neurotransmitter systems and genes in rodents. This protocol describes how to perform four touchscreen assays of learning and memory: visual discrimination, object-location paired-associates learning, visuomotor conditional learning and autoshaping. It is accompanied by two further protocols (also published in this issue) that use the touchscreen platform to assess executive function, working memory and pattern separation.

A Microbiological Revolution Meets an Ancient Disease: Improving the Management of Tuberculosis with Genomics

PubMed Central

Wlodarska, Marta; Johnston, James C.; Gardy, Jennifer L.

2015-01-01

SUMMARY Tuberculosis (TB) is an ancient disease with an enormous global impact. Despite declining global incidence, the diagnosis, phenotyping, and epidemiological investigation of TB require significant clinical microbiology laboratory resources. Current methods for the detection and characterization of Mycobacterium tuberculosis consist of a series of laboratory tests varying in speed and performance, each of which yields incremental information about the disease. Since the sequencing of the first M. tuberculosis genome in 1998, genomic tools have aided in the diagnosis, treatment, and control of TB. Here we summarize genomics-based methods that are positioned to be introduced in the modern clinical TB laboratory, and we highlight how recent advances in genomics will improve the detection of antibiotic resistance-conferring mutations and the understanding of M. tuberculosis transmission dynamics and epidemiology. We imagine the future TB clinic as one that relies heavily on genomic interrogation of the M. tuberculosis isolate, allowing for more rapid diagnosis of TB and real-time monitoring of outbreak emergence. PMID:25810419

Imaging pancreatobiliary ductal system with optical coherence tomography: A review

PubMed Central

Mahmud, Mohammad S; May, Gray R; Kamal, Mohammad M; Khwaja, Ahmed S; Sun, Carry; Vitkin, Alex; Yang, Victor XD

2013-01-01

An accurate, noninvasive and cost-effective method of in situ tissue evaluation during endoscopy would be highly advantageous for the detection of dysplasia or early cancer and for identifying different disease stages. Optical coherence tomography (OCT) is a noninvasive, high-resolution (1-10 μm) emerging optical imaging method with potential for identifying microscopic subsurface features in the pancreatic and biliary ductal system. Tissue microstructure of pancreaticobiliary ductal system has been successfully imaged by inserting an OCT probe through a standard endoscope operative channel. High-resolution OCT images and the technique’s endoscopic compatibility have allowed for the microstructural diagnostic of the pancreatobiliary diseases. In this review, we discussed currently available pancreaticobiliary ductal imaging systems to assess the pancreatobiliary tissue microstructure and to evaluate varieties of pancreaticobiliary disorders and diseases. Results show that OCT can improve the quality of images of pancreatobiliary system during endoscopic retrograde cholangiopancheatography procedure, which may be important in distinguishing between the neoplastic and non-neoplastic lesions. PMID:24255746

Analytical considerations for mass spectrometry profiling in serum biomarker discovery.

PubMed

Whiteley, Gordon R; Colantonio, Simona; Sacconi, Andrea; Saul, Richard G

2009-03-01

The potential of using mass spectrometry profiling as a diagnostic tool has been demonstrated for a wide variety of diseases. Various cancers and cancer-related diseases have been the focus of much of this work because of both the paucity of good diagnostic markers and the knowledge that early diagnosis is the most powerful weapon in treating cancer. The implementation of mass spectrometry as a routine diagnostic tool has proved to be difficult, however, primarily because of the stringent controls that are required for the method to be reproducible. The method is evolving as a powerful guide to the discovery of biomarkers that could, in turn, be used either individually or in an array or panel of tests for early disease detection. Using proteomic patterns to guide biomarker discovery and the possibility of deployment in the clinical laboratory environment on current instrumentation or in a hybrid technology has the possibility of being the early diagnosis tool that is needed.

Microfluidic approaches to malaria detection

PubMed Central

Gascoyne, Peter; Satayavivad, Jutamaad; Ruchirawat, Mathuros

2009-01-01

Microfluidic systems are under development to address a variety of medical problems. Key advantages of micrototal analysis systems based on microfluidic technology are the promise of small size and the integration of sample handling and measurement functions within a single, automated device having low mass-production costs. Here, we review the spectrum of methods currently used to detect malaria, consider their advantages and disadvantages, and discuss their adaptability towards integration into small, automated micro total analysis systems. Molecular amplification methods emerge as leading candidates for chip-based systems because they offer extremely high sensitivity, the ability to recognize malaria species and strain, and they will be adaptable to the detection of new genotypic signatures that will emerge from current genomic-based research of the disease. Current approaches to the development of chip-based molecular amplification are considered with special emphasis on flow-through PCR, and we present for the first time the method of malaria specimen preparation by dielectrophoretic field-flow-fractionation. Although many challenges must be addressed to realize a micrototal analysis system for malaria diagnosis, it is concluded that the potential benefits of the approach are well worth pursuing. PMID:14744562

Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

NASA Astrophysics Data System (ADS)

Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

2017-03-01

Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into cancer angiogenesis, and thus potentially improve cancer diagnosis and management.

Biomechanisms of Comorbidity: Reviewing Integrative Analyses of Multi-omics Datasets and Electronic Health Records.

PubMed

Pouladi, N; Achour, I; Li, H; Berghout, J; Kenost, C; Gonzalez-Garay, M L; Lussier, Y A

2016-11-10

Disease comorbidity is a pervasive phenomenon impacting patients' health outcomes, disease management, and clinical decisions. This review presents past, current and future research directions leveraging both phenotypic and molecular information to uncover disease similarity underpinning the biology and etiology of disease comorbidity. We retrieved ~130 publications and retained 59, ranging from 2006 to 2015, that comprise a minimum number of five diseases and at least one type of biomolecule. We surveyed their methods, disease similarity metrics, and calculation of comorbidities in the electronic health records, if present. Among the surveyed studies, 44% generated or validated disease similarity metrics in context of comorbidity, with 60% being published in the last two years. As inputs, 87% of studies utilized intragenic loci and proteins while 13% employed RNA (mRNA, LncRNA or miRNA). Network modeling was predominantly used (35%) followed by statistics (28%) to impute similarity between these biomolecules and diseases. Studies with large numbers of biomolecules and diseases used network models or naïve overlap of disease-molecule associations, while machine learning, statistics, and information retrieval were utilized in smaller and moderate sized studies. Multiscale computations comprising shared function, network topology, and phenotypes were performed exclusively on proteins. This review highlighted the growing methods for identifying the molecular mechanisms underpinning comorbidities that leverage multiscale molecular information and patterns from electronic health records. The survey unveiled that intergenic polymorphisms have been overlooked for similarity imputation compared to their intragenic counterparts, offering new opportunities to bridge the mechanistic and similarity gaps of comorbidity.

Current practice of epidemiology in Africa: highlights of the 3rd conference of the African epidemiological association and 1st conference of the Cameroon society of epidemiology, Yaoundé, Cameroon, 2014

PubMed Central

Nkwescheu, Armand Seraphin; Fokam, Joseph; Tchendjou, Patrice; Nji, Akindeh; Ngouakam, Hermann; Andre, Bita Fouda; Joelle, Sobngwi; Uzochukwu, Benjamin; Akinroye, Kingsley; Mbacham, Wilfred; Colizzi, Vittorio; Leke, Rose; Victora, Cesar

2015-01-01

As the study of disease occurrence and health indicators in human populations, Epidemiology is a dynamic field that evolves with time and geographical context. In order to update African health workers on current epidemiological practices and to draw awareness of early career epidemiologists on concepts and opportunities in the field, the 3rd African Epidemiology Association and the 1st Cameroon Society of Epidemiology Conference was organized in June 2-6, 2014 at the Yaoundé Mont Febe Hotel, in Cameroon. Under the theme«Practice of Epidemiology in Africa: Stakes, Challenges and Perspectives», the conference attracted close to five hundred guest and participants from all continents. The two main programs were the pre-conference course for capacity building of African Early Career epidemiologists, and the conference itself, providing a forum for scientific exchanges on recent epidemiological concepts, encouraging the use of epidemiological methods in studying large disease burden and neglected tropical diseases; and highlighting existing opportunities. PMID:26523191

Current practice of epidemiology in Africa: highlights of the 3rd conference of the African epidemiological association and 1st conference of the Cameroon society of epidemiology, Yaoundé, Cameroon, 2014.

PubMed

Nkwescheu, Armand Seraphin; Fokam, Joseph; Tchendjou, Patrice; Nji, Akindeh; Ngouakam, Hermann; Andre, Bita Fouda; Joelle, Sobngwi; Uzochukwu, Benjamin; Akinroye, Kingsley; Mbacham, Wilfred; Colizzi, Vittorio; Leke, Rose; Victora, Cesar

2015-01-01

As the study of disease occurrence and health indicators in human populations, Epidemiology is a dynamic field that evolves with time and geographical context. In order to update African health workers on current epidemiological practices and to draw awareness of early career epidemiologists on concepts and opportunities in the field, the 3(rd) African Epidemiology Association and the 1st Cameroon Society of Epidemiology Conference was organized in June 2-6, 2014 at the Yaoundé Mont Febe Hotel, in Cameroon. Under the theme«Practice of Epidemiology in Africa: Stakes, Challenges and Perspectives», the conference attracted close to five hundred guest and participants from all continents. The two main programs were the pre-conference course for capacity building of African Early Career epidemiologists, and the conference itself, providing a forum for scientific exchanges on recent epidemiological concepts, encouraging the use of epidemiological methods in studying large disease burden and neglected tropical diseases; and highlighting existing opportunities.

Molecular diagnosis of putative Stargardt disease probands by exome sequencing

PubMed Central

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

Screening for small molecule inhibitors of Toxoplasma gondii.

PubMed

Kortagere, Sandhya

2012-12-01

Toxoplasma gondii, the agent that causes toxoplasmosis, is an opportunistic parasite that infects many mammalian species. It is an obligate intracellular parasite that causes severe congenital neurological and ocular disease mostly in immunocompromised humans. The current regimen of therapy includes only a few medications that often lead to hypersensitivity and toxicity. In addition, there are no vaccines available to prevent the transmission of this agent. Therefore, safer and more effective medicines to treat toxoplasmosis are urgently needed. The author presents in silico and in vitro strategies that are currently used to screen for novel targets and unique chemotypes against T. gondii. Furthermore, this review highlights the screening technologies and characterization of some novel targets and new chemical entities that could be developed into highly efficacious treatments for toxoplasmosis. A number of diverse methods are being used to design inhibitors against T. gondii. These include ligand-based methods, in which drugs that have been shown to be efficacious against other Apicomplexa parasites can be repurposed to identify lead molecules against T. gondii. In addition, structure-based methods use currently available repertoire of structural information in various databases to rationally design small-molecule inhibitors of T. gondii. Whereas the screening methods have their advantages and limitations, a combination of methods is ideally suited to design small-molecule inhibitors of complex parasites such as T. gondii.

Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

PubMed

Rysz-Górzyńska, Magdalena; Banach, Maciej

2016-08-01

A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

Standardized morbidity ratio for leptospirosis mapping in Malaysia

NASA Astrophysics Data System (ADS)

Awang, Aznida Che; Samat, Nor Azah

2017-05-01

Leptospirosis is a worldwide zoonotic disease that affects human health in many parts of the world including Malaysia. Leptospirosis is a disease caused by the infection of pathogenic Leptospira genus called Spirochaetes. Leptospirosis can be transmitted directly or indirectly from rats to human. The human infection is usually caused by human contact with urine or tissues of infected animal. This disease can be spread through mucus membrane such as mouth, nose and eyes, ingestion of contaminated food and water and also exposed injured skin to contaminated water or soil. There is still no vaccine currently available for the prevention or treatment of leptospirosis disease but this disease can be treated if it is diagnosed early. Therefore, the aim of this study is to estimate the relative risk for leptospirosis disease based initially on the most common statistic used in the study of disease mapping called Standardized Morbidity Ratio (SMR). We then apply SMR to leptospirosis data obtained in Malaysia. The results show that the states of Melaka have very high risk areas. The states of Kedah, Terengganu and Kelantan are identified as high risk areas. The states of Perak, Perlis, Sabah and Sarawak showed medium risk areas. This is followed by low risk by other states except Pahang, Johor and Labuan with very low risk areas. In conclusion, SMR method is the best method for mapping leptospirosis because by referring to the relative risk maps, the states that deserve closer look and disease prevention can be identified.

Laboratory screening markers in gastroenterology--state of the art.

PubMed

Kocna, Petr; Vanickova, Zdislava; Zima, Tomas

2013-06-01

Screening tests for gastrointestinal diseases acceptable for population with a high sensitivity and high specificity can now be offered by clinical laboratories. This paper summarizes major recent advances in this area of laboratory medicine. Relevant articles published within the last 5 years in the NLM (National Library of Medicine) PubMed - Medline database covering the three gastrointestinal diseases - colorectal cancer, coeliac disease, and atrophic gastritis were included for this overview. In Europe, colorectal cancer (CRCA) is the second most frequent malignant disease. Quantitative immunochemical analysis of the stool for haemoglobin provides the best screening test to date, with both sensitivity and specificity approaching 95%. Even though coeliac disease (CD) affects approximately 1% of the general population, it remains largely unrecognised. Recommended methods for screening currently involve the detection of IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptide. Evaluations of screening are now discussed for other diseases of the gastrointestinal tract - such as chronic atrophic gastritis (CAG), and inflammatory bowel disease (IBD). Detection of infection by Helicobacter pylori and stomach-specific plasmatic biomarkers, especially pepsinogen I/II ratio, could help with the prevention of gastric carcinomas. The use of faecal calprotectin as a screening test could substantially reduce the number of invasive methods necessary for the diagnostic work-up of patients with IBD. Screening tests for CRCA and CD have been used worldwide for many years. Screening strategies for gastrointestinal diseases are suggested in the text, based on recent basic science, clinical papers as well as our own experience.

A practical guideline for intracranial volume estimation in patients with Alzheimer's disease

PubMed Central

2015-01-01

Background Intracranial volume (ICV) is an important normalization measure used in morphometric analyses to correct for head size in studies of Alzheimer Disease (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation in patients with Alzheimer disease in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and the type of software most suitable for use in estimating the ICV measure. Methods Two groups of 22 subjects are considered, including adult controls (AC) and patients with Alzheimer Disease (AD). Reference measurements were calculated for each subject by manually tracing intracranial cavity by the means of visual inspection. The reliability of reference measurements were assured through intra- and inter- variation analyses. Three publicly well-known software packages (Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the groups. Results Analysis of the results supported the significant effect of estimation method, gender, cognitive condition of the subject and the interaction among method and cognitive condition factors in the measured ICV. Results on sub-sampling studies with a 95% confidence showed that in order to keep the accuracy of the interleaved slice sampling protocol above 99%, the sampling period cannot exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed promising estimates for both adult groups. However SPM showed more consistency in its ICV estimation over the different phases of the study. Conclusions This study emphasized the importance in selecting the appropriate protocol, the choice of the sampling period in the manual estimation of ICV and selection of suitable software for the automated estimation of ICV. The current study serves as an initial framework for establishing an appropriate protocol in both manual and automatic ICV estimations with different subject populations. PMID:25953026

Targeted journal curation as a method to improve data currency at the Comparative Toxicogenomics Database

PubMed Central

Davis, Allan Peter; Johnson, Robin J.; Lennon-Hopkins, Kelley; Sciaky, Daniela; Rosenstein, Michael C.; Wiegers, Thomas C.; Mattingly, Carolyn J.

2012-01-01

The Comparative Toxicogenomics Database (CTD) is a public resource that promotes understanding about the effects of environmental chemicals on human health. CTD biocurators read the scientific literature and manually curate a triad of chemical–gene, chemical–disease and gene–disease interactions. Typically, articles for CTD are selected using a chemical-centric approach by querying PubMed to retrieve a corpus containing the chemical of interest. Although this technique ensures adequate coverage of knowledge about the chemical (i.e. data completeness), it does not necessarily reflect the most current state of all toxicological research in the community at large (i.e. data currency). Keeping databases current with the most recent scientific results, as well as providing a rich historical background from legacy articles, is a challenging process. To address this issue of data currency, CTD designed and tested a journal-centric approach of curation to complement our chemical-centric method. We first identified priority journals based on defined criteria. Next, over 7 weeks, three biocurators reviewed 2425 articles from three consecutive years (2009–2011) of three targeted journals. From this corpus, 1252 articles contained relevant data for CTD and 52 752 interactions were manually curated. Here, we describe our journal selection process, two methods of document delivery for the biocurators and the analysis of the resulting curation metrics, including data currency, and both intra-journal and inter-journal comparisons of research topics. Based on our results, we expect that curation by select journals can (i) be easily incorporated into the curation pipeline to complement our chemical-centric approach; (ii) build content more evenly for chemicals, genes and diseases in CTD (rather than biasing data by chemicals-of-interest); (iii) reflect developing areas in environmental health and (iv) improve overall data currency for chemicals, genes and diseases. Database URL: http://ctdbase.org/ PMID:23221299

Plastic biliary stents for benign biliary diseases.

PubMed

Perri, Vincenzo; Familiari, Pietro; Tringali, Andrea; Boskoski, Ivo; Costamagna, Guido

2011-07-01

Biliary plastic stenting plays a key role in the endoscopic management of benign biliary diseases. Complications following surgery of the biliary tract and liver transplantation are amenable to endoscopic treatment by plastic stenting. Insertion of an increasing number of plastic stents is currently the method of choice to treat postoperative biliary strictures. Benign biliary strictures secondary to chronic pancreatitis or primary sclerosing cholangitis may benefit from plastic stenting in select cases. There is a role for plastic stent placement in nonoperative candidates with acute cholecystitis and in patients with irretrievable bile duct stones. Copyright © 2011 Elsevier Inc. All rights reserved.

Biological Activities of Polyphenols from Grapes

PubMed Central

Xia, En-Qin; Deng, Gui-Fang; Guo, Ya-Jun; Li, Hua-Bin

2010-01-01

The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included. PMID:20386657

Clinical appraisal of arterial stiffness: the Argonauts in front of the Golden Fleece

PubMed Central

Vlachopoulos, C; Aznaouridis, K; Stefanadis, C

2006-01-01

Interest in evaluating arterial elastic properties has grown in parallel with the widespread availability of non‐invasive methods for assessing arterial stiffness. A clinically useful diagnostic index must be pathophysiologically relevant, must be readily measurable, and must indicate the severity of the disease and predict the corresponding risk. Interventional modification of this index must parallel disease regression and benefit prognosis. The current evidence for the clinical value of estimating arterial stiffness (mainly of large, elastic‐type arteries, such as the aorta and the carotids) in the contemporary era of cardiovascular medicine is reviewed. PMID:16339817

Brain Aggregates: An Effective In Vitro Cell Culture System Modeling Neurodegenerative Diseases.

PubMed

Ahn, Misol; Kalume, Franck; Pitstick, Rose; Oehler, Abby; Carlson, George; DeArmond, Stephen J

2016-03-01

Drug discovery for neurodegenerative diseases is particularly challenging because of the discrepancies in drug effects between in vitro and in vivo studies. These discrepancies occur in part because current cell culture systems used for drug screening have many limitations. First, few cell culture systems accurately model human aging or neurodegenerative diseases. Second, drug efficacy may differ between dividing and stationary cells, the latter resembling nondividing neurons in the CNS. Brain aggregates (BrnAggs) derived from embryonic day 15 gestation mouse embryos may represent neuropathogenic processes in prion disease and reflect in vivo drug efficacy. Here, we report a new method for the production of BrnAggs suitable for drug screening and suggest that BrnAggs can model additional neurological diseases such as tauopathies. We also report a functional assay with BrnAggs by measuring electrophysiological activities. Our data suggest that BrnAggs could serve as an effective in vitro cell culture system for drug discovery for neurodegenerative diseases. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Preparation and Characterization of UV Emitting Fluoride Phosphors for Phototherapy Lamps

NASA Astrophysics Data System (ADS)

Belsare, P. D.; Moharil, S. V.; Joshi, C. P.; Omanwar, S. K.

2011-10-01

The use of ultraviolet radiation for the treatment of various skin diseases is well known for long time. Phototherapy employs ultraviolet-blue radiation to cure skin diseases. The basis of phototherapy is believed to be the direct interaction of light of certain frequencies with tissue to cause a change in immune response. Currently dermatologists use UV lamps having specific emissions in UV region for treating various skin diseases. The treatment of skin diseases using artificial sources of UV radiation is now well established and more than 50 types of skin diseases are treated by phototherapy. This is an effective treatment for many skin disorders, such as psoriasis, vitiligo, ofujis disease, morphea , scleroderma, cutaneous T-cell lymphoma, lupus erythematosus, hyperbilirubinemia commonly known as infant jaundice, acne vulgaris, This paper reports photoluminescence properties of UV emitting fluoride phosphors prepared by wet chemical method. Emission characteristics of these phosphors are found similar to those of commercial UV lamp phosphors with comparable intensities. The usefulness of UV emitting fluoride phosphor is discussed in the paper.

Metabolomics for Biomarker Discovery: Moving to the Clinic

PubMed Central

Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

2015-01-01

To improve the clinical course of diseases, more accurate diagnostic and assessment methods are required as early as possible. In order to achieve this, metabolomics offers new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has become an important tool in clinical research and the diagnosis of human disease and has been applied to discovery and identification of the perturbed pathways. It provides a powerful approach to discover biomarkers in biological systems and offers a holistic approach with the promise to clinically enhance diagnostics. When carried out properly, it could provide insight into the understanding of the underlying mechanisms of diseases, help to identify patients at risk of disease, and predict the response to specific treatments. Currently, metabolomics has become an important tool in clinical research and the diagnosis of human disease and becomes a hot topic. This review will highlight the importance and benefit of metabolomics for identifying biomarkers that accurately screen potential biomarkers of diseases. PMID:26090402

The Effectiveness of self management program on quality of life in patients with sickle cell disease

PubMed Central

Ahmadi, M; Jahani, S; Poormansouri, S; Shariati, A; Tabesh, H

2015-01-01

Background Sickle cell patients suffer from many physical, psychological, and social problems that can affect their quality of life. To deal with this chronic condition and manage their disease and prevent complications associated with the disease, they must learn skills and behaviours. The aim of this study was to determine the effectiveness of self-management programs on quality of life in these patients. Material and Methods Samples of this quasi-experimental study, which included 69 patients with sickle cell disease referring to the Thalassemia Clinic of Shafa Hospital, were entered into the study by census method. Patients received a self-management program using the 5A model for 12 weeks, while their quality of life before the intervention were assessed at the twelfth week and thirty-sixth week using SF-36 questionnaire. Data were analyzed by descriptive statistics, paired t-test, Wilcoxon test, Hotelling's T2, and repeated measures test. Results The eight dimensions and the total QoL score after intervention were significantly increased compared to those before the intervention (P<0.001). Repeated measures test showed that the mean score of eight QoL dimensions and the total QoL score decreased in the thirty-sixth week, compared to twelfth week. However, it was significantly enhanced in comparison with the intervention baseline (P<0.05). Conclusions Current study revealed the efficacy of self-management interventions on the quality of life in patients with sickle cell disease. Therefore, application of this supportive method could be useful to empower the patients and help them to manage the disease. PMID:25914799

Frequencies of neuronal autoantibodies in healthy controls

PubMed Central

Lang, Katharina

2017-01-01

Objective: To provide an extensive overview on the prevalence of antibodies against neuronal surfaces (neuronal surface antibody [NSAb]) in healthy participants and disease controls. Methods: We searched the PubMed database (1974 to October 2016) for studies that analyzed frequencies of 22 different NSAbs in serum or CSF and included controls. Antibody prevalence was calculated for patients with NSAb-mediated disease and controls, including healthy participants, and those with neurologic and nonneurologic diseases. Different assays for antibody detection were compared. Results: In 309 articles, 743,299 antibody tests for 22 NSAbs were performed, including 30,485 tests for 19 NSAbs in healthy controls (HCs). Of these, 26,423 (86.7%) were tested with current standard methods, usually cell-based assays. Prevalence was very low in HCs (mean 0.23%, absent for 9/19 antibodies), and test numbers ranged from 21 to 3,065 per antibody. One study reported >1,000 healthy participants, and the others contained 21–274 samples. CSF samples were virtually not available from HCs. NSAb prevalence was considerably higher (1.5%) in 69,850 disease controls, i.e., patients not initially suspected to have NSAb-mediated diseases. Antibody determination in controls using nonstandard assays (such as ELISA) resulted in 6% positivity. Conclusions: NSAbs are rarely found in healthy participants, particularly with standard detection methods, suggesting high disease specificity and supporting their diagnostic usefulness. Conversely, positive titers in atypical patients might point to the still expanding phenotypic spectrum. Future studies should include more CSF samples, data from HCs, and experimental evidence for antibody pathogenicity. PMID:28761905

Induced Pluripotent Stem Cells in Dermatology: Potentials, Advances, and Limitations

PubMed Central

Bilousova, Ganna; Roop, Dennis R.

2014-01-01

The discovery of methods for reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) has raised the possibility of producing truly personalized treatment options for numerous diseases. Similar to embryonic stem cells (ESCs), iPSCs can give rise to any cell type in the body and are amenable to genetic correction by homologous recombination. These ESC properties of iPSCs allow for the development of permanent corrective therapies for many currently incurable disorders, including inherited skin diseases, without using embryonic tissues or oocytes. Here, we review recent progress and limitations of iPSC research with a focus on clinical applications of iPSCs and using iPSCs to model human diseases for drug discovery in the field of dermatology. PMID:25368014

HttQ111/+ Huntington’s Disease Knock-in Mice Exhibit Brain Region-Specific Morphological Changes and Synaptic Dysfunction

PubMed Central

Kovalenko, Marina; Milnerwood, Austen; Giordano, James; St. Claire, Jason; Guide, Jolene R.; Stromberg, Mary; Gillis, Tammy; Sapp, Ellen; DiFiglia, Marian; MacDonald, Marcy E.; Carroll, Jeffrey B.; Lee, Jong-Min; Tappan, Susan; Raymond, Lynn; Wheeler, Vanessa C.

2018-01-01

Background: Successful disease-modifying therapy for Huntington’s disease (HD) will require therapeutic intervention early in the pathogenic process. Achieving this goal requires identifying phenotypes that are proximal to the HTT CAG repeat expansion. Objective: To use Htt CAG knock-in mice, precise genetic replicas of the HTT mutation in patients, as models to study proximal disease events. Methods: Using cohorts of B6J.HttQ111/+ mice from 2 to 18 months of age, we analyzed pathological markers, including immunohistochemistry, brain regional volumes and cortical thickness, CAG instability, electron microscopy of striatal synapses, and acute slice electrophysiology to record glutamatergic transmission at striatal synapses. We also incorporated a diet perturbation paradigm for some of these analyses. Results: B6J.HttQ111/+ mice did not exhibit significant neurodegeneration or gliosis but revealed decreased striatal DARPP-32 as well as subtle but regional-specific changes in brain volumes and cortical thickness that parallel those in HD patients. Ultrastructural analyses of the striatum showed reduced synapse density, increased postsynaptic density thickness and increased synaptic cleft width. Acute slice electrophysiology showed alterations in spontaneous AMPA receptor-mediated postsynaptic currents, evoked NMDA receptor-mediated excitatory postsynaptic currents, and elevated extrasynaptic NMDA currents. Diet influenced cortical thickness, but did not impact somatic CAG expansion, nor did it show any significant interaction with genotype on immunohistochemical, brain volume or cortical thickness measures. Conclusions: These data show that a single HttQ111 allele is sufficient to elicit brain region-specific morphological changes and early neuronal dysfunction, highlighting an insidious disease process already apparent in the first few months of life. PMID:29480209

The burden of antenatal heart disease in South Africa: a systematic review

PubMed Central

2012-01-01

Background Maternal mortality in South Africa is rising, and heart conditions currently account for 41 per cent of indirect causes of deaths. Little is known about the burden of heart disease in pregnant South Africans. Methods We systematically reviewed the contemporary epidemiology and peripartum outcomes of heart disease in South African women attending antenatal care. Searches were performed in PubMed, ISI Web of Science, the EBSCO Africa-Wide database, the South African Union Catalogue, and the Current and Completed Research database (South Africa). References of included articles were also hand-searched. Studies reporting epidemiologic data on antenatal heart disease in South Africa were included. Data on morbidity and mortality were also collected. Results Seven studies were included in the systematic review. The prevalence of heart disease ranged from 123 to 943 per 100,000 deliveries, with a median prevalence of 616 per 100,000. Rheumatic valvular lesions were the commonest abnormalities, although cardiomyopathies were disproportionately high in comparison with other developing countries. Peripartum case-fatality rates were as high as 9.5 per cent in areas with limited access to care. The most frequent complications were pulmonary oedema, thromboembolism, and major bleeding with warfarin use. Perinatal mortality ranged from 8.9 to 23.8 per cent, whilst mitral lesions were associated with low birth weight. Meta-analysis could not be performed due to clinical and statistical heterogeneity of the included studies. Conclusion Approximately 0.6 per cent of pregnant South Africans have pre-existing cardiac abnormalities, with rheumatic lesions being the commonest. Maternal and perinatal morbidity and mortality continue to be very high. We conclude this review by summarising limitations of the current literature and recommending standard reporting criteria for future reports. PMID:22463484

β-glucans and cholesterol (Review)

PubMed Central

Sima, Petr; Vetvicka, Vaclav

2018-01-01

Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. β-glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fibers in the digestive tract. As there are two forms of β-glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of β-glucans on cholesterol levels. PMID:29393350

Mokken scaling analysis of the Hospital Anxiety and Depression Scale in individuals with cardiovascular disease.

PubMed

Cosco, Theodore D; Doyle, Frank; Watson, Roger; Ward, Mark; McGee, Hannah

2012-01-01

The Hospital Anxiety and Depression Scale (HADS) is a prolifically used scale of anxiety and depression. The original bidimensional anxiety-depression latent structure of the HADS has come under significant scrutiny, with previous studies revealing one-, two-, three- and four-dimensional structures. The current study examines the latent structure of the HADS using a non-parametric item response theory method. Using data conglomerated from four independent studies of cardiovascular disease employing the HADS (n=893), Mokken scaling procedure was conducted to assess the latent structure of the HADS. A single scale consisting of 12 of 14 HADS items was revealed, indicating a unidimensional latent HADS structure. The HADS was initially intended to measure mutually exclusive levels of anxiety and depression; however, the current study indicates that a single dimension of general psychological distress is captured. Copyright © 2012 Elsevier Inc. All rights reserved.

Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases.

PubMed

Keeling, Kim M; Bedwell, David M

2011-01-01

Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy. Copyright © 2011 John Wiley & Sons, Ltd.

Current trends in electrochemical sensing and biosensing of DNA methylation.

PubMed

Krejcova, Ludmila; Richtera, Lukas; Hynek, David; Labuda, Jan; Adam, Vojtech

2017-11-15

DNA methylation plays an important role in physiological and pathological processes. Several genetic diseases and most malignancies tend to be associated with aberrant DNA methylation. Among other analytical methods, electrochemical approaches have been successfully employed for characterisation of DNA methylation patterns that are essential for the diagnosis and treatment of particular diseases. This article discusses current trends in the electrochemical sensing and biosensing of DNA methylation. Particularly, it provides an overview of applied electrode materials, electrode modifications and biorecognition elements applications with an emphasis on strategies that form the core DNA methylation detection approaches. The three main strategies as (i) bisulfite treatment, (ii) cleavage by restriction endonucleases, and (iii) immuno/affinity reaction were described in greater detail. Additionally, the availability of the reviewed platforms for early cancer diagnosis and the approval of methylation inhibitors for anticancer therapy were discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Diggin’ on U(biquitin): A Novel Method for the Identification of Physiological E3 Ubiquitin Ligase Substrates

PubMed Central

Rubel, Carrie E.; Schisler, Jonathan C.; Hamlett, Eric D.; DeKroon, Robert M.; Gautel, Mathias; Alzate, Oscar; Patterson, Cam

2013-01-01

The ubiquitin-proteasome system (UPS) plays a central role in maintaining protein homeostasis, emphasized by a myriad of diseases that are associated with altered UPS function such as cancer, muscle-wasting, and neurodegeneration. Protein ubiquitination plays a central role in both the promotion of proteasomal degradation as well as cellular signaling through regulation of the stability of transcription factors and other signaling molecules. Substrate specificity is a critical regulatory step of ubiquitination and is mediated by ubiquitin ligases. Recent studies implicate ubiquitin ligases in multiple models of cardiac diseases such as cardiac hypertrophy, atrophy, and ischemia/reperfusion injury, both in a cardioprotective and maladaptive role. Therefore, identifying physiological substrates of cardiac ubiquitin ligases provides both mechanistic insights into heart disease as well as possible therapeutic targets. Current methods identifying substrates for ubiquitin ligases rely heavily upon non-physiologic in vitro methods, impeding the unbiased discovery of physiological substrates in relevant model systems. Here we describe a novel method for identifying ubiquitin ligase substrates utilizing Tandem Ubiquitin Binding Entities (TUBE) technology, two-dimensional differential in gel electrophoresis (2-D DIGE), and mass spectrometry, validated by the identification of both known and novel physiological substrates of the ubiquitin ligase MuRF1 in primary cardiomyocytes. This method can be applied to any ubiquitin ligase, both in normal and disease model systems, in order to identify relevant physiological substrates under various biological conditions, opening the door to a clearer mechanistic understanding of ubiquitin ligase function and broadening their potential as therapeutic targets. PMID:23695782

Opportunities for Improved Serodiagnosis of Human Tuberculosis, Bovine Tuberculosis, and Paratuberculosis

PubMed Central

Wadhwa, Ashutosh; Hickling, Graham J.; Eda, Shigetoshi

2012-01-01

Mycobacterial infections—tuberculosis (TB), bovine tuberculosis (bTB), and Johne's disease (JD)—are major infectious diseases of both human and animals. Methods presently in use for diagnosis of mycobacterial infections include bacterial culture, nucleic acid amplification, tuberculin skin test, interferon-γ assay, and serology. Serological tests have several advantages over other methods, including short turn-around time, relatively simple procedures, and low cost. However, current serodiagnostic methods for TB, bTB and JD exhibit low sensitivity and/or specificity. Recent studies that have aimed to develop improved serodiagnostic tests have mostly focused on identifying useful species-specific protein antigens. A review of recent attempts to improve diagnostic test performance indicates that the use of multiple antigens can improve the accuracy of serodiagnosis of these mycobacterial diseases. Mycobacteria also produce a variety of species-specific nonprotein molecules; however, only a few such molecules (e.g., cord factor and lipoarabinomannan) have so far been evaluated for their effectiveness as diagnostic antigens. For TB and bTB, there has been recent progress in developing laboratory-free diagnostic methods. New technologies such as microfluidics and “Lab-on-Chip” are examples of promising new technologies that can underpin development of laboratory-free diagnostic devices for these mycobacterial infections. PMID:22720192

Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems.

PubMed

Lam, Maggie P Y; Venkatraman, Vidya; Xing, Yi; Lau, Edward; Cao, Quan; Ng, Dominic C M; Su, Andrew I; Ge, Junbo; Van Eyk, Jennifer E; Ping, Peipei

2016-11-04

Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on high-impact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies.

Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans.

PubMed

Bundle, David R; McGiven, John

2017-12-19

Brucellosis is a serious zoonotic bacterial disease that is ranked by the World Health Organization among the top seven "neglected zoonoses" that threaten human health and cause poverty. It is a costly, highly contagious disease that affects ruminants, cattle, sheep, goats, and other productive animals such as pigs. Symptoms include abortions, infertility, decreased milk production, weight loss, and lameness. Brucellosis is also the most common bacterial disease that is transmitted from animals to humans, with approximately 500 000 new human cases each year. Detection and slaughter of infected animals is required to eradicate the disease, as vaccination alone is currently insufficient. However, as the most protective vaccines compromise serodiagnosis, this creates policy dilemmas, and these often result in the failure of eradication and control programs. Detection of antibodies to the Brucella bacterial cell wall O-polysaccharide (OPS) component of smooth lipopolysaccharide is used in diagnosis of this disease, and the same molecule contributes important protective efficacy to currently deployed veterinary whole-cell vaccines. This has set up a long-standing paradox that while Brucella OPS confers protective efficacy to vaccines, its presence results in similar antibody profiles in infected and vaccinated animals. Consequently, differentiation of infected from vaccinated animals (DIVA) is not possible, and this limits efforts to combat the disease. Recent clarification of the chemical structure of Brucella OPS as a block copolymer of two oligosaccharide sequences has provided an opportunity to utilize unique oligosaccharides only available via chemical synthesis in serodiagnostic tests for the disease. These oligosaccharides show excellent sensitivity and specificity compared with the native polymer used in current commercial tests and have the added advantage of assisting discrimination between brucellosis and infections caused by several bacteria with OPS that share some structural features with those of Brucella. During synthesis and immunochemical evaluation of these synthetic antigens, it became apparent that an opportunity existed to create a polysaccharide-protein conjugate vaccine that would not create antibodies that give false positive results in diagnostic tests for infection. This objective was reduced to practice, and immunization of mice showed that antibodies to the Brucella A antigen could be developed without reacting in a diagnostic test based on the M antigen. A conjugate vaccine of this type could readily be developed for use in humans and animals. However, as chemical methods advance and modern methods of bacterial engineering mature, it is expected that the principles elucidated by these studies could be applied to the development of an inexpensive and cost-effective vaccine to combat endemic brucellosis in animals.

Recent developments in detection and enumeration of waterborne bacteria: a retrospective minireview.

PubMed

Deshmukh, Rehan A; Joshi, Kopal; Bhand, Sunil; Roy, Utpal

2016-12-01

Waterborne diseases have emerged as global health problems and their rapid and sensitive detection in environmental water samples is of great importance. Bacterial identification and enumeration in water samples is significant as it helps to maintain safe drinking water for public consumption. Culture-based methods are laborious, time-consuming, and yield false-positive results, whereas viable but nonculturable (VBNCs) microorganisms cannot be recovered. Hence, numerous methods have been developed for rapid detection and quantification of waterborne pathogenic bacteria in water. These rapid methods can be classified into nucleic acid-based, immunology-based, and biosensor-based detection methods. This review summarizes the principle and current state of rapid methods for the monitoring and detection of waterborne bacterial pathogens. Rapid methods outlined are polymerase chain reaction (PCR), digital droplet PCR, real-time PCR, multiplex PCR, DNA microarray, Next-generation sequencing (pyrosequencing, Illumina technology and genomics), and fluorescence in situ hybridization that are categorized as nucleic acid-based methods. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are classified into immunology-based methods. Optical, electrochemical, and mass-based biosensors are grouped into biosensor-based methods. Overall, these methods are sensitive, specific, time-effective, and important in prevention and diagnosis of waterborne bacterial diseases. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

The management of staghorn calculi in children

PubMed Central

Horuz, Rahim; Sarica, Kemal

2012-01-01

Objectives To review reports focusing on the surgical treatment of staghorn stones in children, as despite all the improvements in the surgical treatment of paediatric urolithiasis the management of staghorn calculi still represents a challenging problem in urology practice. Methods To evaluate current knowledge about treating staghorn calculi in children, we searched PubMed for relevant articles published between 1991 and 2011, using a combination of related keywords, i.e. staghorn stone, child, kidney calculi, surgical treatment, electrohydraulic shockwave therapy (ESWL), percutaneous nephrolithotomy (PCNL), and open surgery. Reports relating to the treatment of paediatric stone disease in general (open surgery, PCNL, ESWL) were also searched with the same method. Additional references were obtained from the reference list of full-text reports. Results Although open surgery had been widely used in the past for treating such stones in children, currently it has only limited indications in highly selected patients. Current published data clearly indicate that, in experienced hands, both PCNL and ESWL are now effective methods for treating staghorn calculi in children. Conclusions Due to advanced techniques and instrumentation, it is now possible to successfully treat staghorn calculi in children, with very limited safety concerns. Currently, while PCNL is recommended as the first-line surgical treatment, ESWL, open surgery and/or combined methods are valuable but secondary options in the treatment of paediatric staghorn calculi. PMID:26558045

Quantitative characterization of fatty liver disease using x-ray scattering

NASA Astrophysics Data System (ADS)

Elsharkawy, Wafaa B.; Elshemey, Wael M.

2013-11-01

Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

Sub-Network Kernels for Measuring Similarity of Brain Connectivity Networks in Disease Diagnosis.

PubMed

Jie, Biao; Liu, Mingxia; Zhang, Daoqiang; Shen, Dinggang

2018-05-01

As a simple representation of interactions among distributed brain regions, brain networks have been widely applied to automated diagnosis of brain diseases, such as Alzheimer's disease (AD) and its early stage, i.e., mild cognitive impairment (MCI). In brain network analysis, a challenging task is how to measure the similarity between a pair of networks. Although many graph kernels (i.e., kernels defined on graphs) have been proposed for measuring the topological similarity of a pair of brain networks, most of them are defined using general graphs, thus ignoring the uniqueness of each node in brain networks. That is, each node in a brain network denotes a particular brain region, which is a specific characteristics of brain networks. Accordingly, in this paper, we construct a novel sub-network kernel for measuring the similarity between a pair of brain networks and then apply it to brain disease classification. Different from current graph kernels, our proposed sub-network kernel not only takes into account the inherent characteristic of brain networks, but also captures multi-level (from local to global) topological properties of nodes in brain networks, which are essential for defining the similarity measure of brain networks. To validate the efficacy of our method, we perform extensive experiments on subjects with baseline functional magnetic resonance imaging data obtained from the Alzheimer's disease neuroimaging initiative database. Experimental results demonstrate that the proposed method outperforms several state-of-the-art graph-based methods in MCI classification.

Bayesian Model Averaging with Change Points to Assess the Impact of Vaccination and Public Health Interventions

PubMed Central

Warren, Joshua L.; Schuck-Paim, Cynthia; Lustig, Roger; Lewnard, Joseph A.; Fuentes, Rodrigo; Bruhn, Christian A. W.; Taylor, Robert J.; Simonsen, Lone; Weinberger, Daniel M.

2017-01-01

Background: Pneumococcal conjugate vaccines (PCVs) prevent invasive pneumococcal disease and pneumonia. However, some low-and middle-income countries have yet to introduce PCV into their immunization programs due, in part, to lack of certainty about the potential impact. Assessing PCV benefits is challenging because specific data on pneumococcal disease are often lacking, and it can be difficult to separate the effects of factors other than the vaccine that could also affect pneumococcal disease rates. Methods: We assess PCV impact by combining Bayesian model averaging with change-point models to estimate the timing and magnitude of vaccine-associated changes, while controlling for seasonality and other covariates. We applied our approach to monthly time series of age-stratified hospitalizations related to pneumococcal infection in children younger 5 years of age in the United States, Brazil, and Chile. Results: Our method accurately detected changes in data in which we knew true and noteworthy changes occurred, i.e., in simulated data and for invasive pneumococcal disease. Moreover, 24 months after the vaccine introduction, we detected reductions of 14%, 9%, and 9% in the United States, Brazil, and Chile, respectively, in all-cause pneumonia (ACP) hospitalizations for age group 0 to <1 years of age. Conclusions: Our approach provides a flexible and sensitive method to detect changes in disease incidence that occur after the introduction of a vaccine or other intervention, while avoiding biases that exist in current approaches to time-trend analyses. PMID:28767518

The SH-SY5Y cell line in Parkinson's disease research: a systematic review.

PubMed

Xicoy, Helena; Wieringa, Bé; Martens, Gerard J M

2017-01-24

Parkinson's disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance. However, there is no consensus on many fundamental aspects that are associated with its use, such as the effects of culture media composition and of variations in differentiation protocols. Here we present the outcome of a systematic review of scientific articles that have used SH-SY5Y cells to explore PD. We describe the cell source, culture conditions, differentiation protocols, methods/approaches used to mimic PD and the preclinical validation of the SH-SY5Y findings by employing alternative cellular and animal models. Thus, this overview may help to standardize the use of the SH-SY5Y cell line in PD research and serve as a future user's guide.

Therapeutic Drug Monitoring and Clinical Outcomes in Immune Mediated Diseases: The Missing Link.

PubMed

Sorrentino, Dario; Nguyen, Vu; Henderson, Carl; Bankole, Adegabenga

2016-10-01

As the incidence of inflammatory bowel diseases and the number of patients treated with anti-TNF agents keep on increasing so are the phenomena of primary non response (PNR) and secondary loss of response (SLR) to these medications. Traditionally PNR and SLR have been managed empirically-that is, switching medications for PNR and increasing the anti-TNF dose for SNR. More recently an approach based on testing drug levels and antibodies to the drug (therapeutic drug monitoring) has gained increasing popularity in the management of inflammatory bowel diseases. However, while this strategy might offer an insight into the mechanisms leading to PNR/SLR it often falls short of providing a simple, reproducible method to manage these issues in clinical practice. Here, we will review the currently recommended therapeutic strategies when using therapeutic drug monitoring; the evidence for and against such approach and the current standard strategies in Rheumatology (the specialty with the largest and longest experience with anti-TNF agents). We will then discuss the possible reasons of the shortcomings of therapeutic drug monitoring and the rationale and need to move the therapeutic target to the disease burden in inflammatory bowel diseases-along with the supporting preliminary evidence. Finally, we will focus on future crucial studies that need to be done to make approaches to PNR/SLR more rigorous and at the same time user-friendly for the practicing gastroenterologist.

Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

PubMed Central

Arora, Anil; Sharma, Praveen

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent

PubMed Central

Starosolski, Zbigniew; Villamizar, Carlos A.; Rendon, David; Paldino, Michael J.; Milewicz, Dianna M.; Ghaghada, Ketan B.; Annapragada, Ananth V.

2015-01-01

Abnormalities in the cerebrovascular system play a central role in many neurologic diseases. The on-going expansion of rodent models of human cerebrovascular diseases and the need to use these models to understand disease progression and treatment has amplified the need for reproducible non-invasive imaging methods for high-resolution visualization of the complete cerebral vasculature. In this study, we present methods for in vivo high-resolution (19 μm isotropic) computed tomography imaging of complete mouse brain vasculature. This technique enabled 3D visualization of large cerebrovascular networks, including the Circle of Willis. Blood vessels as small as 40 μm were clearly delineated. ACTA2 mutations in humans cause cerebrovascular defects, including abnormally straightened arteries and a moyamoya-like arteriopathy characterized by bilateral narrowing of the internal carotid artery and stenosis of many large arteries. In vivo imaging studies performed in a mouse model of Acta2 mutations demonstrated the utility of this method for studying vascular morphometric changes that are practically impossible to identify using current histological methods. Specifically, the technique demonstrated changes in the width of the Circle of Willis, straightening of cerebral arteries and arterial stenoses. We believe the use of imaging methods described here will contribute substantially to the study of rodent cerebrovasculature. PMID:25985192

Network-Based Method for Identifying Co-Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues

PubMed Central

Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Cai, Yu-Dong

2017-01-01

Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein–protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method. PMID:28974058

Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

PubMed

Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

2017-10-02

Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

A Parallel Genetic Algorithm to Discover Patterns in Genetic Markers that Indicate Predisposition to Multifactorial Disease

PubMed Central

Rausch, Tobias; Thomas, Alun; Camp, Nicola J.; Cannon-Albright, Lisa A.; Facelli, Julio C.

2008-01-01

This paper describes a novel algorithm to analyze genetic linkage data using pattern recognition techniques and genetic algorithms (GA). The method allows a search for regions of the chromosome that may contain genetic variations that jointly predispose individuals for a particular disease. The method uses correlation analysis, filtering theory and genetic algorithms (GA) to achieve this goal. Because current genome scans use from hundreds to hundreds of thousands of markers, two versions of the method have been implemented. The first is an exhaustive analysis version that can be used to visualize, explore, and analyze small genetic data sets for two marker correlations; the second is a GA version, which uses a parallel implementation allowing searches of higher-order correlations in large data sets. Results on simulated data sets indicate that the method can be informative in the identification of major disease loci and gene-gene interactions in genome-wide linkage data and that further exploration of these techniques is justified. The results presented for both variants of the method show that it can help genetic epidemiologists to identify promising combinations of genetic factors that might predispose to complex disorders. In particular, the correlation analysis of IBD expression patterns might hint to possible gene-gene interactions and the filtering might be a fruitful approach to distinguish true correlation signals from noise. PMID:18547558

Mendelian randomization analysis of a time-varying exposure for binary disease outcomes using functional data analysis methods.

PubMed

Cao, Ying; Rajan, Suja S; Wei, Peng

2016-12-01

A Mendelian randomization (MR) analysis is performed to analyze the causal effect of an exposure variable on a disease outcome in observational studies, by using genetic variants that affect the disease outcome only through the exposure variable. This method has recently gained popularity among epidemiologists given the success of genetic association studies. Many exposure variables of interest in epidemiological studies are time varying, for example, body mass index (BMI). Although longitudinal data have been collected in many cohort studies, current MR studies only use one measurement of a time-varying exposure variable, which cannot adequately capture the long-term time-varying information. We propose using the functional principal component analysis method to recover the underlying individual trajectory of the time-varying exposure from the sparsely and irregularly observed longitudinal data, and then conduct MR analysis using the recovered curves. We further propose two MR analysis methods. The first assumes a cumulative effect of the time-varying exposure variable on the disease risk, while the second assumes a time-varying genetic effect and employs functional regression models. We focus on statistical testing for a causal effect. Our simulation studies mimicking the real data show that the proposed functional data analysis based methods incorporating longitudinal data have substantial power gains compared to standard MR analysis using only one measurement. We used the Framingham Heart Study data to demonstrate the promising performance of the new methods as well as inconsistent results produced by the standard MR analysis that relies on a single measurement of the exposure at some arbitrary time point. © 2016 WILEY PERIODICALS, INC.

Fullerenols as a new therapeutic approach in nanomedicine.

PubMed

Grebowski, Jacek; Kazmierska, Paulina; Krokosz, Anita

2013-01-01

Recently, much attention has been paid to the bioactive properties of water-soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics. Anthracycline therapy, in spite of its effective antitumor activity, induces systemic oxidative stress, which interferes with the effectiveness of the treatment and results in serious side effects. Fullerenols may counteract the harmful effects of anthracyclines by scavenging free radicals and thereby improve the effects of chemotherapy. Additionally, due to the hollow spherical shape, fullerenols may be used as drug carriers. Moreover, because of the existence of the currently ineffective ways for neurodegenerative diseases treatment, alternative compounds, which could prevent the negative effects of oxidative stress in the brain, are still sought. In the search of alternative methods of treatment and diagnosis, today's science is increasingly reaching for tools in the field of nanomedicine, for example, fullerenes and their water-soluble derivatives, which is addressed in the present paper.

Meganucleases and Other Tools for Targeted Genome Engineering: Perspectives and Challenges for Gene Therapy

PubMed Central

Silva, George; Poirot, Laurent; Galetto, Roman; Smith, Julianne; Montoya, Guillermo; Duchateau, Philippe; Pâques, Frédéric

2011-01-01

The importance of safer approaches for gene therapy has been underscored by a series of severe adverse events (SAEs) observed in patients involved in clinical trials for Severe Combined Immune Deficiency Disease (SCID) and Chromic Granulomatous Disease (CGD). While a new generation of viral vectors is in the process of replacing the classical gamma-retrovirus–based approach, a number of strategies have emerged based on non-viral vectorization and/or targeted insertion aimed at achieving safer gene transfer. Currently, these methods display lower efficacies than viral transduction although many of them can yield more than 1% engineered cells in vitro. Nuclease-based approaches, wherein an endonuclease is used to trigger site-specific genome editing, can significantly increase the percentage of targeted cells. These methods therefore provide a real alternative to classical gene transfer as well as gene editing. However, the first endonuclease to be in clinic today is not used for gene transfer, but to inactivate a gene (CCR5) required for HIV infection. Here, we review these alternative approaches, with a special emphasis on meganucleases, a family of naturally occurring rare-cutting endonucleases, and speculate on their current and future potential. PMID:21182466

Fullerenols as a New Therapeutic Approach in Nanomedicine

PubMed Central

2013-01-01

Recently, much attention has been paid to the bioactive properties of water-soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics. Anthracycline therapy, in spite of its effective antitumor activity, induces systemic oxidative stress, which interferes with the effectiveness of the treatment and results in serious side effects. Fullerenols may counteract the harmful effects of anthracyclines by scavenging free radicals and thereby improve the effects of chemotherapy. Additionally, due to the hollow spherical shape, fullerenols may be used as drug carriers. Moreover, because of the existence of the currently ineffective ways for neurodegenerative diseases treatment, alternative compounds, which could prevent the negative effects of oxidative stress in the brain, are still sought. In the search of alternative methods of treatment and diagnosis, today's science is increasingly reaching for tools in the field of nanomedicine, for example, fullerenes and their water-soluble derivatives, which is addressed in the present paper. PMID:24222914

Current options and future possibilities for the treatment of dyskinesia and motor fluctuations in Parkinson's disease.

PubMed

Cenci, M A; Ohlin, K E; Odin, P

2011-09-01

Dyskinesia and motor fluctuations affect up to 90% of patients with Parkinson's disease (PD) within ten years of L-DOPA pharmacotherapy, and represent a major challenge to a successful clinical management of this disorder. There are currently two main treatment options for these complications, namely, deep brain electrical stimulation or continuous infusion of dopaminergic agents. The latter is achieved using either subcutaneous apomorphine infusion or enteric L-DOPA delivery. Some patients also benefit from the antidyskinetic effect of amantadine as an adjunct to L-DOPA treatment. Ongoing research in animal models of PD aims at discovering additional, novel treatment options that can either prevent or reverse dyskinesia and motor fluctuations. Alternative methods of continuous L-DOPA delivery (including gene therapy), and pharmacological agents that target nondopaminergic receptor systems are currently under intense experimental scrutiny. Because clinical response profiles show large individual variation in PD, an increased number of treatment options for dyskinesia and motor fluctuations will eventually allow for antiparkinsonian and antidyskinetic therapies to be tailor-made to the needs of different patients and/or PD subtypes.

Waste-handling practices at red meat abattoirs in South Africa.

PubMed

Roberts, Hester; de Jager, Linda; Blight, Geoffrey

2009-02-01

Abattoir waste disposal must be carefully managed because the wastes can be a source of food-borne diseases (Nemerow & Dasgupta Industrial and Hazardous Waste Treatment, p. 284, Van Nostrand Reinhold, New York, 1991; Bradshaw et al. The Treatment and Handling of Wastes, p. 183, The Royal Society, Chapman & Hall, London, 1992). Disposal of food that has been condemned because it is known to be diseased is of particular concern, and this paper looks at current disposal methods for such waste in the light of new scientific developments and waste-management strategies. Questionnaires were presented to management and workers at low- and high-throughput red meat abattoirs in the Free State Province, South Africa to determine current waste-handling procedures for condemned products. The waste-handling practices, almost without exception, did not fully comply with the requirements of the South African Red Meat Regulations of 2004, framed under the Meat Safety Act (Act 40 of 2000). The survey highlighted the need to improve current waste-handling strategies to prevent condemned products from re-entering the food chain and contributing to environmental pollution.

Understanding and meeting injection device needs in multiple sclerosis: a survey of patient attitudes and practices

PubMed Central

Verdun di Cantogno, Elisabetta; Russell, Susan; Snow, Tom

2011-01-01

Background: All established disease-modifying drugs for multiple sclerosis require parenteral administration, which can cause difficulties for some patients, sometimes leading to suboptimal adherence. A new electronic autoinjection device has been designed to address these issues. Methods: Patients with relapsing multiple sclerosis currently receiving subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, or glatiramer acetate completed an online questionnaire (July 4–25, 2008) that surveyed current injection practices, experiences with current injection methods, and impressions and appeal of the new device. Results: In total, 422 patients completed the survey, of whom 44% used autoinjectors, 43% prefilled syringes, and 13% syringes and vials; overall, 66% currently self-injected. Physical and psychological barriers to self-injection included difficulty with injections, needle phobia, and concerns over correct injection technique. Only 40% of respondents were “very satisfied” with their current injection method. The new electronic autoinjector was rated as “very appealing” by 65% of patients. The benefits of the new device included the ability to customize injection settings and to review dosing history. Conclusion: New technologies may help patients overcome physical and psychological barriers to self-injection. The combination of a reliable and flexible autoinjection device with dose-monitoring technology may improve communication between health care professionals and patients, and improve treatment adherence. PMID:21573048

Design and Testing of a Novel, Protective Human-Baited Tent Trap for the Collection of Anthropophilic Disease Vectors

PubMed Central

KRAJACICH, BENJAMIN J.; SLADE, JEREMIAH R.; MULLIGAN, ROBERT T.; LABRECQUE, BRENDAN; KOBYLINSKI, KEVIN C.; GRAY, MEG; KUKLINSKI, WOJTEK S.; BURTON, TIMOTHY A.; SEAMAN, JONATHAN A.; SYLLA, MASSAMBA; FOY, BRIAN D.

2014-01-01

Currently, there exists a deficit of safe, active trapping methods for the collection of host-seeking Anopheles and other disease-causing arthropod vectors. The gold-standard approach for mosquito collection is that of human landing catch (HLC), in which an individual exposes bare skin to possibly infected vectors. Here, we present the development of a new method for mosquito collection, the Infoscitex tent, which uses modern tent materials coupled with a novel trap design. This provides an efficacious, a non-labor-intensive, and a safe method for vector collection. In these initial studies, we found it collected an average of 27.7 Anophelesgambiae s.l. per trap per night in rural villages in southeastern Senegal, and 43.8 Culex group V per trap per night in the semiurban town of Kedougou, Senegal. In direct comparisons with HLC, the tent was not statistically different for collection of Culex quinquefasciatus in crepuscular sampling, but was significantly less efficacious at trapping the highly motile dusk-biter Aedes aegypti. These studies suggest that the Infoscitex tent is a viable and safe alternative to HLC for Anopheles and Culex sampling in areas of high vector-borne disease infection risk. PMID:24605476

Novel Contrast Mechanisms at 3 Tesla and 7 Tesla

PubMed Central

Regatte, Ravinder R.; Schweitzer, Mark E.

2013-01-01

Osteoarthritis (OA) is the most common musculoskeletal degenerative disease, affecting millions of people. Although OA has been considered primarily a cartilage disorder associated with focal cartilage degeneration, it is accompanied by well-known changes in subchondral and trabecular bone, including sclerosis and osteophyte formation. The exact cause of OA initiation and progression remains under debate, but OA typically first affects weightbearing joints such as the knee. Magnetic resonance imaging (MRI) has been recognized as a potential tool for quantitative assessment of cartilage abnormalities due to its excellent soft tissue contrast. Over the last two decades, several new MR biochemical imaging methods have been developed to characterize the disease process and possibly predict the progression of knee OA. These new MR biochemical methods play an important role not only for diagnosis of disease at an early stage, but also for their potential use in monitoring outcome of various drug therapies (success or failure). Recent advances in multicoil radiofrequency technology and high field systems (3 T and above) significantly improve the sensitivity and specificity of imaging studies for the diagnosis of musculoskeletal disorders. The current state-of-the-art MR imaging methods are briefly reviewed for the quantitative biochemical and functional imaging assessment of musculoskeletal systems. PMID:18850506

Multivariate data analysis and machine learning in Alzheimer's disease with a focus on structural magnetic resonance imaging.

PubMed

Falahati, Farshad; Westman, Eric; Simmons, Andrew

2014-01-01

Machine learning algorithms and multivariate data analysis methods have been widely utilized in the field of Alzheimer's disease (AD) research in recent years. Advances in medical imaging and medical image analysis have provided a means to generate and extract valuable neuroimaging information. Automatic classification techniques provide tools to analyze this information and observe inherent disease-related patterns in the data. In particular, these classifiers have been used to discriminate AD patients from healthy control subjects and to predict conversion from mild cognitive impairment to AD. In this paper, recent studies are reviewed that have used machine learning and multivariate analysis in the field of AD research. The main focus is on studies that used structural magnetic resonance imaging (MRI), but studies that included positron emission tomography and cerebrospinal fluid biomarkers in addition to MRI are also considered. A wide variety of materials and methods has been employed in different studies, resulting in a range of different outcomes. Influential factors such as classifiers, feature extraction algorithms, feature selection methods, validation approaches, and cohort properties are reviewed, as well as key MRI-based and multi-modal based studies. Current and future trends are discussed.

Fungal disease detection in plants: Traditional assays, novel diagnostic techniques and biosensors.

PubMed

Ray, Monalisa; Ray, Asit; Dash, Swagatika; Mishra, Abtar; Achary, K Gopinath; Nayak, Sanghamitra; Singh, Shikha

2017-01-15

Fungal diseases in commercially important plants results in a significant reduction in both quality and yield, often leading to the loss of an entire plant. In order to minimize the losses, it is essential to detect and identify the pathogens at an early stage. Early detection and accurate identification of pathogens can control the spread of infection. The present article provides a comprehensive overview of conventional methods, current trends and advances in fungal pathogen detection with an emphasis on biosensors. Traditional techniques are the "gold standard" in fungal detection which relies on symptoms, culture-based, morphological observation and biochemical identifications. In recent times, with the advancement of biotechnology, molecular and immunological approaches have revolutionized fungal disease detection. But the drawback lies in the fact that these methods require specific and expensive equipments. Thus, there is an urgent need for rapid, reliable, sensitive, cost effective and easy to use diagnostic methods for fungal pathogen detection. Biosensors would become a promising and attractive alternative, but they still have to be subjected to some modifications, improvements and proper validation for on-field use. Copyright © 2016 Elsevier B.V. All rights reserved.

Global mapping of infectious disease

PubMed Central

Hay, Simon I.; Battle, Katherine E.; Pigott, David M.; Smith, David L.; Moyes, Catherine L.; Bhatt, Samir; Brownstein, John S.; Collier, Nigel; Myers, Monica F.; George, Dylan B.; Gething, Peter W.

2013-01-01

The primary aim of this review was to evaluate the state of knowledge of the geographical distribution of all infectious diseases of clinical significance to humans. A systematic review was conducted to enumerate cartographic progress, with respect to the data available for mapping and the methods currently applied. The results helped define the minimum information requirements for mapping infectious disease occurrence, and a quantitative framework for assessing the mapping opportunities for all infectious diseases. This revealed that of 355 infectious diseases identified, 174 (49%) have a strong rationale for mapping and of these only 7 (4%) had been comprehensively mapped. A variety of ambitions, such as the quantification of the global burden of infectious disease, international biosurveillance, assessing the likelihood of infectious disease outbreaks and exploring the propensity for infectious disease evolution and emergence, are limited by these omissions. An overview of the factors hindering progress in disease cartography is provided. It is argued that rapid improvement in the landscape of infectious diseases mapping can be made by embracing non-conventional data sources, automation of geo-positioning and mapping procedures enabled by machine learning and information technology, respectively, in addition to harnessing labour of the volunteer ‘cognitive surplus’ through crowdsourcing. PMID:23382431

Estimating comparable English healthcare costs for multiple diseases and unrelated future costs for use in health and public health economic modelling.

PubMed

Briggs, Adam D M; Scarborough, Peter; Wolstenholme, Jane

2018-01-01

Healthcare interventions, and particularly those in public health may affect multiple diseases and significantly prolong life. No consensus currently exists for how to estimate comparable healthcare costs across multiple diseases for use in health and public health cost-effectiveness models. We aim to describe a method for estimating comparable disease specific English healthcare costs as well as future healthcare costs from diseases unrelated to those modelled. We use routine national datasets including programme budgeting data and cost curves from NHS England to estimate annual per person costs for diseases included in the PRIMEtime model as well as age and sex specific costs due to unrelated diseases. The 2013/14 annual cost to NHS England per prevalent case varied between £3,074 for pancreatic cancer and £314 for liver disease. Costs due to unrelated diseases increase with age except for a secondary peak at 30-34 years for women reflecting maternity resource use. The methodology described allows health and public health economic modellers to estimate comparable English healthcare costs for multiple diseases. This facilitates the direct comparison of different health and public health interventions enabling better decision making.