Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

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Srinivas, Nuggehally R

2006-05-01

The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select

Development of disease-specific growth charts in Turner syndrome and Noonan syndrome

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Tsuyoshi Isojima

2017-12-01

Full Text Available Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

Development of disease-specific growth charts in Turner syndrome and Noonan syndrome.

Science.gov (United States)

Isojima, Tsuyoshi; Yokoya, Susumu

2017-12-01

Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

Possible Link between Metabolic Syndrome and Chronic Kidney Disease in the Development of Cardiovascular Disease

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Kosaku Nitta

2011-01-01

Full Text Available Metabolic syndrome (MetS is a clinical syndrome that consists of visceral obesity, dyslipidemia, hypertension, and impaired insulin sensitivity. Although individual components of MetS have been implicated in the development of chronic kidney disease (CKD, few studies have examined the effect of combinations of the components of MetS on the development of CKD and cardiovascular disease (CVD. The prevalence of MetS is increasing worldwide in both developing and developed countries, and early detection and treatment of MetS would be a cost-effective strategy for preventing the development of CKD. Visceral obesity and insulin resistance are two important features of MetS that may be associated with renal damage. Lifestyle modifications, including caloric restriction and exercise, are necessary to treat MetS. Initial antihypertensive therapy should consist of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. An improved understanding of the mechanism responsible for the association between MetS and renal damage should be helpful in determining the treatment regimens directed at cardiovascular and renal protection.

Short-term Evaluation of a Comprehensive Education Program Including Inhaler Training and Disease Management on Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

Yoo, Kwang Ha; Chung, Wou Young; Park, Joo Hun; Hwang, Sung Chul; Kim, Tae Eun; Oh, Min Jung; Kang, Dae Ryong; Rhee, Chin Kook; Yoon, Hyoung Kyu; Kim, Tae Hyung; Kim, Deog Kyeom; Park, Yong Bum; Kim, Sang Ha; Yum, Ho Kee

2017-10-01

Proper education regarding inhaler usage and optimal management of chronic obstructive pulmonary disease (COPD) is essential for effectively treating patients with COPD. This study was conducted to evaluate the effects of a comprehensive education program including inhaler training and COPD management. We enlisted 127 patients with COPD on an outpatient basis at 43 private clinics in Korea. The patients were educated on inhaler usage and disease management for three visits across 2 weeks. Physicians and patients were administered a COPD assessment test (CAT) and questionnaires about the correct usage of inhalers and management of COPD before commencement of this program and after their third visit. The outcomes of 127 COPD patients were analyzed. CAT scores (19.6±12.5 vs. 15.1±12.3) improved significantly after this program (pmanagement and the correct technique for using inhalers than those who did not have improved CAT scores (peducation program including inhaler training and COPD management at a primary care setting improved CAT scores and led to patients' better understanding of COPD management. Copyright©2017. The Korean Academy of Tuberculosis and Respiratory Diseases

Drug development for airway diseases: looking forward

NARCIS (Netherlands)

Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F.

2015-01-01

Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations

Developing a provisional and national renal disease registry for Iran

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Sima Ajami

2015-01-01

Full Text Available Background: Disease registry is a database that includes information about people suffering a special kind of disease. The aim of this study was to first identify and compare the National Renal Disease Registry (NRDR characteristics in some countries with Iran; and second, develop a provisional and NRDR for Iran. Materials and Methods: Retrieval of data of the NRDR was performed by scholars responsible in related agencies, including the Ministry of Health and Medical Education, Renal Disease charity, and data registries in the United States, United Kingdom, Malaysia, and Iran. This research was applied, and the study was descriptive-comparative. The study population consisted of the NRDR in selected countries in which data were collected by forms that were designed according to the study objectives. Sources of data were researchers, articles, books, journals, databases, websites, related documents, and people who are active in this regard, and related agencies, including the Ministry of Health and Medical Education, and patient support charity. The researchers collected data for each country based on the study objectives and then put them in comparative tables. Data were analyzed by descriptive, comparative, and theoretical methods. Results: Most of the renal transplant teams report their own results as a single center experiences. America and Britain have a preeminent national registry of renal disease compared to other countries. Conclusion: Given that control, prevention, and treatment of chronic renal diseases incur high expenses and the disease is one of leading mortality factors in Iran and across the world and since national registry system for chronic renal diseases can provide better tools and strategies to manage and evaluate patients′ characteristics as well as risk factors which eventually leads to making better decisions.

Chronic kidney disease hotspots in developing countries in South Asia.

Science.gov (United States)

Abraham, Georgi; Varughese, Santosh; Thandavan, Thiagarajan; Iyengar, Arpana; Fernando, Edwin; Naqvi, S A Jaffar; Sheriff, Rezvi; Ur-Rashid, Harun; Gopalakrishnan, Natarajan; Kafle, Rishi Kumar

2016-02-01

In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan.

Effect of changes in human ecology and behavior on patterns of sexually transmitted diseases, including human immunodeficiency virus infection.

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Wasserheit, J N

1994-01-01

The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance. For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people. The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990. In both cases, disease patterns shifted from homosexual men to include minority heterosexuals. Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared. Three interrelated types of environments affect STD patterns. The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae. These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors. The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection. These are, therefore, the environments that most directly affect changing disease patterns. Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors. Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns. PMID:8146135

Lung Disease Including Asthma and Adult Vaccination

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... can make it hard to breathe. Certain vaccinepreventable diseases can also increase swelling of your airways and lungs. The combination of the two can lead to pneumonia and other serious respiratory illnesses. Vaccines are one of the safest ways ...

Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis

NARCIS (Netherlands)

Lukas, C.; Landewé, R.; Sieper, J.; Dougados, M.; Davis, J.; Braun, J.; van der Linden, S.; van der Heijde, D.

2009-01-01

To develop a new index for disease activity in ankylosing spondylitis (ASDAS) that is truthful, discriminative and feasible, and includes domains/items that are considered relevant by patients and doctors. Eleven candidate variables covering six domains of disease activity, selected by ASAS experts

Extracellular RNAs: development as biomarkers of human disease

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Joseph F. Quinn

2015-08-01

Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

RNAseq Transcriptional Profiling following Whip Development in Sugarcane Smut Disease.

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Patricia D C Schaker

Full Text Available Sugarcane smut disease is caused by the biotrophic fungus Sporisorium scitamineum. The disease is characterized by the development of a whip-like structure from the primary meristems, where billions of teliospores are produced. Sugarcane smut also causes tillering and low sucrose and high fiber contents, reducing cane productivity. We investigated the biological events contributing to disease symptoms in a smut intermediate-resistant sugarcane genotype by examining the transcriptional profiles (RNAseq shortly after inoculating the plants and immediately after whip emission. The overall picture of disease progression suggests that premature transcriptional reprogramming of the shoot meristem functions continues until the emergence of the whip. The guidance of this altered pattern is potentially primarily related to auxin mobilization in addition to the involvement of other hormonal imbalances. The consequences associated with whip emission are the modulation of typical meristematic functions toward reproductive organ differentiation, requiring strong changes in carbon partitioning and energy production. These changes include the overexpression of genes coding for invertases and trehalose-6P synthase, as well as other enzymes from key metabolic pathways, such as from lignin biosynthesis. This is the first report describing changes in the transcriptional profiles following whip development, providing a hypothetical model and candidate genes to further study sugarcane smut disease progression.

RNAseq Transcriptional Profiling following Whip Development in Sugarcane Smut Disease

Science.gov (United States)

Taniguti, Lucas M.; Peters, Leila P.; Creste, Silvana; Aitken, Karen S.; Van Sluys, Marie-Anne; Kitajima, João P.; Vieira, Maria L. C.; Monteiro-Vitorello, Claudia B.

2016-01-01

Sugarcane smut disease is caused by the biotrophic fungus Sporisorium scitamineum. The disease is characterized by the development of a whip-like structure from the primary meristems, where billions of teliospores are produced. Sugarcane smut also causes tillering and low sucrose and high fiber contents, reducing cane productivity. We investigated the biological events contributing to disease symptoms in a smut intermediate-resistant sugarcane genotype by examining the transcriptional profiles (RNAseq) shortly after inoculating the plants and immediately after whip emission. The overall picture of disease progression suggests that premature transcriptional reprogramming of the shoot meristem functions continues until the emergence of the whip. The guidance of this altered pattern is potentially primarily related to auxin mobilization in addition to the involvement of other hormonal imbalances. The consequences associated with whip emission are the modulation of typical meristematic functions toward reproductive organ differentiation, requiring strong changes in carbon partitioning and energy production. These changes include the overexpression of genes coding for invertases and trehalose-6P synthase, as well as other enzymes from key metabolic pathways, such as from lignin biosynthesis. This is the first report describing changes in the transcriptional profiles following whip development, providing a hypothetical model and candidate genes to further study sugarcane smut disease progression. PMID:27583836

The basics of preclinical drug development for neurodegenerative disease indications.

Science.gov (United States)

Steinmetz, Karen L; Spack, Edward G

2009-06-12

Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): a clinicoradiological profile of three cases including two with skeletal disease

International Nuclear Information System (INIS)

Gupta, Priya; Babyn, Paul

2008-01-01

Originally described as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. A rare entity, RDD is often under-diagnosed because of a low index of suspicion by both radiologist and pathologist. Through this article, we wish to apprise radiologists of the spectrum of disease that can be encountered in this disorder. RDD can mimic other common childhood skeletal diseases including benign Langerhans cell histiocytosis and lymphoma. The clinical and radiological manifestations of RDD vary depending upon organ involvement, and its imaging features are often confused with those of other disorders. RDD should be considered in the differential diagnosis of unifocal and multifocal skeletal involvement caused by granulomatous diseases, infections, pseudogranulomatous lesions and malignancy. As long-term outcome is usually good, a conservative approach is justified in most cases. Contrasted with its typical appearance, presenting with bilateral symmetrical cervical adenopathy (as shown in one patient), we also report extranodal involvement of bone in two patients. Extranodal disease occurs along with concomitant nodal disease in about 43% of patients. In 23% of patients, isolated extranodal RDD can be seen, most commonly in the head and neck. In two of our patients, we observed extranodal involvement with skeletal involvement away from the head and neck not associated with lymphadenopathy. Skeletal involvement in RDD without lymphadenopathy is rare, occurring only in 2% of all the patients reported to date. (orig.)

The disease related deaths due to differentiated thyroid carcinomas treated multidisciplinary, including radioiodine

International Nuclear Information System (INIS)

Stefanovic, Lj.; Kermeci, K.; Malesevic, M.; Mihailovic, J.; Srbovan, D.; Popadic, S.

2002-01-01

Aim: To analyse the disease related deaths of differentiated thyroid carcinoma (DTC) patients treated multidisciplinary, including radioiodine. Patients and Methods: 364 DTC patients were treated from 1977 to the end of 2000. All patients were operated, treated by radioiodine and by hormonal therapy, external radiotherapy was applied in 22 and chemotherapy in 6 of them. 54 treated patients were lost from the follow-up. The course of disease and outcomes are known in 310 patients, among them 53 patients died. The disease related deaths occurred in 33 (10.6%) patients. Results: Between 33 patients whose deaths were in relation with DTC the disease progression was the cause of deaths in 30 (9.7% of treated) patients (the locoregional disease in 10, distant metastases /M1/ in 17, locoregional disease + M1 in 3 patients). From the late complications of treatment died 3 (1%) patients (all of them were in complete remission to the deaths). The mean survival of these 33 patients from the diagnosis to the end of the life was 6.9 years, median 5.1 years, range 2 months to 23.9 years. The five years survived 54.6% of them, 10 years 21.2% and more than 20 years 3%. M1 had 72.7% of patients (lung and/or bone M1 were present in 91.7% of them), N1 had 69.7% and in 30.3% local tumor was T4. In relation to all treated patients died 14.6% men compared to 9% women (p<0.05), 15.7% of patients 45 years old or older compared to 4.4% of younger then 45 years (p<0.001) and 21.3% of patients with follicular type of DTC compared to 7.3% with papillary type (p<0.001). From all patients without radioiodine accumulation in tumor tissue died 60%. Conclusion: The DTC related deaths were the consequence of M1 and less frequently the result of locoregional disease (T4 and/or N1) in about 1/10 of all treated patients. The deaths as result of the late complications of treatment were exceptional. The deaths were significantly more frequent between males, patients 45 years old or older and patients

Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics.

Science.gov (United States)

Weber, Kathryn T; Jacobsen, Timothy D; Maidhof, Robert; Virojanapa, Justin; Overby, Chris; Bloom, Ona; Quraishi, Shaheda; Levine, Mitchell; Chahine, Nadeen O

2015-03-01

Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repair, biomaterials, and tissue engineering. Findings on the effects of the omega-6 fatty acid, linoleic acid, on nucleus pulposus tissue engineering are presented. Studies described in this review provide greater insights into the pathogenesis of disc degeneration and may define new paradigms for early or differential diagnostics of degeneration using new techniques such as systemic biomarkers. In addition, research on the mechanobiology of disease enriches the development of therapeutics for disc repair, with potential to diminish pain and disability associated with disc degeneration.

The burden of non communicable diseases in developing countries

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Boutayeb Abdesslam

2005-01-01

Full Text Available Abstract Background By the dawn of the third millennium, non communicable diseases are sweeping the entire globe, with an increasing trend in developing countries where, the transition imposes more constraints to deal with the double burden of infective and non-infective diseases in a poor environment characterised by ill-health systems. By 2020, it is predicted that these diseases will be causing seven out of every 10 deaths in developing countries. Many of the non communicable diseases can be prevented by tackling associated risk factors. Methods Data from national registries and international organisms are collected, compared and analyzed. The focus is made on the growing burden of non communicable diseases in developing countries. Results Among non communicable diseases, special attention is devoted to cardiovascular diseases, diabetes, cancer and chronic pulmonary diseases. Their burden is affecting countries worldwide but with a growing trend in developing countries. Preventive strategies must take into account the growing trend of risk factors correlated to these diseases. Conclusion Non communicable diseases are more and more prevalent in developing countries where they double the burden of infective diseases. If the present trend is maintained, the health systems in low-and middle-income countries will be unable to support the burden of disease. Prominent causes for heart disease, diabetes, cancer and pulmonary diseases can be prevented but urgent (preventive actions are needed and efficient strategies should deal seriously with risk factors like smoking, alcohol, physical inactivity and western diet.

Drugs in development for Parkinson's disease: an update.

Science.gov (United States)

Johnston, Tom H; Brotchie, Jonathan M

2006-01-01

The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.

Extracellular matrix in lung development, homeostasis and disease.

Science.gov (United States)

Zhou, Yong; Horowitz, Jeffrey C; Naba, Alexandra; Ambalavanan, Namasivayam; Atabai, Kamran; Balestrini, Jenna; Bitterman, Peter B; Corley, Richard A; Ding, Bi-Sen; Engler, Adam J; Hansen, Kirk C; Hagood, James S; Kheradmand, Farrah; Lin, Qing S; Neptune, Enid; Niklason, Laura; Ortiz, Luis A; Parks, William C; Tschumperlin, Daniel J; White, Eric S; Chapman, Harold A; Thannickal, Victor J

2018-03-08

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases. Copyright © 2017. Published by Elsevier B.V.

Broader prevalence of Wolbachia in insects including potential human disease vectors.

Science.gov (United States)

de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

2015-06-01

Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

The basics of preclinical drug development for neurodegenerative disease indications

Directory of Open Access Journals (Sweden)

Spack Edward G

2009-06-01

Full Text Available Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s. Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot

Modeling congenital disease and inborn errors of development in Drosophila melanogaster

Science.gov (United States)

Moulton, Matthew J.; Letsou, Anthea

2016-01-01

ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

Early life influences on the development of chronic obstructive pulmonary disease.

Science.gov (United States)

Stocks, Janet; Sonnappa, Samatha

2013-06-01

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.

Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development

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Matthew K. Ross

2014-01-01

Full Text Available Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.

Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development.

Science.gov (United States)

Ross, Matthew K; Matthews, Anberitha T; Mangum, Lee C

Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.

Developing and evaluating polygenic risk prediction models for stratified disease prevention.

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Chatterjee, Nilanjan; Shi, Jianxin; García-Closas, Montserrat

2016-07-01

Knowledge of genetics and its implications for human health is rapidly evolving in accordance with recent events, such as discoveries of large numbers of disease susceptibility loci from genome-wide association studies, the US Supreme Court ruling of the non-patentability of human genes, and the development of a regulatory framework for commercial genetic tests. In anticipation of the increasing relevance of genetic testing for the assessment of disease risks, this Review provides a summary of the methodologies used for building, evaluating and applying risk prediction models that include information from genetic testing and environmental risk factors. Potential applications of models for primary and secondary disease prevention are illustrated through several case studies, and future challenges and opportunities are discussed.

The ATM signaling network in development and disease

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Stracker, Travis H.; Roig, Ignasi; Knobel, Philip A.; Marjanović, Marko

2013-01-01

The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability (Stracker and Petrini, 2011; McKinnon, 2012). Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia mutated (ATM) kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease. PMID:23532176

The ATM signaling network in development and disease

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Travis H. Stracker

2013-03-01

Full Text Available The DNA damage response (DDR rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism and cell fate decisions, such as apoptosis or senescence(Jackson and Bartek, 2009. DNA double-strand breaks (DSBs represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability(Stracker and Petrini, 2011;McKinnon, 2012. Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system (CNS, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ATM kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease.

Neuromuscular rate of force development deficit in Parkinson disease.

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Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

2017-06-01

Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

Crowdfunding drug development: the state of play in oncology and rare diseases.

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Dragojlovic, Nick; Lynd, Larry D

2014-11-01

In this article, we present descriptive data on 125 crowdfunding campaigns aimed at financing research in oncology (including basic research, drug discovery, and clinical trials). We also describe five campaigns that have succeeded in raising substantial funds to support the development of treatments for ultrarare diseases. The data suggest that crowdfunding is a viable approach to supporting early proof-of-concept research that could allow researchers in oncology and rare diseases to succeed in traditional grant competitions or to attract private investment. The data also suggest that such an approach could become a valuable additional source of funding for early-stage innovators in the drug development arena. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multisystem Disease, Including Eosinophilia and Progressive Hyper-Creatine-Kinase-emia over 10 Years, Suggests Mitochondrial Disorder

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Josef Finsterer

2017-04-01

Full Text Available Background: Eosinophilia has not been reported as a manifestation of a mitochondrial disorder (MID. Here, we report a patient with clinical features suggesting a MID and permanent eosinophilia, multisystem disease, and progressive hyper-creatine-kinase (CK-emia for at least 10 years. Materials and Methods: Methods applied included a clinical exam, blood chemical investigations, electrophysiological investigations, imaging, and invasive cardiological investigations. The patient was repeatedly followed up over several years. He required replacement cardiac surgery. Results: In a 57-year-old male, eosinophilia was first detected at the age of 44 years and has remained almost constantly present until today. In addition to eosinophilia, he developed progressive hyper-CK-emia at the age of 47 years. His history was further positive for hepatopathy, hyperlipidemia, hypothyroidism, renal insufficiency, spontaneous Achilles tendon rupture, double vision, exercise intolerance, muscle aching, mild hypoacusis, sensory neuropathy, seizures, and mitral insufficiency/stenosis requiring valve replacement therapy, oral anticoagulation, and pacemaker implantation. Based on the multisystem nature of his abnormalities and permanent hyper-CK-emia, a MID was suspected. Conclusion: Eosinophilia can be associated with a MID with myopathy, possibly as a reaction to myofiber necrosis. If eosinophilia is associated with progressive hyper-CK-emia and multisystem disease, a MID should be suspected.

Multiple factors, including non-motor impairments, influence decision making with regard to exercise participation in Parkinson's disease: a qualitative enquiry.

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O'Brien, Christine; Clemson, Lindy; Canning, Colleen G

2016-01-01

To explore how the meaning of exercise and other factors interact and influence the exercise behaviour of individuals with Parkinson's disease (PD) enrolled in a 6-month minimally supervised exercise program to prevent falls, regardless of whether they completed the prescribed exercise or not. This qualitative study utilised in-depth semi-structured interviews analysed using grounded theory methodology. Four main themes were constructed from the data: adapting to change and loss, the influence of others, making sense of the exercise experience and hope for a more active future. Participation in the PD-specific physiotherapy program involving group exercise provided an opportunity for participants to reframe their identity of their "active" self. Three new influences on exercise participation were identified and explored: non-motor impairments of apathy and fatigue, the belief in a finite energy quota, and the importance of feedback. A model was developed incorporating the themes and influences to explain decision-making for exercise participation in this group. Complex and interacting issues, including non-motor impairments, need to be considered in order to enhance the development and ongoing implementation of effective exercise programmes for people with PD. Exercise participation can assist individuals to reframe their identity as they are faced with losses associated with Parkinson's disease and ageing. Non-motor impairments of apathy and fatigue may influence exercise participation in people with Parkinson's disease. Particular attention needs to be paid to the provision of feedback in exercise programs for people with Parkinson's disease as it important for their decision-making about continuing exercise.

Fibre intake and the development of inflammatory bowel disease

DEFF Research Database (Denmark)

Andersen, Vibeke; Chan, Simon; Luben, Robert

2018-01-01

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large...... for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed. Results: In total, 104 and 221 participants developed incident CD...

The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases.

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Janegova, Andrea; Janega, Pavol; Rychly, Boris; Kuracinova, Kristina; Babal, Pavel

2015-01-01

Autoimmune thyroid diseases, including Graves' and Hashimoto's thyroiditis, are the most frequent autoimmune disorders. Viral infection, including Epstein-Barr virus (EBV), is one of the most frequently considered environmental factors involved in autoimmunity. Its role in the development of AITD has not been confirmed so far. Surgical specimens of Graves' and Hashimoto's diseases and nodular goitres were included in the study. The expression of EBV latent membrane protein 1 (LMP1) was analysed by immunohistochemistry, with the parallel detection of virus-encoded small nuclear non-polyadenylated RNAs (EBER) by in situ hybridisation. In none of the Graves' disease specimens but in 34.5% of Hashimoto's thyroiditis cases the cytoplasmic expression of LMP1 was detected in follicular epithelial cells and in infiltrating lymphocytes. EBER nuclear expression was detected in 80.7% of Hashimoto's thyroiditis cases and 62.5% of Graves' disease cases, with positive correlation between LMP1 and EBER positivity in all Hashimoto's thyroiditis LMP1-positive cases. We assume that high prevalence of EBV infection in cases of Hashimoto's and Graves' diseases imply a potential aetiological role of EBV in autoimmune thyroiditis. The initiation of autoimmune thyroiditis could start with EBV latency type III infection of follicular epithelium characterised by LMP1 expression involving the production of inflammatory mediators leading to recruitment of lymphocytes. The EBV positivity of the infiltrating lymphocytes could be only the presentation of a carrier state, but in cases with EBER+/ LMP1+ lymphocytes (transforming latent infection) it could represent a negative prognostic marker pointing to a higher risk of primary thyroid lymphoma development.

Poverty-related and neglected diseases - an economic and epidemiological analysis of poverty relatedness and neglect in research and development.

Science.gov (United States)

von Philipsborn, Peter; Steinbeis, Fridolin; Bender, Max E; Regmi, Sadie; Tinnemann, Peter

2015-01-01

Economic growth in low- and middle-income countries (LMIC) has raised interest in how disease burden patterns are related to economic development. Meanwhile, poverty-related diseases are considered to be neglected in terms of research and development (R&D). Developing intuitive and meaningful metrics to measure how different diseases are related to poverty and neglected in the current R&D system. We measured how diseases are related to economic development with the income relation factor (IRF), defined by the ratio of disability-adjusted life-years (DALYs) per 100,000 inhabitants in LMIC versus that in high-income countries. We calculated the IRF for 291 diseases and injuries and 67 risk factors included in the Global Burden of Disease Study 2010. We measured neglect in R&D with the neglect factor (NF), defined by the ratio of disease burden in DALYs (as percentage of the total global disease burden) and R&D expenditure (as percentage of total global health-related R&D expenditure) for 26 diseases. The disease burden varies considerably with the level of economic development, shown by the IRF (median: 1.38; interquartile range (IQR): 0.79-6.3). Comparison of IRFs from 1990 to 2010 highlights general patterns of the global epidemiological transition. The 26 poverty-related diseases included in our analysis of neglect in R&D are responsible for 13.8% of the global disease burden, but receive only 1.34% of global health-related R&D expenditure. Within this group, the NF varies considerably (median: 19; IQR: 6-52). The IRF is an intuitive and meaningful metric to highlight shifts in global disease burden patterns. A large shortfall exists in global R&D spending for poverty-related and neglected diseases, with strong variations between diseases.

Global stability for infectious disease models that include immigration of infected individuals and delay in the incidence

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Chelsea Uggenti

2018-03-01

Full Text Available We begin with a detailed study of a delayed SI model of disease transmission with immigration into both classes. The incidence function allows for a nonlinear dependence on the infected population, including mass action and saturating incidence as special cases. Due to the immigration of infectives, there is no disease-free equilibrium and hence no basic reproduction number. We show there is a unique endemic equilibrium and that this equilibrium is globally asymptotically stable for all parameter values. The results include vector-style delay and latency-style delay. Next, we show that previous global stability results for an SEI model and an SVI model that include immigration of infectives and non-linear incidence but not delay can be extended to systems with vector-style delay and latency-style delay.

Clinicopathological review of immunohistochemically defined Kikuchi-Fujimoto disease-including some interesting cases.

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Seong, Gil Myeong; Kim, Jo-Heon; Lim, Gil Chai; Kim, Jinseok

2012-10-01

Kikuchi-Fujimoto Disease (KFD) is a benign, self-limited disease characterized by tender regional lymphadenopathy with fever. KFD remains a poorly defined disease, and no clear diagnostic criteria are available. Here, we assess the clinical, laboratory, and histopathologic findings of KFD cases and report two unusual cases. Forty KFD patients that underwent lymph node (LN) biopsy and diagnosed by immunohistochemical staining, from January 2003 to November 2010, were enrolled in this retrospective study. The patients had a mean age of 29.3 years, and 29 (72.5 %) were women. Affected LNs were mainly located unilaterally in the cervical area. Mean LN size was 15.3 mm. Twenty-eight (70 %) patients had LN tenderness, and 25 (62.5 %) patients had fever. Leukopenia was observed in 18 of 35 evaluable patients. C-reactive protein and erythrocyte sedimentation rate were elevated in most patients. Anti-nuclear antibody was positive in four of 19 evaluable patients, but all had been diagnosed with concurrent systemic lupus erythematosus. Histologically, the 40 cases were classified into three types, that is, as proliferative (37.5 %), necrotizing (55.0 %), or xanthomatous (7.5 %). Interesting cases: Case 1 was a 35-year-old female with KFD and uveitis, retinal vasculitis, and superior sagittal sinus thrombosis. Case 2 was a 47-year-old male with KFD and bone marrow involvement and presented with severe bicytopenia. Although KFD is an uncommon self-limited benign disorder, it must be included in the differential diagnosis of lymphadenopathy with fever and cytopenia. It is important that the clinical features of KFD be understood to reach a correct diagnosis.

The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

Science.gov (United States)

Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

2016-08-01

Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

Hip and pelvis diseases on lumbar AP radiographs including both hip joints

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Lim, Hyun Soo; Juhng, Seon Kwan; Kim, Eun A; Kim, Jeong Ho; Song, Ha Heon; Shim, Dae Moo [Wonkwang University School of Medicine, Iksan (Korea, Republic of)

2002-12-01

To determine the frequency of disease, and to evaluate the methods used for lumbar spine radiography in Korea. Sixty university and training hospitals were randomly selected and asked to describe the projections, film size and radiographic techniques employed for routine radiography in patients with suspected disease of the lumbar spine. Plain radiographs of 1215 patients, taken using 14x17 inch film and depicting both hip joints and the lumbar region, were analysed between March 1999 and February 2000. In 15 patients (1.2%), the radiographs revealed hip or pelvic lesion, confirmed as follows: avascular necrosis of the femoral head (n=11, with bilateral lesion in four cases); sustained ankylosing spondylitis (n=2); acetabular dysplasia (n=1); and insufficiency fracture of the pubic rami secondary to osteoporosis (n=1). In 11 or the 20 hospitals which responded, 14{sup x}17{sup f}ilm was being used for lumbar radiography, while in the other nine, film size was smaller. Plain radiography of the lumbar spine including both hip joints, may be a useful way to simultaneously evaluate lesions not only of the lumbar spine but also of the hip and/or pelvis.

Orphan drugs in development for Huntington's disease: challenges and progress

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Burgunder JM

2015-02-01

Full Text Available Jean-Marc Burgunder1–4 1Swiss Huntington’s Disease Centre, Department of Neurology, University of Bern, Bern, Switzerland; 2Department of Neurology, West China Hospital, Sichuan University, Chengdu, 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, 4Department of Neurology, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Huntington’s disease is a monogenic disorder encompassing a variable phenotype with progressive cognitive, psychiatric, and movement disorders. Knowledge of the mechanisms involved in this disorder has made substantial advances since the discovery of the gene mutation. The dynamic mutation is the expansion of a CAG (cytosine-adenine-guanine repeat in the huntingtin (HTT gene, which is transcribed into an abnormal protein with an elongated polyglutamine tract. Polyglutamine HTT accumulates and is changed in its function in multifaceted ways related to the numerous roles of the normal protein. The protein is expressed in numerous areas of the brain and also in other organs. The major brain region involved in the disease process is the striatum, but it is clear that other systems are involved as well. This accumulated knowledge has now led to the development of treatment strategies based on specific molecular pathways for symptomatic and disease course-modifying treatment. The most proximal way to handle the disturbed protein is to hinder the gene transcription, translation, and/or to increase protein clearance. Other mechanisms now being approached include modulation of energy and intracellular signaling, induction of factors potentially leading to neuroprotection, as well as modulation of glial function. Several clinical trials based on these approaches are now under way, and it is becoming clear that a future disease-modifying therapy will be a combination of several approaches harmonized with symptomatic treatments. In this review, some of the most promising and

The commensal microbiota and the development of human disease - an introduction.

Science.gov (United States)

Marsh, Philip D

2015-01-01

Humans have co-evolved with microorganisms, and both exist in a symbiotic or mutualistic relationship. We are colonised by a diverse, resident microbiota, which develop into structurally and functionally organised biofilms. The resident microorganisms gain a secure, warm, nutritious habitat from the host and, in return, contribute to the development of many important host functions. The resident microbiota of each habitat is natural and provides important benefits for the host including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and prevention of colonisation by exogenous microbes. The biological properties of each habitat determine which microorganisms can colonise and grow, and dictate which will be major or minor components of the resident microbiota of a site. This results in different surfaces having distinct but characteristic microbiotas. This relationship between the resident microbiota and the host is dynamic and, on occasions, this symbiotic relationship breaks down due to, for example, changes in lifestyle, immune status or following broad spectrum antibiotic therapy. This 'dysbiosis' can result in previously minor components of the microbiota out-competing the normally dominant and beneficial bacteria, thereby increasing the risk of disease. Such perturbations have been associated with a number of clinical disorders such as obesity, allergy, and a variety of inflammatory diseases, including periodontal diseases. A better understanding of the delicate balance between the host and its resident microbiota could lead to novel approaches to the promotion of health and the prevention of dysbiosis.

Developing novel blood-based biomarkers for Alzheimer's disease

DEFF Research Database (Denmark)

Snyder, Heather M; Carrillo, Maria C; Grodstein, Francine

2014-01-01

Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue...... of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant...

More appropriate disease control policies for the developing world : policy and trade issues

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J.C. Mariner

2009-09-01

Full Text Available Investment in disease control should be targeted to critical points that provide the greatest benefit to the livelihoods of livestock-dependent stakeholders. Risk-based targeting should balance the impacts of diseases against the feasibility of their control. This requires sensitive and specific surveillance systems that provide representative overviews of the animal health situation for accurate assessment of disease impact and transmission patterns. Assessment of impact should include household and market effects. The key in surveillance is involving livestock owners using active methods that ensure their disease priorities are addressed. Epidemiological targeting of interventions to critical points in disease transmission cycles should be done to obtain maximal disease reduction. Interventions should be delivered in full partnership with both private and community-based stakeholders to assure high uptake and sustainability. In developing countries, approaches such as participatory disease surveillance and community-based animal health programs have been effective and comply with international animal health standards.

Upregulation of Mir-21 Levels in the Vitreous Humor Is Associated with Development of Proliferative Vitreoretinal Disease.

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Ayumi Usui-Ouchi

Full Text Available MicroRNAs (miRNAs are small noncoding RNAs that regulate gene expression by post-transcriptional inhibition of mRNA translation. Dysregulation of miRNAs, including circulating miRNAs, has been reported to play an important role in the development of various diseases, including fibrotic diseases. Aberrant expression of miRNAs in the vitreous humor of vitreoretinal diseased eyes has been reported. However, the expression pattern of miRNAs present in the vitreous humor of proliferative vitreoretinal disease (PVD patients, including proliferative diabetic retinopathy (PDR, and proliferative vitreoretinopathy (PVR, remains unknown. To investigate the factors important for the development of PVD, we characterized the miRNAs present in the vitreous humor of PVD patients and analyzed the expression profiles of 377 miRNAs using quantitative polymerase chain reaction-based miRNA arrays. The expression of a specific subset of miRNAs, previously reported to be associated with the development of angiogenesis and fibrosis, was significantly altered in the vitreous of PVD patients. Among these miRNAs, we identified miR-21 as a candidate fibrotic miRNA with an important role in the pathogenesis of PVD. Increased miR-21 levels in the vitreous were associated with retinal fibrosis, including PVR and PDR. Because epithelial-mesenchymal transition (EMT of retinal pigment epithelial cells (RPECs plays a critical role in retinal fibrosis, the expression of miR-21 in human RPECs was determined. Its expression in RPECs was induced by transforming growth factor-β, a key growth factor involved in fibrogenesis, and was enhanced by high glucose culture conditions, suggesting that miR-21 expression positively correlates with disease progression. Gain- and loss-of-function studies revealed that miR-21 promoted cell proliferation and migration of ARPE-19 cells without affecting EMT-related gene expression. Together, our studies have identified miR-21 as a potential disease

Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease

NARCIS (Netherlands)

Lenferink, Anke; Brusse-Keizer, Marjolein; van der Valk, Paul D.L.P.M.; Frith, Peter A.; Zwerink, Marlies; Monninkhof, Evelyn M.; van der Palen, Job; Effing-Tijdhof, Tanja W

2017-01-01

Background: Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease.

Personality traits and chronic disease: implications for adult personality development.

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Sutin, Angelina R; Zonderman, Alan B; Ferrucci, Luigi; Terracciano, Antonio

2013-11-01

Personality traits have been associated with chronic disease. Less is known about the longitudinal relation between personality and disease and whether chronic disease is associated with changes in personality. Method. Participants from the Baltimore Longitudinal Study of Aging (N = 2,008) completed the Revised NEO Personality Inventory and a standard medical interview at regularly scheduled visits; the Charlson Comorbidity Index, a weighted sum of 19 serious diseases, was derived from this interview. Using data from 6,685 visits, we tested whether personality increased risk of disease and whether disease was associated with personality change. Measured concurrently, neuroticism and conscientiousness were associated with greater disease burden. The impulsiveness facet of neuroticism was the strongest predictor of developing disease across the follow-up period: For every standard deviation increase in impulsiveness, there was a 26% increased risk of developing disease and a 36% increased risk of getting more ill. Personality traits changed only modestly with disease: As participants developed chronic illnesses, they became more conservative (decreased openness). Discussion. This research indicates that personality traits confer risk for disease, in part, through health-risk behaviors. These traits, however, were relatively resistant to the effect of serious disease.

The dentate nucleus in children: normal development and patterns of disease

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McErlean, Aoife; Abdalla, Khaled; Donoghue, Veronica; Ryan, Stephanie [Children' s University Hospital, Radiology Department, Dublin (Ireland)

2010-03-15

The dentate nuclei lie deep within the cerebellum and play a vital role in the pathways involved in fine motor control and coordination. They are susceptible to a variety of diseases. Some pathological processes preferentially affect the dentate nuclei, while concomitant basal ganglia or white matter involvement can be a striking finding in others. A familiarity with the normal appearance of the dentate nuclei at different ages in combination with the radiological distribution of pathology in the brain allows the paediatric radiologist to develop a logical approach to the interpretation of MR imaging of these deep cerebellar nuclei. In this article we review the normal appearance and MR features of the dentate nuclei, including changes that are seen with myelination. We describe the specific imaging characteristics of childhood diseases that involve the dentate nuclei, and develop a systematic approach to the differential diagnosis of dentate nucleus abnormalities on MR imaging. (orig.)

The dentate nucleus in children: normal development and patterns of disease

International Nuclear Information System (INIS)

McErlean, Aoife; Abdalla, Khaled; Donoghue, Veronica; Ryan, Stephanie

2010-01-01

The dentate nuclei lie deep within the cerebellum and play a vital role in the pathways involved in fine motor control and coordination. They are susceptible to a variety of diseases. Some pathological processes preferentially affect the dentate nuclei, while concomitant basal ganglia or white matter involvement can be a striking finding in others. A familiarity with the normal appearance of the dentate nuclei at different ages in combination with the radiological distribution of pathology in the brain allows the paediatric radiologist to develop a logical approach to the interpretation of MR imaging of these deep cerebellar nuclei. In this article we review the normal appearance and MR features of the dentate nuclei, including changes that are seen with myelination. We describe the specific imaging characteristics of childhood diseases that involve the dentate nuclei, and develop a systematic approach to the differential diagnosis of dentate nucleus abnormalities on MR imaging. (orig.)

[An early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development].

Science.gov (United States)

Abe, Koji

2018-03-28

The present review focuses an early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development. In relation to foreign previous reports, five topics are introduced and discussed on ALS with dementia, ALS/Parkinsonism dementia complex (ALS/PDC), familial ALS (FALS), spinal bulbar muscular atrophy (SBMA), and multisystem involvement especially in cerebellar system of ALS including ALS/SCA (spinocerebellar ataxia) crossroad mutation Asidan. This review found the great contribution of Japanese reports on the above five topics, and confirmed the great development of ALS-related diseases over the past 120 years.

[Development of expert diagnostic system for common respiratory diseases].

Science.gov (United States)

Xu, Wei-hua; Chen, You-ling; Yan, Zheng

2014-03-01

To develop an internet-based expert diagnostic system for common respiratory diseases. SaaS system was used to build architecture; pattern of forward reasoning was applied for inference engine design; ASP.NET with C# from the tool pack of Microsoft Visual Studio 2005 was used for website-interview medical expert system.The database of the system was constructed with Microsoft SQL Server 2005. The developed expert system contained large data memory and high efficient function of data interview and data analysis for diagnosis of various diseases.The users were able to perform this system to obtain diagnosis for common respiratory diseases via internet. The developed expert system may be used for internet-based diagnosis of various respiratory diseases,particularly in telemedicine setting.

Poverty-related and neglected diseases – an economic and epidemiological analysis of poverty relatedness and neglect in research and development

Science.gov (United States)

von Philipsborn, Peter; Steinbeis, Fridolin; Bender, Max E.; Regmi, Sadie; Tinnemann, Peter

2015-01-01

Background Economic growth in low- and middle-income countries (LMIC) has raised interest in how disease burden patterns are related to economic development. Meanwhile, poverty-related diseases are considered to be neglected in terms of research and development (R&D). Objectives Developing intuitive and meaningful metrics to measure how different diseases are related to poverty and neglected in the current R&D system. Design We measured how diseases are related to economic development with the income relation factor (IRF), defined by the ratio of disability-adjusted life-years (DALYs) per 100,000 inhabitants in LMIC versus that in high-income countries. We calculated the IRF for 291 diseases and injuries and 67 risk factors included in the Global Burden of Disease Study 2010. We measured neglect in R&D with the neglect factor (NF), defined by the ratio of disease burden in DALYs (as percentage of the total global disease burden) and R&D expenditure (as percentage of total global health-related R&D expenditure) for 26 diseases. Results The disease burden varies considerably with the level of economic development, shown by the IRF (median: 1.38; interquartile range (IQR): 0.79–6.3). Comparison of IRFs from 1990 to 2010 highlights general patterns of the global epidemiological transition. The 26 poverty-related diseases included in our analysis of neglect in R&D are responsible for 13.8% of the global disease burden, but receive only 1.34% of global health-related R&D expenditure. Within this group, the NF varies considerably (median: 19; IQR: 6–52). Conclusions The IRF is an intuitive and meaningful metric to highlight shifts in global disease burden patterns. A large shortfall exists in global R&D spending for poverty-related and neglected diseases, with strong variations between diseases. PMID:25623607

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

Science.gov (United States)

Lambertus, Stanley; Bax, Nathalie M; Fakin, Ana; Groenewoud, Joannes M M; Klevering, B Jeroen; Moore, Anthony T; Michaelides, Michel; Webster, Andrew R; van der Wilt, Gert Jan; Hoyng, Carel B

2017-01-01

Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

Directory of Open Access Journals (Sweden)

Stanley Lambertus

Full Text Available Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration.We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14 and the United Kingdom (external validation cohort, n = 18. The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52. Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904. These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872. We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients.These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease

Determinants for the development of visceral leishmaniasis disease.

Directory of Open Access Journals (Sweden)

Laura-Isobel McCall

2013-01-01

Full Text Available Leishmaniasis is a vector-borne neglected tropical disease associated with a spectrum of clinical manifestations, ranging from self-healing cutaneous lesions to fatal visceral infections. Among the most important questions in Leishmania research is why some species like L. donovani infect visceral organs, whereas other species like L. major remain in the skin. The determinants of visceral leishmaniasis are still poorly understood, although genomic, immunologic, and animal models are beginning to provide important insight into this disease. In this review, we discuss the vector, host, and pathogen factors that mediate the development of visceral leishmaniasis. We examine the progression of the parasite from the initial site of sand fly bite to the visceral organs and its ability to survive there. The identification of visceral disease determinants is required to understand disease evolution, to understand visceral organ survival mechanisms, and potentially to develop better interventions for this largely neglected disease.

[The trend of developing new disease-modifying drugs in Alzheimer's disease].

Science.gov (United States)

Arai, Hiroyuki; Furukawa, Katsutoshi; Tomita, Naoki; Ishiki, Aiko; Okamura, Nobuyuki; Kudo, Yukitsuka

2016-03-01

Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development.

Development of formulation device for periodontal disease.

Science.gov (United States)

Sato, Yasuhiko; Oba, Takuma; Watanabe, Norio; Danjo, Kazumi

2012-01-01

In addition to providing standard surgical treatment that removes the plaque and infected tissues, medications that can regenerate periodontal tissue are also required in the treatment of periodontal disease. As a form of regenerative medication, various growth factors are expected to be used while treating periodontal disease. A protein-like growth factor is often developed as a lyophilized product with dissolution liquid, considering its instability in the solution state. We have clarified that the formulation for periodontal disease needs to be viscous. When the lyophilized product was dissolved using a sticky solution, various problems were encountered, difficulty in dissolving and air bubbles, for example, and some efforts were needed to prepare the formulation. In this research, to identify the problem of preparing a viscous formulation, a lyophilized product (placebo) and sticky liquid were prepared by using vial and ampoule as the conventional containers. Based on these problems, a prototype administration device was developed, and its functionality was confirmed. As a result, it was suggested that the device with a useful mixing system that could shorten the preparation time was developed.

Why industry propaganda and political interference cannot disguise the inevitable role played by human exposure to aluminum in neurodegenerative diseases, including Alzheimer's disease.

Science.gov (United States)

Exley, Christopher

2014-01-01

In the aluminum age, it is clearly unpalatable for aluminum, the globe's most successful metal, to be implicated in human disease. It is unpalatable because for approximately 100 years human beings have reaped the rewards of the most abundant metal of the Earth's crust without seriously considering the potential consequences for human health. The aluminum industry is a pillar of the developed and developing world and irrespective of the tyranny of human exposure to aluminum it cannot be challenged without significant consequences for businesses, economies, and governments. However, no matter how deep the dependency or unthinkable the withdrawal, science continues to document, if not too slowly, a burgeoning body burden of aluminum in human beings. Herein, I will make the case that it is inevitable both today and in the future that an individual's exposure to aluminum is impacting upon their health and is already contributing to, if not causing, chronic diseases such as Alzheimer's disease. This is the logical, if uncomfortable, consequence of living in the aluminum age.

A physical theory of focus development in plant disease

NARCIS (Netherlands)

Zawolek, M.W.

1989-01-01

Chapter 1. The 'diffusion theory' of focus development in plant disease is introduced. Foci develop in space and time. The theory applies primarily to air-borne fungal diseases of the foliage.

Chapter 2. The contents of the present volume are outlined.

Chapter 3. The

Patient Disease Perceptions and Coping Strategies for Arthritis in a Developing Nation: A Qualitative Study

Directory of Open Access Journals (Sweden)

Bogart Laura M

2011-10-01

Full Text Available Abstract Background There is little prior research on the burden of arthritis in the developing world. We sought to document how patients with advanced arthritis living in the Dominican Republic are affected by and cope with their disease. Methods We conducted semi-structured, one-to-one interviews with economically disadvantaged Dominican patients with advanced knee and/or hip arthritis in the Dominican Republic. The interviews, conducted in Spanish, followed a moderator's guide that included topics such as the patients' understanding of disease etiology, their support networks, and their coping mechanisms. The interviews were audiotaped, transcribed verbatim in Spanish, and systematically analyzed using content analysis. We assessed agreement in coding between two investigators. Results 18 patients were interviewed (mean age 60 years, median age 62 years, 72% women, 100% response rate. Patients invoked religious and environmental theories of disease etiology, stating that their illness had been caused by God's will or through contact with water. While all patients experienced pain and functional limitation, the social effects of arthritis were gender-specific: women noted interference with homemaking and churchgoing activities, while men experienced disruption with occupational roles. The coping strategies used by patients appeared to reflect their beliefs about disease causation and included prayer and avoidance of water. Conclusions Patients' explanatory models of arthritis influenced the psychosocial effects of the disease and coping mechanisms used. Given the increasing reach of global health programs, understanding these culturally influenced perceptions of disease will be crucial in successfully treating chronic diseases in the developing world.

How does brain insulin resistance develop in Alzheimer's disease?

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De Felice, Fernanda G; Lourenco, Mychael V; Ferreira, Sergio T

2014-02-01

Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signaling on cognition. Discoveries summarized here provide pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

National Priority Setting of Clinical Practice Guidelines Development for Chronic Disease Management.

Science.gov (United States)

Jo, Heui-Sug; Kim, Dong Ik; Oh, Moo-Kyung

2015-12-01

By November 2013, a total of 125 clinical practice guidelines (CPGs) have been developed in Korea. However, despite the high burden of diseases and the clinical importance of CPGs, most chronic diseases do not have available CPGs. Merely 83 CPGs are related to chronic diseases, and only 40 guidelines had been developed in the last 5 yr. Considering the rate of the production of new evidence in medicine and the worsening burden from chronic diseases, the need for developing CPGs for more chronic diseases is becoming increasingly pressing. Since 2011, the Korean Academy of Medical Sciences and the Korea Centers for Disease Control and Prevention have been jointly developing CPGs for chronic diseases. However, priorities have to be set and resources need to be allocated within the constraint of a limited funding. This study identifies the chronic diseases that should be prioritized for the development of CPGs in Korea. Through an objective assessment by using the analytic hierarchy process and a subjective assessment with a survey of expert opinion, high priorities were placed on ischemic heart disease, cerebrovascular diseases, Alzheimer's disease and other dementias, osteoarthritis, neck pain, chronic kidney disease, and cirrhosis of the liver.

Early determinants of chronic disease in developing countries.

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Crowther, Nigel J

2012-10-01

The prevalence of non-communicable diseases (NCDs) is rising in developing countries. The extent to which this is due to a nutritional mismatch in foetal and adult life is unknown however, studies in such countries show that the risk of chronic diseases is increased in low birthweight subjects who become obese adults. Immune dysfunction is also linked to low birthweight. Therefore, in countries where communicable diseases are prevalent, infection may be exacerbated by factors acting in utero. It is also possible that the foetal growth-retarding effects of maternal Human Immunodeficiency Virus (HIV) and malaria infection may contribute to an increased risk of NCDs later in life. Low birthweight and postnatal growth faltering followed by rapid weight gain define subjects who develop NCDs. Dietary interventions at specific time points in the life course may therefore be important for reducing disease risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

ENHANCED IMMUNIZATION COVERAGE THROUGH INTERVENTIONS FOR CHILDHOOD CLUSTER DISEASES IN DEVELOPING COUNTRIES.

Science.gov (United States)

Mureed, Sheh; Somronghtong, Ratana; Kumar, Ramesh; Ghaffar, Abdul; Chapman, Robert S

2015-01-01

Globally immunisation has to be considered as a most effective and efficient public health intervention to reduce morbidity and mortality among children. Most of the children from developing countries are still not fully immunized due to multiple factors including lack of interventions, awareness, and financial constraints and due to limited resource. Conversely, this review has identified the effectiveness of interventions to increase the immunisation coverage among children of developing countries. Systematic review by using PRISMA statement ("preferred reporting items for systematic reviews and meta-analyses") has been conducted in English. published articles on Pub Med, Scopus, Cochrane, Medline and ISI by searching keywords like immunizations, childhood vaccination and developing countries has been accessed. Only randomised controlled trial and quasi-experimental studies designs were included in the final analysis based on quality assessment by adopting the Down and Black checklist and finally pooled analysis was done by random effect model. This systematic review has been approved and registered by University of York. A total of 16,570 published articles were accessed and finally 10 fulfilled our criteria that were analysed and interpreted. It demonstrated that the interventions has shown significantly increase vaccine coverage for childhood cluster diseases (OR 2.136 and p 0.05) and full vaccination schedule (OR 1.342 and p>0.05). Systematic review has concluded that the professional interventions are an effective while in improving the child immunisation coverage for cluster diseases in developing countries, major effect on DTP an.d measles.

The development of a massive open online course during the 2014-15 Ebola virus disease epidemic.

Science.gov (United States)

Evans, Dabney P; Luffy, Samantha M; Parisi, Stephanie; Del Rio, Carlos

2017-09-01

Timely training was urgently needed at the onset of the 2014 Ebola virus disease epidemic. Massive open online courses (MOOCs) have grown in popularity, though little is known about their utility in time-sensitive situations, including infectious disease outbreaks. We created the first English language massive open online course on Ebola virus disease. Designed by a team representing various units of Emory University and six partner institutions, the six module course was aimed at a global general audience but also relevant for health care professionals. Over 7,000 learners from 170 countries participated in the initial course offering. More than a third of learners were from emerging economies, including seven percent from Africa, and another 13% from countries outside the United States who received individuals requiring treatment for Ebola virus disease. Creating and producing the first English language MOOC on EVD in a short time period required effective collaboration and strong coordination between subject matter and course development experts from Emory. Through these collaborative efforts, the development team was able to provide urgently needed training and educational materials while the epidemic of EVD continued to radiate through West Africa. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a quality-of-life instrument for autoimmune bullous disease: the Autoimmune Bullous Disease Quality of Life questionnaire.

Science.gov (United States)

Sebaratnam, Deshan F; Hanna, Anna Marie; Chee, Shien-ning; Frew, John W; Venugopal, Supriya S; Daniel, Benjamin S; Martin, Linda K; Rhodes, Lesley M; Tan, Jeremy Choon Kai; Wang, Charles Qian; Welsh, Belinda; Nijsten, Tamar; Murrell, Dédée F

2013-10-01

Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. To develop a QOL instrument specific to autoimmune bullous disease (AIBD). A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. The development of an AIBD-specific QOL instrument. Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. anzctr.org.au Identifier: ACTRN12612000750886.

Transgenic approaches for development of disease resistance in banana

International Nuclear Information System (INIS)

Shekhawat, Upendra K.S.; Ghag, Siddhesh B.; Ganapathi, Thumballi R.

2014-01-01

Banana (Musa spp.) is an important food and cash crop worldwide. Diseases and pests pose the most serious constraint to banana cultivation. Among the diseases, Fusarium wilt and Banana Bunchy Top Virus (BBTV) are the most important economically. We have explored different transgenic approaches for development of efficient resistance in banana against these two diseases. For countering Fusarium wilt, we have over expressed Petunia floral defensins using a strong constitutive promoter in transgenic banana plants. We have also tested a host induced gene silencing strategy targeting two vital fungal genes to obtain Fusarium resistant banana plants. For development of BBTV resistant banana plants also, we have used a host-induced gene silencing approach utilizing the full and partial coding sequence of the viral replication initiation protein. Successful bioassays performed in controlled greenhouse conditions have shown the efficacy of using these strategies to develop disease resistant banana plants. (author)

A Reformed CDM - including new mechanisms for sustainable development

Energy Technology Data Exchange (ETDEWEB)

Holm Olsen, K; Fenhann, J

2009-07-01

The annual CD4CDM Perspectives Series features a topic of pivotal importance to the global carbon market. The series seeks to communicate the diverse insights and visions of leading actors in the carbon market to better inform the decisions of professionals and policymakers in developing countries. The second theme of the series focuses on how the CDM can be reformed in a post-2012 climate regime, including new mechanism for sustainable development. Seventeen contributors from the private sector, Designated National Authorities, the Executive Board, research, and development agencies present their perspective on meeting challenges such as the unequal regional distribution of CDM projects, concerns about environmental integrity and technology transfer, complex governance procedures, and questions about the CDM's contribution to sustainable development. The new ideas and solutions to these challenges proposed by the authors in this edition of Perspectives have been solicited to help professionals and policy makers make the best decisions in the lead-up to COP 15 in Copenhagen and beyond. (au)

A Reformed CDM - including new mechanisms for sustainable development

Energy Technology Data Exchange (ETDEWEB)

Holm Olsen, K.; Fenhann, J.

2009-07-01

The annual CD4CDM Perspectives Series features a topic of pivotal importance to the global carbon market. The series seeks to communicate the diverse insights and visions of leading actors in the carbon market to better inform the decisions of professionals and policymakers in developing countries. The second theme of the series focuses on how the CDM can be reformed in a post-2012 climate regime, including new mechanism for sustainable development. Seventeen contributors from the private sector, Designated National Authorities, the Executive Board, research, and development agencies present their perspective on meeting challenges such as the unequal regional distribution of CDM projects, concerns about environmental integrity and technology transfer, complex governance procedures, and questions about the CDM's contribution to sustainable development. The new ideas and solutions to these challenges proposed by the authors in this edition of Perspectives have been solicited to help professionals and policy makers make the best decisions in the lead-up to COP 15 in Copenhagen and beyond. (au)

Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease (Review)

NARCIS (Netherlands)

Lenferink, Anke; Brusse-Keizer, Marjolein; van der Valk, Paul; Frith, Peter A.; Zwerink, Marlies; Monninkhof, Evelyn M.; van der Palen, J.A.M.; Effing, Tanja

2017-01-01

Background  Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals ofmotivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease.

Diabetes and the risk of developing Parkinson's disease in Denmark

DEFF Research Database (Denmark)

Schernhammer, Eva; Hansen, Johnni; Rugbjerg, Kathrine

2011-01-01

Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson's disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs...... was associated with Parkinson's disease....

Newcastle disease: An in-depth review including epidemiology and molecular diagnostics

Science.gov (United States)

Infections of birds with strains of avian paramyxovirus serotype 1 (APMV-1), (synonyms: Newcastle disease virus (NDV), pigeon PMV-1 (PPMV-1)) are associated with two clinical outcomes: 1) Newcastle disease (ND) results from infections with virulent APMV-1, and is also called Exotic ND (END) in U. S...

Psychological Perspectives on the Development of Coronary Heart Disease

Science.gov (United States)

Matthews, Karen A.

2005-01-01

Psychological science has new opportunities to have major input into the understanding of the development of coronary heart disease. This article provides an overview of advances in understanding the etiology of heart disease, recently applied technologies for measuring early stages of heart disease, and an accumulating base of evidence on the…

Scientific research on diseases: the distinct profile of developed and developing countries

Energy Technology Data Exchange (ETDEWEB)

Yegros-Yegros, A.; Rafols, I.; Abad-Garcia, M.F.; Mugnaini, R.; Meijer, I.

2016-07-01

In most of the countries across the globe, health is seen as a priority. The European Commission (2013), for example, considers health as a precondition for economic prosperity given that people’s health influences economic outcomes in terms of productivity, labor supply, human capital and public spending. Accordingly, the Commission places health in one of the big Societal Challenges (‘health, demographic change and wellbeing’) in Horizon 2020. Part of the investment on research and development is devoted to specific diseases. In order to assess whether scientific research is targeting the most pressing diseases, some studies have tried to analyze the degree of alignment between the funding allocated to specific diseases and the burden of disease (e.g. Gillum et al, 2011; Kingel et al, 2014). Others, like Evans et al (2014), focus on the relationship between research outputs dealing with specific diseases and the burden of disease. (Author)

The German government's global health strategy--a strategy also to support research and development for neglected diseases?

Science.gov (United States)

Fehr, Angela; Razum, Oliver

2014-01-01

Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D) deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

Development of Evidence-Based Disease Education Literature for Pakistani Rheumatoid Arthritis Patients

Directory of Open Access Journals (Sweden)

Atta Abbas Naqvi

2017-11-01

Full Text Available Rheumatoid arthritis affects 0.5% to 1% of the population globally and is one of the most common causes of disability. Patient education plays a key role in improving treatment outcomes. The purpose of this study was to discuss the process involved in designing an evidence-based disease education literature for rheumatoid arthritis patients of Pakistan in Urdu language with culturally relevant illustrations. A study was conducted to develop disease education literature using Delphi consensus, content validity, and patient feedback. A panel of experts comprised of university professors and health care experts, including health practitioners and pharmacists as well as a social scientist, was set up to assess the need. Eight patients were randomly selected and were asked to give their feedback. Their feedback was incorporated in the development process. The entire process was carried out in eight steps. A disease education literature for patients of rheumatoid arthritis was developed and edited in the form of a booklet. The booklet contained evidence-based information that must be provided to patients in both Urdu and English languages with culturally relevant illustrations. The availability of such literature is significant, as it enables the patients to seek knowledge at home at their convenience. This home-based knowledge support is as helpful as any other means of medical care. The developed literature is planned to be used in further studies which will evaluate its impact in improving knowledge of RA patients.

Does Vitamin C Deficiency Promote Fatty Liver Disease Development?

Directory of Open Access Journals (Sweden)

David Højland Ipsen

2014-12-01

Full Text Available Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH. The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

Science.gov (United States)

Bax, Nathalie M.; Fakin, Ana; Groenewoud, Joannes M. M.; Klevering, B. Jeroen; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.; van der Wilt, Gert Jan; Hoyng, Carel B.

2017-01-01

Background Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options—including gene therapy—are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. Methods and findings We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30–0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33–0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. Conclusions These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a

Novel approaches to models of Alzheimer's disease pathology for drug screening and development.

Science.gov (United States)

Shaughnessy, Laura; Chamblin, Beth; McMahon, Lori; Nair, Ayyappan; Thomas, Mary Beth; Wakefield, John; Koentgen, Frank; Ramabhadran, Ram

2004-01-01

Development of therapeutics for Alzheimer's disease (AD) requires appropriate cell culture models that reflect the errant biochemical pathways and animal models that reflect the pathological hallmarks of the disease as well as the clinical manifestations. In the past two decades AD research has benefited significantly from the use of genetically engineered cell lines expressing components of the amyloid-generating pathway, as well as from the study of transgenic mice that develop the pathological hallmarks of the disease, mainly neuritic plaques. The choice of certain cell types and the choice of mouse as the model organism have been mandated by the feasibility of introduction and expression of foreign genes into these model systems. We describe a universal and efficient gene-delivery system, using lentiviral vectors, that permits the development of relevant cell biological systems using neuronal cells, including primary neurons and animal models in mammalian species best suited for the study of AD. In addition, lentiviral gene delivery provides avenues for creation of novel models by direct and prolonged expression of genes in the brain in any vertebrate animal. TranzVector is a lentiviral vector optimized for efficiency and safety that delivers genes to cells in culture, in tissue explants, and in live animals regardless of the dividing or differentiated status of the cells. Genes can also be delivered efficiently to fertilized single-cell-stage embryos of a wide range of mammalian species, broadening the range of the model organism (from rats to nonhuman primates) for the study of disease mechanism as well as for development of therapeutics. Copyright 2004 Humana Press Inc.

Prevention of metabolic diseases: fruits (including fruit sugars) vs. vegetables.

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Kuzma, Jessica N; Schmidt, Kelsey A; Kratz, Mario

2017-07-01

To discuss recent evidence from observational and intervention studies on the relationship between fruit and vegetable (F&V) consumption and metabolic disease. Observational studies have consistently demonstrated a modest inverse association between the intake of fruit and leafy green vegetables, but not total vegetables, and biomarkers of metabolic disease as well as incident type 2 diabetes mellitus. This is in contrast to limited evidence from recently published randomized controlled dietary intervention trials, which - in sum - suggests little to no impact of increased F&V consumption on biomarkers of metabolic disease. Evidence from observational studies that fruit and leafy green vegetable intake is associated with lower type 2 diabetes risk and better metabolic health could not be confirmed by dietary intervention trials. It is unclear whether this discrepancy is because of limitations inherent in observational studies (e.g., subjective dietary assessment methods, residual confounding) or due to limitations in the few available intervention studies (e.g., short duration of follow-up, interventions combining whole fruit and fruit juice, or lack of compliance). Future studies that attempt to address these limitations are needed to provide more conclusive insight into the impact of F&V consumption on metabolic health.

The commensal microbiota and the development of human disease – an introduction

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Philip D. Marsh

2015-09-01

Full Text Available Humans have co-evolved with microorganisms, and both exist in a symbiotic or mutualistic relationship. We are colonised by a diverse, resident microbiota, which develop into structurally and functionally organised biofilms. The resident microorganisms gain a secure, warm, nutritious habitat from the host and, in return, contribute to the development of many important host functions. The resident microbiota of each habitat is natural and provides important benefits for the host including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and prevention of colonisation by exogenous microbes. The biological properties of each habitat determine which microorganisms can colonise and grow, and dictate which will be major or minor components of the resident microbiota of a site. This results in different surfaces having distinct but characteristic microbiotas. This relationship between the resident microbiota and the host is dynamic and, on occasions, this symbiotic relationship breaks down due to, for example, changes in lifestyle, immune status or following broad spectrum antibiotic therapy. This ‘dysbiosis’ can result in previously minor components of the microbiota out-competing the normally dominant and beneficial bacteria, thereby increasing the risk of disease. Such perturbations have been associated with a number of clinical disorders such as obesity, allergy, and a variety of inflammatory diseases, including periodontal diseases. A better understanding of the delicate balance between the host and its resident microbiota could lead to novel approaches to the promotion of health and the prevention of dysbiosis.

Diseases of poverty and lifestyle, well-being and human development.

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Singh, Ajai R; Singh, Shakuntala A

2008-01-01

The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical concerns in regimes and scientific power centres.While there has been great progress in the treatment of individual diseases, human pathology continues to increase. Sicknesses are not decreasing in number, they are only changing in type.The primary diseases of poverty like TB, malaria, and HIV/AIDS-and the often co-morbid and ubiquitous malnutrition-take their toll on helpless populations in developing countries. Poverty is not just income deprivation but capability deprivation and optimism deprivation as well.While life expectancy may have increased in the haves, and infant and maternal mortality reduced, these gains have not necessarily ensured that well-being results. There are ever-multiplying numbers of individuals whose well-being is compromised due to lifestyle diseases. These diseases are the result of faulty lifestyles and the consequent crippling stress. But it serves no one's purpose to understand them as such. So, the prescription pad continues to prevail over lifestyle-change counselling or research.The struggle to achieve well-being and positive health, to ensure longevity, to combat lifestyle stress and professional burnout, and to reduce psychosomatic ailments continues unabated, with hardly an end in sight.WE THUS REALISE THAT MORBIDITY, DISABILITY, AND DEATH ASSAIL ALL THREE SOCIETIES: the ones with infectious diseases, the ones with diseases of poverty, and the ones with lifestyle diseases. If it is bacteria in their various forms that are the culprit in

Vaccine development for emerging virulent infectious diseases.

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Maslow, Joel N

2017-10-04

The recent outbreak of Zaire Ebola virus in West Africa altered the classical paradigm of vaccine development and that for emerging infectious diseases (EIDs) in general. In this paper, the precepts of vaccine discovery and advancement through pre-clinical and clinical assessment are discussed in the context of the recent Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Zika virus outbreaks. Clinical trial design for diseases with high mortality rates and/or high morbidity in the face of a global perception of immediate need and the factors that drive design in the face of a changing epidemiology are presented. Vaccines for EIDs thus present a unique paradigm to standard development precepts. Copyright © 2017 Elsevier Ltd. All rights reserved.

DYNAMICS AND INTENSITY OF APLE DISEASE DEVELOPMENT DURING ITS STORAGE

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D. Ivić

2006-12-01

Full Text Available Post-harvest apple fruit diseases are primarily caused by fungi. The object of this research was to quantify yield loss caused by post-harvest diseases and to determine fungal species responsible for storage rots on the cv. Idared during three months of storage, as well as to compare the development of fungi inoculated on apple fruits in the laboratory conditions. Only fruits with the visible rot symptoms were regarded as "diseased". Total yield loss during all three months of storage was 1.9%. The percentage of diseased fruits increased from the harvest moment to the end of storage. The most frequent cause of post-harvest rot in all assessments was Monilia fructigena. Penicillium species and Botrytis cinerea were present in relatively high percentage. All fungal isolates from diseased fruits caused fruit rot when inoculated on apples and incubated for 28 days at 22°C. On fruits inoculated with the same isolates and incubated at 4°C rot development was slower. Isolates of M. fructigena developed most rapidly on inoculated fruits at 22°C, while the isolates of B. cinerea developed most rapidly at 4°C.

Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies

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Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

2016-01-01

Objective Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. Methods This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Results Videofluoroscopy sw...

Congenital Heart Disease and Impacts on Child Development

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Mariana Alievi Mari

2016-02-01

Full Text Available Abstract Objective: To evaluate the child development and evaluate a possible association with the commitment by biopsychosocial factors of children with and without congenital heart disease. Methods: Observational study of case-control with three groups: Group 1 - children with congenital heart disease without surgical correction; Group 2 - children with congenital heart disease who underwent surgery; and Group 3 - healthy children. Children were assessed by socio-demographic and clinical questionnaire and the Denver II Screening Test. Results: One hundred and twenty eight children were evaluated, 29 in Group 1, 43 in Group 2 and 56 in Group 3. Of the total, 51.56% are girls and ages ranged from two months to six years (median 24.5 months. Regarding the Denver II, the children with heart disease had more "suspicious" and "suspect/abnormal" ratings and in the group of healthy children 53.6% were considered with "normal" development (P≤0.0001. The biopsychosocial variables that were related to a possible developmental delay were gender (P=0.042, child's age (P=0.001 and income per capita (P=0.019. Conclusion: The results suggest that children with congenital heart disease are likely to have a developmental delay with significant difference between children who have undergone surgery and those awaiting surgery under clinical follow-up.

Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases.

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Barrett, P Noel; Terpening, Sara J; Snow, Doris; Cobb, Ronald R; Kistner, Otfried

2017-09-01

Rapid development and production of vaccines against emerging diseases requires well established, validated, robust technologies to allow industrial scale production and accelerated licensure of products. Areas covered: A versatile Vero cell platform has been developed and utilized to deliver a wide range of candidate and licensed vaccines against emerging viral diseases. This platform builds on the 35 years' experience and safety record with inactivated whole virus vaccines such as polio vaccine. The current platform has been optimized to include a novel double inactivation procedure in order to ensure a highly robust inactivation procedure for novel emerging viruses. The utility of this platform in rapidly developing inactivated whole virus vaccines against pandemic (-like) influenza viruses and other emerging viruses such as West Nile, Chikungunya, Ross River and SARS is reviewed. The potential of the platform for development of vaccines against other emerging viruses such as Zika virus is described. Expert commentary: Use of this platform can substantially accelerate process development and facilitate licensure because of the substantial existing data set available for the cell matrix. However, programs to provide vaccines against emerging diseases must allow alternative clinical development paths to licensure, without the requirement to carry out large scale field efficacy studies.

Wnt and the Wnt signaling pathway in bone development and disease

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Wang, Yiping; Li, Yi-Ping; Paulson, Christie; Shao, Jian-Zhong; Zhang, Xiaoling; Wu, Mengrui; Chen, Wei

2014-01-01

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases. PMID:24389191

Cost of tobacco-related diseases, including passive smoking, in Hong Kong.

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McGhee, S M; Ho, L M; Lapsley, H M; Chau, J; Cheung, W L; Ho, S Y; Pow, M; Lam, T H; Hedley, A J

2006-04-01

Costs of tobacco-related disease can be useful evidence to support tobacco control. In Hong Kong we now have locally derived data on the risks of smoking, including passive smoking. To estimate the health-related costs of tobacco from both active and passive smoking. Using local data, we estimated active and passive smoking-attributable mortality, hospital admissions, outpatient, emergency and general practitioner visits for adults and children, use of nursing homes and domestic help, time lost from work due to illness and premature mortality in the productive years. Morbidity risk data were used where possible but otherwise estimates based on mortality risks were used. Utilisation was valued at unit costs or from survey data. Work time lost was valued at the median wage and an additional costing included a value of USD 1.3 million for a life lost. In the Hong Kong population of 6.5 million in 1998, the annual value of direct medical costs, long term care and productivity loss was USD 532 million for active smoking and USD 156 million for passive smoking; passive smoking accounted for 23% of the total costs. Adding the value of attributable lives lost brought the annual cost to USD 9.4 billion. The health costs of tobacco use are high and represent a net loss to society. Passive smoking increases these costs by at least a quarter. This quantification of the costs of tobacco provides strong motivation for legislative action on smoke-free areas in the Asia Pacific Region and elsewhere.

The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

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Peter Mubanga Cheuka

2016-12-01

Full Text Available Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness, leishmaniasis, schistosomiasis and lymphatic filariasis.

Diseases of Poverty and Lifestyle, Well-Being and Human Development

OpenAIRE

Singh, Ajai R.; Singh, Shakuntala A.

2008-01-01

The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical c...

Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

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Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

2014-01-01

The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities

Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies.

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Ryoko Katagiri

Full Text Available Although several reports concerning the association of iodine excess and thyroid disease have appeared, no systematic review of the association between iodine excess intake and thyroid diseases, especially hyperthyroidism and hypothyroidism, has yet been reported.We conducted a systematic search of Ovid MEDLINE, PubMed, Cochrane Central Register of Controlled Trials databases, Ichushi-Web and CiNii database for intervention trials and observational studies. Search terms were constructed from related words for excess AND iodine intake or excretion AND thyroid hormones or diseases AND study designs. After considering the qualitative heterogeneity among studies, a meta-analysis was conducted and odds ratios and 95% confidence intervals (CI were estimated in random-effects models. A protocol was registered with PROSPERO (No. CRD42015028081.50 articles were included, including three intervention trials, six case-control studies, six follow-up studies and 35 cross-sectional studies. Three cross-sectional studies in adults included in meta-analysis. Odds ratio of overt and subclinical hypothyroidism between excess and adequate populations were 2.78 (CI:1.47 to 5.27 and 2.03 (CI:1.58 to 2.62 in adults, respectively. Source of excess iodine status was mainly iodized salt or water in included studies.Although universal salt iodization has improved goiter rates, chronic exposure to excess iodine from water or poorly monitored salt are risk factors for hypothyroidism in free-living populations. Monitoring of both iodine concentration in salt as well as the iodine concentration in local drinking water are essential to preventing thyroid diseases. Hypothyroidism should be also carefully monitored in areas with excess iodine. Because of the low quality and limited number of included studies, further evidence and review are required.

Wnt Signaling in Kidney Development and Disease.

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Wang, Yongping; Zhou, Chengji J; Liu, Youhua

2018-01-01

Wnt signal cascade is an evolutionarily conserved, developmental pathway that regulates embryogenesis, injury repair, and pathogenesis of human diseases. It is well established that Wnt ligands transmit their signal via canonical, β-catenin-dependent and noncanonical, β-catenin-independent mechanisms. Mounting evidence has revealed that Wnt signaling plays a key role in controlling early nephrogenesis and is implicated in the development of various kidney disorders. Dysregulations of Wnt expression cause a variety of developmental abnormalities and human diseases, such as congenital anomalies of the kidney and urinary tract, cystic kidney, and renal carcinoma. Multiple Wnt ligands, their receptors, and transcriptional targets are upregulated during nephron formation, which is crucial for mediating the reciprocal interaction between primordial tissues of ureteric bud and metanephric mesenchyme. Renal cysts are also associated with disrupted Wnt signaling. In addition, Wnt components are important players in renal tumorigenesis. Activation of Wnt/β-catenin is instrumental for tubular repair and regeneration after acute kidney injury. However, sustained activation of this signal cascade is linked to chronic kidney diseases and renal fibrosis in patients and experimental animal models. Mechanistically, Wnt signaling controls a diverse array of biologic processes, such as cell cycle progression, cell polarity and migration, cilia biology, and activation of renin-angiotensin system. In this chapter, we have reviewed recent findings that implicate Wnt signaling in kidney development and diseases. Targeting this signaling may hold promise for future treatment of kidney disorders in patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

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Denis Bernardi Bichuetti

2013-05-01

Full Text Available Although neuromyelitis optica (NMO is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS, few studies comparing both conditions in a single center have been done. Methods: Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007. Results: Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062 with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013 and progression index (0.9 versus 0.6, p≪0.0001, with more patients reaching expanded disability status scale (EDSS 6.0 (39 versus 17%, p=0.0036. The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15. Conclusion: Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

Stage 1 development of a patient-reported experience measure (PREM) for chronic obstructive pulmonary disease (COPD).

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Walker, Susan; Andrew, Sharon; Hodson, Matthew; Roberts, C Michael

2017-07-24

The study aimed to explore patients' experience of living with chronic obstructive pulmonary disease and their perspective of their community healthcare for chronic obstructive pulmonary disease to extract affective responses in order to develop potential items for a patient-reported experience measure for chronic obstructive pulmonary disease. Qualitative face-face interviews were conducted, in the community, with 64 patients with chronic obstructive pulmonary disease recruited from General Practices and Breathe-Easy community groups in the Outer North East, East and City areas of London and Essex, UK. A two phase analysis of the qualitative data was conducted to identify themes arising from patients' description of living with chronic obstructive pulmonary disease and their perceptions of their community healthcare and subsequently the affective responses underlying the themes raised by patients, which gave emotional colour to the themes, bringing the thematic analysis closer to the subjective patient experience. Five themes were identified from the interview data: 'Journey to diagnosis'; 'Smoking'; 'Usual care'; 'My everyday life'; and 'Exacerbations'. Twenty-one affective responses were identified and categorised as either 'negative', 'positive' or 'bivalent'. 'Frustration', a negative affective response was prevalent in four themes. 'Gratitude', 'hope' and 'happiness/enjoyment' were among the more positive responses more prevalent across several themes. By conducting a novel two-way analysis (thematic and affective) it was possible to identify themes and affective responses that were aligned to those themes. This enabled the development of 38 chronic obstructive pulmonary disease-specific experience items to take forward for further testing including item reduction and validity and reliability in the next stage of the patient-reported experience measure development. GIVING IMPORTANCE TO PATIENTS' EMOTIONS: An exploration of patient perceptions of living with

Cardiovascular Diseases on the Global Agenda: The United Nations High Level Meeting, Sustainable Development Goals, and the Way Forward.

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Ralston, Johanna; Reddy, K Srinath; Fuster, Valentin; Narula, Jagat

2016-12-01

In 2011, the United Nations (UN) organized the first ever meeting for heads of state to discuss the problem of noncommunicable diseases (NCD), including cardiovascular disease (CVD), cancer, chronic respiratory disease, and diabetes mellitus. Recognizing that these had emerged as leading causes of morbidity and mortality in the world, including in many low- and middle-income countries, advocates from government and civil society had called for increased attention and a UN response. Earlier, NCD including CVD were absent from the global health agenda in part because of their omission from the Millennium Development Goals. The UN meeting and the global advocacy response offered a game-changing opportunity to redress this omission. The World Heart Federation (WHF) played an instrumental role in the UN meeting and follow up, including inclusion of CVD in the Sustainable Development Goals. The next phase of the global CVD movement is expected through national action, including CVD roadmaps and partnering with the World Health Organization. The WHF is heavily committed to these goals and the other nongovernmental organizations invested in the mission must help take this historical mandate forward. Instrumental to this will be the engagement of people affected by or at risk of developing CVD, to draw more attention and resources to NCD and to ensure that successes to date in global policy translate into action at the national level. Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease

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Tomasz Wollny

2017-03-01

Full Text Available Beyond their role as structural molecules, sphingolipids are involved in many important cellular processes including cell proliferation, apoptosis, inflammation, and migration. Altered sphingolipid metabolism is observed in many pathological conditions including gastrointestinal diseases. Inflammatory bowel disease (IBD represents a state of complex, unpredictable, and destructive inflammation of unknown origin within the gastrointestinal tract. The mechanisms explaining the pathophysiology of IBD involve signal transduction pathways regulating gastro-intestinal system’s immunity. Progressive intestinal tissue destruction observed in chronic inflammation may be associated with an increased risk of colon cancer. Sphingosine-1-phosphate (S1P, a sphingolipid metabolite, functions as a cofactor in inflammatory signaling and becomes a target in the treatment of IBD, which might prevent its conversion to cancer. This paper summarizes new findings indicating the impact of (S1P on IBD development and IBD-associated carcinogenesis.

The role of hepatocyte nuclear factor 4 alpha in development and progression of liver diseases

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YANG Jinlian

2016-02-01

Full Text Available Hepatocyte nuclear factor 4 alpha (HNF4α, a member of the nuclear receptor superfamily, has a high expression level in mature hepatocytes. HNF4α can regulate hepatocyte-specific gene expression at a transcriptional level, promote hepatocyte development and differentiation, participate in establishment and maintenance of hepatocyte polarity, and enhance the synthetic, metabolic, and detoxifying functions of the liver. Through inhibiting the activation of hepatic stellate cells, reversing epithelial-mesenchymal transition, and inhibiting the proliferation, invasion, and metastasis of hepatoma cells, HNF4α may be involved in the development and progression of various liver diseases including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. This paper elaborates on the biological functions of HNF4α, and summarizes and analyzes the research advances in the mechanisms of action of HNF4α in the pathological process of liver diseases, in order to provide references for further investigation of the potential targeted therapies for liver diseases.

The Alzheimer's Disease Knowledge Scale: Development and Psychometric Properties

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Carpenter, Brian D.; Balsis, Steve; Otilingam, Poorni G.; Hanson, Priya K.; Gatz, Margaret

2009-01-01

Purpose: This study provides preliminary evidence for the acceptability, reliability, and validity of the new Alzheimer's Disease Knowledge Scale (ADKS), a content and psychometric update to the Alzheimer's Disease Knowledge Test. Design and Methods: Traditional scale development methods were used to generate items and evaluate their psychometric…

Pathogenetics aspects of relationship mouth infectious diseases with development and progression atherosclerosis and possibility for their integrated prevention

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M. V. Avdeeva

2012-01-01

Full Text Available The article contains the modern literature data about impact of various infectious agents on the development and progression of atherosclerotic disease. The data are demonstrated the role of various infectious diseases, including periodontal diseases, in the development of biological degradation and destabilization of atherosclerotic plaques. The article questions of organization of primary prevention of cardiovascular disease based on the screening assessment by stomatologist the oral sanitary status. Necessary to carry out sanitation of chronic infection foci of the mouth on the basis of existing children’s health centers. The children’s health centers have a set of dental equipment, with which can perform a screening diagnosis of dental caries, periodontal diseases, non-carious lesions, diseases of the mucous membranes, and conduct preventive oral sanitation. The duties of dental hygienists is teaching children of different age groups to the rules of oral care, demonstration of skills, brushing teeth, information about the importance of prevention of dental caries and periodontal disease, as it is not only important for the preservation of the teeth, but also may prevent the development of ardiovasculardisease adulthood.

Combined scintigraphic and radiographic diagnosis of bone and joint diseases. Including gamma correction interpretation. 4. rev. and enl. ed.

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Bahk, Yong-Whee [Sung Ae General Hospital, Seoul (Korea, Republic of). Dept. of Nuclear Medicine and Radiology

2013-07-01

In this fourth edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases, the text has been thoroughly amended, updated, and partially rearranged to reflect the latest advances. In addition to discussing the role of pinhole imaging in the range of disorders previously covered, the new edition pays detailed attention to the novel diagnostic use of gamma correction pinhole bone scan in a broad spectrum of skeletal disorders, including physical, traumatic, and sports injuries, infectious and non-infectious bone diseases, benign and malignant bone tumors, and soft tissue diseases. A large number of state of the art pinhole scans and corroborative CT, MRI, and/or ultrasound images are presented side by side. The book has been enlarged to encompass various new topics, including occult fractures; cervical sprain and whiplash trauma; bone marrow edema; microfractures of trabeculae; evident, gaping, and stress fractures; and differential diagnosis. This new edition will be essential reading for practitioners and researchers in not only nuclear medicine but also radiology, orthopedic surgery, and pathology.

Combined scintigraphic and radiographic diagnosis of bone and joint diseases. Including gamma correction interpretation. 4. rev. and enl. ed.

International Nuclear Information System (INIS)

Bahk, Yong-Whee

2013-01-01

In this fourth edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases, the text has been thoroughly amended, updated, and partially rearranged to reflect the latest advances. In addition to discussing the role of pinhole imaging in the range of disorders previously covered, the new edition pays detailed attention to the novel diagnostic use of gamma correction pinhole bone scan in a broad spectrum of skeletal disorders, including physical, traumatic, and sports injuries, infectious and non-infectious bone diseases, benign and malignant bone tumors, and soft tissue diseases. A large number of state of the art pinhole scans and corroborative CT, MRI, and/or ultrasound images are presented side by side. The book has been enlarged to encompass various new topics, including occult fractures; cervical sprain and whiplash trauma; bone marrow edema; microfractures of trabeculae; evident, gaping, and stress fractures; and differential diagnosis. This new edition will be essential reading for practitioners and researchers in not only nuclear medicine but also radiology, orthopedic surgery, and pathology.

The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease

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Marco Sanduzzi Zamparelli

2016-07-01

Full Text Available The prevalence of metabolic disorders, such as type 2 diabetes (T2D, obesity, and non-alcoholic fatty liver disease (NAFLD, which are common risk factors for cardiovascular disease (CVD, has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.

Description of an oral Chagas disease outbreak in Venezuela, including a vertically transmitted case.

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Noya, Belkisyolé Alarcón de; Pérez-Chacón, Gladymar; Díaz-Bello, Zoraida; Dickson, Sonia; Muñoz-Calderón, Arturo; Hernández, Carlos; Pérez, Yadira; Mauriello, Luciano; Moronta, Eyleen

2017-08-01

We describe the eleventh major outbreak of foodborne Trypanosoma cruzi transmission in urban Venezuela, including evidence for vertical transmission from the index case to her fetus. After confirming fetal death at 24 weeks of gestation, pregnancy interruption was performed. On direct examination of the amniotic fluid, trypomastigotes were detected. T. cruzi specific-polymerase chain reaction (PCR) also proved positive when examining autopsied fetal organs. Finally, microscopic fetal heart examination revealed amastigote nests. Acute orally transmitted Chagas disease can be life threatening or even fatal for pregnant women and unborn fetuses owing to vertical transmission. There is therefore an urgent need to improve national epidemiologic control measures.

Model for product development of vaccines against neglected tropical diseases: a vaccine against human hookworm.

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Bottazzi, Maria Elena; Brown, Ami Shah

2008-12-01

This article provides an overview of the advances in product development and technology transfer of the vaccine against human hookworm, with particular emphasis on the lessons learned and the challenges of developing a vaccine in the nonprofit sector. The comprehensive approach to vaccine development established by the Human Hookworm Vaccine Initiative (HHVI) identifies key operational and technical aspects that are essential for a successful partnership with a developing country vaccine manufacturer. This article also highlights the importance of a global access roadmap to guide the vaccine development program. The advancement of new products for the control of neglected tropical diseases portends great challenges for global access, including aspects related to vaccine design, product development and manufacture, vaccine introduction and distribution, financing, knowledge dissemination and intellectual property management. With only three vaccines for neglected tropical diseases in clinical trials - hookworm, leishmaniasis and schistosomiasis - we are at the nascent stages of developing vaccines for neglected populations. Product development public-private partnerships, such as the HHVI, continue to show great promise on this front and will eventually provide significant control tools for achieving millennium development goals related to poverty reduction, as well as child and maternal health.

Tay-Sachs Disease

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... better understanding of how neurological deficits arise in lipid storage diseases and on the development of new treatments targeting disease mechanisms. Specific research on the gangliodisoses including expanding the use of ...

Stomach development, stem cells and disease

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Kim, Tae-Hee; Shivdasani, Ramesh A.

2016-01-01

The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms. PMID:26884394

Graves disease with ophthalmopathy following radiotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Jacobson, D.R.; Fleming, B.J.

1984-01-01

The number of patients achieving long-term survival following neck irradiation for Hodgkin's disease and other malignancies is increasing. Paralleling this increase in survivors is the development of late complications of the therapy itself. Eleven patients have previously been reported who developed Graves ophthalmopathy 18 months to seven years after receiving neck radiotherapy for nonthyroidal malignancies. The seven patients who had HLA typing were all HLA-B8 negative, despite the reported association of the HLA-B8 antigen with Graves disease. A patient who is HLA-B8 positive who developed Graves ophthalmopathy and hyperthyroidism nine years after receiving mantle radiotherapy for Hodgkin's disease is reported. It is recommended that Graves disease be included among the thyroid diseases that receive consideration during follow-up of patients who have received mantle radiotherapy

[Globalization and infectious diseases].

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Mirski, Tomasz; Bartoszcze, Michał; Bielawska-Drózd, Agata

2011-01-01

Globalization is a phenomenon characteristic of present times. It can be considered in various aspects: economic, environmental changes, demographic changes, as well as the development of new technologies. All these aspects of globalization have a definite influence on the emergence and spread of infectious diseases. Economic aspects ofglobalization are mainly the trade development, including food trade, which has an impact on the spread of food-borne diseases. The environmental changes caused by intensive development of industry, as a result of globalization, which in turn affects human health. The demographic changes are mainly people migration between countries and rural and urban areas, which essentially favors the global spread of many infectious diseases. While technological advances prevents the spread of infections, for example through better access to information, it may also increase the risk, for example through to create opportunities to travel into more world regions, including the endemic regions for various diseases. The phenomenon ofglobalization is also closely associated with the threat of terrorism, including bioterrorism. It forces the governments of many countries to develop effective programs to protect and fight against this threat.

The German government's global health strategy – a strategy also to support research and development for neglected diseases?

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Angela Fehr

2014-07-01

Full Text Available Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

Early sensitisation and development of allergic airway disease - risk factors and predictors

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Halken, Susanne

2003-01-01

The development and phenotypic expression of allergic airway disease depends on a complex interaction between genetic and several environmental factors, such as exposure to food, inhalant allergens and non-specific adjuvant factors (e.g. tobacco smoke, air pollution and infections). The first...... development of allergic disease at birth. Early sensitisation, cow's milk allergy and atopic eczema are predictors for later development of allergic airway disease. Exposure to indoor allergens, especially house dust mite allergens, is a risk factor for sensitisation and development of asthma later...

Multi-disease data management system platform for vector-borne diseases.

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Lars Eisen

2011-03-01

Full Text Available Emerging information technologies present new opportunities to reduce the burden of malaria, dengue and other infectious diseases. For example, use of a data management system software package can help disease control programs to better manage and analyze their data, and thus enhances their ability to carry out continuous surveillance, monitor interventions and evaluate control program performance.We describe a novel multi-disease data management system platform (hereinafter referred to as the system with current capacity for dengue and malaria that supports data entry, storage and query. It also allows for production of maps and both standardized and customized reports. The system is comprised exclusively of software components that can be distributed without the user incurring licensing costs. It was designed to maximize the ability of the user to adapt the system to local conditions without involvement of software developers. Key points of system adaptability include 1 customizable functionality content by disease, 2 configurable roles and permissions, 3 customizable user interfaces and display labels and 4 configurable information trees including a geographical entity tree and a term tree. The system includes significant portions of functionality that is entirely or in large part re-used across diseases, which provides an economy of scope as new diseases downstream are added to the system at decreased cost.We have developed a system with great potential for aiding disease control programs in their task to reduce the burden of dengue and malaria, including the implementation of integrated vector management programs. Next steps include evaluations of operational implementations of the current system with capacity for dengue and malaria, and the inclusion in the system platform of other important vector-borne diseases.

Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases

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Tetsuro Tago

2018-01-01

Full Text Available Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs, which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the details of the interaction between changes in HDAC levels in the brain and disease progression remain unknown. In this review, we focus on recent advances in development of radioligands for HDAC imaging in the brain with positron emission tomography (PET. We summarize the results of radiosynthesis and biological evaluation of the HDAC ligands to identify their successful results and challenges. Since 2006, several small molecules that are radiolabeled with a radioisotope such as carbon-11 or fluorine-18 have been developed and evaluated using various assays including in vitro HDAC binding assays and PET imaging in rodents and non-human primates. Although most compounds do not readily cross the blood-brain barrier, adamantane-conjugated radioligands tend to show good brain uptake. Until now, only one HDAC radioligand has been tested clinically in a brain PET study. Further PET imaging studies to clarify age-related and disease-related changes in HDACs in disease models and humans will increase our understanding of the roles of HDACs in neurodegenerative diseases.

Enhanced immunization coverage through interventions for childhood cluster diseases in developing countries

International Nuclear Information System (INIS)

Mureed, S.; Somronghtong, R.; Kumar, R.

2015-01-01

Globally immunisation has to be considered as a most effective and efficient public health intervention to reduce morbidity and mortality among children. Most of the children from developing countries are still not fully immunized due to multiple factors including lack of interventions, awareness, and financial constraints and due to limited resource. Conversely, this review has identified the effectiveness of interventions to increase the immunisation coverage among children of developing countries. Methods: Systematic review by using PRISMA statement (preferred reporting items for systematic reviews and meta-analyses) has been conducted in English published articles on Pub Med, Scopus, Cochrane, Medline and ISI by searching keywords like immunizations, childhood vaccination and developing countries has been accessed. Only randomised controlled trial and quasi-experimental studies designs were included in the final analysis based on quality assessment by adopting the Down and Black checklist and finally pooled analysis was done by random effect model. This systematic review has been approved and registered by University of York. Results: A total of 16,570 published articles were accessed and finally 10 fulfilled our criteria that were analysed and interpreted. It demonstrated that the interventions has shown significantly increase vaccine coverage for childhood cluster diseases (OR 2.136 and p <0.05).Furthermore, it has been proved that an effect was more prominent for DTP (OR 2.397 and p<0.05) and measles (OR 2.628 and p<0.05), not as much for polio (OR 2.284 and p>0.05) and full vaccination schedule (OR 1.342 and p>0.05). Conclusions: Systematic review has concluded that the professional interventions are an effective while in improving the child immunisation coverage for cluster diseases in developing countries, major effect on DTP and measles. (author)

Genetic Influences on the Development of Fibrosis in Crohn's Disease

OpenAIRE

Verstockt, Bram; Cleynen, Isabelle

2016-01-01

Fibrostenotic strictures are an important complication in patients with Crohn’s disease (CD), very often necessitating surgery. This fibrotic process develops in a genetically susceptible individual and is influenced by an interplay with environmental, immunological, and disease-related factors. A deeper understanding of the genetic factors driving this fibrostenotic process might help to unravel the pathogenesis, and ultimately lead to development of new, anti-fibrotic therapy. Here, we revi...

Eye Disease and Development

DEFF Research Database (Denmark)

Andersen, Thomas Barnebeck; Dalgaard, Carl-Johan Lars; Selaya, Pablo

This research advances the hypothesis that cross-country variation in the historical incidence of eye disease has influenced the current global distribution of per capita income. The theory is that pervasive eye disease diminished the incentive to accumulate skills, thereby delaying the fertility...... transition and the take-off to sustained economic growth. In order to estimate the influence from eye disease incidence empirically, we draw on an important fact from the field of epidemiology: Exposure to solar ultraviolet B radiation (UVB-R) is an underlying determinant of several forms of eye disease...

A Comparison of Spatio-Temporal Disease Mapping Approaches Including an Application to Ischaemic Heart Disease in New South Wales, Australia

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Craig Anderson

2017-02-01

Full Text Available The field of spatio-temporal modelling has witnessed a recent surge as a result of developments in computational power and increased data collection. These developments allow analysts to model the evolution of health outcomes in both space and time simultaneously. This paper models the trends in ischaemic heart disease (IHD in New South Wales, Australia over an eight-year period between 2006 and 2013. A number of spatio-temporal models are considered, and we propose a novel method for determining the goodness-of-fit for these models by outlining a spatio-temporal extension of the Moran’s I statistic. We identify an overall decrease in the rates of IHD, but note that the extent of this health improvement varies across the state. In particular, we identified a number of remote areas in the north and west of the state where the risk stayed constant or even increased slightly.

Nutrition and Allergic Diseases

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R.J.J. van Neerven

2017-07-01

Full Text Available The development of IgE-mediated allergic diseases is influenced by many factors, including genetic and environmental factors such as pollution and farming, but also by nutrition. In the last decade, substantial progress has been made in our understanding of the impact that nutrition can have on allergic diseases. Many studies have addressed the effect of breastfeeding, pre-, pro- and synbiotics, vitamins and minerals, fiber, fruit and vegetables, cow’s milk, and n-3 fatty acids, on the development of allergies. In addition, nutrition can also have indirect effects on allergic sensitization. This includes the diet of pregnant and breastfeeding women, which influences intrauterine development, as well as breastmilk composition. These include the diet of pregnant and breastfeeding women that influences intrauterine development as well as breastmilk composition, effects of food processing that may enhance allergenicity of foods, and effects via modulation of the intestinal microbiota and their metabolites. This editorial review provides a brief overview of recent developments related to nutrition and the development and management of allergic diseases.

Genetic influences on the development of fibrosis in Crohn’s Disease

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Bram eVerstockt

2016-05-01

Full Text Available Fibrostenotic strictures are an important complication in patients with Crohn’s Disease, very often necessitating surgery. This fibrotic process develops in a genetically susceptible individual, and is influenced by an interplay with environmental, immunological and disease-related factors. A deeper understanding of the genetic factors driving this fibrostenotic process might help to unravel the pathogenesis, and ultimately lead to development of new, anti-fibrotic therapy. Here we review the genetic factors that have been associated with the development of fibrosis in patients with Crohn’s disease, as well as their potential pathophysiological mechanism(s. We also hypothesize on clinical implications if any, and future research directions.

Varied autopsy findings in five treated patients with Gaucher disease and parkinsonism include the absence of Gaucher cells.

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Monestime, Gianina; Borger, Daniel K; Kim, Jenny; Lopez, Grisel; Allgaeuer, Michael; Jain, Dhanpat; Vortmeyer, Alexander; Wang, Hao-Wei; Sidransky, Ellen

2016-05-01

Enzyme replacement therapy is standard of care for patients with Gaucher disease, as it significantly improves skeletal, visceral, and hematological symptoms. Few pathological studies have documented the extent of pathological findings in treated patients. Autopsy findings in five treated patients, who ultimately developed parkinsonism, ranged from the complete absence of Gaucher pathology to extensive involvement of multiple tissues, without correlation to age, genotype, spleen status, or dose/duration of therapy. Additional autopsies may elucidate modifiers and biomarkers contributing to disease burden and response to therapy. Published by Elsevier Inc.

General Diseases Influence on Peri-Implantitis Development: a Systematic Review

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Zygimantas Guobis

2016-09-01

Full Text Available Objectives: To systematically review the influence of systemic diseases or medications used in their treatment on the dental implant therapy success. Material and Methods: The search strategy was implemented on the National Library of Medicine database (MEDLINE (Ovid and EMBASE electronic databases between January 2006 and January 2016. Human studies with available English articles analysing the relationship between dental implant therapy success and systemic diseases, such as diabetes mellitus, AIDS/HIV, rheumatoid arthritis, osteoporosis, Crohn’s disease, cardiovascular diseases, scleroderma, Sjögren’s syndrome, lichen planus, ectodermal dysplasia, post-transplantation status, were included in present review according to the PRISMA guidelines. The review protocol was registered on PROSPERO system with the code CRD42016033662. Results: Present review included forty one retrospective and prospective follow-up studies, case-control studies, case report series and cohort studies. Despite some limitations this study reveals positive results of implantation in most systemic conditions that should be interpreted with caution. Influence of cardiovascular diseases on the dental implantation success should be explored deeply, because of controversial results and likelihood of comorbidity expressed by a history of cardiovascular diseases and periodontitis. There is only a weak relationship with bone density in osteoporosis and implant failure. All the other diseases did not show significant effect on implantation success. Conclusions: Recent studies with low strength of evidence and controversy show that systemic diseases may have potential effect on the success of implantation, but further detailed studies are needed to provide these findings.

Origins and Hallmarks of Macrophages: Development, Homeostasis, and Disease

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Wynn, Thomas A.; Chawla, Ajay; Pollard, Jeffrey W.

2013-01-01

Preface Macrophages the most plastic cells of the hematopoietic system are found in all tissues and exhibit great functional diversity. They have roles in development, homeostasis, tissue repair, and immunity. While anatomically distinct, resident tissue macrophages exhibit different transcriptional profiles, and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this review, we discuss how macrophages regulate normal physiology and development and provide several examples of their pathophysiologic roles in disease. We define the “hallmarks” of macrophages performing particular functions, taking into account novel insights into the diversity of their lineages, identity, and regulation. This diversity is essential to understand because macrophages have emerged as important therapeutic targets in many important human diseases. PMID:23619691

Surgical management of inflammatory bowel disease: A low prevalence, developing country perspective.

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Nasim, Sana; Chawla, Tabish; Murtaza, Ghulam

2016-03-01

To determine the outcomes of surgical management of inflammatory bowel disease. The retrospective case series was conducted at Aga Khan University Hospital, Karachi, and comprised medical record of adult patients operated between January 1986 and December 2010 for inflammatory bowel disease. Outcomes consisted of complications till last follow-up and 30-day mortality (disease or procedure related). Functional status of patients with ileal pouch was determined via telephone. SPSS 16 was used to analyse data. Of the 36 patients whose records were reviewed, 21(58%) were males, and body mass index was less than 23 in 34(91%). A total of 27(75%) patients underwent elective surgery for their condition. Ileal pouch was formed in 9(25%). Overall mortality was 14(38.8%). Overall incidence of complications was 26(72%), with wound infection being the most common early morbidity in 11(30.5%). Late morbidity included pouchitisin 4/9 (44.9%) and strictures 2/36 (5.5%).On telephonic follow-up, 6 of the remaining 7patients (85%) with ileal pouch were satisfied with the functional results of the procedure. The retrospective case series represents results from a developing country with low prevalence of inflammatory bowel disease and hence limited experience.

Recent developments in epigenetics of acute and chronic kidney diseases.

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Reddy, Marpadga A; Natarajan, Rama

2015-08-01

The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

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Molins, Claudia R.; Sexton, Christopher; Young, John W.; Ashton, Laura V.; Pappert, Ryan; Beard, Charles B.

2014-01-01

Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first- and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests. PMID:25122862

Developing Community-Based Rehabilitation Programs for Musculoskeletal Diseases in Low-Income Areas of Mexico: The Community-Based Rehabilitation for Low-Income Communities Living With Rheumatic Diseases (CONCORD) Protocol

Science.gov (United States)

2014-01-01

Background The negative impact of musculoskeletal diseases on the physical function and quality of life of people living in developing countries is considerable. This disabling effect is even more marked in low-socioeconomic communities within developing countries. In Mexico, there is a need to create community-based rehabilitation programs for people living with musculoskeletal diseases in low-socioeconomic areas. These programs should be directed to prevent and decrease disability, accommodating the specific local culture of communities. Objective The objective of this paper is to describe a research protocol designed to develop, implement, and evaluate culturally sensitive community-based rehabilitation programs aiming to decrease disability of people living with musculoskeletal diseases in two low-income Mexican communities. Methods A community-based participatory research approach is proposed, including multi and transdisciplinary efforts among the community, medical anthropology, and the health sciences. The project is structured in 4 main stages: (1) situation analysis, (2) program development, (3) program implementation, and (4) program evaluation. Each stage includes the use of quantitative and qualitative methods (mixed method program). Results So far, we obtained resources from a Mexican federal agency and completed stage one of the project at Chankom, Yucatán. We are currently receiving funding from an international agency to complete stage two at this same location. We expect that the project at Chankom will be concluded by December of 2017. On the other hand, we just started the execution of stage one at Nuevo León with funding from a Mexican federal agency. We expect to conclude the project at this site by September of 2018. Conclusions Using a community-based participatory research approach and a mixed method program could result in the creation of culturally sensitive community-based rehabilitation programs that promote community development and

Development of a disease-specific quality of life questionnaire in Addison's disease.

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Løvås, Kristian; Curran, Suzanne; Oksnes, Marianne; Husebye, Eystein S; Huppert, Felicia A; Chatterjee, V Krishna K

2010-02-01

Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL). We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects. Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's alpha and Rasch analysis. Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's alpha 0.95 and Person Separation Index 0.94 (Rasch analysis). We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).

FGF10: A multifunctional mesenchymal-epithelial signaling growth factor in development, health, and disease.

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Itoh, Nobuyuki

2016-04-01

The FGF family comprises 22 members with diverse functions in development and health. FGF10 specifically activates FGFR2b in a paracrine manner with heparan sulfate as a co-factor. FGF10and FGFR2b are preferentially expressed in the mesenchyme and epithelium, respectively. FGF10 is a mesenchymal signaling molecule in the epithelium. FGF10 knockout mice die shortly after birth due to the complete absence of lungs as well as fore- and hindlimbs. FGF10 is also essential for the development of multiple organs. The phenotypes of Fgf10 knockout mice are very similar to those of FGFR2b knockout mice, indicating that FGF10 acts as a ligand that is specific to FGFR2b in mouse multi-organ development. FGF10 also plays roles in epithelial-mesenchymal transition, the repair of tissue injury, and embryonic stem cell differentiation. In humans, FGF10 loss-of-function mutations result in inherited diseases including aplasia of lacrimal and salivary gland, lacrimo-auriculo-dento-digital syndrome, and chronic obstructive pulmonary disease. FGF10 is also involved in the oncogenicity of pancreatic and breast cancers. Single nucleotide polymorphisms in FGF10 are also potential risk factors for limb deficiencies, cleft lip and palate, and extreme myopia. These findings indicate that FGF10 is a crucial paracrine signal from the mesenchyme to epithelium for development, health, and disease. Copyright © 2015. Published by Elsevier Ltd.

Arterial innervation in development and disease.

Science.gov (United States)

Eichmann, Anne; Brunet, Isabelle

2014-09-03

Innervation of arteries by sympathetic nerves is well known to control blood supply to organs. Recent studies have elucidated the mechanisms that regulate the development of arterial innervation and show that in addition to vascular tone, sympathetic nerves may also influence arterial maturation and growth. Understanding sympathetic arterial innervation may lead to new approaches to treat peripheral arterial disease and hypertension. Copyright © 2014, American Association for the Advancement of Science.

Polio eradication initiative in Africa: influence on other infectious disease surveillance development

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Cochi Stephen

2002-12-01

Full Text Available Abstract Background The World Health Organization (WHO and partners are collaborating to eradicate poliomyelitis. To monitor progress, countries perform surveillance for acute flaccid paralysis (AFP. The WHO African Regional Office (WHO-AFRO and the U.S Centers for Disease Control and Prevention are also involved in strengthening infectious disease surveillance and response in Africa. We assessed whether polio-eradication initiative resources are used in the surveillance for and response to other infectious diseases in Africa. Methods During October 1999-March 2000, we developed and administered a survey questionnaire to at least one key informant from the 38 countries that regularly report on polio activities to WHO. The key informants included WHO-AFRO staff assigned to the countries and Ministry of Health personnel. Results We obtained responses from 32 (84% of the 38 countries. Thirty-one (97% of the 32 countries had designated surveillance officers for AFP surveillance, and 25 (78% used the AFP resources for the surveillance and response to other infectious diseases. In 28 (87% countries, AFP program staff combined detection for AFP and other infectious diseases. Fourteen countries (44% had used the AFP laboratory specimen transportation system to transport specimens to confirm other infectious disease outbreaks. The majority of the countries that performed AFP surveillance adequately (i.e., non polio AFP rate = 1/100,000 children aged Conclusions Despite concerns regarding the targeted nature of AFP surveillance, it is partially integrated into existing surveillance and response systems in multiple African countries. Resources provided for polio eradication should be used to improve surveillance for and response to other priority infectious diseases in Africa.

Gap analysis of Mycoplasma bovis disease, diagnosis and control: An aid to identify future development requirements.

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Calcutt, M J; Lysnyansky, I; Sachse, K; Fox, L K; Nicholas, R A J; Ayling, R D

2018-05-01

There is a worldwide problem of disease caused by Mycoplasma (M.) bovis in cattle; it has a significant detrimental economic and animal welfare impact on cattle rearing. Infection can manifest as a plethora of clinical signs including mastitis, pneumonia, arthritis, keratoconjunctivitis, otitis media and genital disorders that may result in infertility and abortion. Current diagnosis and control information are reviewed and analysed to identify gaps in knowledge of the causative organism in respect of the disease pathology, diagnosis and control methods. The main considerations are as follows: no vaccines are commercially available; antimicrobial resistance is increasing; diagnostic and antimicrobial sensitivity testing needs to be improved; and a pen-side test would facilitate more rapid diagnosis and implementation of treatment with antimicrobials. More data on host susceptibility, stress factors, immune response and infectious dose levels are required. The impact of asymptomatic carriers, M. bovis survival in the environment and the role of wildlife in transmitting the disease also needs investigation. To facilitate development of vaccines, further analysis of more M. bovis genomes, its pathogenic mechanisms, including variable surface proteins, is required, along with reproducible disease models. © 2018 Blackwell Verlag GmbH.

Developing stochastic epidemiological models to quantify the dynamics of infectious diseases in domestic livestock.

Science.gov (United States)

MacKenzie, K; Bishop, S C

2001-08-01

A stochastic model describing disease transmission dynamics for a microparasitic infection in a structured domestic animal population is developed and applied to hypothetical epidemics on a pig farm. Rational decision making regarding appropriate control strategies for infectious diseases in domestic livestock requires an understanding of the disease dynamics and risk profiles for different groups of animals. This is best achieved by means of stochastic epidemic models. Methodologies are presented for 1) estimating the probability of an epidemic, given the presence of an infected animal, whether this epidemic is major (requires intervention) or minor (dies out without intervention), and how the location of the infected animal on the farm influences the epidemic probabilities; 2) estimating the basic reproductive ratio, R0 (i.e., the expected number of secondary cases on the introduction of a single infected animal) and the variability of the estimate of this parameter; and 3) estimating the total proportion of animals infected during an epidemic and the total proportion infected at any point in time. The model can be used for assessing impact of altering farm structure on disease dynamics, as well as disease control strategies, including altering farm structure, vaccination, culling, and genetic selection.

Histone methylations in heart development, congenital and adult heart diseases.

Science.gov (United States)

Zhang, Qing-Jun; Liu, Zhi-Ping

2015-01-01

Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases.

Learning lessons from operational research in infectious diseases: can the same model be used for noncommunicable diseases in developing countries?

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Bosu WK

2014-12-01

Full Text Available William K Bosu Department of Epidemics and Disease Control, West African Health Organisation, Bobo-Dioulasso, Burkina Faso Abstract: About three-quarters of global deaths from noncommunicable diseases (NCDs occur in developing countries. Nearly a third of these deaths occur before the age of 60 years. These deaths are projected to increase, fueled by such factors as urbanization, nutrition transition, lifestyle changes, and aging. Despite this burden, there is a paucity of research on NCDs, due to the higher priority given to infectious disease research. Less than 10% of research on cardiovascular diseases comes from developing countries. This paper assesses what lessons from operational research on infectious diseases could be applied to NCDs. The lessons are drawn from the priority setting for research, integration of research into programs and routine service delivery, the use of routine data, rapid-assessment survey methods, modeling, chemoprophylaxis, and the translational process of findings into policy and practice. With the lines between infectious diseases and NCDs becoming blurred, it is justifiable to integrate the programs for the two disease groups wherever possible, eg, screening for diabetes in tuberculosis. Applying these lessons will require increased political will, research capacity, ownership, use of local expertise, and research funding. Keywords: infectious diseases, noncommunicable diseases, operational research, developing countries, integration

De novo development of artistic creativity in Alzheimer's disease.

Science.gov (United States)

Chakravarty, Ambar

2011-10-01

The case of an 82-year-old female with probable Alzheimer's disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed.

Epigenetics of kidney disease.

Science.gov (United States)

Wanner, Nicola; Bechtel-Walz, Wibke

2017-07-01

DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

Science.gov (United States)

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

Interactive Media on Chagas Disease: Development and Content

Directory of Open Access Journals (Sweden)

Claudinei Caetano de Souza

2013-10-01

Full Text Available An interactive media on Chagas disease was developed as an educational tool, on the context of the scientific research and dissemination actions of the National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases (INBEQMeDI. Different computational resources were used either in terms of hardware and software. The media contains 13 videos that range from 30 seconds to 4 minutes, all with information about Chagas disease, showing the social and economic aspects; the research made by the INBEQMeDI group; different aspects of the disease illustrated by slides arranged in a mobile carousel, and radio programs, with funny skits. The target audience for use of this feature is students aged 10 to 17 years. Teachers of areas of science and biology, through a partnership with the Agency of Education of the State of São Paulo, will be invited to plan a strategy for media use with their students.

Coronary Artery Disease - Coronary Heart Disease

Science.gov (United States)

... not as great as men's. Heredity (Including Race) Children of parents with heart disease are more likely to develop it themselves. African Americans have more severe high blood pressure than Caucasians and a higher risk of heart ...

Developing markers for Sigatoka leaf spot disease (Mycosphaerella ...

African Journals Online (AJOL)

Jane

2011-07-06

Jul 6, 2011 ... Developing markers for Sigatoka leaf spot disease ... OPERON primer pairs were used to screen genomic DNA from two resistant cultivars: Calcutta 4 ( ..... Blomme G, Eden-Green S, Mustaffa M, Nwauzoma B, Thangavelu R.

Alzheimer's disease: A review of recent developments | Salawu ...

African Journals Online (AJOL)

The subject headings and keywords used were Alzheimer's disease, dementia, primary neuronal degeneration and senile plagues. Only the articles written in English were included. The diagnosis is still primarily made based on history and physical and neurologic examinations. Approved treatments are few and of limited ...

Screen-detected gallstone disease and cardiovascular disease

DEFF Research Database (Denmark)

Shabanzadeh, Daniel Mønsted; Skaaby, Tea; Sørensen, Lars Tue

2017-01-01

Knowledge about temporal associations for screen-detected gallstone disease and cardiovascular disease is limited. The objective of this study was to determine if screen-detected gallstones or cholecystectomy was associated with development of cardiovascular disease. A cohort study of three...... of cardiovascular disease through nationwide registers until December 2014. Multivariable Cox regression analyses were performed including traditional cardiovascular disease risk factors and apolipoprotein E genotype. Gallstone disease was identified in 10% (591/5928) of participants at baseline of whom 6.8% had...... gallstones and 3.2% had cholecystectomy. The study population was followed for a period of 32 years with only 1% lost to follow-up. Gallstone disease was associated with all cardiovascular disease (hazard ratio (HR) 1.36, 95% confidence interval (CI) [1.17;1.59]) and to the subgroups coronary artery (HR 1...

Gene-Environment Interactions in the Development of Complex Disease Phenotypes

Directory of Open Access Journals (Sweden)

Kenneth Olden

2008-03-01

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

Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice

Science.gov (United States)

Sharpton, Thomas; Lyalina, Svetlana; Luong, Julie; Pham, Joey; Deal, Emily M.; Armour, Courtney; Gaulke, Christopher; Sanjabi, Shomyseh

2017-01-01

ABSTRACT The gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late-stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regard to function. To investigate microbiome-mediated disease mechanisms and discover early biomarkers of IBD, we conducted a longitudinal metagenomic investigation in an established mouse model of IBD, where damped transforming growth factor β (TGF-β) signaling in T cells leads to peripheral immune activation, weight loss, and severe colitis. IBD development is associated with abnormal gut microbiome temporal dynamics, including damped acquisition of functional diversity and significant differences in abundance trajectories for KEGG modules such as glycosaminoglycan degradation, cellular chemotaxis, and type III and IV secretion systems. Most differences between sick and control mice emerge when mice begin to lose weight and heightened T cell activation is detected in peripheral blood. However, levels of lipooligosaccharide transporter abundance diverge prior to immune activation, indicating that it could be a predisease indicator or microbiome-mediated disease mechanism. Taxonomic structure of the gut microbiome also significantly changes in association with IBD development, and the abundances of particular taxa, including several species of Bacteroides, correlate with immune activation. These discoveries were enabled by our use of generalized linear mixed-effects models to test for differences in longitudinal profiles between healthy and diseased mice while accounting for the distributions of taxon and gene counts in metagenomic data. These findings demonstrate that longitudinal metagenomics is useful for discovering the potential mechanisms through which the gut microbiome becomes altered in IBD. IMPORTANCE IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people

Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice.

Science.gov (United States)

Sharpton, Thomas; Lyalina, Svetlana; Luong, Julie; Pham, Joey; Deal, Emily M; Armour, Courtney; Gaulke, Christopher; Sanjabi, Shomyseh; Pollard, Katherine S

2017-01-01

The gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late-stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regard to function. To investigate microbiome-mediated disease mechanisms and discover early biomarkers of IBD, we conducted a longitudinal metagenomic investigation in an established mouse model of IBD, where damped transforming growth factor β (TGF-β) signaling in T cells leads to peripheral immune activation, weight loss, and severe colitis. IBD development is associated with abnormal gut microbiome temporal dynamics, including damped acquisition of functional diversity and significant differences in abundance trajectories for KEGG modules such as glycosaminoglycan degradation, cellular chemotaxis, and type III and IV secretion systems. Most differences between sick and control mice emerge when mice begin to lose weight and heightened T cell activation is detected in peripheral blood. However, levels of lipooligosaccharide transporter abundance diverge prior to immune activation, indicating that it could be a predisease indicator or microbiome-mediated disease mechanism. Taxonomic structure of the gut microbiome also significantly changes in association with IBD development, and the abundances of particular taxa, including several species of Bacteroides , correlate with immune activation. These discoveries were enabled by our use of generalized linear mixed-effects models to test for differences in longitudinal profiles between healthy and diseased mice while accounting for the distributions of taxon and gene counts in metagenomic data. These findings demonstrate that longitudinal metagenomics is useful for discovering the potential mechanisms through which the gut microbiome becomes altered in IBD. IMPORTANCE IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people. But is

Developing standard transmission system for radiology reporting including key images

International Nuclear Information System (INIS)

Kim, Seon Chil

2007-01-01

Development of hospital information system and Picture Archiving Communication System is not new in the medical field, and the development of internet and information technology are also universal. In the course of such development, however, it is hard to share medical information without a refined standard format. Especially in the department of radiology, the role of PACS has become very important in interchanging information with other disparate hospital information systems. A specific system needs to be developed that radiological reports are archived into a database efficiently. This includes sharing of medical images. A model is suggested in this study in which an internal system is developed where radiologists store necessary images and transmit them is the standard international clinical format, Clinical Document Architecture, and share the information with hospitals. CDA document generator was made to generate a new file format and separate the existing storage system from the new system. This was to ensure the access to required data in XML documents. The model presented in this study added a process where crucial images in reading are inserted in the CDA radiological report generator. Therefore, this study suggests a storage and transmission model for CDA documents, which is different from the existing DICOM SR. Radiological reports could be better shared, when the application function for inserting images and the analysis of standard clinical terms are completed

Reliability and limitation of various diagnostic methods including nuclear medicine in myocardial disease

International Nuclear Information System (INIS)

Tokuyasu, Yoshiki; Kusakabe, Kiyoko; Yamazaki, Toshio

1981-01-01

Electrocardiography (ECG), echocardiography, nuclear method, cardiac catheterization, left ventriculography and endomyocardial biopsy (biopsy) were performed in 40 cases of cardiomyopathy (CM), 9 of endocardial fibroelastosis and 19 of specific heart muscle disease, and the usefulness and limitation of each method was comparatively estimated. In CM, various methods including biopsy were performed. The 40 patients were classified into 3 groups, i.e., hypertrophic (17), dilated (20) and non-hypertrophic.non-dilated (3) on the basis of left ventricular ejection fraction and hypertrophy of the ventricular wall. The hypertrophic group was divided into 4 subgroups: 9 septal, 4 apical, 2 posterior and 2 anterior. The nuclear study is useful in assessing the site of the abnormal ventricular thickening, perfusion defect and ventricular function. Echocardiography is most useful in detecting asymmetric septal hypertrophy. The biopsy gives the sole diagnostic clue, especially in non-hypertrophic.non-dilated cardiomyopathy. ECG is useful in all cases but correlation with the site of disproportional hypertrophy was not obtained. (J.P.N.)

Diabetes and the Risk of Developing Parkinson’s Disease in Denmark

OpenAIRE

Schernhammer, Eva S; Hansen, Johnni; Rugbjerg, Kathrine; Wermuth, Lene; Ritz, Beate

2011-01-01

Objective: Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson’s disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs was associated with Parkinson’s disease. Research Design and Methods: From the nationwide Danish Hospital Register hospital records, we identified 1,931 patients with a first-time diagnosis of ...

78 FR 66747 - Sickle Cell Disease Public Meeting on Patient-Focused Drug Development

Science.gov (United States)

2013-11-06

... effects have the greatest impact on your life? (Examples may include pain crises, breathing problems... negative effects of your sickle cell disease? Please describe these treatments, which may include blood... you do to prevent or treat any negative effects of your sickle cell disease? Please describe any...

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

Science.gov (United States)

Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

From research on rare diseases to new orphan drug development

NARCIS (Netherlands)

Heemstra, H.E.

2010-01-01

Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs

Developing a Continuous Quality Improvement Assessment Using a Patient-Centered Approach in Optimizing Systemic Lupus Erythematosus Disease Control.

Science.gov (United States)

Updyke, Katelyn Mariko; Urso, Brittany; Beg, Shazia; Solomon, James

2017-10-09

Systemic lupus erythematosus (SLE) is a multi-organ, autoimmune disease in which patients lose self-tolerance and develop immune complexes which deposit systemically causing multi-organ damage and inflammation. Patients often experience unpredictable flares of symptoms with poorly identified triggers. Literature suggests exogenous exposures may contribute to flares in symptoms. An online pilot survey was marketed globally through social media to self-reported SLE patients with the goal to identify specific subpopulations who are susceptible to disease state changes based on analyzed exogenous factors. The pilot survey was promoted for two weeks, 80 respondents fully completed the survey and were included in statistical analysis. Descriptive statistical analysis was performed on de-identified patient surveys and compared to previous literature studies reporting known or theorized triggers in the SLE disease state. The pilot survey identified similar exogenous triggers compared to previous literature, including antibiotics, increasing beef intake, and metal implants. The goal of the pilot survey is to utilize similar questions to develop a detailed internet-based patient interactive form that can be edited and time stamped as a method to promote continuous quality improvement assessments. The ultimate objective of the platform is to interact with SLE patients from across the globe longitudinally to optimize disease control and improve quality of care by allowing them to avoid harmful triggers.

Developing community-driven quality improvement initiatives to enhance chronic disease care in Indigenous communities in Canada: the FORGE AHEAD program protocol.

Science.gov (United States)

Naqshbandi Hayward, Mariam; Paquette-Warren, Jann; Harris, Stewart B

2016-07-26

Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed. The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013-2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations. The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to

Development of a metabolic biosignature for detection of early Lyme disease.

Science.gov (United States)

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Hess, Ann M; Delorey, Mark J; Mahapatra, Sebabrata; Schriefer, Martin E; Belisle, John T

2015-06-15

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. 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. 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. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Development of the Crohn's disease digestive damage score, the Lémann score

DEFF Research Database (Denmark)

Pariente, Benjamin; Cosnes, Jacques; Danese, Silvio

2011-01-01

is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lémann score), should take...

Obesity and cardiovascular disease in developing countries: a growing problem and an economic threat.

Science.gov (United States)

Raymond, Susan U; Leeder, Stephen; Greenberg, Henry M

2006-03-01

This review examines the rise of risk factors for cardiovascular disease, especially obesity, in developing countries and the implications for both health and economics. In the majority of developing countries fertility and infant and child mortality have fallen markedly, and life expectancies have increased. Rapid urbanization, falling food prices, and globalization of economies have contributed to an increase in risk factors for chronic disease. Recent work indicates that the prevalence of these risk factors, including obesity, is rising faster than the historical experience of the West. The transition is affecting women in particular, and increases in risk factors are more marked among lower incomes in growing economies than among the wealthy. Rather than the stereotypical problem of the rich, chronic disease is now a problem for the poor. Significant research in this area of global health has only been undertaken in the last decade. Additional field research is needed in every dimension of the transition, both to document the problem itself and to determine its economic and societal impact and cost effective responses. Two critical factors are virtually absent from existing work and should be emphasized. First, the impact of rising risk factors for, and mortality from, cardiovascular disease in the work force may imply a growing threat to continued economic progress. Second, because risk factor reduction requires society-wide strategies, broad public-private coalitions will be needed to mobilize sectors beyond healthcare.

Lower urinary tract development and disease

Science.gov (United States)

Rasouly, Hila Milo; Lu, Weining

2013-01-01

Congenital Anomalies of the Lower Urinary Tract (CALUT) are a family of birth defects of the ureter, the bladder and the urethra. CALUT includes ureteral anomalies such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUV). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, bladder, and urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, bladder and urethra and associated gene mutations are also presented. As we are entering the post-genomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. PMID:23408557

77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

Science.gov (United States)

2012-10-01

...] Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public Workshop... to the clinical development of disease-modifying agents for the treatment of peripheral neuropathy... disease-modifying products for the management of peripheral neuropathy. Date and Time: The public workshop...

Development of a disease-specific instrument to measure quality of life in patients with alopecia areata.

Science.gov (United States)

Endo, Yuichiro; Miyachi, Yoshiki; Arakawa, Akiko

2012-01-01

Alopecia areata (AA) is a common hair loss disorder that frequently follows a chronic course. Although AA is apparently associated with disturbance of quality of life (QoL), no disease-specific instrument to measure the QoL has been developed. This study was conducted to develop a disease-specific self-administered instrument to measure AA patients' QoL (AAQ). A two-step cross-sectional study was conducted. Items were generated from qualitative interviews with five patients with AA (two men and three women, age 28±6.4 years). Then, a preliminary questionnaire was produced and delivered to the patients (n=122). The AAQ was examined in terms of statistical performance. The AAQ included 7 items in the following three subscales: 'restriction of activity', 'concealment' and 'adaptation'. The reliability of internal consistency was fair with Cronbach's alpha coefficients of 0.59-81 for each subscale. Confirmatory factor analysis and correlation analysis demonstrated that the AAQ had good construct validity. Interestingly, the AAQ was only correlated with subjective severity scores as rated by the patients, but not with objective disease severity assessed by investigators.

Ustekinumab in treatment of Crohn’s disease: design, development, and potential place in therapy

Directory of Open Access Journals (Sweden)

Deepak P

2016-11-01

Full Text Available Parakkal Deepak, Edward V Loftus Jr Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA Abstract: Crohn’s disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23 pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis. Very promising data have emerged through phase II and phase III trials (UNITI-1, UNITI-2, and IM-UNITI for both induction and maintenance of clinical response and remission in moderate-to-severe Crohn’s disease, resulting in approval by the Food and Drug Administration for this condition. This article reviews the immunology of the IL-12/23 pathway, available data regarding the initial designing of ustekinumab, drug development through clinical trials including pharmacokinetics, efficacy, and safety, and its potential place in the treatment of Crohn’s disease.Keywords: ustekinumab, Crohn’s disease, inflammatory bowel disease, interleukin-12/23 monoclonal antibody, interleukin-12, interleukin-23

Geography, ecology and emerging infectious diseases.

Science.gov (United States)

Mayer, J D

2000-04-01

Emerging infectious diseases are the focus of increased attention and even alarm in the scholarly and popular literature. The emergence of new diseases and the resurgence of older and previously recognized infectious diseases both in developing and developed country poses challenges for understanding the ecological web of causation, including social, economic, environmental and biological components. This paper is a synthesis of the major characteristics of emerging diseases, in an interdisciplinary context. Political ecology is one framework for analysis that is promising in developing a modified ecology of disease.

Double burden of noncommunicable and infectious diseases in developing countries

DEFF Research Database (Denmark)

Bygbjerg, I C

2012-01-01

On top of the unfinished agenda of infectious diseases in low- and middle-income countries, development, industrialization, urbanization, investment, and aging are drivers of an epidemic of noncommunicable diseases (NCDs). Malnutrition and infection in early life increase the risk of chronic NCDs...... for limited funds, is an important policy consideration requiring new thinking and approaches....

Animal models of cardiovascular diseases.

Science.gov (United States)

Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begoña; Mallavia, Beñat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus

2011-01-01

Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

Risk Matrix for Prediction of Disease Progression in a Referral Cohort of Patients with Crohn's Disease.

Science.gov (United States)

Lakatos, Peter L; Sipeki, Nora; Kovacs, Gyorgy; Palyu, Eszter; Norman, Gary L; Shums, Zakera; Golovics, Petra A; Lovasz, Barbara D; Antal-Szalmas, Peter; Papp, Maria

2015-10-01

Early identification of patients with Crohn's disease (CD) at risk of subsequent complications is essential for adapting the treatment strategy. We aimed to develop a prediction model including clinical and serological markers for assessing the probability of developing advanced disease in a prospective referral CD cohort. Two hundred and seventy-one consecutive CD patients (42.4% males, median follow-up 108 months) were included and followed up prospectively. Anti-Saccharomyces cerevisiae antibodies (ASCA IgA/IgG) were determined by enzyme-linked immunosorbent assay. The final analysis was limited to patients with inflammatory disease behaviour at diagnosis. The final definition of advanced disease outcome was having intestinal resection or disease behaviour progression. Antibody (ASCA IgA and/or IgG) status, disease location and need for early azathioprine were included in a 3-, 5- and 7-year prediction matrix. The probability of advanced disease after 5 years varied from 6.2 to 55% depending on the combination of predictors. Similar findings were obtained in Kaplan-Meier analysis; the combination of ASCA, location and early use of azathioprine was associated with the probability of developing advanced disease (p < 0.001, log rank test). Our prediction models identified substantial differences in the probability of developing advanced disease in the early disease course of CD. Markers identified in this referral cohort were different from those previously published in a population-based cohort, suggesting that different prediction models should be used in the referral setting. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Development and characterization of targeted poly(NIPAm) nanoparticles for delivery of anti-inflammatory peptides in peripheral artery disease and osteoarthritis

Science.gov (United States)

McMasters, James F.

Inflammation is the underlying cause of several severe diseases including cardiovascular disease and osteoarthritis. Peripheral artery disease (PAD) is characterized by atherosclerotic occlusions within the peripheral vasculature. Current treatment for severe PAD involves mechanical widening of the artery via percutaneous transluminal angioplasty. Unfortunately, deployment of the balloon damages the endothelial layer, exposing the underlying collagenous matrix. Circulating platelets can bind to this collagen and become activated, releasing proinflammatory cytokines that promote proliferation of local smooth muscle cells. These proliferating cells eventually reocclude the vessel, resulting in restenosis and necessitating the need for a second procedure to reopen the vessel. Current treatments for moderate osteoarthritis include local injection of anti-inflammatory compounds such as glucocorticoids. Unfortunately, prolonged treatment carries with it significant side effects including osteoporosis, and cardiovascular complications. Our lab has developed an anti-inflammatory cell-penetrating peptide that inhibits mitogen-activated protein kinase activated protein kinase 2 (MK2). MK2 is implicated in the inflammatory cascade of atherosclerosis and osteoarthritis, making it a potentially effective strategy for reducing inflammation in both disease states. Unfortunately, these peptides are untargeted and quickly degraded in the presence of serum proteases, making the development of an effective delivery system of paramount importance. The overall goal of the research presented here is to detail the development of a poly(N-isopropylacrylamide) nanoparticle that is able to effectively load and release anti-inflammatory peptides for the treatment of these inflammatory diseases. In this dissertation, I will discuss the development of a collagen-binding nanoparticle that is able to inhibit platelet binding following angioplasty, thereby halting the initial inflammatory cascade

Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development.

Science.gov (United States)

Sommerfeld, J; Oduola, A M J

2007-01-01

The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.

Association between periodontal disease and cardiovascular disease

International Nuclear Information System (INIS)

Rehman, M.M.; Salama, R.P.

2004-01-01

Studies have supported the notion that subjects with periodontitis and patients with multiple tooth extractions as a result of chronic advanced periodontal disease (PDD) have a greater risk of developing Cardiovascular disease (CVD) than those who had little or no periodontal infection. Periodontitis may predispose affected patients to CVD by elevating systemic C-reactive protein level and pro-inflammatory activity in atherosclerotic lesions and accelerate development of cardiovascular diseases, Oral health variables including loss of teeth, positive plaque Benzoyl-D-L-Arginine- Naphthyl Amide test (BANA) scores, and compliant of xerostomia may by considered as risk indicators for CVD. Exact mechanism which links PDD and CVD has not been firmly established. The link between PDD and CVD may be attributed to bacteria entering blood stream and attaching to the fatty plaque in coronary artery and contributing to clot formation which can lead to heart attack. Inflammation caused by PDD increases the plaque build up. The association between the two disease entities is cause for concern. However, dental and medical practitioners should be aware of these findings to move intelligently to interact with inquiring patients with periodontitis. They should be urged to maintain medical surveillance of their cardiovascular status, and work on controlling or reducing all known risk factors associated with CVD, including periodontal infection. (author)

Association between periodontal disease and cardiovascular disease

Energy Technology Data Exchange (ETDEWEB)

Rehman, M M; Salama, R P [Ajman Univ. of Science and Technology Network, Abu-Dhabi Campus (United Arab Emirates)

2004-06-01

Studies have supported the notion that subjects with periodontitis and patients with multiple tooth extractions as a result of chronic advanced periodontal disease (PDD) have a greater risk of developing Cardiovascular disease (CVD) than those who had little or no periodontal infection. Periodontitis may predispose affected patients to CVD by elevating systemic C-reactive protein level and pro-inflammatory activity in atherosclerotic lesions and accelerate development of cardiovascular diseases, Oral health variables including loss of teeth, positive plaque Benzoyl-D-L-Arginine- Naphthyl Amide test (BANA) scores, and compliant of xerostomia may by considered as risk indicators for CVD. Exact mechanism which links PDD and CVD has not been firmly established. The link between PDD and CVD may be attributed to bacteria entering blood stream and attaching to the fatty plaque in coronary artery and contributing to clot formation which can lead to heart attack. Inflammation caused by PDD increases the plaque build up. The association between the two disease entities is cause for concern. However, dental and medical practitioners should be aware of these findings to move intelligently to interact with inquiring patients with periodontitis. They should be urged to maintain medical surveillance of their cardiovascular status, and work on controlling or reducing all known risk factors associated with CVD, including periodontal infection. (author)

Development of smartphone educational application for patients with coronary artery disease.

Science.gov (United States)

Cho, Min Jung; Sim, Jae Lan; Hwang, Seon Young

2014-04-01

This study was conducted to develop a smartphone application (app) as an educational learning instrument for coronary artery disease (CAD) patients and to assess the users' level of satisfaction. This methodological research involves elicited learning content for CAD patients to develop a learning instrument using the smartphone app. The app was developed according to the steps of Assessment, Design, Development, Implementation, and Evaluation, which is a systematic instructional design model. The levels of satisfaction with the developed smartphone app among 30 outpatients with CAD were assessed via a questionnaire during their visits to a cardiology outpatient department. A smartphone app 'Strong Heart' was developed through reviewing the literature associated with education for CAD patients under professional supervision and searching for medical smartphone apps that are already available. The learning contents include six main sections containing essential learning issues in managing CAD and additional information to attract the user's attention, such as patient cases and quizzes. After modification with feedback from experts, the app was finally developed and evaluated by patients who reported that they were satisfied with the usefulness of the app. The developed smartphone app is available on both the iPhone App Store and the Android Play Store. Patients with CAD may utilize the app for supporting educational material without limitations of time and space.

Retrofitting the Low Impact Development Practices into Developed Urban areas Including Barriers and Potential Solution

Science.gov (United States)

Shafique, Muhammad; Kim, Reeho

2017-06-01

Low impact development (LID)/green infrastructure (GI) practices have been identified as the sustainable practices of managing the stormwater in urban areas. Due to the increasing population, most of the cities are more developing which results in the change of natural area into impervious areas (roads, buildings etc.). Moreover, urbanization and climate change are causing many water-related problems and making over cities unsafe and insecure. Under these circumstances, there is a need to introduce new stormwater management practices into developed cities to reduce the adverse impacts of urbanization. For this purpose, retrofitting low impact development practices demands more attention to reduce these water-related problems and trying to make our cities sustainable. In developed areas, there is a little space is available for the retrofitting of LID practices for the stormwater management. Therefore, the selection of an appropriate place to retrofitting LID practices needs more concern. This paper describes the successfully applied retrofitting LID practices around the globe. It also includes the process of applying retrofitting LID practices at the suitable place with the suitable combination. Optimal places for the retrofitting of different LID practices are also mentioned. This paper also highlights the barriers and potential solutions of retrofitting LID practices in urban areas.

Retrofitting the Low Impact Development Practices into Developed Urban areas Including Barriers and Potential Solution

Directory of Open Access Journals (Sweden)

Shafique Muhammad

2017-06-01

Full Text Available Low impact development (LID/green infrastructure (GI practices have been identified as the sustainable practices of managing the stormwater in urban areas. Due to the increasing population, most of the cities are more developing which results in the change of natural area into impervious areas (roads, buildings etc.. Moreover, urbanization and climate change are causing many water-related problems and making over cities unsafe and insecure. Under these circumstances, there is a need to introduce new stormwater management practices into developed cities to reduce the adverse impacts of urbanization. For this purpose, retrofitting low impact development practices demands more attention to reduce these water-related problems and trying to make our cities sustainable. In developed areas, there is a little space is available for the retrofitting of LID practices for the stormwater management. Therefore, the selection of an appropriate place to retrofitting LID practices needs more concern. This paper describes the successfully applied retrofitting LID practices around the globe. It also includes the process of applying retrofitting LID practices at the suitable place with the suitable combination. Optimal places for the retrofitting of different LID practices are also mentioned. This paper also highlights the barriers and potential solutions of retrofitting LID practices in urban areas.

Efficacy of a Multimodal Cognitive Rehabilitation Including Psychomotor and Endurance Training in Parkinson's Disease

Directory of Open Access Journals (Sweden)

I. Reuter

2012-01-01

Full Text Available Mild cognitive impairment, especially executive dysfunction might occur early in the course of Parkinson's disease. Cognitive training is thought to improve cognitive performance. However, transfer of improvements achieved in paper and pencil tests into daily life has been difficult. The aim of the current study was to investigate whether a multimodal cognitive rehabilitation programme including physical exercises might be more successful than cognitive training programmes without motor training. 240 PD-patients were included in the study and randomly allocated to three treatment arms, group A cognitive training, group B cognitive training and transfer training and group C cognitive training, transfer training and psychomotor and endurance training. The primary outcome measure was the ADAS-Cog. The secondary outcome measure was the SCOPA-Cog. Training was conducted for 4 weeks on a rehabilitation unit, followed by 6 months training at home. Caregivers received an education programme. The combination of cognitive training using paper and pencil and the computer, transfer training and physical training seems to have the greatest effect on cognitive function. Thus, patients of group C showed the greatest improvement on the ADAS-Cog and SCOPA-COG and were more likely to continue with the training programme after the study.

Astrocytes in development, aging and disease: starring GFAP

NARCIS (Netherlands)

Middeldorp, J.

2010-01-01

We show in this thesis that different subtypes of astrocytes comprise specialized GFAP-IF networks, that change during development, aging and Alzheimer’s disease. The novel functions that have emerged for the IF network suggest these changes can play an important part in the specialized function of

Major life events and development of major depression in Parkinson's disease patients

DEFF Research Database (Denmark)

Rod, Naja Hulvej; Bordelon, Y; Thompson, A

2012-01-01

BACKGROUND AND PURPOSE: Non-motor symptoms including depression are important features of Parkinson's disease (PD). We aim to address the relationship between major life events and depression amongst PD patients free of depressive symptoms at baseline. METHODS: New-onset PD patients from California...... were recruited in 2001-2007 and followed up for 3-4 years. The participants (n = 221) were examined by neurologists and responded to comprehensive interviews that included major life events, social support, and coping measures from validated scales. Major depression was assessed using the Structured...... Clinical Interview for the DSM-IV depression module (SCID). RESULTS: More than half of all patients had experienced major life events since diagnosed with PD, and 22 patients developed a major depression. The number of life events was associated with risk of depression in an exposure-dependent manner...

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

Science.gov (United States)

Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

2017-04-01

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH. © 2017 Wiley Periodicals, Inc.

Development of molecular tools for use in beech bark disease management

Science.gov (United States)

Jennifer L. Koch; David W. Carey; Mary E. Mason; C. Dana Nelson; Abdelali Barakat; John E. Carlson; David. Neale

2011-01-01

Beech bark disease (BBD) has been killing American beech trees in eastern North America since the late 1890s. The disease is initiated by feeding of the beech scale insect, Cryptococcus fagisuga, which leads to the development of small fissures in the bark.

Development of Ontology and 3D Software for the Diseases of Spine

Directory of Open Access Journals (Sweden)

Seungbock Lee

2015-01-01

Full Text Available KISTI is carrying out an e-Spine project for spinal diseases to prepare for the aged society, so-called NAP. The purpose of the study is to build a spine ontology that represents the anatomical structure and disease information which is compatible with simulation model of KISTI. The final use of the ontology includes diagnosis of diseases and setting treatment directions by the clinicians. The ontology was represented using 3D software. Twenty diseases were selected to be represented after discussions with a spine specialist. Several ontology studies were reviewed, reference books were selected for each disease and were organized in MS Excel. All the contents were then reviewed by the specialists. Altova SemanticWorks and Protégé were used to code spine ontology with OWL Full model. Links to the images from KISTI and sample images of diseases were included in the ontology. The OWL ontology was also reviewed by the specialists again with Protégé. We represented unidirectional ontology from anatomical structure to disease, images, and treatment. The ontology was human understandable. It would be useful for the education of medical students or residents studying diseases of spine. But in order for the computer to understand the ontology, a new model with OWL DL or Lite is needed.

Development of the Paris Definition of Early Crohn's Disease for Disease-Modification Trials: Results of an International Expert Opinion Process

NARCIS (Netherlands)

Peyrin-Biroulet, Laurent; Billioud, Vincent; D'Haens, Geert; Panaccione, Remo; Feagan, Brian; Panés, Julian; Danese, Silvio; Schreiber, Stefan; Ogata, Haruhiko; Hibi, Toshifumi; Higgins, Peter D. R.; Beaugerie, Laurent; Chowers, Yehuda; Louis, Edouard; Steinwurz, Flávio; Reinisch, Walter; Rutgeerts, Paul; Colombel, Jean-Frédéric; Travis, Simon; Sandborn, William J.

2012-01-01

We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and

Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis

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Maria A. Lim

2017-11-01

Full Text Available Despite a broad spectrum of anti-arthritic drugs currently on the market, there is a constant demand to develop improved therapeutic agents. Efficient compound screening and rapid evaluation of treatment efficacy in animal models of rheumatoid arthritis (RA can accelerate the development of clinical candidates. Compound screening by evaluation of disease phenotypes in animal models facilitates preclinical research by enhancing understanding of human pathophysiology; however, there is still a continuous need to improve methods for evaluating disease. Current clinical assessment methods are challenged by the subjective nature of scoring-based methods, time-consuming longitudinal experiments, and the requirement for better functional readouts with relevance to human disease. To address these needs, we developed a low-touch, digital platform for phenotyping preclinical rodent models of disease. As a proof-of-concept, we utilized the rat collagen-induced arthritis (CIA model of RA and developed the Digital Arthritis Index (DAI, an objective and automated behavioral metric that does not require human-animal interaction during the measurement and calculation of disease parameters. The DAI detected the development of arthritis similar to standard in vivo methods, including ankle joint measurements and arthritis scores, as well as demonstrated a positive correlation to ankle joint histopathology. The DAI also determined responses to multiple standard-of-care (SOC treatments and nine repurposed compounds predicted by the SMarTRTM Engine to have varying degrees of impact on RA. The disease profiles generated by the DAI complemented those generated by standard methods. The DAI is a highly reproducible and automated approach that can be used in-conjunction with standard methods for detecting RA disease progression and conducting phenotypic drug screens.

Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer.

Science.gov (United States)

Yu, Hea Min; Park, Soon Hyun; Lee, Jae Min; Park, Kang Seo

2013-09-01

Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

Puberty development among children and adolescents with chronic disease in Saudi Arabia.

Science.gov (United States)

AlBuhairan, Fadia; Tamimi, Waleed; Tamim, Hani; Al Mutair, Angham; Felimban, Naila; Altwaijri, Yasmin; Shoukri, Mohamed; Al Alwan, Ibrahim

2012-01-01

Increasing numbers of children with chronic health conditions are now surviving into adolescence and adulthood because of advancing health care. These chronic health conditions are generally known to impact a child's growth and development, including pubertal development. In Saudi Arabia, chronic diseases are prevalent, yet no reports of pubertal onset and its relation to chronic illness are available. The aim of this study was to explore pubertal development among Saudi children and adolescents with a chronic illness. Cross-sectional study conducted at schools in Riyadh, Saudi Arabia in 2006. Those students whose parents reported that their son/daughter had a chronic illness and/or was taking a long-term medication underwent a physical examination to determine sexual maturity rating and growth parameters. Of 1371 students who participated in the study, 155 (11.3%) had a chronic illness. Of those, 79 (51%) were male, and the mean SD age of all the students was 11.4 (2.4) years. Ninety (58%) students were taking medication for their health condition. Bronchial asthma was reported to be the most common chronic condition (n=66; 42.6%), followed by blood disorders (n=41; 26.5%). Fifty-three (34%) students were overweight or obese. For male gonadal (G) development, the mean age of boys with G stage 2 was 11.7 years; stage 3: 13.5 years; stage 4: 14.1 years; and stage 5: 14.6 years. For female breast (B) development, the mean age of girls with B stage 2 was 10.7 years; stage 3: 11.3 years; stage 4: 12.4 years; and stage 5: 14.1 years. The pubic hair development for both boys and girls was similar to the corresponding gonadal or breast development, respectively. The age of onset of pubertal development for both boys and girls with a chronic illness are within normal limits. The high prevalence of overweight and obesity may contribute to this phenomenon, yet further studies should consider the effects of disease severity and chronicity and medication use as possible

The periodontal disease problem. A comparison between industrialised and developing countries

NARCIS (Netherlands)

Pilot, T

There is no reason to believe that periodontal diseases in industrialised and developing countries are in principle different. That is, not in the sense that the problem is caused by a different set of periodontal diseases, with different micro-organisms and a different natural history, needing a

The risk of falling into poverty after developing heart disease: a survival analysis.

Science.gov (United States)

Callander, Emily J; Schofield, Deborah J

2016-07-15

Those with a low income are known to have a higher risk of developing heart disease. However, the inverse relationship - falling into income poverty after developing heart disease has not been explored with longitudinal data. This paper aims to determine if those with heart disease have an elevated risk of falling into poverty. Survival analysis was conducted using the longitudinal Household Income and Labour Dynamics in Australia survey, between the years 2007 and 2012. The study focused on the Australian population aged 21 years and over in 2007 who were not already in poverty and did not already have heart disease, who were followed from 2007 to 2012. Cox regression models adjusting for age, sex and time-varying co-variates (marital status, home ownership and remoteness of area of residence) were constructed to assess the risk of falling into poverty. For those aged 20 who developed heart disease, the hazard ratio for falling into income poverty was 9.24 (95 % CI: 8.97-9.51) and for falling into multidimensional poverty the hazard ratio was 14.21 (95 % CI: 13.76-14.68); for those aged 40 the hazard ratio for falling into income poverty was 3.45 (95 % CI: 3.39-3.51) and for multidimensional poverty, 5.20 (95 % CI: 5.11-5.29); and for those aged 60 the hazard ratio for falling into income poverty was 1.29 (95 % CI: 1.28-1.30) and for multidimensional poverty, 1.52 (95 % CI: 1.51-1.54), relative those who never developed heart disease. The risk for both income and multidimensional poverty decreases with age up to the age of 70, over which, those who developed heart disease had a reduced risk of poverty. For those under the age of 70, developing heart disease is associated with an increased risk of falling into both income poverty and multidimensional poverty.

Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

Science.gov (United States)

Shaw, Julia G.; Friedman, Jennifer F.

2011-01-01

Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

Directory of Open Access Journals (Sweden)

Julia G. Shaw

2011-01-01

Full Text Available Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed.

Unsaturated Seepage Analysis of Cracked Soil including Development Process of Cracks

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Ling Cao

2016-01-01

Full Text Available Cracks in soil provide preferential pathways for water flow and their morphological parameters significantly affect the hydraulic conductivity of the soil. To study the hydraulic properties of cracks, the dynamic development of cracks in the expansive soil during drying and wetting has been measured in the laboratory. The test results enable the development of the relationships between the cracks morphological parameters and the water content. In this study, the fractal model has been used to predict the soil-water characteristic curve (SWCC of the cracked soil, including the developmental process of the cracks. The cracked expansive soil has been considered as a crack-pore medium. A dual media flow model has been developed to simulate the seepage characteristics of the cracked expansive soil. The variations in pore water pressure at different part of the model are quite different due to the impact of the cracks. This study proves that seepage characteristics can be better predicted if the impact of cracks is taken into account.

Recent development and gene therapy for glycogen storage disease type Ia.

Science.gov (United States)

Chou, Janice Y; Kim, Goo-Young; Cho, Jun-Ho

2017-09-01

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) that is expressed primarily in the liver, kidney, and intestine. G6Pase-α catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis, and is a key enzyme for endogenous glucose production. The active site of G6Pase-α is inside the endoplasmic reticulum (ER) lumen. For catalysis, the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter (G6PT). The functional coupling of G6Pase-α and G6PT maintains interprandial glucose homeostasis. Dietary therapies for GSD-Ia are available, but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma. Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches, including gene therapy.

Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review.

Science.gov (United States)

Lo Iacono, Giovanni; Armstrong, Ben; Fleming, Lora E; Elson, Richard; Kovats, Sari; Vardoulakis, Sotiris; Nichols, Gordon L

2017-06-01

Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access

Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review.

Directory of Open Access Journals (Sweden)

Giovanni Lo Iacono

2017-06-01

Full Text Available Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM and time series and spatial epidemiology (TS-SE. In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae; TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter. Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior, reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias

Bibliometric study of research and development for neglected diseases in the BRICS.

Science.gov (United States)

Bai, Jing; Li, Wei; Huang, Yang-Mu; Guo, Yan

2016-09-06

Large numbers of people are suffering from a group of diseases that mainly affect developing countries, as there are no available or affordable products for prevention or treatment. Research and development (R&D) for these diseases is still a low priority on the health agenda. Brazil, Russia, India, China and South Africa (BRICS) are quickly growing economies and having more and more positive impact on global health. Additionally, their R&D capacity is believed to be enhanced through decades of investment in education and life science research. The BRICS, as a group of emerging and developing countries, are expected to make greater contributions to solving the problem that mainly affects the entire developing countries community. However, there has been little research to provide a macroscopic overview of BRICS' effort in R&D for neglected diseases. The aim of this study is to investigate scientific production in BRICS countries in this area and their main research hotspots. Global relevant literature was searched without time limits through PubMed and high yield countries were identified using GoPubMed. Literature up to the end of 2013 from the BRICS was obtained and high frequency words were extracted and clustered using Bibliography Item Co-occurrence Mining System 2.0 (BICOMS) and Graphical Clustering Toolkit 1.0 (gCLUTO). In total, 32, 47, 51, 31 and 44 high frequency words from Brazil, Russia, India, China and South Africa respectively were extracted for clustering analysis. The clustering indicated that eight diseases were research hotspots in BRICS countries. India had the most extensive hotspots and Brazil came in second. The other three countries shared common research foci: helminthiasis, Human Immunodeficiency Virus infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) and tuberculosis. Developed countries still make the majority of contributions to R&D on neglected diseases, but BRICS countries are playing a growing role. Instead of the "big

Technology innovation for infectious diseases in the developing world.

Science.gov (United States)

So, Anthony D; Ruiz-Esparza, Quentin

2012-10-25

Enabling innovation and access to health technologies remains a key strategy in combating infectious diseases in low- and middle-income countries (LMICs). However, a gulf between paying markets and the endemicity of such diseases has contributed to the dearth of R&D in meeting these public health needs. While the pharmaceutical industry views emerging economies as potential new markets, most of the world's poorest bottom billion now reside in middle-income countries--a fact that has complicated tiered access arrangements. However, product development partnerships--particularly those involving academic institutions and small firms--find commercial opportunities in pursuing even neglected diseases; and a growing pharmaceutical sector in BRICS countries offers hope for an indigenous base of innovation. Such innovation will be shaped by 1) access to building blocks of knowledge; 2) strategic use of intellectual property and innovative financing to meet public health goals; 3) collaborative norms of open innovation; and 4) alternative business models, some with a double bottom line. Facing such resource constraints, LMICs are poised to develop a new, more resource-effective model of innovation that holds exciting promise in meeting the needs of global health.

A microsimulation model for the development and progression of chronic obstructive pulmonary disease

NARCIS (Netherlands)

Tan, E.; Boessen, R.; Fishwick, D.; Klein Entink, R.H.; Meijster, T.; Pronk, A.; Van Duuren-Stuurman, B.; Warren, N.

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease that is thought to affect over one million people in Great Britain. The main factor contributing to the development of COPD is tobacco smoke. This paper presents a microsimulation model for the development of COPD, incorporating

A microsimulation model for the development and progression of chronic obstructive pulmonary disease

NARCIS (Netherlands)

Tan, E.; Boessen, R.; Fishwick, D.; Klein Entink, R.; Meijster, T.; Pronk, A.; Duuren-Stuurman, B. van; Warren, N.

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease that is thought to affect over one million people in Great Britain. The main factor contributing to the development of COPD is tobacco smoke. This paper presents a microsimulation model for the development of COPD, incorporating

Development process of muzzle flows including a gun-launched missile

Directory of Open Access Journals (Sweden)

Zhuo Changfei

2015-04-01

Full Text Available Numerical investigations on the launch process of a gun-launched missile from the muzzle of a cannon to the free-flight stage have been performed in this paper. The dynamic overlapped grids approach are applied to dealing with the problems of a moving gun-launched missile. The high-resolution upwind scheme (AUSMPW+ and the detailed reaction kinetics model are adopted to solve the chemical non-equilibrium Euler equations for dynamic grids. The development process and flow field structure of muzzle flows including a gun-launched missile are discussed in detail. This present numerical study confirms that complicated transient phenomena exist in the shortly launching stages when the gun-launched missile moves from the muzzle of a cannon to the free-flight stage. The propellant gas flows, the initial environmental ambient air flows and the moving missile mutually couple and interact. A complete structure of flow field is formed at the launching stages, including the blast wave, base shock, reflected shock, incident shock, shear layer, primary vortex ring and triple point.

Animal Models of Cardiovascular Diseases

Directory of Open Access Journals (Sweden)

Carlos Zaragoza

2011-01-01

Full Text Available Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

Involvement of the Helicobacter pylori plasticity region and cag pathogenicity island genes in the development of gastroduodenal diseases.

Science.gov (United States)

Pacheco, A R; Proença-Módena, J L; Sales, A I L; Fukuhara, Y; da Silveira, W D; Pimenta-Módena, J L; de Oliveira, R B; Brocchi, M

2008-11-01

Infection by Helicobacter pylori is associated with the development of several gastroduodenal diseases, including gastritis, peptic ulcer disease (gastric ulcers and duodenal ulcers), and gastric adenocarcinoma. Although a number of putative virulence factors have been reported for H. pylori, there are conflicting results regarding their association with specific H. pylori-related diseases. In this work, we investigated the presence of virB11 and cagT, located in the left half of the cag pathogenicity island (cagPAI), and the jhp917-jhp918 sequences, components of the dupA gene located in the plasticity zone of H. pylori, in Brazilian isolates of H. pylori. We also examined the association between these genes and H. pylori-related gastritis, peptic ulcer disease, and gastric and duodenal ulcers in an attempt to identify a gene marker for clinical outcomes related to infection by H. pylori. The cagT gene was associated with peptic ulcer disease and gastric ulcers, whereas the virB11 gene was detected in nearly all of the samples. The dupA gene was not associated with duodenal ulcers or any gastroduodenal disease here analyzed. These results suggest that cagT could be a useful prognostic marker for the development of peptic ulcer disease in the state of São Paulo, Brazil. They also indicate that cagT is associated with greater virulence and peptic ulceration, and that this gene is an essential component of the type IV secretion system of H. pylori.

Development of medial coronoid disease in Labrador retrievers: Diagnostic and pathogenic studies

NARCIS (Netherlands)

Lau, S.F.|info:eu-repo/dai/nl/344825485

2013-01-01

Medial coronoid disease (MCD) of the canine elbow joint was first reported in 1974 as a developmental skeletal disease causing forelimb lameness in dogs. It is known as one of the most frequently diagnosed heritable disorders of dogs and usually affects young, large breed dogs, including Labrador

Influence of alcohol abuse on development and course of vibration disease among miners

Energy Technology Data Exchange (ETDEWEB)

Gut, V.G.; Balan, G.M.

1987-12-01

Examines effect of alcohol use on the development of vibration disease among tunnellers, facemen and machine drill operators, miners exposed to dangerous amounts of vibration. Men were investigated using clinical-psychiatric and experimental psychological methods (memory tests, comprehension and scales of anxiety). Results of investigation demonstrated extent alcohol use affects time period during which vibration disease develops: occasional users developed disease in 12 years, moderate and heavy users in 9 1/2 years and chronic alcoholics in 7 1/2 years. With heavy use of alcohol, severity of vibration disease increased. Progressive tendency of disease continued among alcoholics even though contact with vibration ceased. In addition to vibration disease, frequency of psychopathological syndromes increased with alcohol use (occasional, moderate, heavy and chronic alcoholism). Increase in asthenic affective and psycho-organic syndromes paralleled degree of alcohol use from occasional to chronic alcoholism. With increased use, anxieties increase, ability to recall on memory tests declines, facility in switching from one task to another decreases. Results of study make clear need for better methods of preventing and treating drunkeness and alcoholism among miners in occupations subject to hazardous amounts of vibration. 10 refs.

[Development of anti-Alzheimer's disease drug based on beta-amyloid hypothesis].

Science.gov (United States)

Sugimoto, Hachiro

2010-04-01

Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of beta-amyloid is the fundamental cause. This theory suggests that beta-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the beta-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

OpenAIRE

Lambertus, Stanley; Bax, Nathalie M.; Fakin, Ana; Groenewoud, Joannes M. M.; Klevering, B. Jeroen; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.; van der Wilt, Gert Jan; Hoyng, Carel B.

2017-01-01

BACKGROUND: Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including vari...

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

OpenAIRE

Lambertus, S.; Bax, N. M.; Fakin, A.; Groenewoud, J. M. M.; Klevering, B. J.; Moore, A. T.; Michaelides, M.; Webster, A. R.; van der Wilt, G. J.; Hoyng, C. B.

2017-01-01

BACKGROUND: Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options—including gene therapy—are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including ...

Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer

Directory of Open Access Journals (Sweden)

Hea Min Yu

2013-09-01

Full Text Available Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

Differentiation of mucosal disease from partial development of the paranasal sinuses in pediatric patients

International Nuclear Information System (INIS)

Duerinckx, A.J.; Whyte, A.M.; Lufkin, R.B.; Hall, T.R.; Kangarloo, H.

1988-01-01

On magnetic resonance (MR) images of pediatric patients, sinus mucosal disease may have an appearance similar to that of the normal partially developed sinus, leading to an increase in the number of patients labeled as having incidental sinusitis. The paranasal sinuses were retrospectively evaluated in 27 infants and children aged 0-11 years undergoing brain MR imaging for indications both unrelated and related to sinus disease. The authors developed criteria for grading paranasal sinus development and mucosal disease. Incidental mucosal disease is not uncommon, occurring in 28% of patients aged 0-7 years. In children under 3 years of age, inflammatory mucosal thickening and marrow surrounding the partially developed sinus have a high signal on many MR sequences and may be confused. Recognition of the low-intensity peripheral cortical margin of the sinus and awareness of the stages of normal sinus development allow differentiation

An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

Science.gov (United States)

Kwun, Sunna; Tucci, Joseph R

2013-01-01

To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

Development and validation of a self-reported periodontal disease measure among Jordanians.

Science.gov (United States)

Khader, Yousef; Alhabashneh, Rola; Alhersh, Fadi

2015-08-01

The development of self-reported measures of periodontal disease would be of great benefit to facilitate epidemiological studies of periodontal disease on a larger scale, and to allow for surveillance of the periodontal condition of populations over time. To develop a culturally adapted self-reported measure of periodontal disease, test its predictive and discriminative validity and establish a cut-off value for this measure to diagnose periodontal disease. A total of 288 Jordanian adults completed the questionnaire assessing self-reported periodontal health (18 questions) and underwent periodontal examination. Of the 18 questions, six were significantly associated with at least one clinical definition of periodontitis and were used to constitute the self-reported periodontal disease measure. Receiver-operating characteristics (ROC) curve analyses were used to examine the overall discriminatory power, sensitivity and specificity, and corresponding cut-off points of the self-reported periodontal disease measure. ROC analysis showed that the self-reported periodontal disease measure had an excellent performance to discriminate between those with and without periodontal disease, regardless of the clinical definition used. A score of 2, on a scale of 0 to 6, had the highest sensitivity and specificity to detect periodontal disease when defined by all study criteria. Significant associations were observed between self-reported periodontal disease measures and all clinical definitions in the regression analysis (the odds ratio ranged from 8.31 to 18.96), according to the clinical definition to be predicted. Self-reported periodontal disease measures have excellent predictive and discriminative validity when tested against clinical definitions, and severity and extent of periodontal disease. © 2015 FDI World Dental Federation.

Pancreatic cyst development: insights from von Hippel-Lindau disease

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van Asselt Sophie J

2013-02-01

Full Text Available Abstract Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL. VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.

A common brain network links development, aging, and vulnerability to disease.

Science.gov (United States)

Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

2014-12-09

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Global issues in drug development for Alzheimer's disease.

Science.gov (United States)

Doody, Rachelle S; Cole, Patricia E; Miller, David S; Siemers, Eric; Black, Ronald; Feldman, Howard; Schindler, Rachel; Graham, Stephen; Heath, Theresa; Khachaturian, Ara S; Evans, Rebecca; Carrillo, Maria C

2011-03-01

The number of clinical trials for Alzheimer's disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer's Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer's disease. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

Science.gov (United States)

Linehan, W. Marston

2012-01-01

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease. PMID:23038766

Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity.

Science.gov (United States)

Rintala, Anniina; Riikonen, Iiris; Toivonen, Anne; Pietilä, Sami; Munukka, Eveliina; Pursiheimo, Juha-Pekka; Elo, Laura L; Arikoski, Pekka; Luopajärvi, Kristiina; Schwab, Ursula; Uusitupa, Matti; Heinonen, Seppo; Savilahti, Erkki; Eerola, Erkki; Ilonen, Jorma

2018-04-01

Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype. We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses. No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n = 9) and the control children without disease or associated autoantibodies (n = 18). Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.

Prevention of allergic disease in childhood

DEFF Research Database (Denmark)

Halken, Susanne

2004-01-01

rhinoconjunctivitis. In one prospective observational study of a birth cohort of unselected infants we evaluated possible predictive/risk factors. In two prospective intervention studies including 1 yr birth cohorts of high-risk(HR) infants we investigated the effect of feeding HR infants exclusively breast milk (BM......The development and phenotypic expression of atopic diseases depends on a complex interaction between genetic factors, environmental exposure to allergens,and non-specific adjuvant factors, such as tobacco smoke, air pollution and infections. Preventive measures may include both exposure...... to allergens and adjuvant risk/protective factors and pharmacological treatment. These measures may address the general population, children at risk for development of atopic disease (high-risk infants), children with early symptoms of allergic disease or children with chronic disease. The objective...

Impact of nasopharyngeal microbiota on the development of respiratory tract diseases.

Science.gov (United States)

Esposito, S; Principi, N

2018-01-01

Knowledge of whether and how respiratory microbiota composition can prime the immune system and provide colonisation resistance, limiting consecutive pathobiont overgrowth and infections, is essential to improving the prevention and therapy of respiratory disorders. Modulation of dysbiotic ecosystems or reconstitution of missing microbes might be a possible measure to reduce respiratory diseases. The aim of this review is to analyse the role of nasopharyngeal microbiota in the development of respiratory tract disease in paediatric-age subjects. PubMed was used to search for all studies published over the last 15 years using the following key words: "microbiota" or "microbioma" and "nasopharyngeal" or "respiratory" or "nasal" and "children" or "paediatric" or "infant". Analysis of the literature showed that respiratory microbiota can regulate health and disease development in the respiratory tract. Like the gut microbiota, the respiratory microbiota is established at birth, and early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Protective and dangerous bacteria have been identified, and this can be considered the base for developing new approaches to diseases that respond poorly to traditional interventions. Reconstitution of missing microbes can be achieved by the administration of pre- and probiotics. Modulation of respiratory microbiota by favouring colonisation of the upper respiratory tract by beneficial commensals can interfere with the proliferation and activity of resident pathobionts and is a possible new measure to reduce the risk of disease. However, further studies are needed because a deeper understanding of these and related issues can be transferred to clinical practice.

Potential Use of School Absenteeism Record for Disease Surveillance in Developing Countries, Case Study in Rural Cambodia

Science.gov (United States)

Cheng, Calvin K. Y.; Channarith, Hing; Cowling, Benjamin J.

2013-01-01

Background Disease surveillance allows prospective monitoring of patterns in disease incidence in the general community, specific institutions (e.g. hospitals, elderly care homes), and other important population subgroups. Surveillance activities are now routinely conducted in many developed countries and in certain easy-to-reach areas of the developing ones. However due to limited health resources, population in rural area that consisted of the most the vulnerable groups are not under surveillance. Cheaper alternative ways for disease surveillance were needed in resource-limited settings. Methods and Findings In this study, a syndromic surveillance system using disease specific absenteeism rates was established in 47 pre-schools with 1,417 students 3–6 y of age in a rural area of Kampot province, Cambodia. School absenteeism data were collected via short message service. Data collected between 1st January and 31st December 2012 was used for system evaluation for future potential use in larger scale. The system appeared to be feasible and acceptable in the rural study setting. Moderate correlation was found between rates of school absenteeism due to illness and the reference data on rates of attendance at health centers in persons absenteeism data is pre-existing, easily accessible and requires minimum time and resources after initial development, and our results suggest that this system may be able to provide complementary data for disease surveillance, especially in resource limited settings where there is very little information on illnesses in the community and traditional surveillance systems are difficult to implement. An important next step is to validate the syndromic data with other forms of surveillance including laboratory data. PMID:24155907

Mycobacterium tuberculosis: approach to development of improved strategies for disease control through vaccination and immunodiagnosis.

Science.gov (United States)

Mirlekar, B; Pathak, S; Pathade, G

2013-01-01

Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease. Estimates till date ascertain the fact that Tuberculosis (TB) is continuing to be the leading cause of death worldwide. The infection from single infectious agent Mycobacterium tuberculosis is killing about 3 million individuals every year and accounts for around 18.5% of all deaths in adults between the age group of 15 and 65. An average of 1.79 billion people, which constitutes roughly one-third of the world's population, is infected with the causative agent M. tuberculosis and is at risk of developing the disease. This situation highlights the relative shortcomings of the current treatment and diagnosis strategies for TB and the limited effectiveness of public health systems, particularly in resource-poor countries where the main TB burden lies. The timely identification of persons infected with Mycobacterium tuberculosis and rapid laboratory confirmation of tuberculosis are two key factors for the treatment and prevention of the disease. Novel molecular assays for diagnosis and drug susceptibility testing offer several potential advantages over the above methods including faster turnaround times, very sensitive and specific detection of nucleic acids, and minimal, or possibly no, prior culture. The need for new technologies for rapid diagnosis of tuberculosis is clear. Most studies of mycobacterial immunity attributes focus on proliferation of T cells, production of cytokines and cytolytic activity. A proper vaccine for tuberculosis can be developed by using a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. Development of new vaccines against TB should include some important aspects learned from BCG use such as mucosal routes of immunization; revaccination of BCG immunized subjects, booster immunization and prime-boost strategy with wild-type BCG, and other

Fragrance allergy and quality of life - development and validation of a disease-specific quality of life instrument.

Science.gov (United States)

Heisterberg, Maria V; Menné, Torkil; Johansen, Jeanne D

2014-02-01

Fragrance allergy is a lifelong condition that may give rise to permanent or recurrent contact dermatitis and may affect quality of life (QoL). The effect on QoL has not yet been investigated, and no disease-specific QoL instrument for fragrance allergy exists. To develop and validate a disease-specific instrument to investigate QoL among fragrance-allergic subjects. A fragrance QoL instrument (FQL index) was developed on the basis of narratives from 68 fragrance-allergic subjects, and consisted of 13 items. It was tested in a postal survey among 1650 participants patch tested at Gentofte University Hospital (2000–2010). The survey included other QoL instruments [Dermatology Life Quality Index (DLQI) and Short Form 36 (SF36) version 2] and questions on eczema severity (response rate of 66%). A retest was conducted after 3–6 months (response rate of 72.5%). The FQL index showed a significant and strong correlation with the DLQI (rS = 0.70), and disease severity, but a weak correlation with SF36 [mental component summary score, rS = − 0.22; physical component summary score, rS = − 0.31]. Good reliability and responsiveness to changes in disease severity were seen. The FQL index is a good instrument with which to investigate QoL in subjects with fragrance allergy. Good correlations with the DLQI and self-estimated disease severity were seen, and it showed good reliability, reproducibility and ability to distinguish changes in disease severity.

Cardiac telomere length in heart development, function, and disease.

Science.gov (United States)

Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

Review on potential phytocompounds in drug development for Parkinson disease: A pharmacoinformatic approach

Directory of Open Access Journals (Sweden)

S. Vijayakumar

Full Text Available Parkinson's disease (PD is caused by human physiological function and is ranked as the second most common neurodegenerative disorder. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Currently, available pharmaceutical drugs provide only temporary relief of the disease. Phytocompounds have been identified as promising target of research in the quest for new pharmaceutical compounds as they can produce secondary metabolites with novel chemical structure. In this review the drug development of Parkinson disease has been analyzed using computational tools. Keywords: Parkinson disease, Phytocompounds, Computational methods, Drug development and design

Epidemiology of infectious diseases transmitted by drinking water in developed countries.

Science.gov (United States)

Hartemann, P; Newman, R; Foliguet, J M

1986-01-01

Research on the epidemiology of infectious diseases attributable to drinking water, common in the US during the past 20 years at least, is not yet really widespread in France. The role played by water in the transmission of certain infectious agents was important in European countries during past centuries but at present the incidence of waterborne diseases can be considered as very low. The absence of well-established data is due to the difficulty in reporting correctly a few minor outbreaks in a situation of very low endemicity. After a survey of the reported outbreaks, this paper deals with risk assessment of waterborne diseases in developed countries as well as special problems linked with proving transmission via water and with the nature of the infectious agents, and the development of monitoring methods for increasing our knowledge of this epidemiology.

Development and psychometric evaluation of a cardiovascular risk and disease management knowledge assessment tool.

Science.gov (United States)

Rosneck, James S; Hughes, Joel; Gunstad, John; Josephson, Richard; Noe, Donald A; Waechter, Donna

2014-01-01

This article describes the systematic construction and psychometric analysis of a knowledge assessment instrument for phase II cardiac rehabilitation (CR) patients measuring risk modification disease management knowledge and behavioral outcomes derived from national standards relevant to secondary prevention and management of cardiovascular disease. First, using adult curriculum based on disease-specific learning outcomes and competencies, a systematic test item development process was completed by clinical staff. Second, a panel of educational and clinical experts used an iterative process to identify test content domain and arrive at consensus in selecting items meeting criteria. Third, the resulting 31-question instrument, the Cardiac Knowledge Assessment Tool (CKAT), was piloted in CR patients to ensure use of application. Validity and reliability analyses were performed on 3638 adults before test administrations with additional focused analyses on 1999 individuals completing both pretreatment and posttreatment administrations within 6 months. Evidence of CKAT content validity was substantiated, with 85% agreement among content experts. Evidence of construct validity was demonstrated via factor analysis identifying key underlying factors. Estimates of internal consistency, for example, Cronbach's α = .852 and Spearman-Brown split-half reliability = 0.817 on pretesting, support test reliability. Item analysis, using point biserial correlation, measured relationships between performance on single items and total score (P knowledge instrument specifically designed for an adult CR population was systematically developed and tested in a large representative patient population, satisfying psychometric parameters, including validity and reliability.

Short message service (SMS) applications for disease prevention in developing countries.

Science.gov (United States)

Déglise, Carole; Suggs, L Suzanne; Odermatt, Peter

2012-01-12

The last decade has witnessed unprecedented growth in the number of mobile phones in the developing world, thus linking millions of previously unconnected people. The ubiquity of mobile phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention efforts. The aim of this review was to describe the characteristics and outcomes of SMS interventions for disease prevention in developing countries and provide recommendations for future work. A systematic search of peer-reviewed and gray literature was performed for papers published in English, French, and German before May 2011 that describe SMS applications for disease prevention in developing countries. A total of 34 SMS applications were described, among which 5 had findings of an evaluation reported. The majority of SMS applications were pilot projects in various levels of sophistication; nearly all came from gray literature sources. Many applications were initiated by the project with modes of intervention varying between one-way or two-way communication, with or without incentives, and with educative games. Evaluated interventions were well accepted by the beneficiaries. The primary barriers identified were language, timing of messages, mobile network fluctuations, lack of financial incentives, data privacy, and mobile phone turnover. This review illustrates that while many SMS applications for disease prevention exist, few have been evaluated. The dearth of peer-reviewed studies and the limited evidence found in this systematic review highlight the need for high-quality efficacy studies examining behavioral, social, and economic outcomes of SMS applications and mobile phone interventions aimed to promote health in developing country contexts.

Linking Microbiota to Human Diseases

DEFF Research Database (Denmark)

Wu, Hao; Tremaroli, Valentina; Bäckhed, F

2015-01-01

The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...

Risk factors for the development of atopic disease in infancy and early childhood

NARCIS (Netherlands)

L.P. Koopman (Laurens)

2002-01-01

textabstractThe etiology of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, is multifactorial, involving interaction of both genetic and environmental factors [1]. The prevalence of allergic diseases has doubled in the last 3 decades. especially in Western

Interleukin-23 in early disease development in rheumatoid arthritis

DEFF Research Database (Denmark)

Andersen, Thomas; Hvid, M; Johansen, C

2015-01-01

randomized to methotrexate (MTX) plus adalimumab (ADA; n = 75) or MTX plus placebo-ADA (PLA; n = 76). Plasma samples were obtained at baseline and at months 3, 6, and 12 together with values for C-reactive protein (CRP), the 28-joint Disease Activity Score based on CRP (DAS28CRP), scores on the Clinical......OBJECTIVES: To investigate the levels of interleukin (IL)-23 in patients with early rheumatoid arthritis (eRA) and the effect of anti-tumour necrosis factor (anti-TNF)-α treatment on IL-23 levels. METHOD: Treatment-naïve eRA patients from the OPERA cohort were included (n = 151). Patients were...... Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI), visual analogue scale (VAS) for pain/fatigue/physician global and total Sharp/van der Heijde score (TSS). IL-23 was measured at each time point. RESULTS: IL-23 levels decreased significantly in the ADA group from 20.6 pg...

Farber's Disease

Science.gov (United States)

... management, and therapy of rare diseases, including the lipid storage diseases. Research on lipid storage diseases within the Network includes ... management, and therapy of rare diseases, including the lipid storage diseases. Research on lipid storage diseases within the Network includes ...

NAFLD and Chronic Kidney Disease.

Science.gov (United States)

Marcuccilli, Morgan; Chonchol, Michel

2016-04-14

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases.

How glyphosate affects plant disease development: it is more than enhanced susceptibility.

Science.gov (United States)

Hammerschmidt, Ray

2018-05-01

Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Spectral quality affects disease development of three pathogens on hydroponically grown plants

Science.gov (United States)

Schuerger, A. C.; Brown, C. S.; Sager, J. C. (Principal Investigator)

1997-01-01

effects of spectral quality on disease development when other wavelengths were included in the light source (MH-, 660/BF-, and 660/735-grown plants) were equivocal. These results demonstrate that spectral quality may be useful as a component of an integrated pest management program for future space-based controlled ecological life support systems.

A clinical approach to Lyme disease.

Science.gov (United States)

Nadelman, R B; Wormser, G P

1990-05-01

Lyme disease (also known as Lyme borreliosis) is an emerging, newly described infectious disease with diverse clinical manifestations. The disease is caused by the spirochetal agent Borrelia burgdorferi, which is transmitted to humans by the bite of certain species of Ixodes ticks harboring the organism. The most readily identifiable clinical feature is the distinctive skin lesion, erythema migrans. If recently infected patients go untreated, approximately 15% will develop neurologic conditions (most commonly facial nerve palsy), 8% will develop myocarditis (typically with heart block), and 60% will develop migratory mono- or pauci-articular arthritis. Diagnosis depends on clinical suspicion, recognition of the characteristic signs and symptoms, and appropriate testing for antibody to B. burgdorferi. Serology for Lyme disease, although in need of better standardization, is most useful in diagnosing patients with manifestations of Lyme disease other than erythema migrans. All manifestations of Lyme disease are potentially treatable with either a beta-lactam antibiotic (for instance penicillin, amoxicillin, or ceftriaxone) or a tetracycline preparation. However, the optimal antimicrobial regimen, including choice of drug, drug dose, route of administration, and length of therapy, is unknown. Other important areas for future research include Ixodes biology and control, improved laboratory tests for diagnosis and for assessing response to therapy, and vaccine development.

The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

Directory of Open Access Journals (Sweden)

Javier Gervas-Arruga

Full Text Available Gaucher disease, the most common lysosomal storage disorder, is caused by β-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1. Genetic components strongly influence bone remodelling. In addition, chronic inflammation produced by Gaucher cells induces the production of several cytokines, which leads to direct changes in the bone remodelling process and can also affect the process indirectly through other immune cells. In this study, we analysed the association between bone mineral density (BMD, bone marrow burden score, and relevant genetic polymorphisms related to bone metabolism, as well as profiles of proinflammatory cytokines in a GD1 cohort. This study included 83 patients distributed according to bone status. BMD was measured with DXA and broadband ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also analysed 26 SNPs located in 14 genes related to bone metabolism. To assess proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1β, and TNFα in plasma samples from 71 control participants and GD1 patients. SNP genotype proportions and BMD differed significantly between ESRI c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant associations between GD1 genotypes and bone affectation. When patients were stratified by spleen status, we observed significant correlations between non-/splenectomized groups and Spanish MRI (S-MRI score. Across genotype proportions of non-/splenectomized patients and S-MRI, we observed significant differences in ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We observed different significant proinflammatory profiles between control participants, treatment-naïve patients, and patients on enzyme replacement therapy (ERT; between non-/splenectomized patients (between untreated and ERT-treated patients and among those with differing GBA

The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

Directory of Open Access Journals (Sweden)

Gayle E. Woloschak

2012-12-01

Full Text Available The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.

Is the disease course predictable in inflammatory bowel diseases?

Science.gov (United States)

Lakatos, Peter Laszlo; Kiss, Lajos S

2010-01-01

During the course of the disease, most patients with Crohn’s disease (CD) may eventually develop a stricturing or a perforating complication, and a significant number of patients with both CD and ulcerative colitis will undergo surgery. In recent years, research has focused on the determination of factors important in the prediction of disease course in inflammatory bowel diseases to improve stratification of patients, identify individual patient profiles, including clinical, laboratory and molecular markers, which hopefully will allow physicians to choose the most appropriate management in terms of therapy and intensity of follow-up. This review summarizes the available evidence on clinical, endoscopic variables and biomarkers in the prediction of short and long-term outcome in patients with inflammatory bowel diseases. PMID:20518079

The development of partnership after hypertensive diseases in pregnancy.

Science.gov (United States)

Leeners, Brigitte; Rath, Werner; Kuse, Sabine; Tschudin, Sibil

2015-04-01

Hypertensive diseases in pregnancy (HDP) occur in 5-8% of all pregnancies and represent one of the most important causes of maternal and fetal morbidity. Even after a normal pregnancy/delivery adaptation to parenthood is a major challenge. However, a successful adjustment is important for future family health. As pregnancy complications may put additional strain on early parenthood, the current study investigated satisfaction with partnership including factors which determine (dis)satisfaction as well as separation rates after pregnancies complicated by HDP. A total of 737 women after HDP and 624 matched-control women completed a self-administered questionnaire on psycho-social factors in the development of HDP. Free-text answers on satisfaction with partnership were analyzed by conceptual analysis. Women with HDP were significantly less often satisfied with their partnership than control women (76%/81.1%; p reasons for a satisfying marital relationship in women with and without a diagnosis of HDP. HDP represent an additional challenge in family adjustment. Adapted perinatal psycho-social support may help to facilitate the start into family life.

The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop

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D. Pagliari

2015-01-01

Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

Targeting Medication Non-Adherence Behavior in Selected Autoimmune Diseases: A Systematic Approach to Digital Health Program Development.

Directory of Open Access Journals (Sweden)

Trevor van Mierlo

Full Text Available 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn's Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans.Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies.Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn's Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence.Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were

Development of an Online, Evidence-Based Patient Information Portal for Congenital Heart Disease: A Pilot Study

Directory of Open Access Journals (Sweden)

Jonathan R. G. Etnel

2017-05-01

trial.ConclusionThe present pilot project succeeded in developing an online, evidence-based information portal that is supported by both patients and physicians. The information portal will be further developed and expanded to include all other major forms of congenital heart disease, translations into other languages, and a public information portal to serve patients’ relatives and the general public at large.

Pharmacogenomics to Revive Drug Development in Cardiovascular Disease.

Science.gov (United States)

Dubé, Marie-Pierre; de Denus, Simon; Tardif, Jean-Claude

2016-02-01

Investment in cardiovascular drug development is on the decline as large cardiovascular outcomes trials require considerable investments in time, efforts and financial resources. Pharmacogenomics has the potential to help revive the cardiovascular drug development pipeline by providing new and better drug targets at an earlier stage and by enabling more efficient outcomes trials. This article will review some of the recent developments highlighting the value of pharmacogenomics for drug development. We discuss how genetic biomarkers can enable the conduct of more efficient clinical outcomes trials by enriching patient populations for good responders to the medication. In addition, we assess past drug development programs which support the added value of selecting drug targets that have established genetic evidence supporting the targeted mechanism of disease. Finally, we discuss how pharmacogenomics can provide valuable evidence linking a drug target to clinically relevant outcomes, enabling novel drug discovery and drug repositioning opportunities.

Changing patterns of wildlife diseases

Science.gov (United States)

McLean, R.G.

2001-01-01

The purpose of this paper was not to analyze the effects of global warming on wildlife disease patterns, but to serve as a springboard for future efforts to identify those wildlife diseases, including zoonotic diseases, that could be influenced the most by warming climates and to encourage the development of models to examine the potential effects. Hales et al. (1999) examined the relationship of the incidence of a vector-borne human disease, Dengue fever, and El Nino southern oscillations for South Pacific Island nations. The development of similar models on specific wildlife diseases which have environmental factors strongly associated with transmission would provide information and options for the future management of our wildlife resources.

The evolution of the Global Burden of Disease framework for disease, injury and risk factor quantification: developing the evidence base for national, regional and global public health action

Directory of Open Access Journals (Sweden)

Lopez Alan D

2005-04-01

for 2000, but substantial uncertainty around the disease burden caused by major conditions, including, HIV, remains. The rapid implementation of cost-effective data collection systems in developing countries is a key priority if global public policy to promote health is to be more effectively informed.

ROLE OF GLYCAEMIA LEVEL IN THE DEVELOPMENT OF INTERSTITIAL COLLAGEN IN PATIENTS WITH CORONARY HEART DISEASE AND TYPE 2 DIABETES

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T. Rudenko

2015-12-01

Full Text Available A role of blood glucose levels in the development of interstitial collagen has been studied in 84 patients (53 women and 31 men, average age 60 ± 2.4 years with coronary heart disease (CHD. All patients were divided into twocomparable groups: a study group including patients with coronary heart disease andtype 2 diabetes mellitus (DM and a control group consisting of patients with coronary heart disease without DM. All patients received standard medical therapy as recommended by the European Society of Cardiology. The level of blood glucose in both groups was assessed by the standard technique, a degree of interstitial collagen volume fraction (ICVF was measured using the formula of J. Shirani et al. The data were processed by parametric and nonparametric statistical methods. It has been proved that hyperglycemia in type 2 diabetes contributes to the development of ICVF, the degree of which increases with the rise of blood glucose level. A high level ofICVF in patients with coronary heart disease and diabetes type 2 can be a predictor of myocardial dyssynchrony development and heart failure progression, therefore, a close monitoring and timely correction of changes of blood glucose levelsare recommended to prevent the complication development. ICVF evaluation should become a routine diagnostic method in all patients with type 2 diabetes.

Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems.

Science.gov (United States)

Trevisan, Marta; Sinigaglia, Alessandro; Desole, Giovanna; Berto, Alessandro; Pacenti, Monia; Palù, Giorgio; Barzon, Luisa

2015-07-13

The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host-pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

Directory of Open Access Journals (Sweden)

Marta Trevisan

2015-07-01

Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

Refeeding syndrome in children in developing countries who have celiac disease.

Science.gov (United States)

Agarwal, Jaya; Poddar, Ujjal; Yachha, Surender K; Srivastava, Anshu

2012-04-01

The clinical presentations of celiac crisis and refeeding syndrome in celiac disease are almost similar, but information about refeeding syndrome is scarce. We are reporting for the first time 5 cases of refeeding syndrome in children with celiac disease that could have otherwise been labeled as celiac crisis. From January to December 2010, a chart review of hospital records of all celiac disease cases was performed, and refeeding syndrome was ascribed in those celiac patients who deteriorated clinically after initiation of a gluten-free diet and had biochemical parameters suggestive of refeeding syndrome such as hypophosphatemia, hypokalemia, hypocalcemia, and hypoalbuminemia. Of the total 35 celiac disease patients, 5 (median age 6.5 [range 2.2-10] years, 3 boys) were identified as having refeeding syndrome. All 5 children were severely malnourished (body mass index refeeding syndrome. At the same time, their clinical features fulfilled the criteria for celiac crisis except that their symptoms have worsened after the introduction of a gluten-free diet. Nevertheless, instead of using steroids, they were managed as refeeding syndrome in terms of correction of electrolytes and gradual feeding, and that led to a successful outcome in all of them. Severely malnourished patients with celiac disease are at risk of developing potentially life-threatening refeeding syndrome, which may mimic celiac crisis, especially in developing countries. Early recognition and appropriate treatment are the keys to a successful outcome.

Effect of shade on Arabica coffee berry disease development: Toward an agroforestry system to reduce disease impact.

Science.gov (United States)

Mouen Bedimo, J A; Njiayouom, I; Bieysse, D; Ndoumbè Nkeng, M; Cilas, C; Nottéghem, J L

2008-12-01

Coffee berry disease (CBD), caused by Colletotrichum kahawae, is a major constraint for Arabica coffee cultivation in Africa. The disease is specific to green berries and can lead to 60% harvest losses. In Cameroon, mixed cropping systems of coffee with other crops, such as fruit trees, are very widespread agricultural practices. Fruit trees are commonly planted at random on coffee farms, providing a heterogeneous shading pattern for coffee trees growing underneath. Based on a recent study of CBD, it is known that those plants can reduce disease incidence. To assess the specific effect of shade, in situ and in vitro disease development was compared between coffee trees shaded artificially by a net and trees located in full sunlight. In the field, assessments confirmed a reduction in CBD on trees grown under shade compared with those grown in full sunlight. Artificial inoculations in the laboratory showed that shade did not have any effect on the intrinsic susceptibility of coffee berries to CBD. Coffee shading mainly acts on environmental parameters in limiting disease incidence. In addition to reducing yield losses, agroforestry system may also be helpful in reducing chemical control of the disease and in diversifying coffee growers' incomes.

Necrotrophic pathogens use the salicylic acid signaling pathway to promote disease development in tomato.

Science.gov (United States)

Rahman, Taha Abd El; Oirdi, Mohamed El; Gonzalez-Lamothe, Rocio; Bouarab, Kamal

2012-12-01

Plants use different immune pathways to combat pathogens. The activation of the jasmonic acid (JA)-signaling pathway is required for resistance against necrotrophic pathogens; however, to combat biotrophic pathogens, the plants activate mainly the salicylic acid (SA)-signaling pathway. SA can antagonize JA signaling and vice versa. NPR1 (noninducible pathogenesis-related 1) is considered a master regulator of SA signaling. NPR1 interacts with TGA transcription factors, ultimately leading to the activation of SA-dependent responses. SA has been shown to promote disease development caused by the necrotrophic pathogen Botrytis cinerea through NPR1, by suppressing the expression of two JA-dependent defense genes, proteinase inhibitors I and II. We show here that the transcription factor TGA1.a contributes to disease development caused by B. cinerea in tomato by suppressing the expression of proteinase inhibitors I and II. Finally, we present evidence that the SA-signaling pathway contributes to disease development caused by another necrotrophic pathogen, Alternaria solani, in tomato. Disease development promoted by SA through NPR1 requires the TGA1.a transcription factor. These data highlight how necrotrophs manipulate the SAsignaling pathway to promote their disease in tomato.

Cellular self-assembly and biomaterials-based organoid models of development and diseases.

Science.gov (United States)

Shah, Shivem B; Singh, Ankur

2017-04-15

Organogenesis and morphogenesis have informed our understanding of physiology, pathophysiology, and avenues to create new curative and regenerative therapies. Thus far, this understanding has been hindered by the lack of a physiologically relevant yet accessible model that affords biological control. Recently, three-dimensional ex vivo cellular cultures created through cellular self-assembly under natural extracellular matrix cues or through biomaterial-based directed assembly have been shown to physically resemble and recapture some functionality of target organs. These "organoids" have garnered momentum for their applications in modeling human development and disease, drug screening, and future therapy design or even organ replacement. This review first discusses the self-organizing organoids as materials with emergent properties and their advantages and limitations. We subsequently describe biomaterials-based strategies used to afford more control of the organoid's microenvironment and ensuing cellular composition and organization. In this review, we also offer our perspective on how multifunctional biomaterials with precise spatial and temporal control could ultimately bridge the gap between in vitro organoid platforms and their in vivo counterparts. Several notable reviews have highlighted PSC-derived organoids and 3D aggregates, including embryoid bodies, from a development and cellular assembly perspective. The focus of this review is to highlight the materials-based approaches that cells, including PSCs and others, adopt for self-assembly and the controlled development of complex tissues, such as that of the brain, gut, and immune system. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Sites of infection by pythium species in rice seedlings and effects of plant age and water depth on disease development.

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Chun, S C; Schneider, R W

1998-12-01

ABSTRACT Seedling disease, caused primarily by several species of Pythium, is one of the major constraints to water-seeded rice production in Louisiana. The disease, also known as water-mold disease, seed rot, and seedling damping-off, causes stand reductions and growth abnormalities. In severe cases, fields must be replanted, which may result in delayed harvests and reduced yields. To develop more effective disease management tactics including biological control, this study was conducted primarily to determine sites of infection in seeds and seedlings; effect of plant age on susceptibility to P. arrhenomanes, P. myriotylum, and P. dissotocum; and minimum exposure times required for infection and seedling death. In addition, the effect of water depth on seedling disease was investigated. Infection rates of seed embryos were significantly higher than those of endosperms for all three Pythium spp. The development of roots from dry-seeded seedlings was significantly reduced by P. arrhenomanes and P. myriotylum at 5 days after planting compared with that of roots from noninoculated controls. Susceptibility of rice to all three species was sharply reduced within 2 to 6 days after planting, and seedlings were completely resistant at 8 days after planting. There was a steep reduction in emergence through the flood water, relative to the noninoculated control, following 2 to 3 days of exposure to inoculum of P. arrhenomanes and P. myriotylum. In contrast, P. dissotocum was much less virulent and required longer exposure times to cause irreversible seedling damage. Disease incidence was higher when seeds were planted into deeper water, implying that seedlings become resistant after they emerge through the flood water. These results suggest that disease control tactics including flood water management need to be employed for a very short period of time after planting. Also, given that the embryo is the primary site of infection and it is susceptible for only a few days, the

Thyroid disease

Energy Technology Data Exchange (ETDEWEB)

Falk, S.

1990-01-01

Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications.

Thyroid disease

International Nuclear Information System (INIS)

Falk, S.

1990-01-01

Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications

78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

Science.gov (United States)

2013-02-08

...] Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage... ``Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease.'' This guidance outlines FDA... trials that are specifically focused on the treatment of patients with established Alzheimer's disease...

Nuclear Receptor TLX in Development and Diseases.

Science.gov (United States)

Sun, Guoqiang; Cui, Qi; Shi, Yanhong

2017-01-01

The nuclear receptor TLX (NR2E1) is a transcription factor that is critical for neural development and adult neurogenesis through its actions in regulating neural stem cell proliferation, self-renewal, and fate determination. These roles are primarily executed by regulating TLX downstream target genes involved in myriad pathways such as cell cycle progression, RNA processing, angiogenesis, and senescence. Recent studies suggest that dysregulation of TLX pathways plays an important role in the pathogenesis of human neurological disorders and brain tumors. Here, we will highlight recent progress in the roles of TLX in brain development and adult neurogenesis, and the relevance of TLX to neurological diseases and brain tumors. We will also discuss the potential of TLX as a therapeutic target for these disorders. © 2017 Elsevier Inc. All rights reserved.

Development of Obesity and Related Diseases in African Refugees After Resettlement to United States.

Science.gov (United States)

Rhodes, Corinne M; Chang, Yuchiao; Percac-Lima, Sanja

2016-12-01

Despite increases in obesity and related diseases in developing nations, initial refugee clinical visits do not address these issues. We explored the development of obesity and related diseases in a longitudinal prospective cohort of African refugees resettling in northeastern US. Using state Department of Health data, refugees were linked to a health system. Body mass index, diabetes, hypertension, and hyperlipidemia status were extracted from charts. US regional controls from NAMCS/NHAMCS data were matched by age, sex, race, and visit year. African refugee BMI increased after resettlement at 1 (1.7 ± 2.9, p resettlement to prevent development of obesity and related disease in this vulnerable population.

Development of Extracorporeal Shock Wave Therapy for the Treatment for Ischemic Cardiovascular Diseases

Science.gov (United States)

Shimokawa, Hiroaki

Cardiovascular diseases, such as coronary artery disease and peripheral artery disease, are the major causes of death in developed countries, and the number of elderly patients has been rapidly increasing worldwide. Thus, it is crucial to develop new non-invasive therapeutic strategies for these patients. We found that a low-energy shock wave (SW) (about 10% of the energy density that is used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Subsequently, we demonstrated that extracorporeal cardiac SW therapy with low-energy SW up-regulates the expression of VEGF, enhances angiogenesis, and improves myocardial ischemia in a pig model of chronic myocardial ischemia without any adverse effects in vivo. Based on these promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic therapy with low-energy SW for cardiovascular diseases. Our extracorporeal cardiac SW therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe coronary artery disease without indication of percutaneous coronary intervention or coronary artery bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction in pigs and in enhancing angiogenesis in hindlimb ischemia in animals and patients with coronary artery disease. Furthermore, our recent experimental studies suggest that the SW therapy is also effective for indications other than cardiovascular diseases. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic strategy for cardiovascular medicine.

Heart Development, Diseases, and Regeneration　- New Approaches From Innervation, Fibroblasts, and Reprogramming.

Science.gov (United States)

Ieda, Masaki

2016-09-23

It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081-2088).

[Post-Lyme disease syndrome].

Science.gov (United States)

Błaut-Jurkowska, Justyna; Jurkowski, Marcin

2016-02-01

Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non-specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick-borne diseases needs to increase physicians awareness of these issues. © 2016 MEDPRESS.

Developing the Australasian Hepatology Association's Consensus-based Guidelines for the Nursing Care of Patients with Liver Disease.

Science.gov (United States)

Richmond, Jacqueline; Wheeler, Emily; Warner, Sherryne; Mason, Susan

2014-05-03

Abstract Purpose: Hepatology nursing is an emerging speciality. To define best practice, the Australasian Hepatology Association developed consensus-based guidelines for the nursing care of patients with liver disease. Methods: Using the Delphi technique, six rounds of consultation were conducted with Australian hepatology nurses and non-nursing hepatology professionals. Input was captured through face-to-face and electronic communication and questionnaires. Results: The experts' opinions were collated and consensus on the delivery of hepatology nursing care was achieved. In total, 90 consensus guidelines were developed. The principles underpinning the Guidelines include patient-centred care, non-discriminatory practice, cultural competence, collaboration and partnership and working within own scope of practice. Conclusion: Internationally, the Australasian Hepatology Association Guidelines are the first to document a consensus on the scope of hepatology nursing practice. The Guidelines reflect the expansion of hepatology nursing, from viral hepatitis to caring for patients with advanced liver disease and hepatocellular carcinoma, and provides a framework for future nursing practice.

Thе role of zinc in the development of cardiovascular complications in patients with Graves’ disease

Directory of Open Access Journals (Sweden)

Lyudmila V. Kvitkova

2018-02-01

Full Text Available Backgraund. The development of cardiovascular complications in patients with diffuse-toxic goiter (DTZ is an actual problem of thyroidology. (SSS in patients with DTZ. Aims. To assess the contribution of zinc deficiency in the formation of cardiovascular complications in patients with Graves’ disease. Methods. The study included 113 women aged 25–60 years with the diagnosis of DTZ: 54.0% (n = 61 with an average severity of thyrotoxicosis, 46.0% (n = 52 with severe. Duration of the disease is 1–5 years. The control group consisted of 37 women aged 25–60 years without pathology of the thyroid gland and CCC. All patients were evaluated: in the blood – the level of thyroid-stimulating hormone (TTG, free thyroxine (over T4, the concentration of antibodies to the thyroid-stimulating hormone receptor (AT to RTTG; in the hair – the concentration of zinc; ultrasound (ultrasound of the thyroid gland, echocardiography (EchoCG, daily monitoring of electrocardiography (CM ECG. Results. At DTZ deficiency of zinc in hair was observed in 66.4% (n = 75, in the control group – in 27.0% (n = 10 patients (p = 0.01. More often, zinc deficiency was found at a severe degree of DTZ in 82.7% (n = 43, atrial fibrillation (AF in 77.4% (n = 24 cases, in CHF – 78.8% (n = 41 cases. The diagnostic model and the table of risk factors of CHF in points, including the definition of the level of zinc in the hair, are developed with the help of logistic regression. It is advisable to use the table for all patients with DTZ to determine the degree of CHF risk, with an average and high risk of developing CHF in the treatment of DTZ, it is shown to include zinc preparations. Conclusion. The obtained data allow to consider that the zinc deficiency increases the probability of development of AF and CHF in patients with DTZ of severe severity, needs diagnostics and correction.

Development, evaluation and validation of a new instrument for measurement quality of life in the parents of children with chronic disease

Directory of Open Access Journals (Sweden)

Skrzypek Michał

2010-12-01

Full Text Available Abstract Background Childhood chronic disease may affect patients' and their family's functioning. Particularly parents, who play an important role in cooperation between patient and health care professionals, report impaired health - related quality of life (HRQOL. The aim of this study was development, evaluation and validation of a new instrument: Quality of Life in a Child's Chronic Disease Questionnaire (QLCCDQ. The questionnaire is addressed to parents of children with a chronic disease. Methods Study design included semi structured interview and qualitative study, which allowed to identify most troublesome problems. Following the results the questionnaire was developed, which consists of 15 questions and covers domains - emotions, patients -perceived symptoms, roles limitations. An observational study involving parents of asthma and diabetes children was conducted to assess the psychometric characteristics of the measure. Psychometric testing was based on the reliability of defined subscales, construct validity, reproducibility assessment, as well as comparison between stable/unstable disease stages and parents of healthy children. Results Most troublesome concerns for parents of child with chronic disease included emotional distress and feeling depressed due to child's disease, avoiding social interactions due to child's disease or symptoms. 98 parents of children with asthma or insulin - depended diabetes participated in the psychometric testing of QLCCDQ. Internal consistency reliability for the defined subscales ranged between 0.77 and 0.93. Reproducibility based on the weighted kappa coefficients showed expected level of agreement and was almost perfect in case of 8 questions, substantial for 5 questions and moderate for 2 questions. QLCCDQ demonstrated very good construct validity - all subscales showed statistically significant correlations ranging from 0.4 to 0.9. QLCCDQ scores differed significantly by clinical status - parents

Development, evaluation and validation of a new instrument for measurement quality of life in the parents of children with chronic disease.

Science.gov (United States)

Farnik, Małgorzata; Brożek, Grzegorz; Pierzchała, Władysław; Zejda, Jan E; Skrzypek, Michał; Walczak, Łukasz

2010-12-23

Childhood chronic disease may affect patients' and their family's functioning. Particularly parents, who play an important role in cooperation between patient and health care professionals, report impaired health-related quality of life (HRQOL). The aim of this study was development, evaluation and validation of a new instrument: Quality of Life in a Child's Chronic Disease Questionnaire (QLCCDQ). The questionnaire is addressed to parents of children with a chronic disease. Study design included semi structured interview and qualitative study, which allowed to identify most troublesome problems. Following the results the questionnaire was developed, which consists of 15 questions and covers domains--emotions, patients -perceived symptoms, roles limitations. An observational study involving parents of asthma and diabetes children was conducted to assess the psychometric characteristics of the measure. Psychometric testing was based on the reliability of defined subscales, construct validity, reproducibility assessment, as well as comparison between stable/unstable disease stages and parents of healthy children. Most troublesome concerns for parents of child with chronic disease included emotional distress and feeling depressed due to child's disease, avoiding social interactions due to child's disease or symptoms. 98 parents of children with asthma or insulin - depended diabetes participated in the psychometric testing of QLCCDQ. Internal consistency reliability for the defined subscales ranged between 0.77 and 0.93. Reproducibility based on the weighted kappa coefficients showed expected level of agreement and was almost perfect in case of 8 questions, substantial for 5 questions and moderate for 2 questions. QLCCDQ demonstrated very good construct validity--all subscales showed statistically significant correlations ranging from 0.4 to 0.9. QLCCDQ scores differed significantly by clinical status--parents of children qualified as stable presented higher scores in

Development of Snake Fungal Disease after Experimental Challenge with Ophidiomyces ophiodiicola in Cottonmouths (Agkistrodon piscivorous.

Directory of Open Access Journals (Sweden)

Matthew C Allender

Full Text Available Snake fungal disease (SFD is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.

Human Environmental Disease Network

DEFF Research Database (Denmark)

Taboureau, Olivier; Audouze, Karine

2017-01-01

During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

Energy Technology Data Exchange (ETDEWEB)

Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

2007-08-06

Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis

Predicting Climate-sensitive Infectious Diseases: Development of a Federal Science Plan and the Path Forward

Science.gov (United States)

Trtanj, J.; Balbus, J. M.; Brown, C.; Shimamoto, M. M.

2017-12-01

The transmission and spread of infectious diseases, especially vector-borne diseases, water-borne diseases and zoonosis, are influenced by short and long-term climate factors, in conjunction with numerous other drivers. Public health interventions, including vaccination, vector control programs, and outreach campaigns could be made more effective if the geographic range and timing of increased disease risk could be more accurately targeted, and high risk areas and populations identified. While some progress has been made in predictive modeling for transmission of these diseases using climate and weather data as inputs, they often still start after the first case appears, the skill of those models remains limited, and their use by public health officials infrequent. And further, predictions with lead times of weeks, months or seasons are even rarer, yet the value of acting early holds the potential to save more lives, reduce cost and enhance both economic and national security. Information on high-risk populations and areas for infectious diseases is also potentially useful for the federal defense and intelligence communities as well. The US Global Change Research Program, through its Interagency Group on Climate Change and Human Health (CCHHG), has put together a science plan that pulls together federal scientists and programs working on predictive modeling of climate-sensitive diseases, and draws on academic and other partners. Through a series of webinars and an in-person workshop, the CCHHG has convened key federal and academic stakeholders to assess the current state of science and develop an integrated science plan to identify data and observation systems needs as well as a targeted research agenda for enhancing predictive modeling. This presentation will summarize the findings from this effort and engage AGU members on plans and next steps to improve predictive modeling for infectious diseases.

A case developing minimal change disease during the course of IgG4-related disease.

Science.gov (United States)

Yamada, Kazunori; Zoshima, Takeshi; Ito, Kiyoaki; Mizushima, Ichiro; Hara, Satoshi; Horita, Shigeto; Nuka, Hiromi; Hamano, Ryoko; Fujii, Hiroshi; Yamagishi, Masakazu; Kawano, Mitsuhiro

2017-07-01

We describe a 66-year-old male with immunoglobulin G4-related disease (IgG4-RD) presenting with minimal change disease (MCD). Three years prior to this admission, the patient had been diagnosed with IgG4-RD. The development of sudden massive proteinuria (4+; 16.7 g/gCr) with a weight gain of 8 kg within a two-week period was noted, and nephrotic syndrome was suspected. The patient's serum IgG4 level did not increase and hypocomplementemia was not found. A renal biopsy showed no cellular infiltration in the renal interstitium, and no spiking or bubbling was found on periodic acid methenamine silver staining. On electron microscopy, foot process effacement was seen, but no subepithelial electron-dense deposits were found. The patient was diagnosed with MCD. Ten days after starting prednisolone (60 mg/day), proteinuria was negative. Since IgG4-RD and MCD share a T-helper 2-dominant immunoreaction, the development of MCD in IgG4-RD patients may reflect more than a mere coincidence.

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

Science.gov (United States)

Ioset, Jean-Robert; Chang, Shing

2011-09-01

The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

Ethical issues in funding research and development of drugs for neglected tropical diseases.

Science.gov (United States)

Oprea, L; Braunack-Mayer, A; Gericke, C A

2009-05-01

Neglected and tropical diseases, pervasive in developing countries, are important contributors to global health inequalities. They remain largely untreated due to lack of effective and affordable treatments. Resource-poor countries cannot afford to develop the public health interventions needed to control neglected diseases. In addition, neglected diseases do not represent an attractive market for pharmaceutical industry. Although a number of international commitments, stated in the Millennium Development Goals, have been made to avert the risk of communicable diseases, tropical diseases still remain neglected due to delays in international assistance. This delay can be explained by the form international cooperation has generally taken, which is limited to promoting countries' national interests, rather than social justice at a global level. This restricts the international responsibility for global inequalities in health to a humanitarian assistance. We propose an alternative view, arguing that expanding the scope of international cooperation by promoting shared health and economic value at a global level will create new opportunities for innovative, effective and affordable interventions worldwide. It will also promote neglected diseases as a global research priority. We build our argument on a proposal to replace the patenting system that currently regulates pharmaceutical research with a global fund to reward this research based on actual decreases in morbidity and mortality at a global level. We argue that this approach is beneficent because it will decrease global health inequalities and promote social justice worldwide.

Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

Science.gov (United States)

Garbayo, E; Ansorena, E; Blanco-Prieto, M J

2013-11-01

Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An Emerging Epidemic of Noncommunicable Diseases in Developing Populations Due to a Triple Evolutionary Mismatch

DEFF Research Database (Denmark)

Koopman, Jacob J E; van Bodegom, David; Ziem, Juventus B

2016-01-01

With their transition from adverse to affluent environments, developing populations experience a rapid increase in the number of individuals with noncommunicable diseases. Here, we emphasize that developing populations are more susceptible than western populations to acquire these chronic disease...

Developing educational material on chronic kidney disease using best practices in health literacy.

Science.gov (United States)

Santos, Luanda Thaís Mendonça; Bastos, Marcus Gomes

2017-03-01

Based in the precepts of Health Literacy (HL), an educational booklet "Do you know the Chronic Kidney Disease?" was written. It was used as a basic text for development of a Brazilian instrument for Assessment of Health Literacy (Teste de Avaliação de Letramento em Saúde or TALES). The guideline used to create the TALES obeyed four steps: systematization of content; creation and drawing of images by an expert designer; submission to a Committee of Experts on nephrology and linguistics; and editing and printing of the content. The content covering six aspects of chronic kidney disease (definition, diagnosis, signs and symptoms, prevention, risk factors and treatment) was developed utilizing multimodality techniques such as: creation of personages; verbal and visual metaphors; metonymy; personifications; direct dialogue; and plain language avoided of technicalities. During the development of TALES, the booklet proved to be useful in translating complicated scientific concepts on kidney disease into meaningfuly health messages. In conclusion, besides of being used as basic text for the development of TALES, the booklet "Do you know chronic kidney disease?", based in best practices in HL, can assist health professionals in communicating to patients using consumer-friendly educational materials that might impact positive health-related behaviors and results.

Developing educational material on chronic kidney disease using best practices in health literacy

Directory of Open Access Journals (Sweden)

Luanda Thaís Mendonça Santos

Full Text Available Abstract Based in the precepts of Health Literacy (HL, an educational booklet "Do you know the Chronic Kidney Disease?" was written. It was used as a basic text for development of a Brazilian instrument for Assessment of Health Literacy (Teste de Avaliação de Letramento em Saúde or TALES. The guideline used to create the TALES obeyed four steps: systematization of content; creation and drawing of images by an expert designer; submission to a Committee of Experts on nephrology and linguistics; and editing and printing of the content. The content covering six aspects of chronic kidney disease (definition, diagnosis, signs and symptoms, prevention, risk factors and treatment was developed utilizing multimodality techniques such as: creation of personages; verbal and visual metaphors; metonymy; personifications; direct dialogue; and plain language avoided of technicalities. During the development of TALES, the booklet proved to be useful in translating complicated scientific concepts on kidney disease into meaningfuly health messages. In conclusion, besides of being used as basic text for the development of TALES, the booklet "Do you know chronic kidney disease?", based in best practices in HL, can assist health professionals in communicating to patients using consumer-friendly educational materials that might impact positive health-related behaviors and results.

Clinical implications of shared genetics and pathogenesis in autoimmune diseases

NARCIS (Netherlands)

Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

2013-01-01

Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the

Liposomes for Targeted Delivery of Active Agents against Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease

Directory of Open Access Journals (Sweden)

Carlos Spuch

2011-01-01

Full Text Available Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease represent a huge unmet medical need. The prevalence of both diseases is increasing, but the efficacy of treatment is still very limited due to various factors including the blood brain barrier (BBB. Drug delivery to the brain remains the major challenge for the treatment of all neurodegenerative diseases because of the numerous protective barriers surrounding the central nervous system. New therapeutic drugs that cross the BBB are critically needed for treatment of many brain diseases. One of the significant factors on neurotherapeutics is the constraint of the blood brain barrier and the drug release kinetics that cause peripheral serious side effects. Contrary to common belief, neurodegenerative and neurological diseases may be multisystemic in nature, and this presents numerous difficulties for their potential treatment. Overall, the aim of this paper is to summarize the last findings and news related to liposome technology in the treatment of neurodegenerative diseases and demonstrate the potential of this technology for the development of novel therapeutics and the possible applications of liposomes in the two most widespread neurodegenerative diseases, Alzheimer's disease and Parkinson's disease.

Endocrine Disease in Aged Horses.

Science.gov (United States)

Durham, Andy E

2016-08-01

Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

Science.gov (United States)

Folimonova, Svetlana Y; Achor, Diann S

2010-09-01

Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

Development of a Novel Targeted RNAi Delivery Technology inTherapies for Metabolic Diseases

Science.gov (United States)

2017-10-01

report Impact on other disciplines: Nothing to report Impact on technology transfer: Nothing to report Impact on society : Nothing to report 5. CHANGES...AWARD NUMBER: W81XWH-15-1-0569 TITLE: Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases PRINCIPAL...COVERED 30Sep2016 - 29Sep2017 4. TITLE AND SUBTITLE Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases 5a

Geriatric medicine, Japanese Alzheimer's disease neuroimaging initiative and biomarker development

International Nuclear Information System (INIS)

Arai, Hiroyuki; Furukawa, Katsutoshi; Okamura, Nobuyuki; Kudo, Yukitsuka

2010-01-01

Due to a change in disease spectrum in aged countries, the primary role of geriatricians should be directed to an appropriate management and prevention of cognitive decline and dementia, swallowing and aspiration pneumonia and falls and fractures. Management of dementia constitutes a central part in the practice of geriatric medicine in order to support independence of life in elderly people. The current paradigm of cognitive function-based testing for the diagnosis and treatment of Alzheimer's disease (AD) is going to drastically shift to a biomarker-based test approach, a shift that will correspond to the emergence of disease-modifying drugs. In addition, a new molecular imaging technique that visualizes neuronal protein deposits or pathological features has been developed in Japan and the U.S.A. Based on these achievements, the Alzheimer's Disease Neuroimaging Initiative (ADNI) was proposed and initiated in 2005. The ADNI is a long-term observational study being conducted in the U.S.A., Europe, Australia, and Japan using identical protocols. The objectives of ADNI are: to establish methodology which will allow standard values related to long-term changes in imaging data, such as MRI and positron emission tomography (PET), in patients with AD and mild cognitive impairment and normal elderly persons; to obtain clinical indices, psychological test data, and blood/cerebrospinal fluid biomarkers to demonstrate the validity of image-based surrogate markers; and to establish optimum methods to monitor the therapeutic effects of disease-modifying drugs for AD. Patient enrollment in the Japanese ADNI has begun in July 2008. Imaging of AD pathology not only acts as a reliable biomarker with which to assay curative drug development by novel pharmaceutical companies, but it also helps health promotion toward AD prevention. (author)

The Nordic Countries Meeting on the Zebrafish as a Model for Development and Disease 2012

Science.gov (United States)

Zetterberg, Henrik

2013-01-01

Abstract The first Nordic Countries Meeting on the Zebrafish as a Model for Development and Disease took place at Karolinska Institutet in Stockholm, November 21–23, 2012. The meeting gathered 130 scientists, students, and company representatives from Iceland, Finland, Norway, Denmark, and Sweden, as well as invited guests and keynote speakers from England, Scotland, Germany, Poland, The Netherlands, Singapore, Japan, and the United States. Presentations covered a wide range of topics, including developmental biology, genetics, evolutionary biology, toxicology, behavioral studies, and disease mechanisms. The need for formal guidance and training in zebrafish housing, husbandry, and health monitoring was recognized, and the meeting expressed its support for the joint working group of the FELASA/COST action BM0804 EuFishBioMed. The decision was made to turn the Nordic meeting into an annual event and create a Nordic network of zebrafish researchers. PMID:23590403

Self-disseminating vaccines for emerging infectious diseases.

Science.gov (United States)

Murphy, Aisling A; Redwood, Alec J; Jarvis, Michael A

2016-01-01

Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.

Development of a disease risk prediction model for downy mildew (Peronospora sparsa) in boysenberry.

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Kim, Kwang Soo; Beresford, Robert M; Walter, Monika

2014-01-01

Downy mildew caused by Peronospora sparsa has resulted in serious production losses in boysenberry (Rubus hybrid), blackberry (Rubus fruticosus), and rose (Rosa sp.) in New Zealand, Mexico, and the United States and the United Kingdom, respectively. Development of a model to predict downy mildew risk would facilitate development and implementation of a disease warning system for efficient fungicide spray application in the crops affected by this disease. Because detailed disease observation data were not available, a two-step approach was applied to develop an empirical risk prediction model for P. sparsa. To identify the weather patterns associated with a high incidence of downy mildew berry infections (dryberry disease) and derive parameters for the empirical model, classification and regression tree (CART) analysis was performed. Then, fuzzy sets were applied to develop a simple model to predict the disease risk based on the parameters derived from the CART analysis. High-risk seasons with a boysenberry downy mildew incidence >10% coincided with months when the number of hours per day with temperature of 15 to 20°C averaged >9.8 over the month and the number of days with rainfall in the month was >38.7%. The Fuzzy Peronospora Sparsa (FPS) model, developed using fuzzy sets, defined relationships among high-risk events, temperature, and rainfall conditions. In a validation study, the FPS model provided correct identification of both seasons with high downy mildew risk for boysenberry, blackberry, and rose and low risk in seasons when no disease was observed. As a result, the FPS model had a significant degree of agreement between predicted and observed risks of downy mildew for those crops (P = 0.002).

Impact of amyloid imaging on drug development in Alzheimer's disease

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Mathis, Chester A. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)], E-mail: mathisca@upmc.edu; Lopresti, Brian J. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Klunk, William E. [Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

2007-10-15

Imaging agents capable of assessing amyloid-beta (A{beta}) content in vivo in the brains of Alzheimer's disease (AD) subjects likely will be important as diagnostic agents to detect A{beta} plaques in the brain as well as to help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of anti-amyloid therapeutics currently under development and in clinical trials. Positron emission tomography (PET) imaging studies of amyloid deposition in human subjects with several A{beta} imaging agents are currently underway. We reported the first PET studies of the carbon 11-labeled thioflavin-T derivative Pittsburgh Compound B in 2004, and this work has subsequently been extended to include a variety of subject groups, including AD patients, mild cognitive impairment patients and healthy controls. The ability to quantify regional A{beta} plaque load in the brains of living human subjects has provided a means to begin to apply this technology as a diagnostic agent to detect regional concentrations of A{beta} plaques and as a surrogate marker of therapeutic efficacy in anti-amyloid drug trials.

Stargardt disease: towards developing a model to predict phenotype.

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Heathfield, Laura; Lacerda, Miguel; Nossek, Christel; Roberts, Lisa; Ramesar, Rajkumar S

2013-10-01

Stargardt disease is an ABCA4-associated retinopathy, which generally follows an autosomal recessive inheritance pattern and is a frequent cause of macular degeneration in childhood. ABCA4 displays significant allelic heterogeneity whereby different mutations can cause retinal diseases with varying severity and age of onset. A genotype-phenotype model has been proposed linking ABCA4 mutations, purported ABCA4 functional protein activity and severity of disease, as measured by degree of visual loss and the age of onset. It has, however, been difficult to verify this model statistically in observational studies, as the number of individuals sharing any particular mutation combination is typically low. Seven founder mutations have been identified in a large number of Caucasian Afrikaner patients in South Africa, making it possible to test the genotype-phenotype model. A generalised linear model was developed to predict and assess the relative pathogenic contribution of the seven mutations to the age of onset of Stargardt disease. It is shown that the pathogenicity of an individual mutation can differ significantly depending on the genetic context in which it occurs. The results reported here may be used to identify suitable candidates for inclusion in clinical trials, as well as guide the genetic counselling of affected individuals and families.

Th17 response and autophagy - main pathways implicated in the development of inflammatory bowel disease by genome-wide association studies: new factors involved in inflammatory bowel disease susceptibility

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Roberto Díaz-Peña

2015-09-01

Full Text Available Inflammatory bowel disease (IBD is an entity that mainly includes ulcerative colitis (UC and Crohn's disease (CD. Improved health care, diet changes, and higher industrialization are associated with an increase in IBD prevalence. This supports the central role of environmental factors in the pathology of this disease. However, IBD also shows a relevant genetic component as shown by high heritability. Classic genetic studies showed relevant associations between IBD susceptibility and genes involved in the immune response. This is consistent with prior theories about IBD development. According to these, contact of the immune system with a high number of harmless antigens from the diet and the bacterial flora should originate tolerance while preserving response against pathogens. Failure to achieve this balance may originate the typical inflammatory response associated with IBD. Recently, genome-wide association studies (GWASs have confirmed the implication of the immune system, particularly the Th17 immune response, previously associated to other autoimmune diseases, and of autophagy. In this paper, the mechanisms involved in these two relevant pathways and their potential role in the pathogenesis of IBD are reviewed.

Reverse translation in tuberculosis: neutrophils as clues for development of active disease

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Anca eDorhoi

2014-02-01

Full Text Available Tuberculosis (TB is a major health issue globally. Although typically the disease can be cured by chemotherapy and prevented – at least in part, in newborn by vaccination, general consensus exists that development of novel intervention measures requires better understanding of disease mechanisms. Human TB is characterized by polarity between host resistance as seen in 2 billion individuals with latent TB infection and susceptibility occurring in 9 million individuals who develop active TB disease every year. Experimental animal models often do not reflect this polarity adequately, calling for a reverse translational approach. Gene expression profiling has allowed identification of biomarkers that discriminate between latent infection and active disease. Functional analysis of most relevant markers in experimental animal models can help to better understand mechanisms driving disease progression. We have embarked on in-depth characterization of candidate markers of pathology and protection hereby harnessing mouse mutants with defined gene deficiencies. Analysis of mutants deficient in miR223 expression and CXCL5 production allowed elucidation of relevant pathogenic mechanisms. Intriguingly, these deficiencies were linked to aberrant neutrophil activities. Our findings point to a detrimental potential of neutrophils in TB. Reciprocally, measures that control neutrophils should be leveraged for amelioration of TB in adjunct to chemotherapy.

Development of an algorithm for assessing the risk to food safety posed by a new animal disease.

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Parker, E M; Jenson, I; Jordan, D; Ward, M P

2012-05-01

An algorithm was developed as a tool to rapidly assess the potential for a new or emerging disease of livestock to adversely affect humans via consumption or handling of meat product, so that the risks and uncertainties can be understood and appropriate risk management and communication implemented. An algorithm describing the sequence of events from occurrence of the disease in livestock, release of the causative agent from an infected animal, contamination of fresh meat and then possible adverse effects in humans following meat handling and consumption was created. A list of questions complements the algorithm to help the assessors address the issues of concern at each step of the decision pathway. The algorithm was refined and validated through consultation with a panel of experts and a review group of animal health and food safety policy advisors via five case studies of potential emerging diseases of cattle. Tasks for model validation included describing the path taken in the algorithm and stating an outcome. Twenty-nine per cent of the 62 experts commented on the model, and one-third of those responding also completed the tasks required for model validation. The feedback from the panel of experts and the review group was used to further develop the tool and remove redundancies and ambiguities. There was agreement in the pathways and assessments for diseases in which the causative agent was well understood (for example, bovine pneumonia due to Mycoplasma bovis). The stated pathways and assessments of other diseases (for example, bovine Johne's disease) were not as consistent. The framework helps to promote objectivity by requiring questions to be answered sequentially and providing the opportunity to record consensus or differences of opinion. Areas for discussion and future investigation are highlighted by the points of diversion on the pathway taken by different assessors. © 2011 Blackwell Verlag GmbH.

Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization.

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Järbrink-Sehgal, M Ellionore; Schmidt, Peter T; Sköldberg, Filip; Hemmingsson, Tomas; Hagström, Hannes; Andreasson, Anna

2018-04-12

The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular

How microbial community composition regulates coral disease development.

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Justin Mao-Jones

2010-03-01

Full Text Available Reef coral cover is in rapid decline worldwide, in part due to bleaching (expulsion of photosynthetic symbionts and outbreaks of infectious disease. One important factor associated with bleaching and in disease transmission is a shift in the composition of the microbial community in the mucus layer surrounding the coral: the resident microbial community-which is critical to the healthy functioning of the coral holobiont-is replaced by pathogenic microbes, often species of Vibrio. In this paper we develop computational models for microbial community dynamics in the mucus layer in order to understand how the surface microbial community responds to changes in environmental conditions, and under what circumstances it becomes vulnerable to overgrowth by pathogens. Some of our model's assumptions and parameter values are based on Vibrio spp. as a model system for other established and emerging coral pathogens. We find that the pattern of interactions in the surface microbial community facilitates the existence of alternate stable states, one dominated by antibiotic-producing beneficial microbes and the other pathogen-dominated. A shift to pathogen dominance under transient stressful conditions, such as a brief warming spell, may persist long after environmental conditions have returned to normal. This prediction is consistent with experimental findings that antibiotic properties of Acropora palmata mucus did not return to normal long after temperatures had fallen. Long-term loss of antibiotic activity eliminates a critical component in coral defense against disease, giving pathogens an extended opportunity to infect and spread within the host, elevating the risk of coral bleaching, disease, and mortality.

How microbial community composition regulates coral disease development.

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Mao-Jones, Justin; Ritchie, Kim B; Jones, Laura E; Ellner, Stephen P

2010-03-30

Reef coral cover is in rapid decline worldwide, in part due to bleaching (expulsion of photosynthetic symbionts) and outbreaks of infectious disease. One important factor associated with bleaching and in disease transmission is a shift in the composition of the microbial community in the mucus layer surrounding the coral: the resident microbial community-which is critical to the healthy functioning of the coral holobiont-is replaced by pathogenic microbes, often species of Vibrio. In this paper we develop computational models for microbial community dynamics in the mucus layer in order to understand how the surface microbial community responds to changes in environmental conditions, and under what circumstances it becomes vulnerable to overgrowth by pathogens. Some of our model's assumptions and parameter values are based on Vibrio spp. as a model system for other established and emerging coral pathogens. We find that the pattern of interactions in the surface microbial community facilitates the existence of alternate stable states, one dominated by antibiotic-producing beneficial microbes and the other pathogen-dominated. A shift to pathogen dominance under transient stressful conditions, such as a brief warming spell, may persist long after environmental conditions have returned to normal. This prediction is consistent with experimental findings that antibiotic properties of Acropora palmata mucus did not return to normal long after temperatures had fallen. Long-term loss of antibiotic activity eliminates a critical component in coral defense against disease, giving pathogens an extended opportunity to infect and spread within the host, elevating the risk of coral bleaching, disease, and mortality.

Pattern of renal diseases in children: A developing country experience

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Shankar Prasad Yadav

2016-01-01

Full Text Available Spectrum of renal disease varies in different ethnic population, geographical location, and by environmental factors. The purpose of this study was to find out the clinical spectrum and occurrence of different pediatric renal diseases at a teaching hospital in the Eastern part of Nepal. All cases of renal diseases from one month to 15 years of age, attending the pediatric renal outpatient department and/or were admitted to the wards during the period of February 2012 to January 2013, were included in the study. Detailed clinical and laboratory evaluations were performed on all patients. Diseases were categorized as per standard definitions and managed with hospital protocols. Renal diseases accounted to be 206 cases (6.9% of total annual pediatric admissions, of which (58% were male and (42% female. Acute glomerulonephritis (AGN was the most common disorder (37.7% followed by nephrotic syndrome (26.1%, urinary tract infection (21.3%, acute kidney injury (AKI (17.9%, obstructive uropathy (1.9%, chronic kidney disease (CKD (1.2%, and others. In AGN group, the most common cause was post-infectious glomerulonephritis (PIGN (32.9% followed by lupus nephritis (4% and Henoch-Schonlein purpura nephritis (0.8%. Urine culture was positive in (9.22% and the most common organism was Escherichia coli (57.9%. The causes of AKI were urosepsis, septicemia, and AGN (18.9% each, followed by dehydration (13.5%. Mortality was found in 5% of cases and the etiologies were AKI in (72.7%, PIGN (18.1%, and CKD (9%. Renal diseases are a significant problem among children and are one of the common causes of hospital admission. These patients need comprehensive services for early identification and management.

Bone marrow transplantation in patients with storage diseases: a developing country experience

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Lange Marcos C.

2006-01-01

Full Text Available Bone marrow transplantation (BMT is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old were submitted to this procedure in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2, one had adrenoleukodystrophy (ALD and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient, one patient had no disease progression (ALD and in one patient this procedure did not change the natural course of the disease (MPS III.

Global Climate Change and Infectious Diseases

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EK Shuman

2010-12-01

Full Text Available Climate change is occurring as a result of warming of the earth’s atmosphere due to human activity generating excess amounts of greenhouse gases. Because of its potential impact on the hydrologic cycle and severe weather events, climate change is expected to have an enormous effect on human health, including on the burden and distribution of many infectious diseases. The infectious diseases that will be most affected by climate change include those that are spread by insect vectors and by contaminated water. The burden of adverse health effects due to these infectious diseases will fall primarily on developing countries, while it is the developed countries that are primarily responsible for climate change. It is up to governments and individuals to take the lead in halting climate change, and we must increase our understanding of the ecology of infectious diseases in order to protect vulnerable populations.

Stroke and Risks of Development and Progression of Kidney Diseases and End-Stage Renal Disease: A Nationwide Population-Based Cohort Study.

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Chia-Lin Wu

Full Text Available There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes.In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson's comorbidity index score-matched controls.The incidence rate of chronic kidney disease (CKD was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years. After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36-1.50, P<0.001. Subgroup analysis showed that stroke patients <50 years (aHR 1.61, P<0.001 and those with concomitant diabetes mellitus (aHR 2.12, P<0.001, hyperlipidemia (aHR 1.53, P<0.001 or gout (aHR 1.84, P<0.001 were at higher risk of incident CKD. Additionally, the risks of progression to advanced CKD and end-stage renal disease (ESRD were significantly higher for stroke patients (aHRs, 1.22 and 1.30; P = 0.04 and P = 0.008, respectively, independent of age, sex, comorbidities and long-term medications.Stroke is associated with higher risks for incident CKD, decline in renal function and ESRD. Younger stroke patients, as well as those with concomitant diabetes mellitus, hyperlipidemia or gout are at greater risk for kidney diseases.

Developing global climate anomalies suggest potential disease risks for 2006-2007.

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Anyamba, Assaf; Chretien, Jean-Paul; Small, Jennifer; Tucker, Compton J; Linthicum, Kenneth J

2006-12-28

El Niño/Southern Oscillation (ENSO) related climate anomalies have been shown to have an impact on infectious disease outbreaks. The Climate Prediction Center of the National Oceanic and Atmospheric Administration (NOAA/CPC) has recently issued an unscheduled El Niño advisory, indicating that warmer than normal sea surface temperatures across the equatorial eastern Pacific may have pronounced impacts on global tropical precipitation patterns extending into the northern hemisphere particularly over North America. Building evidence of the links between ENSO driven climate anomalies and infectious diseases, particularly those transmitted by insects, can allow us to provide improved long range forecasts of an epidemic or epizootic. We describe developing climate anomalies that suggest potential disease risks using satellite generated data. Sea surface temperatures (SSTs) in the equatorial east Pacific ocean have anomalously increased significantly during July - October 2006 indicating the typical development of El Niño conditions. The persistence of these conditions will lead to extremes in global-scale climate anomalies as has been observed during similar conditions in the past. Positive Outgoing Longwave Radiation (OLR) anomalies, indicative of severe drought conditions, have been observed across all of Indonesia, Malaysia and most of the Philippines, which are usually the first areas to experience ENSO-related impacts. This dryness can be expected to continue, on average, for the remainder of 2006 continuing into the early part of 2007. During the period November 2006 - January 2007 climate forecasts indicate that there is a high probability for above normal rainfall in the central and eastern equatorial Pacific Islands, the Korean Peninsula, the U.S. Gulf Coast and Florida, northern South America and equatorial east Africa. Taking into consideration current observations and climate forecast information, indications are that the following regions are at increased

Economic assessment of S-prism including development and generating costs

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Boardman, Ch.E. [GE Nuclear Energy San Jose (United States)

2001-07-01

S-PRISM is an advanced Fast Reactor plant design that utilizes compact modular pool-type reactors sized to enable factory fabrication and an affordable prototype test of a single Nuclear Steam Supply System (NSSS) for design certification at minimum cost and risk. S-PRISM retains all of the key ALMR (advanced liquid metal reactor) design features including passive reactor shutdown, passive shutdown heat removal, and passive reactor cavity cooling that were developed under an earlier DOE program. Key factors that make S-PRISM competitive include: 1) The use of passive safety systems that eliminate the need for diesel generators and hardened active heat sinks to assure that sufficient heat is removed from the core, reactor, and containment systems following design and beyond design basis events. 2) A seven point advantage in the plant capacity factor (93 versus 86%) over a single large plant. 3) A much shorter construction schedule (45%) made possible by a modular design that allows near parallel (sequenced) construction of three relatively small, simple factory fabricated NSSSs instead of one large complex NSSS. This paper describes the approach, methods, and results of an in-depth economic assessment of S-PRISM. The assessment found that the generation cost from an NOAK plant would be less than 3 cents/kW-hr and that a design certification could be obtained in less than 15 years at a cost of 2.1 billion dollars. (authors)

Economic assessment of S-prism including development and generating costs

International Nuclear Information System (INIS)

Boardman, Ch.E.

2001-01-01

S-PRISM is an advanced Fast Reactor plant design that utilizes compact modular pool-type reactors sized to enable factory fabrication and an affordable prototype test of a single Nuclear Steam Supply System (NSSS) for design certification at minimum cost and risk. S-PRISM retains all of the key ALMR (advanced liquid metal reactor) design features including passive reactor shutdown, passive shutdown heat removal, and passive reactor cavity cooling that were developed under an earlier DOE program. Key factors that make S-PRISM competitive include: 1) The use of passive safety systems that eliminate the need for diesel generators and hardened active heat sinks to assure that sufficient heat is removed from the core, reactor, and containment systems following design and beyond design basis events. 2) A seven point advantage in the plant capacity factor (93 versus 86%) over a single large plant. 3) A much shorter construction schedule (45%) made possible by a modular design that allows near parallel (sequenced) construction of three relatively small, simple factory fabricated NSSSs instead of one large complex NSSS. This paper describes the approach, methods, and results of an in-depth economic assessment of S-PRISM. The assessment found that the generation cost from an NOAK plant would be less than 3 cents/kW-hr and that a design certification could be obtained in less than 15 years at a cost of 2.1 billion dollars. (authors)

Disease Compass- a navigation system for disease knowledge based on ontology and linked data techniques.

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Kozaki, Kouji; Yamagata, Yuki; Mizoguchi, Riichiro; Imai, Takeshi; Ohe, Kazuhiko

2017-06-19

Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states. It represents causes of diseases, disease progression, and downstream consequences of diseases, which is compliant with the intuition of medical experts. In this paper, we discuss a fact repository for causal chains of disease based on the disease ontology. It could be a valuable knowledge base for advanced medical information systems. We developed the fact repository for causal chains of diseases based on our disease ontology and abnormality ontology. This section summarizes these two ontologies. It is developed as linked data so that information scientists can access it using SPARQL queries through an Resource Description Framework (RDF) model for causal chain of diseases. We designed the RDF model as an implementation of the RFM for the fact repository based on the ontological definitions of the RFM. 1554 diseases and 7080 abnormal states in six major clinical areas, which are extracted from the disease ontology, are published as linked data (RDF) with SPARQL endpoint (accessible API). Furthermore, the authors developed Disease Compass, a navigation system for disease knowledge. Disease Compass can browse the causal chains of a disease and obtain related information, including abnormal states, through two web services that provide general information from linked data, such as DBpedia, and 3D anatomical images. Disease Compass can provide a complete picture of disease-associated processes in such a way that fits with a clinician's understanding of diseases. Therefore, it supports user exploration of disease knowledge with access to pertinent information

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

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Dumonteil, Eric; Bottazzi, Maria Elena; Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, B T; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto; Hotez, Peter J

2012-09-01

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.

Meeting report - TGF-β superfamily: signaling in development and disease.

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Zhang, Ying E; Newfeld, Stuart J

2013-11-01

The latest advances on the transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways were reported at the July 2013 FASEB Summer Research Conference 'The TGF-β Superfamily: Development and Disease'. The meeting was held in Steamboat Springs, Colorado, USA at 6700 feet above sea level in the Rocky Mountains. This was the seventh biannual meeting in the series. In attendance were investigators from a broad range of disciplines with a common interest in the mechanics of TGF-β and BMP signaling pathways, their normal developmental and homeostatic functions, and the diseases associated with pathway misregulation.

[Urinary incontinence in degenerative spinal disease].

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De Riggo, J; Benčo, M; Kolarovszki, B; Lupták, J; Svihra, J

2011-01-01

The aim of the study was to evaluate the presence of urinary incontinence in patients with chronic degenerative spinal disease and to identify factors affecting the occurrence and changes in urinary incontinence after surgery. The group evaluated comprised 214 patients undergoing surgery for degenerative spinal disease at our department between January 1 and December 31, 2008. The patients were categorised according to the type of their degenerative disease (cervical disc herniation, lumbar disc herniation, spinal stenosis, spinal instability or olisthesis) and the spine level involved (cervical or lumbar spine). The symptoms of urinary incontinence included leakage of urine and non-obstructive chronic urinary retention developing in association with the manifestation of vertebrogenic disorder. Patients with diseases known to increase the risk of incontinence were not included in the study. Based on a retrospective analysis of the patients' clinical notes, the occurrence of urinary incontinence in each type of degenerative spinal disease was assessed. The effect of gender, age, body mass index (BMI), neurological status and spinal disease type on the development of incontinence was statistically evaluated. The efficacy of surgical treatment was assessed on the basis of the patients' subjective complaints at the first follow-up one month after surgery. The data were evaluated by the statistical programme InSTAT (analysis of variance ANOVA, t-test). All tests were two-sided; a 0.05 level of statistical significance was used. Of the 214 patients with degenerative spinal disease, 27 (12.6%) had urinary incontinence. A higher risk of developing incontinence was found in women (p = 0.008) and in patients with radicular weakness (p = 0.023). The patients with urinary incontinence had their BMI significantly lower than patients without this disorder (p = 0.019). Age had no effect. The differences in the occurrence of urinary incontinence amongst the different types of

Homozygous deletion of six genes including corneodesmosin on chromosome 6p21.3 is associated with generalized peeling skin disease.

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Teye, Kwesi; Hamada, Takahiro; Krol, Rafal P; Numata, Sanae; Ishii, Norito; Matsuda, Mitsuhiro; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

2014-07-01

Peeling skin syndrome (PSS) is a rare autosomal recessive form of ichthyosis showing skin exfoliation. PSS is divided into acral and generalized PSS, and the latter is further classified into non-inflammatory type (PSS type A) and inflammatory type (PSS type B). PSS type B is now called peeling skin disease (PSD). Different loss-of-function mutations in the corneodesmosin (CDSN) gene have been reported to cause PSD. The aim of this study was to determine genetic basis of disease in a 14-year-old Japanese patient with PSD. Immunohistochemical study showed lack of corneodesmosin (CDSN) in the skin, and standard PCR for genomic DNA failed to amplify CDSN product, suggesting CDSN defect. Multiplex ligation-dependent probe amplification and genomic quantitative real-time PCR analyses detected large homozygous deletion of 59,184bp extending from 40.6kb upstream to 13.2kb downstream of CDSN, which included 6 genes (TCF19, CCHCR1, PSORS1C2, PSORS1C1, CDSN and C6orf15). The continuous gene lost did not result in additional clinical features. Inverted repeats with 85% similarity flanking the deletion breakpoint were considered to mediate the deletion by non-homologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication. Parents were clinically unaffected and were heterozygote carriers of the same deletion, which was absent in 284 ethnically matched control alleles. We also developed simple PCR method, which is useful for detection of this deletion. Although 5 other genes were also deleted, homozygous deletion of CDSN was considered to be responsible for this PSD. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review

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Vanessa Patricia L. Pereira

Full Text Available Abstract Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

The neurotechnological revolution: unlocking the brain's secrets to develop innovative technologies as well as treatments for neurological diseases.

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Banks, Jim

2015-01-01

The brain contains all that makes us human, but its complexity is the source of both inspiration and frailty. Aging population is increasingly in need of effective care and therapies for brain diseases, including stroke, Parkinson's disease and Alzheimer's disease. The world's scientific community working hard to unravel the secrets of the brain's computing power and to devise technologies that can heal it when it fails and restore critical functions to patients with neurological conditions. Neurotechnology is the emerging field that brings together the development of technologies to study the brain and devices that improve and repair brain function. What is certain is the momentum behind neurotechnological research is building, and whether through implants, BCIs, or innovative computational systems inspired by the human brain, more light will be shed on our most complex and most precious organ, which will no doubt lead to effective treatment for many neurological conditions.

Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

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Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Lamba, Arundeep K; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

2014-04-01

The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Global Trends in Alzheimer Disease Clinical Development: Increasing the Probability of Success.

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Sugino, Haruhiko; Watanabe, Akihito; Amada, Naoki; Yamamoto, Miho; Ohgi, Yuta; Kostic, Dusan; Sanchez, Raymond

2015-08-01

Alzheimer disease (AD) is a growing global health and economic issue as elderly populations increase dramatically across the world. Despite the many clinical trials conducted, currently no approved disease-modifying treatment exists. In this commentary, the present status of AD drug development and the grounds for collaborations between government, academia, and industry to accelerate the development of disease-modifying AD therapies are discussed. Official government documents, literature, and news releases were surveyed by MEDLINE and website research. Currently approved anti-AD drugs provide only short-lived symptomatic improvements, which have no effect on the underlying pathogenic mechanisms or progression of the disease. The failure to approve a disease-modifying drug for AD may be because the progression of AD in the patient populations enrolled in clinical studies was too advanced for drugs to demonstrate cognitive and functional improvements. The US Food and Drug Administration and the European Medicines Agency recently published draft guidance for industry which discusses approaches for conducting clinical studies with patients in early AD stages. For successful clinical trials in early-stage AD, however, it will be necessary to identify biomarkers highly correlated with the clinical onset and the longitudinal progress of AD. In addition, because of the high cost and length of clinical AD studies, support in the form of global initiatives and collaborations between government, industry, and academia is needed. In response to this situation, national guidance and international collaborations have been established. Global initiatives are focusing on 2025 as a goal to provide new treatment options, and early signs of success in biomarker and drug development are already emerging. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Artificial intelligence techniques applied to the development of a decision-support system for diagnosing celiac disease.

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Tenório, Josceli Maria; Hummel, Anderson Diniz; Cohrs, Frederico Molina; Sdepanian, Vera Lucia; Pisa, Ivan Torres; de Fátima Marin, Heimar

2011-11-01

Celiac disease (CD) is a difficult-to-diagnose condition because of its multiple clinical presentations and symptoms shared with other diseases. Gold-standard diagnostic confirmation of suspected CD is achieved by biopsying the small intestine. To develop a clinical decision-support system (CDSS) integrated with an automated classifier to recognize CD cases, by selecting from experimental models developed using intelligence artificial techniques. A web-based system was designed for constructing a retrospective database that included 178 clinical cases for training. Tests were run on 270 automated classifiers available in Weka 3.6.1 using five artificial intelligence techniques, namely decision trees, Bayesian inference, k-nearest neighbor algorithm, support vector machines and artificial neural networks. The parameters evaluated were accuracy, sensitivity, specificity and area under the ROC curve (AUC). AUC was used as a criterion for selecting the CDSS algorithm. A testing database was constructed including 38 clinical CD cases for CDSS evaluation. The diagnoses suggested by CDSS were compared with those made by physicians during patient consultations. The most accurate method during the training phase was the averaged one-dependence estimator (AODE) algorithm (a Bayesian classifier), which showed accuracy 80.0%, sensitivity 0.78, specificity 0.80 and AUC 0.84. This classifier was integrated into the web-based decision-support system. The gold-standard validation of CDSS achieved accuracy of 84.2% and k=0.68 (pdiagnosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease

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Anderson, Mark E.; Birren, Susan J.; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B.; Kanazawa, Hideaki; Paterson, David J.; Ripplinger, Crystal M.

2016-01-01

Abstract The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural–cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

The effect of Chernobyl accident on the development of non malignant diseases

International Nuclear Information System (INIS)

Zonenberg, A.; Leoniak, M.; Zarzycki, W.

2006-01-01

The early medical complications of Chernobyl accident include post radiation disease, which were diagnosed in 134 subjects affected by ionizing radiation. 28 persons died during the first 100 days after the event. The increase occurrence of coronary heart disease, endocrine, haematological, dermatological and other diseases were observed after disaster in the contaminated territories. We also discussed the impact of ionizing radiation from Chernobyl accident on pregnancy and congenital defects occurrence. Changes following the Chernobyl accident, as the inhabitants migration from contaminated regions, political and economic conversions, led to depression, anxiety, and even to '' epidemic '' of mental diseases. Increased suicide rate, car accidents, alcohol and drug abuse have been observed in this population. Nowadays vegetative neurosis is more often diagnosed in Ukrainian children. Epidemiological studies were conducted on the ionising radiation effect on the health and on the dose of received radiation after Chernobyl accident face numerous problems as the absence of reliable data regarding diseases in the contaminated territories.(authors)

Development of a novel oral vaccine against Mycobacterium avium paratuberculosis and Johne disease

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Johnston, C; Coffey, A; Sleator, RD

2010-01-01

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne disease, a granulomatous enteritis of cattle and other domesticated and wild ruminant species. Johne disease is prevalent worldwide and has a significant impact on the global agricultural economy. Current vaccines against Johne are insufficient in stemming its spread, and associated side-effects prevent their widespread use in control programs. Effective and safe vaccine strategies are needed. The main purpose of this paper is to propose and evaluate the development of a novel oral subunit-vaccine using a patho-biotechnological approach. This novel strategy, which harnesses patho-genetic elements from the intracellular pathogen Listeria monocytogenes, may provide a realistic route towards developing an effective next generation subunit vaccine against Johne disease and paratuberculosis. PMID:21326921

Development of a Discrete Spatial-Temporal SEIR Simulator for Modeling Infectious Diseases

Energy Technology Data Exchange (ETDEWEB)

McKenna, S.A.

2000-11-01

Multiple techniques have been developed to model the temporal evolution of infectious diseases. Some of these techniques have also been adapted to model the spatial evolution of the disease. This report examines the application of one such technique, the SEIR model, to the spatial and temporal evolution of disease. Applications of the SEIR model are reviewed briefly and an adaptation to the traditional SEIR model is presented. This adaptation allows for modeling the spatial evolution of the disease stages at the individual level. The transmission of the disease between individuals is modeled explicitly through the use of exposure likelihood functions rather than the global transmission rate applied to populations in the traditional implementation of the SEIR model. These adaptations allow for the consideration of spatially variable (heterogeneous) susceptibility and immunity within the population. The adaptations also allow for modeling both contagious and non-contagious diseases. The results of a number of numerical experiments to explore the effect of model parameters on the spread of an example disease are presented.

Creutzfeldt-Jakob disease

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LIU Jian-rong

2013-01-01

Full Text Available Creutzfeldt-Jakob disease (CJD is a degenerative central nervous system (CNS disease caused by infection of prion protein (PrP, with clinical features including short course, rapid development and 100% mortality. This article aims to discuss the pathogenesis, histopathological features, clinical manifestations, electroencephalogram (EEG findings, imaging data and treatment progress of this disease based on literature review. Cerebrospinal fluid 14-3-3 protein detection, EEG and MRI are three important methods to make an early diagnosis on patients with suspected CJD, such as elderly patients with rapidly progressive dementia (RPD and young patients with mental symptoms involving multiple systems (MS.

Gaucher disease and other storage disorders.

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Grabowski, Gregory A

2012-01-01

In 1882, Philippe Gaucher described a 32-year-old woman with massive splenomegaly and unusually large cells in the spleen, which he called a "primary epithelioma of the spleen." The systemic nature and inheritance of the disease and its variants involving the viscera and CNS were described over the next century. The delineation of the causal enzymatic defects, genetics, molecular pathology, and genomics have provided pathogenic insights into the phenotypic spectrum and the bases for development of specific therapies for what is now known as Gaucher disease. As a prototype, the clinically and economically successful intracellular enzyme therapy provided the impetus for the expansion of similar research and therapeutic developments for other lysosomal storage diseases (LSDs) and orphan diseases, including Fabry, Pompe, and Niemann-Pick diseases, as well as several mucopolysaccharidoses. Continuing studies of such LSDs, which occur as a group in more than 7000 live births, have revealed the complex molecular interdigitation with the autophagy and apoptotic pathways and proteostasis and the impact of disruptions of the lysosomal/autophagy and proteostasis systems on more common diseases has been recognized. Examples include age-related neurodegenerative diseases (eg, Parkinson disease and Gaucher disease), idiopathic hypertrophic myocardiopathies, stroke and renal failure (eg, Fabry disease), and Nonalcoholic Fatty Liver Disease/Nonalcoholic SteatoHepatitis (NAFLD/NASH) and atherosclerosis (eg, lysosomal acid lipase deficiencies). Although perceived as rare, the availability of treatment and the impact of the LSDs on more common diseases require their integration into routine clinical practice.

Circulating ACE2 activity correlates with cardiovascular disease development

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Katalin Úri

2016-12-01

Full Text Available It was shown recently that angiotensin-converting enzyme activity is limited by endogenous inhibition in vivo, highlighting the importance of angiotensin II (ACE2 elimination. The potential contribution of the ACE2 to cardiovascular disease progression was addressed. Serum ACE2 activities were measured in different clinical states (healthy, n=45; hypertensive, n=239; heart failure (HF with reduced ejection fraction (HFrEF n=141 and HF with preserved ejection fraction (HFpEF n=47. ACE2 activity was significantly higher in hypertensive patients (24.8±0.8 U/ml than that in healthy volunteers (16.2±0.8 U/ml, p=0.01. ACE2 activity further increased in HFrEF patients (43.9±2.1 U/ml, p=0.001 but not in HFpEF patients (24.6±1.9 U/ml when compared with hypertensive patients. Serum ACE2 activity negatively correlated with left ventricular systolic function in HFrEF, but not in hypertensive, HFpEF or healthy populations. Serum ACE2 activity had a fair diagnostic value to differentiate HFpEF from HFrEF patients in this study. Serum ACE2 activity correlates with cardiovascular disease development: it increases when hypertension develops and further increases when the cardiovascular disease further progresses to systolic dysfunction, suggesting that ACE2 metabolism plays a role in these processes. In contrast, serum ACE2 activity does not change when hypertension progresses to HFpEF, suggesting a different pathomechanism for HFpEF, and proposing a biomarker-based identification of these HF forms.

Diabetic kidney disease.

Science.gov (United States)

Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

2015-07-30

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

Key outcomes from stakeholder workshops at a symposium to inform the development of an Australian national plan for rare diseases.

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Molster, Caron; Youngs, Leanne; Hammond, Emma; Dawkins, Hugh

2012-08-10

Calls have been made for governments to adopt a cohesive approach to rare diseases through the development of national plans. At present, Australia does not have a national plan for rare diseases. To progress such a plan an inaugural Australian Rare Diseases Symposium was held in Western Australia in April 2011. This paper describes the key issues identified by symposium attendees for the development of a national plan, compares these to the content of EUROPLAN and national plans elsewhere and discusses how the outcomes might be integrated for national planning. The symposium was comprised of a series of plenary sessions followed by workshops. The topics covered were; 1) Development of national plans for rare diseases; 2) Patient empowerment; 3) Patient care, support and management; 4) Research and translation; 5) Networks, partnerships and collaboration. All stakeholders within the rare diseases community were invited to participate, including: people affected by rare diseases such as patients, carers, and families; clinicians and allied health practitioners; social and disability services; researchers; patient support groups; industry (e.g. pharmaceutical, biotechnology and medical device companies); regulators and policy-makers. All of these stakeholder groups were represented at the symposium. Workshop participants indicated the need for a national plan, a national peak body, a standard definition of 'rare diseases', education campaigns, lobbying of government, research infrastructure, streamlined whole-of-lifetime service provision, case co-ordination, early diagnosis, support for health professionals and dedicated funding. These findings are consistent with frameworks and initiatives being undertaken internationally (such as EUROPLAN), and with national plans in other countries. This implies that the development of an Australian national plan could plausibly draw on frameworks for plan development that have been proposed for use in other jurisdictions. The

Chromatin remodeling, development and disease

International Nuclear Information System (INIS)

Ko, Myunggon; Sohn, Dong H.; Chung, Heekyoung; Seong, Rho H.

2008-01-01

Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

Risk factors of development of inflammatory diseases of parodentium in pregnant women

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Dubrovskaya M.V.

2013-09-01

Full Text Available Pathogenesis of oral hygiene, smoking, gestosis, immunosuppression and cytokine disbalance affect inflammatory periodontal diseases in pregnant women. The research goal is to study clinical and immunological features of parodentium and cytokine profile in oral cavity of pregnant women. Material and methods: The condition of parodentium tissues was studied at 240 women with physiological pregnancy and 360 with pregnancy complicadet by gestosis. Re-sults: Freguency and character of inflammatory periodontal diseases in pregnancy were defined. Immune and cytokine disbalance contributed greatly to pathogenesis of inflammatory periodontal diseases at pregnant women. Conclusion: Violations of immune homeostasis at the pregnancy, complicated gestosis, authentically are more expressed that contributes to the development of gingivitis and periodontal disease. The imbalance of cytokines can serve in oral liquid as additional diagnostic and predictive marker of severity of a course of inflammatory periodontal disease.

Development of a classification scheme for disease-related enzyme information

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Söhngen Carola

2011-08-01

Full Text Available Abstract Background BRENDA (BRaunschweig ENzyme DAtabase, http://www.brenda-enzymes.org is a major resource for enzyme related information. First and foremost, it provides data which are manually curated from the primary literature. DRENDA (Disease RElated ENzyme information DAtabase complements BRENDA with a focus on the automatic search and categorization of enzyme and disease related information from title and abstracts of primary publications. In a two-step procedure DRENDA makes use of text mining and machine learning methods. Results Currently enzyme and disease related references are biannually updated as part of the standard BRENDA update. 910,897 relations of EC-numbers and diseases were extracted from titles or abstracts and are included in the second release in 2010. The enzyme and disease entity recognition has been successfully enhanced by a further relation classification via machine learning. The classification step has been evaluated by a 5-fold cross validation and achieves an F1 score between 0.802 ± 0.032 and 0.738 ± 0.033 depending on the categories and pre-processing procedures. In the eventual DRENDA content every category reaches a classification specificity of at least 96.7% and a precision that ranges from 86-98% in the highest confidence level, and 64-83% for the smallest confidence level associated with higher recall. Conclusions The DRENDA processing chain analyses PubMed, locates references with disease-related information on enzymes and categorises their focus according to the categories causal interaction, therapeutic application, diagnostic usage and ongoing research. The categorisation gives an impression on the focus of the located references. Thus, the relation categorisation can facilitate orientation within the rapidly growing number of references with impact on diseases and enzymes. The DRENDA information is available as additional information in BRENDA.

Gastroesophageal Reflux Disease and Alkaline Reflux: the Mechanisms of the Development and Therapeutic Approach

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T.D. Zviahintseva

2016-11-01

Full Text Available The article deals with gastroesophageal reflux disease (GERD — a pathology, which occupies a leading place among all acid-related diseases. The main mechanism of GERD is a violation of the motor-evacuation function of the stomach — slowing gastric emptying and duodenogastric reflux. Slow gastric emptying contributes to more frequent reflux, and the presence of duodenal contents in refluxate — alkaline reflux — is aggressive for the esophageal mucosa (EM. This is due to the presence of bile acids, lysolecithin and pancreatic enzymes in the esophageal refluxate. A long existing contact of aggressive factors in the stomach and the esophagus leads to the development of inflammatory and destructive lesions of the mucous membrane of these organs. According to many researchers, bile acids play a key role in the pathogenesis of the damaging effects on the EM. Drug correction of GERD with alkaline reflux includes, along with the administration of proton pump inhibitors, prokinetics (itopride hydrochloride and ursodeoxycholic acid preparations.

Obesity and kidney disease

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Geraldo Bezerra da Silva Junior

Full Text Available Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD. Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.

Excessive daytime sleepiness and subsequent development of Parkinson disease.

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Abbott, R D; Ross, G W; White, L R; Tanner, C M; Masaki, K H; Nelson, J S; Curb, J D; Petrovitch, H

2005-11-08

To determine if excessive daytime sleepiness (EDS) can predate future Parkinson disease (PD). EDS was assessed in 3,078 men aged 71 to 93 years in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent PD and dementia. Follow-up for incident PD was based on three repeat neurologic assessments from 1994 to 2001. During the course of follow-up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS vs men without EDS (55.3 vs 17.0/10,000 person-years; odds ratio [OR] = 3.3; 95% CI = 1.4 to 7.0; p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to 6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD. Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.

Intermittent hypoxia, cardiovascular disease and obstructive sleep apnoea.

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Turnbull, Chris D

2018-01-01

Obstructive sleep apnoea (OSA) is a common disorder and is associated with cardiovascular disease. Continuous positive airway pressure (CPAP), whilst reducing blood pressure, has not been shown to reduce cardiovascular events when used as a treatment solely for this purpose in patients with previous cardiovascular disease. Developing a better understanding of the mechanisms underlying cardiovascular disease in OSA is important to develop new treatments. Potential causative mechanisms for cardiovascular disease in OSA include arousal induced sympathetic activation, large intrathoracic pressure swings leading to shear stress on the heart and great vessels, and intermittent hypoxia (IH). This review discusses the role of IH, as a major physiological consequence of OSA, in the development of cardiovascular disease.

Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

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McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

2015-01-01

Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

[Imported diseases in Switzerland: development and perspectives].

Science.gov (United States)

Degrémont, A; Lorenz, N

1990-10-01

During the last years, imported diseases have become more frequent in Switzerland. This is easily explained by the enormous increase of tourism to tropical and subtropical countries. Immigration from these countries has equally seen an important augmentation. The principal imported diseases are still malaria and gastrointestinal infections. Viral infections are rarely diagnosed, with the exception of hepatitis and HIV infection. The prevalence of sexually transmitted diseases is most certainly underestimated. The differential diagnosis of imported skin diseases is still difficult. Rare tropical diseases will probably become more frequent in the coming years as travellers leave more and more the traditional tourist paths. Practitioners have to look out for such problems, and continuous training programmes for them will have to take these new problems into account. Referral centres of infectious diseases should be established in all regions of Switzerland. High priority should be given to the prevention of imported diseases.

Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease

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Anway, Matthew D.; Leathers, Charles; Skinner, Michael K.

2018-01-01

The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1–F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1–F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease. PMID:16973726

Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

Science.gov (United States)

Rastogi, Neelesh; Smith, R Theodore

2016-01-01

Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

The haematological variations during the development of radiation disease in sheep

International Nuclear Information System (INIS)

Tuga, I.

1988-01-01

The changes of the hematologic parameters (erythro cites, leucocytes, platelets, reticulocytes, etc.) during the development of the acute irradiation disease of different degrees in experimental conditions in ovines are described by the author.The use of the obtained results as related to diagnostics and prognostics is recommended,and the recorded irradiation damages are presented. The use of medicinal herbs has been found useful in the symptomatic treatment of the acute irradiation disease in ovines, in addition to the known classical treatment. 15 refs. 3 tabs

Protocol for developing a Database of Zoonotic disease Research in India (DoZooRI).

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Chatterjee, Pranab; Bhaumik, Soumyadeep; Chauhan, Abhimanyu Singh; Kakkar, Manish

2017-12-10

Zoonotic and emerging infectious diseases (EIDs) represent a public health threat that has been acknowledged only recently although they have been on the rise for the past several decades. On an average, every year since the Second World War, one pathogen has emerged or re-emerged on a global scale. Low/middle-income countries such as India bear a significant burden of zoonotic and EIDs. We propose that the creation of a database of published, peer-reviewed research will open up avenues for evidence-based policymaking for targeted prevention and control of zoonoses. A large-scale systematic mapping of the published peer-reviewed research conducted in India will be undertaken. All published research will be included in the database, without any prejudice for quality screening, to broaden the scope of included studies. Structured search strategies will be developed for priority zoonotic diseases (leptospirosis, rabies, anthrax, brucellosis, cysticercosis, salmonellosis, bovine tuberculosis, Japanese encephalitis and rickettsial infections), and multiple databases will be searched for studies conducted in India. The database will be managed and hosted on a cloud-based platform called Rayyan. Individual studies will be tagged based on key preidentified parameters (disease, study design, study type, location, randomisation status and interventions, host involvement and others, as applicable). The database will incorporate already published studies, obviating the need for additional ethical clearances. The database will be made available online, and in collaboration with multisectoral teams, domains of enquiries will be identified and subsequent research questions will be raised. The database will be queried for these and resulting evidence will be analysed and published in peer-reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

Regional Disease Surveillance Meeting - Final Paper

Energy Technology Data Exchange (ETDEWEB)

Lesperance, Ann M.; Mahy, Heidi A.

2006-08-08

On June 1, 2006, public health officials working in surveillance, epidemiological modeling, and information technology communities from the Seattle/Tacoma area and State of Washington met with members of the Pacific Northwest National Laboratory (PNNL) to discuss the current state of disease surveillance and gaps and needs to improve the current systems. The meeting also included a discussion of PNNL initiatives that might be appropriate to enhance disease surveillance and the current tools being used for disease surveillance. Participants broke out into two groups to identify critical gaps and needs for improving a surveillance system, and discuss the requirements for developing improved surveillance. Each group developed a list of key priorities summarizing the requirements for improved surveillance. The objective of this meeting was to work towards the development of an improved disease surveillance system.

A Case-Control study of the prevalence of neurological diseases in inflammatory bowel disease (IBD

Directory of Open Access Journals (Sweden)

Francisco de Assis Aquino Gondim

2015-02-01

Full Text Available Neurological diseases are common in inflammatory bowel disease (IBD patients, but their exact prevalence is unknown. Method We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD and 70 with ulcerative colitis (UC] and 50 controls (gastritis and dyspepsia over 3 years. Results Our standard neurological evaluation (that included electrodiagnostic testing revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045, 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001 and 5.1 times more likely to develop autonomic complaints (p = 0.027. UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027 and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015. Conclusion In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia.

Diverticular disease: A therapeutic overview

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Tursi, Antonio

2010-01-01

Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis. When diverticulosis becomes symptomatic, it becomes diverticular disease. Diverticular disease is common in Western and industrialized countries, and it is associated with numerous abdominal symptoms (including pain, bloating, nausea, diarrhea, and constipation). Standard medical therapies with antibiotics are currently recommended for patients affected by diverticular disease. However, changing concepts on the pathophysiology of the disease suggest that diverticular disease may share many of the hallmarks of inflammatory bowel diseases. On this basis, the addition of therapies using mesalazine and probiotics may enhance treatment efficacy by shortening the course of the disease and preventing recurrences. PMID:21577292

Altered Markers of Brain Development in Crohn's Disease with Extraintestinal Manifestations - A Pilot Study.

Directory of Open Access Journals (Sweden)

Anne K Thomann

Full Text Available Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development.In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling.The overall group comparison (i.e. all patients vs. controls yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05 and hypergyrification in the left lingual gyrus (p<0.001 compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05 and hypergyrification of the right anterior cingulate cortex (p<0.001 were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons.Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes

Including refugees in disease elimination: challenges observed from a sleeping sickness programme in Uganda.

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Palmer, Jennifer J; Robert, Okello; Kansiime, Freddie

2017-01-01

Ensuring equity between forcibly-displaced and host area populations is a key challenge for global elimination programmes. We studied Uganda's response to the recent refugee influx from South Sudan to identify key governance and operational lessons for national sleeping sickness programmes working with displaced populations today. A refugee policy which favours integration of primary healthcare services for refugee and host populations and the availability of rapid diagnostic tests (RDTs) to detect sleeping sickness at this health system level makes Uganda well-placed to include refugees in sleeping sickness surveillance. Using ethnographic observations of coordination meetings, review of programme data, interviews with sleeping sickness and refugee authorities and group discussions with health staff and refugees (2013-2016), we nevertheless identified some key challenges to equitably integrating refugees into government sleeping sickness surveillance. Despite fears that refugees were at risk of disease and posed a threat to elimination, six months into the response, programme coordinators progressed to a sentinel surveillance strategy in districts hosting the highest concentrations of refugees. This meant that RDTs, the programme's primary surveillance tool, were removed from most refugee-serving facilities, exacerbating existing inequitable access to surveillance and leading refugees to claim that their access to sleeping sickness tests had been better in South Sudan. This was not intentionally done to exclude refugees from care, rather, four key governance challenges made it difficult for the programme to recognise and correct inequities affecting refugees: (a) perceived donor pressure to reduce the sleeping sickness programme's scope without clear international elimination guidance on surveillance quality; (b) a problematic history of programme relations with refugee-hosting districts which strained supervision of surveillance quality; (c) difficulties that

[Biologics and mycobacterial diseases].

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Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

2013-03-01

Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for

Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

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Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rapid response to an emerging infectious disease - Lessons learned from development of a synthetic DNA vaccine targeting Zika virus.

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Kudchodkar, Sagar B; Choi, Hyeree; Reuschel, Emma L; Esquivel, Rianne; Jin-Ah Kwon, Jackie; Jeong, Moonsup; Maslow, Joel N; Reed, Charles C; White, Scott; Kim, J Joseph; Kobinger, Gary P; Tebas, Pablo; Weiner, David B; Muthumani, Kar

2018-03-17

Vaccines are considered one of the greatest advances in modern medicine. The global burden of numerous infectious diseases has been significantly reduced, and in some cases, effectively eradicated through the deployment of specific vaccines. However, efforts to develop effective new vaccines against infectious pathogens such as influenza, Human immunodeficiency virus (HIV), dengue virus (DENV), chikungunya virus (CHIKV), Ebola virus, and Zika virus (ZIKV) have proven challenging. Zika virus is a mosquito-vectored flavivirus responsible for periodic outbreaks of disease in Africa, Southeast Asia, and the Pacific Islands dating back over 50 years. Over this period, ZIKV infections were subclinical in most infected individuals and resulted in mild cases of fever, arthralgia, and rash in others. Concerns about ZIKV changed over the past two years, however, as outbreaks in Brazil, Central American countries, and Caribbean islands revealed novel aspects of infection including vertical and sexual transmission modes. Cases have been reported showing dramatic neurological pathologies including microcephaly and other neurodevelopmental problems in babies born to ZIKV infected mothers, as well as an increased risk of Guillain-Barre syndrome in adults. These findings prompted the World Health Organization to declare ZIKV a public health emergency in 2016, which resulted in expanded efforts to develop ZIKV vaccines and immunotherapeutics. Several ZIKV vaccine candidates that are immunogenic and effective at blocking ZIKV infection in animal models have since been developed, with some of these now being evaluated in the clinic. Additional therapeutics under investigation include anti-ZIKV monoclonal antibodies (mAbs) that have been shown to neutralize infection in vitro as well as protect against morbidity in mouse models of ZIKV infection. In this review, we summarize the current understanding of ZIKV biology and describe our efforts to rapidly develop a vaccine against ZIKV

Using epidemiological information to develop effective integrated virus disease management strategies.

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Jones, Roger A C

2004-03-01

Virus diseases cause serious losses in yield and quality of cultivated plants worldwide. These losses and the resulting financial damage can be limited by controlling epidemics using measures that minimise virus infection sources or suppress virus spread. For each combination of virus, cultivated plant and production system, there is an 'economic threshold' above which the financial damage is sufficient to justify using such measures. However, individual measures used alone may bring only small benefits and they may become ineffective, especially over the long term. When diverse control measures that act in different ways are combined and used together, their effects are complementary resulting in far more effective overall control. Such experiences have led to the development of integrated management concepts for virus diseases that combine available host resistance, cultural, chemical and biological control measures. Selecting the ideal mix of measures for each pathosystem and production situation requires detailed knowledge of the epidemiology of the causal virus and the mode of action of each individual control measure so that diverse responses can be devised to meet the unique features of each of the different scenarios considered. The strategies developed must be robust and necessitate minimal extra expense, labour demands and disruption to standard practices. Examples of how epidemiological information can be used to develop effective integrated disease management (IDM) strategies for diverse situations are described. They involve circumstances where virus transmission from plant-to-plant occurs in four different ways: by contact, non-persistently or persistently by insect vectors, and by root-infecting fungi. The examples are: Subterranean clover mottle virus (SCMoV) (contact-transmitted) and Bean yellow mosaic virus (BYMV) (non-persistently aphid-transmitted) in annually self-regenerating clover pasture; three seed-borne viruses (all non-persistently aphid

Environmental pollution and kidney diseases.

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Xu, Xin; Nie, Sheng; Ding, Hanying; Hou, Fan Fan

2018-05-01

The burden of disease and death attributable to environmental pollution is becoming a public health challenge worldwide, especially in developing countries. The kidney is vulnerable to environmental pollutants because most environmental toxins are concentrated by the kidney during filtration. Given the high mortality and morbidity of kidney disease, environmental risk factors and their effect on kidney disease need to be identified. In this Review, we highlight epidemiological evidence for the association between kidney disease and environmental pollutants, including air pollution, heavy metal pollution and other environmental risk factors. We discuss the potential biological mechanisms that link exposure to environmental pollutants to kidney damage and emphasize the contribution of environmental pollution to kidney disease. Regulatory efforts should be made to control environmental pollution and limit individual exposure to preventable or avoidable environmental risk. Population studies with accurate quantification of environmental exposure in polluted regions, particularly in developing countries, might aid our understanding of the dose-response relationship between pollutants and kidney diseases.

Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

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Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

2017-02-07

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature.

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Luhmann, Ulrich F O; Lin, Jihong; Acar, Niyazi; Lammel, Stefanie; Feil, Silke; Grimm, Christian; Seeliger, Mathias W; Hammes, Hans-Peter; Berger, Wolfgang

2005-09-01

To characterize developmental defects and the time course of Norrie disease in retinal and hyaloid vasculature during retinal development and to identify underlying molecular angiogenic pathways that may be affected in Norrie disease, exudative vitreoretinopathy, retinopathy of prematurity, and Coats' disease. Norrie disease pseudoglioma homologue (Ndph)-knockout mice were studied during retinal development at early postnatal (p) stages (p5, p10, p15, and p21). Histologic techniques, quantitative RT-PCR, ELISA, and Western blot analyses provided molecular data, and scanning laser ophthalmoscopy (SLO) angiography and electroretinography (ERG) were used to obtain in vivo data. The data showed that regression of the hyaloid vasculature of Ndph-knockout mice occurred but was drastically delayed. The development of the superficial retinal vasculature was strongly delayed, whereas the deep retinal vasculature did not form because of the blockage of vessel outgrowth into the deep retinal layers. Subsequently, microaneurysm-like lesions formed. Several angiogenic factors were differentially transcribed during retinal development. Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse. These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks. They also suggest an early and a late phase of Norrie disease and may provide an explanation for similar phenotypic features of allelic retinal diseases in mice and patients as secondary consequences of pathologic hypoxia.

A Prototype Exercise-Empowerment Mobile Video Game for Children With Cancer, and Its Usability Assessment: Developing Digital Empowerment Interventions for Pediatric Diseases.

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Bruggers, Carol S; Baranowski, Sabrina; Beseris, Mathew; Leonard, Rachel; Long, Derek; Schulte, Elizabeth; Shorter, Ashton; Stigner, Rowan; Mason, Clinton C; Bedrov, Alisa; Pascual, Ian; Bulaj, Grzegorz

2018-01-01

Medical advances continue to improve morbidity and mortality of serious pediatric diseases, including cancer, driving research addressing diminished physical and psychological quality of life in children with these chronic conditions. Empowerment enhances resilience and positively influences health, disease, and therapy understanding. We describe the development and usability assessment of a prototype Empower Stars! mobile video game grounded in behavioral and exercise theories with the purpose of coupling physical exercise with empowerment over disease in children with cancer. Academic faculty, health-care providers, and community video game developers collaborated in this project. The iPadAir was selected as a delivery platform for its accelerometer and gyroscope features facilitating exercise design. Unity multiplatform technology provided animation and audiovisual features for immediate player feedback. Javascript, C#, Photoshop, Flash, and SketchUp were used for coding, creating graphical assets, Sprite sheets, and printing files, respectively. 3D-printed handles and case backing were used to adapt the iPad for physical exercise. Game usability, engagement, and enjoyment were assessed via a multilevel study of children undergoing cancer chemotherapy, their parents, and pediatric cancer health-care providers. Feedback crucial for ongoing game development was analyzed. A prototype Empower Stars! mobile video game was developed for children 7-14 years old with cancer. Active, sedentary, educational, and empowerment-centered elements intermix for 20 min of exercise within a 30 min "one-day treatment" gameplay session involving superheroes, space exploration, metaphorical cancer challenges, life restoration on a barren planet, and innumerable star rewards. No player "dies." Usability assessment data analyses showed widespread enthusiasm for integrating exercise with empowerment over cancer and the game itself. Favorite elements included collecting star

A Prototype Exercise–Empowerment Mobile Video Game for Children With Cancer, and Its Usability Assessment: Developing Digital Empowerment Interventions for Pediatric Diseases

Directory of Open Access Journals (Sweden)

Carol S. Bruggers

2018-04-01

Full Text Available BackgroundMedical advances continue to improve morbidity and mortality of serious pediatric diseases, including cancer, driving research addressing diminished physical and psychological quality of life in children with these chronic conditions. Empowerment enhances resilience and positively influences health, disease, and therapy understanding. We describe the development and usability assessment of a prototype Empower Stars! mobile video game grounded in behavioral and exercise theories with the purpose of coupling physical exercise with empowerment over disease in children with cancer.MethodsAcademic faculty, health-care providers, and community video game developers collaborated in this project. The iPadAir was selected as a delivery platform for its accelerometer and gyroscope features facilitating exercise design. Unity multiplatform technology provided animation and audiovisual features for immediate player feedback. Javascript, C#, Photoshop, Flash, and SketchUp were used for coding, creating graphical assets, Sprite sheets, and printing files, respectively. 3D-printed handles and case backing were used to adapt the iPad for physical exercise. Game usability, engagement, and enjoyment were assessed via a multilevel study of children undergoing cancer chemotherapy, their parents, and pediatric cancer health-care providers. Feedback crucial for ongoing game development was analyzed.ResultsA prototype Empower Stars! mobile video game was developed for children 7–14 years old with cancer. Active, sedentary, educational, and empowerment-centered elements intermix for 20 min of exercise within a 30 min “one-day treatment” gameplay session involving superheroes, space exploration, metaphorical cancer challenges, life restoration on a barren planet, and innumerable star rewards. No player “dies.” Usability assessment data analyses showed widespread enthusiasm for integrating exercise with empowerment over cancer and the game

Development of a preliminary composite disease activity index in psoriatic arthritis.

LENUS (Irish Health Repository)

Mumtaz, Aizad

2012-02-01

OBJECTIVES: To develop a preliminary composite psoriatic disease activity index (CPDAI) for psoriasis and psoriatic arthritis. METHODS: Five domains were assessed and specific instruments were employed for each domain to determine the extent of domain involvement and the effect of that involvement on quality of life\\/function. Disease activity for each domain was then graded from 0 to 3 giving a CPDAI range of 0-15. Patient and physician global disease activity measures were also recorded and an independent physician was asked to indicate if treatment change was required. Bivariate correlation analysis was performed. Factor, tree analysis and standardised response means were also calculated. RESULTS: Significant correlation was seen between CPDAI and both patient (r = 0.834) and physician (r = 0.825) global disease activity assessments (p = 0.01). Tree analysis revealed that 96.3% of patients had their treatment changed when CPDAI values were greater than 6; no patient had their treatment changed when CPDAI values were less than 5. CONCLUSION: CPDAI correlates well with patient and physician global disease activity assessments and is an effective tool that clearly distinguishes those who require a treatment change from those who do not.

Design and development of the Australian and New Zealand (ANZ myeloma and related diseases registry

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Krystal Bergin

2016-11-01

Full Text Available Abstract Background Plasma cell dyscrasias (PCD are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS to multiple myeloma (MM. MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ for comparison to both local and international guidelines for standards of care. A clinical registry can provide this information and subsequently support development of strategies to address any differences, including providing a platform for clinical trials. The Myeloma and Related Diseases Registry (MRDR was developed to monitor and explore variations in practices, processes and outcomes in ANZ and provide benchmark outcomes nationally and internationally for PCD. This paper describes the MRDR aims, development and implementation and discusses challenges encountered in the process. Methods The MRDR was established in 2012 as an online database for a multi-centre collaboration across ANZ, collecting prospective data on patients with a diagnosis of MGUS, MM, solitary plasmacytoma or plasma cell leukaemia. Development of the MRDR required multi-disciplinary team participation, IT and biostatistical support as well as financial resources. Results More than 1250 patients have been enrolled at 23 sites to date. Here we describe how database development, data entry and securing ethics approval have been major challenges for participating sites and the coordinating centre, and our approaches to resolving them. Now established, the MRDR will provide clinically relevant and credible monitoring, therapy and

Melioidosis: An emerging infectious disease

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Raja N

2005-01-01

Full Text Available Infectious diseases account for a third of all the deaths in the developing world. Achievements in understanding the basic microbiology, pathogenesis, host defenses and expanded epidemiology of infectious diseases have resulted in better management and reduced mortality. However, an emerging infectious disease, melioidosis, is becoming endemic in the tropical regions of the world and is spreading to non-endemic areas. This article highlights the current understanding of melioidosis including advances in diagnosis, treatment and prevention. Better understanding of melioidosis is essential, as it is life-threatening and if untreated, patients can succumb to it. Our sources include a literature review, information from international consensus meetings on melioidosis and ongoing discussions within the medical and scientific community.

Allergic diseases and air pollution.

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Lee, Suh-Young; Chang, Yoon-Seok; Cho, Sang-Heon

2013-07-01

The prevalence of allergic diseases has been increasing rapidly, especially in developing countries. Various adverse health outcomes such as allergic disease can be attributed to rapidly increasing air pollution levels. Rapid urbanization and increased energy consumption worldwide have exposed the human body to not only increased quantities of ambient air pollution, but also a greater variety of pollutants. Many studies clearly demonstrate that air pollutants potently trigger asthma exacerbation. Evidence that transportation-related pollutants contribute to the development of allergies is also emerging. Moreover, exposure to particulate matter, ozone, and nitrogen dioxide contributes to the increased susceptibility to respiratory infections. This article focuses on the current understanding of the detrimental effects of air pollutants on allergic disease including exacerbation to the development of asthma, allergic rhinitis, and eczema as well as epigenetic regulation.

Development and validation of modified disease activity scores in rheumatoid arthritis

DEFF Research Database (Denmark)

Baker, Joshua F; Conaghan, Philip G; Smolen, Josef S

2014-01-01

-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear......OBJECTIVE: To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures.......15 × SJC28 + 0.22 × EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P

Renal disease in patients with celiac disease.

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Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn

2018-04-01

Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.

Developing an active implementation model for a chronic disease management program.

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Smidth, Margrethe; Christensen, Morten Bondo; Olesen, Frede; Vedsted, Peter

2013-04-01

Introduction and diffusion of new disease management programs in healthcare is usually slow, but active theory-driven implementation seems to outperform other implementation strategies. However, we have only scarce evidence on the feasibility and real effect of such strategies in complex primary care settings where municipalities, general practitioners and hospitals should work together. The Central Denmark Region recently implemented a disease management program for chronic obstructive pulmonary disease (COPD) which presented an opportunity to test an active implementation model against the usual implementation model. The aim of the present paper is to describe the development of an active implementation model using the Medical Research Council's model for complex interventions and the Chronic Care Model. We used the Medical Research Council's five-stage model for developing complex interventions to design an implementation model for a disease management program for COPD. First, literature on implementing change in general practice was scrutinised and empirical knowledge was assessed for suitability. In phase I, the intervention was developed; and in phases II and III, it was tested in a block- and cluster-randomised study. In phase IV, we evaluated the feasibility for others to use our active implementation model. The Chronic Care Model was identified as a model for designing efficient implementation elements. These elements were combined into a multifaceted intervention, and a timeline for the trial in a randomised study was decided upon in accordance with the five stages in the Medical Research Council's model; this was captured in a PaTPlot, which allowed us to focus on the structure and the timing of the intervention. The implementation strategies identified as efficient were use of the Breakthrough Series, academic detailing, provision of patient material and meetings between providers. The active implementation model was tested in a randomised trial

Current treatments in Parkinson's including the proposal of an innovative dopamine microimplant

Directory of Open Access Journals (Sweden)

M. Velázquez-Paniagua

2016-04-01

Full Text Available Parkinson's disease is a chronic, debilitating, progressive neurological disorder of multifactorial origin. It affects between 0.3% and 2% of the over-65 population worldwide, with a predilection for men, and is characterised by bradykinesia, muscular rigidity, resting tremor and postural instability. Parkinson's is caused by decreased dopamine levels due to the loss of dopaminergic neurons in the substantia nigra. Because dopamine is a highly oxidisable molecule, precursors such as levodopa, together with catechol-O-methyltransferase and monoamine oxidase inhibitors to prevent degradation, are used in the treatment of this disease. These therapies, however, are not without their adverse effects. Surgical treatments for Parkinson's include pallidotomy, therapy deep brain stimulation, and stem cells. A more recent development involves a titanium dioxide micro-implant containing nanopores that stabilise the dopamine for continuous release. When inserted into the caudate nucleus, this micro-implant was found to counteract 85% of symptoms in hemiparkinsonian rats, and is a promising therapy for patients with Parkinson's disease.

Undernutrition and Overnutrition Burden for Diseases in Developing Countries: The Role of Oxidative Stress Biomarkers to Assess Disease Risk and Interventional Strategies.

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Mastorci, Francesca; Vassalle, Cristina; Chatzianagnostou, Kyriazoula; Marabotti, Claudio; Siddiqui, Khawer; Eba, Ahmed Ould; Mhamed, Soueid Ahmed Sidi; Bandopadhyay, Arun; Nazzaro, Marco Stefano; Passera, Mirko; Pingitore, Alessandro

2017-06-08

The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition, which causes a change in the disease profile from infectious diseases to a chronic degenerative pattern. This review discusses the under- and over-nutrition context in Mauritania and India, two countries that are experiencing a nutritional transition, and where we began a collaboration with local medical staff to integrate interventional and diagnostic guidelines. If many studies about diet and its relationship to non-communicable diseases are available for India, very few nutrition and cardiovascular risk studies have been conducted in Mauritania. Presently, with the exponential increase of nutrition-related diseases, targeted approaches are needed to provide balanced diets in parallel with the development of national preventive health systems and screening programs adapted to local needs. In this context, the measurement of oxidative stress biomarkers could be promising as an additive tool to assess cardiovascular (CV) risk in general population, and ameliorating prevention in patients at CV risk or with overt CV disease. Moreover, the possibility of improving the outcome by the direct employment of antioxidant remains plausible. Moreover, studies on the content of antioxidant in different foods may be helpful to develop a balanced diet, and achieve the maximal nutritional and functional properties of cultivars with benefits for human health.

Undernutrition and Overnutrition Burden for Diseases in Developing Countries: The Role of Oxidative Stress Biomarkers to Assess Disease Risk and Interventional Strategies

Directory of Open Access Journals (Sweden)

Francesca Mastorci

2017-06-01

Full Text Available The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition, which causes a change in the disease profile from infectious diseases to a chronic degenerative pattern. This review discusses the under- and over-nutrition context in Mauritania and India, two countries that are experiencing a nutritional transition, and where we began a collaboration with local medical staff to integrate interventional and diagnostic guidelines. If many studies about diet and its relationship to non-communicable diseases are available for India, very few nutrition and cardiovascular risk studies have been conducted in Mauritania. Presently, with the exponential increase of nutrition-related diseases, targeted approaches are needed to provide balanced diets in parallel with the development of national preventive health systems and screening programs adapted to local needs. In this context, the measurement of oxidative stress biomarkers could be promising as an additive tool to assess cardiovascular (CV risk in general population, and ameliorating prevention in patients at CV risk or with overt CV disease. Moreover, the possibility of improving the outcome by the direct employment of antioxidant remains plausible. Moreover, studies on the content of antioxidant in different foods may be helpful to develop a balanced diet, and achieve the maximal nutritional and functional properties of cultivars with benefits for human health.

R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

Science.gov (United States)

Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

2012-05-09

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

Key outcomes from stakeholder workshops at a symposium to inform the development of an Australian national plan for rare diseases

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Molster Caron

2012-08-01

Full Text Available Abstract Background Calls have been made for governments to adopt a cohesive approach to rare diseases through the development of national plans. At present, Australia does not have a national plan for rare diseases. To progress such a plan an inaugural Australian Rare Diseases Symposium was held in Western Australia in April 2011. This paper describes the key issues identified by symposium attendees for the development of a national plan, compares these to the content of EUROPLAN and national plans elsewhere and discusses how the outcomes might be integrated for national planning. Methods The symposium was comprised of a series of plenary sessions followed by workshops. The topics covered were; 1 Development of national plans for rare diseases; 2 Patient empowerment; 3 Patient care, support and management; 4 Research and translation; 5 Networks, partnerships and collaboration. All stakeholders within the rare diseases community were invited to participate, including: people affected by rare diseases such as patients, carers, and families; clinicians and allied health practitioners; social and disability services; researchers; patient support groups; industry (e.g. pharmaceutical, biotechnology and medical device companies; regulators and policy-makers. Results All of these stakeholder groups were represented at the symposium. Workshop participants indicated the need for a national plan, a national peak body, a standard definition of ‘rare diseases’, education campaigns, lobbying of government, research infrastructure, streamlined whole-of-lifetime service provision, case co-ordination, early diagnosis, support for health professionals and dedicated funding. Conclusions These findings are consistent with frameworks and initiatives being undertaken internationally (such as EUROPLAN, and with national plans in other countries. This implies that the development of an Australian national plan could plausibly draw on frameworks for plan

A taxonomy for disease management: a scientific statement from the American Heart Association Disease Management Taxonomy Writing Group.

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Krumholz, Harlan M; Currie, Peter M; Riegel, Barbara; Phillips, Christopher O; Peterson, Eric D; Smith, Renee; Yancy, Clyde W; Faxon, David P

2006-09-26

Disease management has shown great promise as a means of reorganizing chronic care and optimizing patient outcomes. Nevertheless, disease management programs are widely heterogeneous and lack a shared definition of disease management, which limits our ability to compare and evaluate different programs. To address this problem, the American Heart Association's Disease Management Taxonomy Writing Group developed a system of classification that can be used both to categorize and compare disease management programs and to inform efforts to identify specific factors associated with effectiveness. The AHA Writing Group began with a conceptual model of disease management and its components and subsequently validated this model over a wide range of disease management programs. A systematic MEDLINE search was performed on the terms heart failure, diabetes, and depression, together with disease management, case management, and care management. The search encompassed articles published in English between 1987 and 2005. We then selected studies that incorporated (1) interventions designed to improve outcomes and/or reduce medical resource utilization in patients with heart failure, diabetes, or depression and (2) clearly defined protocols with at least 2 prespecified components traditionally associated with disease management. We analyzed the study protocols and used qualitative research methods to develop a disease management taxonomy with our conceptual model as the organizing framework. The final taxonomy includes the following 8 domains: (1) Patient population is characterized by risk status, demographic profile, and level of comorbidity. (2) Intervention recipient describes the primary targets of disease management intervention and includes patients and caregivers, physicians and allied healthcare providers, and healthcare delivery systems. (3) Intervention content delineates individual components, such as patient education, medication management, peer support, or some

Mutagenesis and phenotyping resources in zebrafish for studying development and human disease

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Varshney, Gaurav Kumar

2014-01-01

The zebrafish (Danio rerio) is an important model organism for studying development and human disease. The zebrafish has an excellent reference genome and the functions of hundreds of genes have been tested using both forward and reverse genetic approaches. Recent years have seen an increasing number of large-scale mutagenesis projects and the number of mutants or gene knockouts in zebrafish has increased rapidly, including for the first time conditional knockout technologies. In addition, targeted mutagenesis techniques such as zinc finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short sequences (CRISPR) or CRISPR-associated (Cas), have all been shown to effectively target zebrafish genes as well as the first reported germline homologous recombination, further expanding the utility and power of zebrafish genetics. Given this explosion of mutagenesis resources, it is now possible to perform systematic, high-throughput phenotype analysis of all zebrafish gene knockouts. PMID:24162064

Diagnosis of animal diseases using nuclear and related techniques: Developments and trends

International Nuclear Information System (INIS)

Anderson, J.; McKay, J.A.

1991-01-01

Nuclear techniques such as radioimmune precipitation, radioimmunoassay, DNA cloning and amino acid sequencing have led to a greater understanding of protein structure and function, antigenic variation and the immune response to infection. Knowledge gained from the use of this technology has led to the development of improved diagnostic assays. Although radioimmunoassay has been used for animal disease diagnosis for many years, more recently it has been replaced by the enzyme linked immunosorbent assay (ELISA). The ELISA offers advantages in speed of reading and longer reagent shelf life and obviates the use of radiochemicals. This is particularly important in developing countries, which may have no facilities for storage, handling and disposal of radioactive materials. In the case of rinderpest diagnosis, taken as an example, the virus neutralization test was replaced by a simple indirect ELISA for seromonitoring throughout the Pan-African Rinderpest Campaign. In the near future, this will be replaced by a competitive ELISA using a rinderpest specific monoclonal antibody, which will offer significant advantages in sensitivity and specificity. In the future it may be possible to replace the rinderpest antigen with vector expressed proteins or synthetic polypeptides. More recent developments such as the 'amplified' ELISA and the use of fluorogenic and bioluminescent substrates may further improve disease diagnosis. The knowledge gained from the use of modern technology is essential to the development of improved diagnostic assays which in turn will lead to improved disease diagnosis and control. (author). 9 refs

Disease: H00692 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available nitive deficits, and renal tubular abnormalities. Inherited metabolic disease; Nerv...he Golgi complex. The symptoms of Lowe syndrome include congenital cataracts and glaucoma, delay in neuropsychomotor development, cog

Nonpeptide neurotrophic agents useful in the treatment of neurodegenerative diseases such as Alzheimer's disease

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Masaaki Akagi

2015-02-01

Full Text Available Developed regions, including Japan, have become “aged societies,” and the number of adults with senile dementias, such as Alzheimer's disease (AD, Parkinson's disease, and Huntington's disease, has also increased in such regions. Neurotrophins (NTs may play a role in the treatment of AD because endogenous neurotrophic factors (NFs prevent neuronal death. However, peptidyl compounds have been unable to cross the blood–brain barrier in clinical studies. Thus, small molecules, which can mimic the functions of NFs, might be promising alternatives for the treatment of neurodegenerative diseases. Natural products, such as or nutraceuticals or those used in traditional medicine, can potentially be used to develop new therapeutic agents against neurodegenerative diseases. In this review, we introduced the neurotrophic activities of polyphenols honokiol and magnolol, which are the main constituents of Magnolia obovata Thunb, and methanol extracts from Zingiber purpureum (BANGLE, which may have potential therapeutic applications in various neurodegenerative disorders.

Renal cystic disease: A practical overview

International Nuclear Information System (INIS)

Hartman, D.S.

1987-01-01

Renal cystic disease includes a group of lesions with extremely diverse clinical, radiographic, and pathologic findings. The recent development of multiple imaging systems to study renal cystic disease has resulted in considerable interest in correlating the images obtained by different modalities with each other and with the underlying gross pathology. A thorough knowledge of the disturbed morphology and natural history of these diseases will lead to a better understanding of their appearance on radiologic imaging. This refresher course correlates disturbed morphology with appearances on diagnostic imaging, urography, US, angiography, CT, and MR imaging. The advantages and limitations of each imaging method are detailed. A practical classification emphasizing differential features is presented. The presentation is divided into two parts. In the first part typical and atypical cystic masses, including acquired cystic disease (from dialysis), Von Hippel-Lindau disease, and the cystic disease of tuberous sclerosis are discussed. In the second part, polycystic kidney disease (dominant and recessive), medullary cystic disease, medullary sponge kidney, multicycle-dysplastic kidney, renal sinus cysts (peripelvic), and pluricystic kidney disease are discussed

45 CFR 287.130 - Can NEW Program activities include job market assessments, job creation and economic development...

Science.gov (United States)

2010-10-01

... assessments, job creation and economic development activities? 287.130 Section 287.130 Public Welfare... creation and economic development activities? (a) A Tribe may conduct job market assessments within its NEW Program. These might include the following: (1) Consultation with the Tribe's economic development staff...

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

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

2018-05-19

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

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

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

2016-03-01

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

Proteomics: a tool to develop novel diagnostic methods and unravel molecular mechanisms of pediatric diseases.

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Torres-Arroyo, Angélica; Ruiz-Lara, Arturo; Castillo-Villanueva, Adriana; Méndez-Cruz, Sara Teresa; Espinosa-Padilla, Sara Elvia; Espinosa-Rosales, Francisco Javier; Zarate-Mondragón, Flora; Cervantes-Bustamante, Roberto; Bosch-Canto, Vanessa; Vizzuett-López, Iris; Ordaz-Fávila, Juan Carlos; Oria-Hernández, Jesús; Reyes-Vivas, Horacio

Proteomics is the study of the expression of changes and post-translational modifications (PTM) of proteins along a metabolic condition either normal or pathological. In the field of health, proteomics allows obtaining valuable data for treatment, diagnosis or pathophysiological mechanisms of different illnesses. To illustrate the aforementioned, we describe two projects currently being performed at the Instituto Nacional de Pediatría: The immuno-proteomic study of cow milk allergy and the Proteomic study of childhood cataract. Cow's milk proteins (CMP) are the first antigens to which infants are exposed and generate allergy in some of them. In Mexico, the incidence of CMP allergy has been estimated at 5-7%. Clinical manifestations include both gastrointestinal and extra-gastrointestinal symptoms, making its diagnosis extremely difficult. An inappropriate diagnosis affects the development and growth of children. The goals of the study are to identify the main immune-reactive CMP in Mexican pediatric population and to design more accurate diagnostic tools for this disease. Childhood cataract is a major ocular disease representing one of the main causes of blindness in infants; in developing countries, this disease promotes up to 27% of cases related to visual loss. From this group, it has been estimated that close to 60% of children do not survive beyond two years after vision lost. PTM have been pointed out as the main cause of protein precipitation at the crystalline and, consequently, clouding of this tissue. The study of childhood cataract represents an outstanding opportunity to identify the PTM associated to the cataract-genesis process. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

DNA copy number, including telomeres and mitochondria, assayed using next-generation sequencing

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Jackson Stuart

2010-04-01

Full Text Available Abstract Background DNA copy number variations occur within populations and aberrations can cause disease. We sought to develop an improved lab-automatable, cost-efficient, accurate platform to profile DNA copy number. Results We developed a sequencing-based assay of nuclear, mitochondrial, and telomeric DNA copy number that draws on the unbiased nature of next-generation sequencing and incorporates techniques developed for RNA expression profiling. To demonstrate this platform, we assayed UMC-11 cells using 5 million 33 nt reads and found tremendous copy number variation, including regions of single and homogeneous deletions and amplifications to 29 copies; 5 times more mitochondria and 4 times less telomeric sequence than a pool of non-diseased, blood-derived DNA; and that UMC-11 was derived from a male individual. Conclusion The described assay outputs absolute copy number, outputs an error estimate (p-value, and is more accurate than array-based platforms at high copy number. The platform enables profiling of mitochondrial levels and telomeric length. The assay is lab-automatable and has a genomic resolution and cost that are tunable based on the number of sequence reads.

Neglected Tropical Diseases and the Millennium Development Goals-why the "other diseases" matter: reality versus rhetoric

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Molyneux David H

2011-12-01

Full Text Available Abstract Since 2004 there has been an increased recognition of the importance of Neglected Tropical Diseases (NTDs as impediments to development. These diseases are caused by a variety of infectious agents - viruses, bacteria and parasites - which cause a diversity of clinical conditions throughout the tropics. The World Health Organisation (WHO has defined seventeen of these conditions as core NTDs. The objectives for the control, elimination or eradication of these conditions have been defined in World Health Assembly resolutions whilst the strategies for the control or elimination of individual diseases have been defined in various WHO documents. Since 2005 there has been a drive for the expanded control of these diseases through an integrated approach of mass drug administration referred to as Preventive Chemotherapy via community-based distribution systems and through schools. This has been made possible by donations from major pharmaceutical companies of quality and efficacious drugs which have a proven track record of safety. As a result of the increased commitment of endemic countries, bilateral donors and non-governmental development organisations, there has been a considerable expansion of mass drug administration. In particular, programmes targeting lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminth infections have expanded to treat 887. 8 million people in 2009. There has been significant progress towards guinea worm eradication, and the control of leprosy and human African trypanosomiasis. This paper responds to what the authors believe are inappropriate criticisms of these programmes and counters accusations of the motives of partners made in recently published papers. We provide a detailed response and update the information on the numbers of global treatments undertaken for NTDs and list the success stories to date. The paper acknowledges that in undertaking any health programme in

Disease and health management in Asian aquaculture.

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Bondad-Reantaso, Melba G; Subasinghe, Rohana P; Arthur, J Richard; Ogawa, Kazuo; Chinabut, Supranee; Adlard, Robert; Tan, Zilong; Shariff, Mohamed

2005-09-30

Asia contributes more than 90% to the world's aquaculture production. Like other farming systems, aquaculture is plagued with disease problems resulting from its intensification and commercialization. This paper describes the various factors, providing specific examples, which have contributed to the current disease problems faced by what is now the fastest growing food-producing sector globally. These include increased globalization of trade and markets; the intensification of fish-farming practices through the movement of broodstock, postlarvae, fry and fingerlings; the introduction of new species for aquaculture development; the expansion of the ornamental fish trade; the enhancement of marine and coastal areas through the stocking of aquatic animals raised in hatcheries; the unanticipated interactions between cultured and wild populations of aquatic animals; poor or lack of effective biosecurity measures; slow awareness on emerging diseases; the misunderstanding and misuse of specific pathogen free (SPF) stocks; climate change; other human-mediated movements of aquaculture commodities. Data on the socio-economic impacts of aquatic animal diseases are also presented, including estimates of losses in production, direct and indirect income and employment, market access or share of investment, and consumer confidence; food availability; industry failures. Examples of costs of investment in aquatic animal health-related activities, including national strategies, research, surveillance, control and other health management programmes are also provided. Finally, the strategies currently being implemented in the Asian region to deal with transboundary diseases affecting the aquaculture sector are highlighted. These include compliance with international codes, and development and implementation of regional guidelines and national aquatic animal health strategies; new diagnostic and therapeutic techniques and new information technology; new biosecurity measures including

The Oral Microbiome of Children: Development, Disease, and Implications Beyond Oral Health.

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Gomez, Andres; Nelson, Karen E

2017-02-01

In the era of applied meta-omics and personalized medicine, the oral microbiome is a valuable asset. From biomarker discovery to being a powerful source of therapeutic targets and to presenting an opportunity for developing non-invasive approaches to health care, it has become clear that oral microbes may hold the answer for understanding disease, even beyond the oral cavity. Although our understanding of oral microbiome diversity has come a long way in the past 50 years, there are still many areas that need to be fine-tuned for better risk assessment and diagnosis, especially in early developmental stages of human life. Here, we discuss the factors that impact development of the oral microbiome and explore oral markers of disease, with a focus on the early oral cavity. Our ultimate goal is to put different experimental and methodological views into perspective for better assessment of early oral and systemic disease at an early age and discuss how oral microbiomes-at the community level-could provide improved assessment in individuals and populations at risk.

Developing global climate anomalies suggest potential disease risks for 2006 – 2007

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Tucker Compton J

2006-12-01

Full Text Available Abstract Background El Niño/Southern Oscillation (ENSO related climate anomalies have been shown to have an impact on infectious disease outbreaks. The Climate Prediction Center of the National Oceanic and Atmospheric Administration (NOAA/CPC has recently issued an unscheduled El Niño advisory, indicating that warmer than normal sea surface temperatures across the equatorial eastern Pacific may have pronounced impacts on global tropical precipitation patterns extending into the northern hemisphere particularly over North America. Building evidence of the links between ENSO driven climate anomalies and infectious diseases, particularly those transmitted by insects, can allow us to provide improved long range forecasts of an epidemic or epizootic. We describe developing climate anomalies that suggest potential disease risks using satellite generated data. Results Sea surface temperatures (SSTs in the equatorial east Pacific ocean have anomalously increased significantly during July – October 2006 indicating the typical development of El Niño conditions. The persistence of these conditions will lead to extremes in global-scale climate anomalies as has been observed during similar conditions in the past. Positive Outgoing Longwave Radiation (OLR anomalies, indicative of severe drought conditions, have been observed across all of Indonesia, Malaysia and most of the Philippines, which are usually the first areas to experience ENSO-related impacts. This dryness can be expected to continue, on average, for the remainder of 2006 continuing into the early part of 2007. During the period November 2006 – January 2007 climate forecasts indicate that there is a high probability for above normal rainfall in the central and eastern equatorial Pacific Islands, the Korean Peninsula, the U.S. Gulf Coast and Florida, northern South America and equatorial east Africa. Taking into consideration current observations and climate forecast information, indications

Women's experiences of developing musculoskeletal diseases: employment challenges and policy recommendations.

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Crooks, Valorie A

2007-07-30

To answer three specific questions: (i) How do women experience the workplace after the onset of a musculoskeletal disease; (ii) What employment policy and programme suggestions can they offer for ways to better support chronically ill women in their abilities to maintain workforce participation; and (iii) How are these women's employment policy and programme recommendations informed by their own lived experiences and desires? In-depth interviews were conducted with 18 women who had developed musculoskeletal diseases while involved in the labour market. Data were coded and analysed thematically. Participants identified three common workplace barriers experienced and three types of workplace accommodations commonly requested. They offered four specific employment policy and programme recommendations for ways to better support women who develop musculoskeletal diseases in maintaining labour market participation. It is found that their employment policy and programme recommendations are informed by their own experiences in the workplace and desires for being supported in maintaining involvement in paid labour. Creating employment programmes and policies that support chronically ill women in their attempts to remain involved in the workforce based on how much paid labour they are able to perform and where they are best able to work is of the utmost importance.

Oxidative stress signaling to chromatin in health and disease

KAUST Repository

Kreuz, Sarah

2016-06-20

Oxidative stress has a significant impact on the development and progression of common human pathologies, including cancer, diabetes, hypertension and neurodegenerative diseases. Increasing evidence suggests that oxidative stress globally influences chromatin structure, DNA methylation, enzymatic and non-enzymatic post-translational modifications of histones and DNA-binding proteins. The effects of oxidative stress on these chromatin alterations mediate a number of cellular changes, including modulation of gene expression, cell death, cell survival and mutagenesis, which are disease-driving mechanisms in human pathologies. Targeting oxidative stress-dependent pathways is thus a promising strategy for the prevention and treatment of these diseases. We summarize recent research developments connecting oxidative stress and chromatin regulation.

Current and future molecular diagnostics for prion diseases.

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Lehto, Marty T; Peery, Harry E; Cashman, Neil R

2006-07-01

It is now widely held that the infectious agents underlying the transmissible spongiform encephalopathies are prions, which are primarily composed of a misfolded, protease-resistant isoform of the host prion protein. Untreatable prion disorders include some human diseases, such as Creutzfeldt-Jakob disease, and diseases of economically important animals, such as bovine spongiform encephalopathy (cattle) and chronic wasting disease (deer and elk). Detection and diagnosis of prion disease (and presymptomatic incubation) is contingent upon developing novel assays, which exploit properties uniquely possessed by this misfolded protein complex, rather than targeting an agent-specific nucleic acid. This review highlights some of the conventional and disruptive technologies developed to respond to this challenge.

Fibropolycystic liver disease in children

International Nuclear Information System (INIS)

Veigel, Myka Call; Prescott-Focht, Julia; Zinati, Reza; Rodriguez, Michael G.; Shao, Lei; Moore, Charlotte A.W.; Lowe, Lisa H.

2009-01-01

Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders. (orig.)

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

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Elizarova S.Yu.

2011-03-01

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

The Convergence of High-Consequence Livestock and Human Pathogen Research and Development: A Paradox of Zoonotic Disease