WorldWideScience

Sample records for disease development including

  1. Lung Disease Including Asthma and Adult Vaccination

    Science.gov (United States)

    ... 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 ...

  2. Diseases of the abdomen including the pelvis

    International Nuclear Information System (INIS)

    Kido, C.; Tanaka, H.

    1983-01-01

    This book discusses the following diseases: fatty liver; cystic disease of the liver; liver abscess; liver cirrhosis; hepatic hemangioma; cholelithiasis; primary liver cancer; cholangioma; cancer of the common bile duct; pancreatic cyst; pancreatic calculi; chronic pancreatitis; pancreatic pseudocyst; chronic pancreatitis: pancreatic fatty degeneration; cancer of the pancreas; nonfunctioning kidney: chalk kidney; polycystic kidney; perirenal calcified abscess; renal infarct; cancer of the renal pelvis; adrenal pheochromocytoma; adenoma of the adrenal cortex; leiomyosarcoma of the stomach; malignant mesothelioma; intraperitoneal abscess; perityphlic abscess; retroperitoneal reticulum cell sarcoma; and retroperitoneal cyst

  3. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    Science.gov (United States)

    ... Submit Button NCHS Home Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema Recommend on Facebook ... Percent of visits to office-based physicians with COPD indicated on the medical record: 3.2% Source: ...

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

    Science.gov (United States)

    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.

  5. The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

    Science.gov (United States)

    Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

    2018-02-01

    Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    Science.gov (United States)

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  7. 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

  8. 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)

  9. 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)

  10. 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...

  11. [The informed consent in international clinical trials including developing countries].

    Science.gov (United States)

    Montenegro Surís, Alexander; Monreal Agüero, Magda Elaine

    2008-01-01

    The informed consent procedure has been one of the most important controversies of ethical debates about clinical trials in developing countries. In this essay we present our recommendations about important aspects to consider in the informed consent procedure for clinical trials in developing countries. We performed a full publications review identified by MEDLINE using these terms combinations: informed consent, developing countries, less developed countries and clinical trials. To protect volunteers in less developed countries should be valuated the importance of the community in the informed consent proceeding. The signing and dating of the informed consent form is not always the best procedure to document the informed consent. The informed consent form should be written by local translators. Alternative medias of communications could be needed for communicatios of the information to volunteers. Comparing with developed countries the informed consent proceeding in clinical trials in developing countries frequently require additional efforts. The developing of pragmatic researches is needed to implement informed consent proceedings assuring subjects voluntarily in each developing country. The main aspects to define in each clinical trial for each country are the influence of the community, the effective communication of the information, the documentation of the informed consent and local authority's control.

  12. STRESS AS PREDISPOSING FACTOR OF SOME CHRONIC DISEASES INCLUDING PERIODONTAL DISEASE

    Directory of Open Access Journals (Sweden)

    Dewi-Nurul M Dewi-Nurul

    2006-04-01

    Full Text Available Stress is hypothesized as a common pathway for several related chronic diseases of man. Psychosocial stress as modified by perceptions and coping by patients can lead to physical processes. Psychoneuroimmunologic (PNI studies have suggested that psychosocial stress can alter immune function and increase vulnerability to illnesses. The patients also have high sensitivity to periodontal disease (PD. This article describes the association of stress as a physiological response to diseases such as PD, rheumatoid arthritis (RA, and inflammatory bowel disease. The psychosocial stress can lead to physiological processes through 1 the hypothalamic-pituitary-adrenal (HPA axis leading to glucocortico-steroid secretion; 2 the autonomic nervous system, resulting in the release of catecholamine; or 3 the hypothalamic-pituitary-gonadal axis, resulting in the release of sex hormones. These processes may affect chronic diseases. It can be concluded that psychosocial stress in periodontal disease patients must be considered and social support must be provided in order to achieve an optimum periodontal therapy result.

  13. Developing HYDMN code to include the transient of MNSR

    International Nuclear Information System (INIS)

    Al-Barhoum, M.

    2000-11-01

    A description of the programs added to HYDMN code (a code for thermal-hydraulic steady state of MNSR) to include the transient of the same MNSR is presented. The code asks the initial conditions for the power (in k W) and the cold initial core inlet temperature (in degrees centigrade). A time-dependent study of the coolant inlet and outlet temperature, its speed, pool and tank temperatures is done for MNSR in general and for the Syrian MNSR in particular. The study solves the differential equations taken from reference (1) by using some numerical methods found in reference (3). The code becomes this way independent of any external information source. (Author)

  14. Linear scleroderma en coup de sabre including abnormal dental development

    DEFF Research Database (Denmark)

    Hørberg, M; Lauesen, S R; Daugaard-Jensen, J

    2015-01-01

    BACKGROUND: Linear scleroderma en coup de sabre (SCS) is a rare skin condition, where dense collagen is deposited in a localised groove of the head and neck area resembling the stroke of a sabre. The SCS may involve the oral cavity, but the severity and relation to this skin abnormality is unknow...... with a left-sided skin defect (SCS) and a left-sided local malformation in her dentition. It is possible that there is a developmental connection between these two left-sided defects, both with an ectodermal origin.......-UP: The patient has been regularly controlled and treated since she was first diagnosed. A surgical and orthodontic treatment was performed to ensure optimal occlusion, space and alveolar bone development. The present age of the patient is 14 years and 10 months. CONCLUSION: This case demonstrated a patient...

  15. Recent developments in Alzheimer's disease therapeutics

    Directory of Open Access Journals (Sweden)

    Aisen Paul S

    2009-02-01

    Full Text Available Abstract Alzheimer's disease is a devastating neurological disorder that affects more than 37 million people worldwide. The economic burden of Alzheimer's disease is massive; in the United States alone, the estimated direct and indirect annual cost of patient care is at least $100 billion. Current FDA-approved drugs for Alzheimer's disease do not prevent or reverse the disease, and provide only modest symptomatic benefits. Driven by the clear unmet medical need and a growing understanding of the molecular pathophysiology of Alzheimer's disease, the number of agents in development has increased dramatically in recent years. Truly *disease-modifying' therapies that target the underlying mechanisms of Alzheimer's disease have now reached late stages of human clinical trials. Primary targets include beta-amyloid, whose presence and accumulation in the brain is thought to contribute to the development of Alzheimer's disease, and tau protein which, when hyperphosphorylated, results in the self-assembly of tangles of paired helical filaments also believed to be involved in the pathogenesis of Alzheimer's disease. In this review, we briefly discuss the current status of Alzheimer's disease therapies under study, as well the scientific context in which they have been developed.

  16. A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

    Science.gov (United States)

    Lee, Kyung-Yil

    2017-06-01

    Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

  17. 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.)

  18. 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

  19. International collaboration including patients is essential to develop new therapies for patients with myositis.

    Science.gov (United States)

    Lundberg, Ingrid E; Vencovsky, Jiri

    2017-05-01

    To discuss the needs for international collaborations between investigators in different disciplines working with myositis and with patients with myositis. Recent advances in detection of several myositis-specific autoantibodies that are associated with distinct clinical phenotypes, will enable studies in new well defined clinically homogenous subgroups of myositis This is likely to lead to development of new information on molecular pathogenesis that might be different in different myositis subgroups. Subgrouping patients according to autoantibody profile may also be important to assess outcome, to identify prognostic biomarkers and in clinical trials. As these are rare disorders international collaboration is essential to enrol large enough cohorts of the subgroups. To facilitate such collaboration we have developed a web-based international myositis register, www.euromyositis.eu, which includes validated outcome measures and patient reported outcome measures. This register is to support research but also to support decision-making in the clinic. We welcome investigators to join the Euromyositis register. Myositis is a heterogeneous disorder with varying treatment response and outcome. There is a high unmet need for new therapies which can only be achieved by increased knowledge on molecular disease mechanisms. Subgrouping patients according to autoantibody profile may be a new way forward to get a better understanding on disease mechanisms and to develop novel therapies.

  20. 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.

  1. 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.

  2. 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

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

    Science.gov (United States)

    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.

  4. Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

    Science.gov (United States)

    Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

    2009-01-01

    Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

  5. 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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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.

  9. 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

  10. 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.

  11. Development of a vaccine for bacterial kidney disease in salmon

    International Nuclear Information System (INIS)

    Kaatari, S.; Turaga, P.; Wiens, G.

    1989-08-01

    This document is the executive summary and background review for the final report of ''Development of a Vaccine for Bacterial Kidney Disease in Salmon''. A description of the disease is provided, with microbiological characterization of the infective agent. A brief discussion of attempts to eradicate the disease is included. Recent progress in vaccine development and attempts to control the disease through pharmacological means are described, along with potential ways to break the cycle of infection. 80 refs

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  14. 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.)

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

    Science.gov (United States)

    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

  16. 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...

  17. Development of Graves' disease following radiation therapy in Hodgkin's disease

    International Nuclear Information System (INIS)

    Loeffler, J.S.; Tarbell, N.J.; Garber, J.R.; Mauch, P.

    1988-01-01

    Radiation-related thyroid dysfunction is a common occurrence in patients with Hodgkin's disease treated with mantle field radiation. Although chemical and clinical hypothyroidism are most commonly seen, Graves' disease has also been described. We have examined the records of 437 surgically staged patients who received mantle field irradiation between April 1969 and December 1980 to ascertain the frequency of manifestations of Graves' disease. Within this group, seven patients developed hyperthyroidism accompanied by ophthalmic findings typical of those seen in Graves' disease. The actuarial risk of developing Graves' disease at 10 years following mantle irradiation for Hodgkin's disease was 3.3% in female patients and 1% in male patients in this study. The observed/expected ratios were 5.9 and 5.1 for female and male patients, respectively. This observed risk significantly exceeded that seen in the general population

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

    Science.gov (United States)

    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

  19. Recent developments in biomarkers in Parkinson disease

    Science.gov (United States)

    Schapira, Anthony H.V.

    2013-01-01

    Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

  20. 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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Development of calculation method for one-dimensional kinetic analysis in fission reactors, including feedback effects

    International Nuclear Information System (INIS)

    Paixao, S.B.; Marzo, M.A.S.; Alvim, A.C.M.

    1986-01-01

    The calculation method used in WIGLE code is studied. Because of the non availability of such a praiseworthy solution, expounding the method minutely has been tried. This developed method has been applied for the solution of the one-dimensional, two-group, diffusion equations in slab, axial analysis, including non-boiling heat transfer, accountig for feedback. A steady-state program (CITER-1D), written in FORTRAN 4, has been implemented, providing excellent results, ratifying the developed work quality. (Author) [pt

  4. The Watts-Strogatz network model developed by including degree distribution: theory and computer simulation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y W [Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai 200433 (China); Zhang, L F [Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai 200433 (China); Huang, J P [Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai 200433 (China)

    2007-07-20

    By using theoretical analysis and computer simulations, we develop the Watts-Strogatz network model by including degree distribution, in an attempt to improve the comparison between characteristic path lengths and clustering coefficients predicted by the original Watts-Strogatz network model and those of the real networks with the small-world property. Good agreement between the predictions of the theoretical analysis and those of the computer simulations has been shown. It is found that the developed Watts-Strogatz network model can fit the real small-world networks more satisfactorily. Some other interesting results are also reported by adjusting the parameters in a model degree-distribution function. The developed Watts-Strogatz network model is expected to help in the future analysis of various social problems as well as financial markets with the small-world property.

  5. The Watts-Strogatz network model developed by including degree distribution: theory and computer simulation

    International Nuclear Information System (INIS)

    Chen, Y W; Zhang, L F; Huang, J P

    2007-01-01

    By using theoretical analysis and computer simulations, we develop the Watts-Strogatz network model by including degree distribution, in an attempt to improve the comparison between characteristic path lengths and clustering coefficients predicted by the original Watts-Strogatz network model and those of the real networks with the small-world property. Good agreement between the predictions of the theoretical analysis and those of the computer simulations has been shown. It is found that the developed Watts-Strogatz network model can fit the real small-world networks more satisfactorily. Some other interesting results are also reported by adjusting the parameters in a model degree-distribution function. The developed Watts-Strogatz network model is expected to help in the future analysis of various social problems as well as financial markets with the small-world property

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  8. 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

  9. Unsaturated Seepage Analysis of Cracked Soil including Development Process of Cracks

    Directory of Open Access Journals (Sweden)

    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.

  10. Supermarket revolution in Asia and emerging development strategies to include small farmers.

    Science.gov (United States)

    Reardon, Thomas; Timmer, C Peter; Minten, Bart

    2012-07-31

    A "supermarket revolution" has occurred in developing countries in the past 2 decades. We focus on three specific issues that reflect the impact of this revolution, particularly in Asia: continuity in transformation, innovation in transformation, and unique development strategies. First, the record shows that the rapid growth observed in the early 2000s in China, Indonesia, Malaysia, and Thailand has continued, and the "newcomers"--India and Vietnam--have grown even faster. Although foreign direct investment has been important, the roles of domestic conglomerates and even state investment have been significant and unique. Second, Asia's supermarket revolution has exhibited unique pathways of retail diffusion and procurement system change. There has been "precocious" penetration of rural towns by rural supermarkets and rural business hubs, emergence of penetration of fresh produce retail that took much longer to initiate in other regions, and emergence of Asian retail developing-country multinational chains. In procurement, a symbiosis between modern retail and the emerging and consolidating modern food processing and logistics sectors has arisen. Third, several approaches are being tried to link small farmers to supermarkets. Some are unique to Asia, for example assembling into a "hub" or "platform" or "park" the various companies and services that link farmers to modern markets. Other approaches relatively new to Asia are found elsewhere, especially in Latin America, including "bringing modern markets to farmers" by establishing collection centers and multipronged collection cum service provision arrangements, and forming market cooperatives and farmer companies to help small farmers access supermarkets.

  11. Development of Reference Equations of State for Refrigerant Mixtures Including Hydrocarbons

    Science.gov (United States)

    Miyamoto, Hiroyuki; Watanabe, Koichi

    In recent years, most accurate equations of state for alternative refrigerants and their mixtures can easily be used via convenient software package, e.g., REFPROP. In the present paper, we described the current state-of-the-art equations of state for refrigerant mixtures including hydrocarbons as components. Throughout our discussion, the limitation of the available experimental data and the necessity of the improvement against the arbitrary fitting of recent modeling were confirmed. The enough number of reliable experimental data, especially for properties in the higher pressures and temperatures and for derived properties, should be accumulated in the near future for the development of the physically-sound theoretical background. The present review argued about the possibility of the progress for the future thermodynamic property modeling throughout the detailed discussion regarding the several types of the equations of state as well as the recent innovative measurement technique.

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

    Science.gov (United States)

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

    2017-08-04

    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. Exacerbation action plans are considered to be a key component of COPD self-management interventions. Studies assessing these interventions show contradictory results. In this Cochrane Review, we compared the effectiveness of COPD self-management interventions that include action plans for acute exacerbations of COPD (AECOPD) with usual care. To evaluate the efficacy of COPD-specific self-management interventions that include an action plan for exacerbations of COPD compared with usual care in terms of health-related quality of life, respiratory-related hospital admissions and other health outcomes. We searched the Cochrane Airways Group Specialised Register of trials, trials registries, and the reference lists of included studies to May 2016. We included randomised controlled trials evaluating a self-management intervention for people with COPD published since 1995. To be eligible for inclusion, the self-management intervention included a written action plan for AECOPD and an iterative process between participant and healthcare provider(s) in which feedback was provided. We excluded disease management programmes classified as pulmonary rehabilitation or exercise classes offered in a hospital, at a rehabilitation centre, or in a community-based setting to avoid overlap with pulmonary rehabilitation as much as possible. Two review authors independently assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. Study authors were contacted to obtain additional information and missing outcome data where possible. When appropriate, study results were pooled using a random-effects modelling meta-analysis. The primary

  13. Economic assessment of S-prism including development and generating costs

    Energy Technology Data Exchange (ETDEWEB)

    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)

  14. 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.

  15. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. 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.

  18. Development method of Hybrid Energy Storage System, including PEM fuel cell and a battery

    International Nuclear Information System (INIS)

    Ustinov, A; Khayrullina, A; Khmelik, M; Sveshnikova, A; Borzenko, V

    2016-01-01

    Development of fuel cell (FC) and hydrogen metal-hydride storage (MH) technologies continuously demonstrate higher efficiency rates and higher safety, as hydrogen is stored at low pressures of about 2 bar in a bounded state. A combination of a FC/MH system with an electrolyser, powered with a renewable source, allows creation of an almost fully autonomous power system, which could potentially replace a diesel-generator as a back-up power supply. However, the system must be extended with an electro-chemical battery to start-up the FC and compensate the electric load when FC fails to deliver the necessary power. Present paper delivers the results of experimental and theoretical investigation of a hybrid energy system, including a proton exchange membrane (PEM) FC, MH- accumulator and an electro-chemical battery, development methodology for such systems and the modelling of different battery types, using hardware-in-the-loop approach. The economic efficiency of the proposed solution is discussed using an example of power supply of a real town of Batamai in Russia. (paper)

  19. Development method of Hybrid Energy Storage System, including PEM fuel cell and a battery

    Science.gov (United States)

    Ustinov, A.; Khayrullina, A.; Borzenko, V.; Khmelik, M.; Sveshnikova, A.

    2016-09-01

    Development of fuel cell (FC) and hydrogen metal-hydride storage (MH) technologies continuously demonstrate higher efficiency rates and higher safety, as hydrogen is stored at low pressures of about 2 bar in a bounded state. A combination of a FC/MH system with an electrolyser, powered with a renewable source, allows creation of an almost fully autonomous power system, which could potentially replace a diesel-generator as a back-up power supply. However, the system must be extended with an electro-chemical battery to start-up the FC and compensate the electric load when FC fails to deliver the necessary power. Present paper delivers the results of experimental and theoretical investigation of a hybrid energy system, including a proton exchange membrane (PEM) FC, MH- accumulator and an electro-chemical battery, development methodology for such systems and the modelling of different battery types, using hardware-in-the-loop approach. The economic efficiency of the proposed solution is discussed using an example of power supply of a real town of Batamai in Russia.

  20. Wnt Signaling in Kidney Development and Disease.

    Science.gov (United States)

    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.

  1. Disease-Specific Care: Spine Surgery Program Development.

    Science.gov (United States)

    Koerner, Katie; Franker, Lauren; Douglas, Barbara; Medero, Edgardo; Bromeland, Jennifer

    2017-10-01

    Minimal literature exists describing the process for development of a Joint Commission comprehensive spine surgery program within a community hospital health system. Components of a comprehensive program include structured communication across care settings, preoperative education, quality outcomes tracking, and patient follow-up. Organizations obtaining disease-specific certification must have clear knowledge of the planning, time, and overall commitment, essential to developing a successful program. Health systems benefit from disease-specific certification because of their commitment to a higher standard of service. Certification standards establish a framework for organizational structure and management and provide institutions a competitive edge in the marketplace. A framework for the development of a spine surgery program is described to help guide organizations seeking disease-specific certification. In developing a comprehensive program, it is critical to define the program's mission and vision, identify key stakeholders, implement clinical practice guidelines, and evaluate program outcomes.

  2. Vaccine development for emerging virulent infectious diseases.

    Science.gov (United States)

    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.

  3. 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.

  4. Professional Development for Researchers in Solid Earth Science Evolved to Include Scientific and Educational Content

    Science.gov (United States)

    Eriksson, S. C.; Arrowsmith, R.; Olds, S. E.

    2011-12-01

    Integrated measures of crustal deformation provide valuable insight about tectonic and human-induced processes for scientists and educators alike. UNAVCO in conjunction with EarthScope initiated a series of short courses for researchers to learn the processing and interpretation of data from new technologies such as high precision GPS, Strainmeter, InSar and LiDAR that provide deformation information relevant to many geoscience sub-disciplines. Intensive short courses of a few days and the widespread availability of processed data through large projects such as EarthScope and GEON enable more geoscientists to incorporate these data into diverse projects. Characteristics of the UNAVCO Short Course Series, reaching over 400 participants since 2005, include having short course faculty who have pioneered development of each technology; open web-access to course materials; processing software installed on class-ready computers; no course fees; scholarships for students, post-doctoral fellows, and emerging faculty when needed; formative evaluation of the courses; community-based decisions on topics; and recruitment of participants across relevant geoscience disciplines. In 2009, when EarthScope airborne LiDAR data became available to the public through OpenTopographhy, teaching materials were provided to these researchers to incorporate the latest technologies into teaching. Multiple data sets across technologies have been developed with instructions on how to access the various data sets and incorporate them into geological problem sets. Courses in GPS, airborne LiDAR, strainmeter, and InSAR concentrate on data processing with examples of various geoscience applications. Ground-based LiDAR courses also include data acquisition. Google Earth is used to integrate various forms of data in educational applications. Various types of EarthScope data can now be used by a variety of geoscientists, and the number of scientists who have the skills and tools to use these various

  5. 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.

  6. Stomach development, stem cells and disease

    Science.gov (United States)

    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

  7. Prenatal parental separation and body weight, including development of overweight and obesity later in childhood.

    Directory of Open Access Journals (Sweden)

    Lena Hohwü

    Full Text Available Early parental separation may be a stress factor causing a long-term alteration in the hypothalamic-pituitary-adrenal-axis activity possibly impacting on the susceptibility to develop overweight and obesity in offspring. We aimed to examine the body mass index (BMI and the risk of overweight and obesity in children whose parents lived separately before the child was born.A follow-up study was conducted using data from the Aarhus Birth Cohort in Denmark and included 2876 children with measurements of height and weight at 9-11-years-of-age, and self-reported information on parental cohabitation status at child birth and at 9-11-years-of-age. Quantile regression was used to estimate the difference in median BMI between children whose parents lived separately (n = 124 or together (n = 2752 before the birth. We used multiple logistic regression to calculate odds ratio (OR for overweight and obesity, adjusted for gender, parity, breast feeding status, and maternal pre-pregnancy BMI, weight gain during pregnancy, age and educational level at child birth; with and without possible intermediate factors birth weight and maternal smoking during pregnancy. Due to a limited number of obese children, OR for obesity was adjusted for the a priori confounder maternal pre-pregnancy BMI only.The difference in median BMI was 0.54 kg/m2 (95% confidence intervals (CI: 0.10; 0.98 between children whose parents lived separately before birth and children whose parents lived together. The risk of overweight and obesity was statistically significantly increased in children whose parents lived separately before the birth of the child; OR 2.29 (95% CI: 1.18; 4.45 and OR 2.81 (95% CI: 1.05; 7.51, respectively. Additional, adjustment for possible intermediate factors did not substantially change the estimates.Parental separation before child birth was associated with higher BMI, and increased risk of overweight and obesity in 9-11-year-old children; this may suggest a fetal

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Model Selection and Evaluation Based on Emerging Infectious Disease Data Sets including A/H1N1 and Ebola

    Directory of Open Access Journals (Sweden)

    Wendi Liu

    2015-01-01

    Full Text Available The aim of the present study is to apply simple ODE models in the area of modeling the spread of emerging infectious diseases and show the importance of model selection in estimating parameters, the basic reproduction number, turning point, and final size. To quantify the plausibility of each model, given the data and the set of four models including Logistic, Gompertz, Rosenzweg, and Richards models, the Bayes factors are calculated and the precise estimates of the best fitted model parameters and key epidemic characteristics have been obtained. In particular, for Ebola the basic reproduction numbers are 1.3522 (95% CI (1.3506, 1.3537, 1.2101 (95% CI (1.2084, 1.2119, 3.0234 (95% CI (2.6063, 3.4881, and 1.9018 (95% CI (1.8565, 1.9478, the turning points are November 7,November 17, October 2, and November 3, 2014, and the final sizes until December 2015 are 25794 (95% CI (25630, 25958, 3916 (95% CI (3865, 3967, 9886 (95% CI (9740, 10031, and 12633 (95% CI (12515, 12750 for West Africa, Guinea, Liberia, and Sierra Leone, respectively. The main results confirm that model selection is crucial in evaluating and predicting the important quantities describing the emerging infectious diseases, and arbitrarily picking a model without any consideration of alternatives is problematic.

  10. Further development of a method to calculate frequencies of loss of control including their uncertainty

    NARCIS (Netherlands)

    Ale, B.J.M.; Van Gulijk, C.; Hanea, D.M.; Hudson, P.; Lin, P.H.; Sillem, S.; Steenhoek, M.; Ababei, D.

    2013-01-01

    An integrated model for risk in a real-time environment for the hydrocarbon industry based on the CATS model for commercial aviation safety has been further developed. The approach described in earlier papers required Bayesian Belief Nets (BBN) to be developed for each process unit separately. A

  11. 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.

  12. Developing a provisional and national renal disease registry for Iran

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. Including pathogen risk in life cycle assessment of wastewater management. 1. Estimating the burden of disease associated with pathogens.

    Science.gov (United States)

    Harder, Robin; Heimersson, Sara; Svanström, Magdalena; Peters, Gregory M

    2014-08-19

    The environmental performance of wastewater and sewage sludge management is commonly assessed using life cycle assessment (LCA), whereas pathogen risk is evaluated with quantitative microbial risk assessment (QMRA). This study explored the application of QMRA methodology with intent to include pathogen risk in LCA and facilitate a comparison with other potential impacts on human health considered in LCA. Pathogen risk was estimated for a model wastewater treatment system (WWTS) located in an industrialized country and consisting of primary, secondary, and tertiary wastewater treatment, anaerobic sludge digestion, and land application of sewage sludge. The estimation was based on eight previous QMRA studies as well as parameter values taken from the literature. A total pathogen risk (expressed as burden of disease) on the order of 0.2-9 disability-adjusted life years (DALY) per year of operation was estimated for the model WWTS serving 28,600 persons and for the pathogens and exposure pathways included in this study. The comparison of pathogen risk with other potential impacts on human health considered in LCA is detailed in part 2 of this article series.

  15. Use of Student Experiments for Teaching Embedded Software Development Including HW/SW Co-Design

    Science.gov (United States)

    Mitsui, H.; Kambe, H.; Koizumi, H.

    2009-01-01

    Embedded systems have been applied widely, not only to consumer products and industrial machines, but also to new applications such as ubiquitous or sensor networking. The increasing role of software (SW) in embedded system development has caused a great demand for embedded SW engineers, and university education for embedded SW engineering has…

  16. Development of numerical dispersion model for radioactive nuclei including resuspension processes

    International Nuclear Information System (INIS)

    Chiba, Masaru; Kurita, Susumu; Sasaki, Hidetaka

    2003-01-01

    Global-scale and local-scale dispersion model are developed combining to global and local scale meteorological forecasting model. By applying this system to another miner constituent such as mineral dust blowing by strong wind in arid region, this system shows very good performance to watch and predict the distribution of it. (author)

  17. Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF.

    Science.gov (United States)

    Rotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafà, Roberta; Gaboriaud, Pauline; Touzé, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Mauro

    2017-07-15

    Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs. Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen-positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control. Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity. Clin Cancer Res; 23(14); 3929-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Optimization of the weekly operation of a multipurpose hydroelectric development, including a pumped storage plant

    International Nuclear Information System (INIS)

    Popa, R; Popa, B; Popa, F; Zachia-Zlatea, D

    2010-01-01

    It is presented an optimization model based on genetic algorithms for the operation of a multipurpose hydroelectric power development consisting in a pumped storage plant (PSP) with weekly operation cycle. The lower reservoir of the PSP is supplied upstream from a peak hydropower plant (HPP) with a large reservoir and supplies the own HPP which provides the required discharges towards downstream. Under these conditions, the optimum operation of the assembly consisting in 3 reservoirs and hydropower plants becomes a difficult problem if there are considered the restrictions as regards: the gradients allowed for the reservoirs filling/emptying, compliance with of a long-term policy of the upper reservoir from the hydroelectric development and of the weekly cycle for the PSP upper reservoir, correspondence between the power output/consumption in the weekly load schedule, turning to account of the water resource at maximum overall efficiencies, etc. Maximization of the net energy value (generated minus consumed) was selected as performance function of the model, considering the differentiated price of the electric energy over the week (working or weekend days, peak, half-peak or base hours). The analysis time step was required to be of 3 hours, resulting a weekly horizon of 56 steps and 168 decision variables, respectively, for the 3 HPPs of the system. These were allowed to be the flows turbined at the HPP and the number of working hydrounits at PSP, on each time step. The numerical application has considered the guiding data of Fantanele-Tarnita-Lapustesti hydroelectric development. Results of various simulations carried out proved the qualities of the proposed optimization model, which will allow its use within a decisional support program for such a development.

  19. DEVELOPMENT OF A VIRTUAL MUSEUM INCLUDING A 4D PRESENTATION OF BUILDING HISTORY IN VIRTUAL REALITY

    OpenAIRE

    T. P. Kersten; F. Tschirschwitz; S. Deggim

    2017-01-01

    In the last two decades the definition of the term “virtual museum” changed due to rapid technological developments. Using today’s available 3D technologies a virtual museum is no longer just a presentation of collections on the Internet or a virtual tour of an exhibition using panoramic photography. On one hand, a virtual museum should enhance a museum visitor's experience by providing access to additional materials for review and knowledge deepening either before or after the real ...

  20. Optimization of the weekly operation of a multipurpose hydroelectric development, including a pumped storage plant

    Energy Technology Data Exchange (ETDEWEB)

    Popa, R; Popa, B [Faculty of Power Engineering, University Politehnica of Bucharest, 313 Spl. Independentei, sect. 6, Bucharest, 060042 (Romania); Popa, F [Institute for Hydropower Studies and Design, 5-7 Vasile Lascar, sect. 2, Bucharest, 020491 (Romania); Zachia-Zlatea, D, E-mail: bogdan.popa@rosha.r [Hidroelectrica S.A., 3 Constantin Nacu, sect. 2, Bucharest, 020995 (Romania)

    2010-08-15

    It is presented an optimization model based on genetic algorithms for the operation of a multipurpose hydroelectric power development consisting in a pumped storage plant (PSP) with weekly operation cycle. The lower reservoir of the PSP is supplied upstream from a peak hydropower plant (HPP) with a large reservoir and supplies the own HPP which provides the required discharges towards downstream. Under these conditions, the optimum operation of the assembly consisting in 3 reservoirs and hydropower plants becomes a difficult problem if there are considered the restrictions as regards: the gradients allowed for the reservoirs filling/emptying, compliance with of a long-term policy of the upper reservoir from the hydroelectric development and of the weekly cycle for the PSP upper reservoir, correspondence between the power output/consumption in the weekly load schedule, turning to account of the water resource at maximum overall efficiencies, etc. Maximization of the net energy value (generated minus consumed) was selected as performance function of the model, considering the differentiated price of the electric energy over the week (working or weekend days, peak, half-peak or base hours). The analysis time step was required to be of 3 hours, resulting a weekly horizon of 56 steps and 168 decision variables, respectively, for the 3 HPPs of the system. These were allowed to be the flows turbined at the HPP and the number of working hydrounits at PSP, on each time step. The numerical application has considered the guiding data of Fantanele-Tarnita-Lapustesti hydroelectric development. Results of various simulations carried out proved the qualities of the proposed optimization model, which will allow its use within a decisional support program for such a development.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Development process of muzzle flows including a gun-launched missile

    OpenAIRE

    Zhuo Changfei; Feng Feng; Wu Xiaosong

    2015-01-01

    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 m...

  3. Development of a quantitative safety assessment method for nuclear I and C systems including human operators

    International Nuclear Information System (INIS)

    Kim, Man Cheol

    2004-02-01

    Conventional PSA (probabilistic safety analysis) is performed in the framework of event tree analysis and fault tree analysis. In conventional PSA, I and C systems and human operators are assumed to be independent for simplicity. But, the dependency of human operators on I and C systems and the dependency of I and C systems on human operators are gradually recognized to be significant. I believe that it is time to consider the interdependency between I and C systems and human operators in the framework of PSA. But, unfortunately it seems that we do not have appropriate methods for incorporating the interdependency between I and C systems and human operators in the framework of Pasa. Conventional human reliability analysis (HRA) methods are not developed to consider the interdependecy, and the modeling of the interdependency using conventional event tree analysis and fault tree analysis seem to be, event though is does not seem to be impossible, quite complex. To incorporate the interdependency between I and C systems and human operators, we need a new method for HRA and a new method for modeling the I and C systems, man-machine interface (MMI), and human operators for quantitative safety assessment. As a new method for modeling the I and C systems, MMI and human operators, I develop a new system reliability analysis method, reliability graph with general gates (RGGG), which can substitute conventional fault tree analysis. RGGG is an intuitive and easy-to-use method for system reliability analysis, while as powerful as conventional fault tree analysis. To demonstrate the usefulness of the RGGG method, it is applied to the reliability analysis of Digital Plant Protection System (DPPS), which is the actual plant protection system of Ulchin 5 and 6 nuclear power plants located in Republic of Korea. The latest version of the fault tree for DPPS, which is developed by the Integrated Safety Assessment team in Korea Atomic Energy Research Institute (KAERI), consists of 64

  4. Projects of SR sources including research and development for insertion devices in the USSR

    International Nuclear Information System (INIS)

    Kulipanov, G.

    1990-01-01

    Some technical information on the electron and positron storage rings - SR sources that are being constructed, used or developed at the Novosibirsk Institute of Nuclear Physics (INP), is given. The parameters and construction of wigglers and undulators (electromagnetic, superconducting, and based on permanent magnets) that are intended to be used at such storage rings are described. Various schemes of installation of wigglers, undulators and FEL at storage rings is considered. The ways of minimizing the influence of their magnetic fields on particle motion in storage rings are treated. (author)

  5. Tell me your life: including life stories in an adult development and aging course.

    Science.gov (United States)

    Villar, Feliciano; Celdran, Montserrat; Fabà, Josep

    2014-01-01

    The goals of this study were to determine the learning impact of an assignment that consisted of interviewing and analyzing older people's life stories, and to explore how the assignment was evaluated by students. Participants in the study were 122 first-year social education students enrolled in an adult development and aging course. They evaluated the assignment using an eight-adjective questionnaire and were asked about the benefits of the task. Their answers to the questionnaire were then reviewed using content analysis. The results indicated that marks on the life story assignment predicted marks on an exam about basic course concepts. Students considered that the assignment was interesting, useful, and integrated into the course, although most of them also thought that it was very time-consuming. They identified benefits related to the explicit goals of the course (improvement in the learning of developmental concepts, the acquisition of research-related skills, and the deactivation of aging stereotypes) and personal, growth-related benefits. The authors discuss the difficulties posed by the assignment and its usefulness as a complement to more traditional, lecture-based teaching methods in adult development and aging courses.

  6. States and compacts: Issues and events affecting facility development efforts, including the Barnwell opening

    Energy Technology Data Exchange (ETDEWEB)

    Larson, G.S.

    1995-12-31

    Ten years have passed since the first regional low-level radioactive waste compacts received Congressional consent and initiated their efforts to develop new disposal capacity. During these 10 years, both significant achievements and serious setbacks have marked our efforts and affect our current outlook. Recent events in the waste marketplace, particularly in the operating status of the Barnwell disposal facility, have now raised legitimate questions about the continued rationale for the regional framework that grew out of the original legislation enacted by Congress in 1980. At the same time, licensing activities for new regional disposal facilities are under way in three states, and a fourth awaits the final go-ahead to begin construction. Uncertainty over the meaning and reliability of the marketplace events makes it difficult to gauge long-term implications. In addition, differences in the status of individual state and compact facility development efforts lead to varying assessments of the influence these events will, or should, have on such efforts.

  7. Development of a Virtual Museum Including a 4d Presentation of Building History in Virtual Reality

    Science.gov (United States)

    Kersten, T. P.; Tschirschwitz, F.; Deggim, S.

    2017-02-01

    In the last two decades the definition of the term "virtual museum" changed due to rapid technological developments. Using today's available 3D technologies a virtual museum is no longer just a presentation of collections on the Internet or a virtual tour of an exhibition using panoramic photography. On one hand, a virtual museum should enhance a museum visitor's experience by providing access to additional materials for review and knowledge deepening either before or after the real visit. On the other hand, a virtual museum should also be used as teaching material in the context of museum education. The laboratory for Photogrammetry & Laser Scanning of the HafenCity University Hamburg has developed a virtual museum (VM) of the museum "Alt-Segeberger Bürgerhaus", a historic town house. The VM offers two options for visitors wishing to explore the museum without travelling to the city of Bad Segeberg, Schleswig-Holstein, Germany. Option a, an interactive computer-based, tour for visitors to explore the exhibition and to collect information of interest or option b, to immerse into virtual reality in 3D with the HTC Vive Virtual Reality System.

  8. States and compacts: Issues and events affecting facility development efforts, including the Barnwell opening

    International Nuclear Information System (INIS)

    Larson, G.S.

    1995-01-01

    Ten years have passed since the first regional low-level radioactive waste compacts received Congressional consent and initiated their efforts to develop new disposal capacity. During these 10 years, both significant achievements and serious setbacks have marked our efforts and affect our current outlook. Recent events in the waste marketplace, particularly in the operating status of the Barnwell disposal facility, have now raised legitimate questions about the continued rationale for the regional framework that grew out of the original legislation enacted by Congress in 1980. At the same time, licensing activities for new regional disposal facilities are under way in three states, and a fourth awaits the final go-ahead to begin construction. Uncertainty over the meaning and reliability of the marketplace events makes it difficult to gauge long-term implications. In addition, differences in the status of individual state and compact facility development efforts lead to varying assessments of the influence these events will, or should, have on such efforts

  9. Development of a hexavalent chromium ISFET sensor with a polymeric membrane including tributylphosphate

    Energy Technology Data Exchange (ETDEWEB)

    Zazoua, A. [Universite de Annaba, BP 12, El-Hadjar, Annaba (Algeria); Zougar, S. [Universite de Annaba, BP 12, El-Hadjar, Annaba (Algeria); Kherrat, R. [Universite de Annaba, BP 12, El-Hadjar, Annaba (Algeria); Samar, M.H. [Universite de Annaba, BP 12, El-Hadjar, Annaba (Algeria); Jaffrezic-Renault, N. [CEGELY-UMR 5005 CNRS, Ecole centrale de Lyon, 69134 Ecully cedex (France)]. E-mail: Nicole.Jaffrezic@ec-lyon.fr; Errachid, A. [Center of Reference for Bioengineering in Catalonia (CREBEC), Laboratory of Nanobioengineering, Parc Cientific de Barcelona, Universidad de Barcelona C/ Josep Samitier 1-5, 08028 Barcelona (Spain); Abbaci, A. [Universite de Annaba, BP 12, El-Hadjar, Annaba (Algeria)

    2006-03-15

    This paper presents a first report on chromium ISFET (ion-sensitive field effect transistor) based on a polymeric membrane (siloprene) including an ionophore (tributylphosphate) sensitive for hexavalent chromium. The sensor sensitivity as a function of the pH was studied; its value is minimum in a pH interval from 5.5 to 7.5. The sensitivity for hexavalent chromium was found to be 15 mV/loga {sub Cr{sup 6+}} in the range of 10{sup -4} to 10{sup -2} M. The detection limit was found to be 10{sup -5} M. The studied interfering ions are Pb(II) and Cd(II) that do not represent a great perturbation upon the response for hexavalent chromium.

  10. Development of a hexavalent chromium ISFET sensor with a polymeric membrane including tributylphosphate

    International Nuclear Information System (INIS)

    Zazoua, A.; Zougar, S.; Kherrat, R.; Samar, M.H.; Jaffrezic-Renault, N.; Errachid, A.; Abbaci, A.

    2006-01-01

    This paper presents a first report on chromium ISFET (ion-sensitive field effect transistor) based on a polymeric membrane (siloprene) including an ionophore (tributylphosphate) sensitive for hexavalent chromium. The sensor sensitivity as a function of the pH was studied; its value is minimum in a pH interval from 5.5 to 7.5. The sensitivity for hexavalent chromium was found to be 15 mV/loga Cr 6+ in the range of 10 -4 to 10 -2 M. The detection limit was found to be 10 -5 M. The studied interfering ions are Pb(II) and Cd(II) that do not represent a great perturbation upon the response for hexavalent chromium

  11. Scope and status of the USA Engineering Test Facility including relevant TFTR research and development

    International Nuclear Information System (INIS)

    Becraft, W.R.; Reardon, P.J.

    1980-01-01

    The vehicle by which the fusion program would move into the engineering testing phase of fusion power development is designated the Engineering Test Facility (ETF). The progress toward the design and construction of the ETF will reflect the significant achievements of past, present, and future experimental tokamak devices. Some of the features of this foundation of experimental results and relevant engineering designs and operation will derive from the Tokamak Fusion Test Reactor (TFTR) Project, now nearing the completion of its construction phase. The ETF would provide a test-bed for reactor components in the fusion environment. In order to initiate preliminary planning for the ETF decision, the Office of Fusion Energy (OFE) established the ETF Design Center activity to prepare the design of the ETF. This paper describes the design status of the ETF and discusses some highlights of the TFTR R and D work

  12. Scope and status of the USA Engineering Test Facility including relevant TFTR research and development

    International Nuclear Information System (INIS)

    Becraft, W.R.; Reardon, P.J.

    1981-01-01

    The vehicle by which the fusion programme would move into the engineering testing phase of fusion power development is designated the Engineering Test Facility (ETF). The progress toward the design and construction of the ETF will reflect the significant achievements of past, present, and future experimental tokamak devices. Some of the features of this foundation of experimental results and relevant engineering designs and operation will derive from the Tokamak Fusion Test Reactor (TFTR) Project, now nearing the completion of its construction phase. The ETF would provide a test-bed for reactor components in the fusion environment. To initiate preliminary planning for the ETF decision, the Office of Fusion Energy (OFE) established the ETF Design Center activity to prepare the design of the ETF. This paper describes the design status of the ETF and discusses some highlights of the TFTR R and D work. (author)

  13. Recent developments of the MARC/PN transport theory code including a treatment of anisotropic scatter

    International Nuclear Information System (INIS)

    Fletcher, J.K.

    1987-12-01

    The computer code MARC/PN provides a solution of the multigroup transport equation by expanding the flux in spherical harmonics. The coefficients of the series so obtained satisfy linked first order differential equations, and on eliminating terms associated with odd parity harmonics a second order system results which can be solved by established finite difference or finite element techniques. This report describes modifications incorporated in MARC/PN to allow for anisotropic scattering, and the modelling of irregular exterior boundaries in the finite element option. The latter development leads to substantial reductions in problem size, particularly for three dimensions. Also, links to an interactive graphics mesh generator (SUPERTAB) have been added. The final section of the report contains results from problems showing the effects of anisotropic scatter and the ability of the code to model irregular geometries. (author)

  14. Development of the nervus terminalis in mammals including toothed whales and humans.

    Science.gov (United States)

    Oelschläger, H A; Buhl, E H; Dann, J F

    1987-01-01

    The early ontogenesis and topography of the mammalian terminalis system was investigated in 43 microslide series of toothed whale and human embryos and fetuses. In early embryonal stages the development of the nasal pit, the olfacto-terminalis placode, and the olfactory bulb anlage is rather similar in toothed whales and humans. However, toothed whales do not show any trace of the vomeronasalis complex. In early fetal stages the olfactory bulb anlage in toothed whales is reduced and leaves the isolated future terminalis ganglion (ganglia) which contains the greatest number of cells within Mammalia. The ganglion is connected with the nasal mucosa via peripheral fiber bundles and with the telencephalon via central terminalis rootlets. The functional implications of the terminalis system in mammals and its evolution in toothed whales are discussed. Obviously, the autonomic component has been enlarged in the course of perfect adaptation to an aquatic environment.

  15. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  16. Coastal erosion's influencing factors include development, dams, wells, and climate change

    International Nuclear Information System (INIS)

    Aubrey, D.G.

    1993-01-01

    The demographic flight to the coast, begun in early civilization, continues unabated worldwide according to latest studies. The percentage of population living on the coast is expected to remain relatively constant over the next few decades, but the total numbers will increase as the population increases. Recent coastal battering by hurricanes and extratropical storms poses questions about coastal habitability and the real economics of coastal development. Repair costs are borne by private individuals as well as the public in various direct and indirect ways. As these costs escalate, it is fitting to ask what the future portends for storm and coastal-flood damage. It is known that development pressures will continue to increase along the coast, but what will happen concurrently to natural-hazard threats to this infrastructure? Though much emphasis has been placed on sea-level rise, the broader issue is climate change in general. Here, the author considers climate change in both its natural and anthropogenic perspectives. Without becoming mired in the debate about the greenhouse effect and human influence on climatic shifts, some of the broad classes of natural hazards that might accompany climate change are examined. There are several categories of possible global-change effects on coastal erosion. In the early 1980's, an Environmental Protection Agency (EPA) report postulated increases in global sea level up to 4 meters during the next 100 years. Though balanced somewhat by other, lower estimates of sea-level rise, this higher extreme grabbed public attention. During the next decade, scientists attempted to concur on a more reasonable estimate of global sea-level rise due to climate change. Recent credible estimates suggest that approximately 10 to 20 percent of EPA's earlier maximum estimate is most reasonable

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. RNAseq Transcriptional Profiling following Whip Development in Sugarcane Smut Disease.

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

  1. [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.

  2. Immune Development and Intestinal Microbiota in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Tamara Pozo-Rubio

    2012-01-01

    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. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding, infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.

  3. 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...

  4. SOCS proteins in development and disease

    Science.gov (United States)

    Trengove, Monique C; Ward, Alister C

    2013-01-01

    Cytokine and growth factor signaling mediates essential roles in the differentiation, proliferation, survival and function of a number of cell lineages. This is achieved via specific receptors located on the surface of target cells, with ligand binding activating key intracellular signal transduction cascades to mediate the requisite cellular outcome. Effective resolution of receptor signaling is also essential, with excessive signaling having the potential for pathological consequences. The Suppressor of cytokine signaling (SOCS) family of proteins represent one important mechanism to extinguish cytokine and growth factor receptor signaling. There are 8 SOCS proteins in mammals; SOCS1-7 and the alternatively named Cytokine-inducible SH2-containing protein (CISH). SOCS1-3 and CISH are predominantly associated with the regulation of cytokine receptor signaling, while SOCS4-7 are more commonly involved in the control of Receptor tyrosine kinase (RTK) signaling. Individual SOCS proteins are typically induced by specific cytokines and growth factors, thereby generating a negative feedback loop. As a consequence of their regulatory properties, SOCS proteins have important functions in development and homeostasis, with increasing recognition of their role in disease, particularly their tumor suppressor and anti-inflammatory functions. This review provides a synthesis of our current understanding of the SOCS family, with an emphasis on their immune and hematopoietic roles. PMID:23885323

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

    Science.gov (United States)

    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.

  6. 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.

  7. Newly Diagnosed Meniere's Disease: Clinical Course With Initiation of Noninvasive Treatment Including an Accounting of Vestibular Migraine.

    Science.gov (United States)

    Sbeih, Firas; Christov, Florian; Gluth, Michael B

    2018-05-01

    To describe the course of Meniere's disease with noninvasive treatment during the first few years after initial diagnosis. A retrospective review of consecutive patients with newly diagnosed definite Meniere's disease between 2013 and 2016 and a minimum follow-up of 1 year. Patients received a written plan for low sodium, water therapy, and treatment with a diuretic and/or betahistine. Subjects were screened and treated for vestibular migraine as needed. Vertigo control and hearing status at most recent follow-up were assessed. Forty-four subjects had an average follow up of 24.3 months. Thirty-four percent had Meniere's disease and vestibular migraine, and 84% had unilateral Meniere's disease. Seventy-five percent had vertigo well controlled at most recent follow-up, with only noninvasive treatments. Age, gender, body mass index, presence of vestibular migraine, bilateral disease, and duration of follow-up did not predict noninvasive treatment failure. Worse hearing threshold at 250 Hz and lower pure tone average (PTA) at the time of diagnosis did predict failure. Fifty-two percent of ears had improved PTA at most recent visit, 20% had no change, and 28% were worse Conclusions: Encountering excellent vertigo control and stable hearing after a new diagnosis of Meniere's disease is possible with noninvasive treatments. Worse hearing status at diagnosis predicted treatment failure.

  8. 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.

  9. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    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.

  10. The burden of non communicable diseases in developing countries

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer

    Science.gov (United States)

    Skinner, Michael K.; Anway, Matthew D.

    2018-01-01

    Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies. PMID:17956218

  13. Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

    Science.gov (United States)

    Doody, R

    2017-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

  14. Influence of oxidative stress on disease development

    Directory of Open Access Journals (Sweden)

    Božić Tatjana

    2013-01-01

    Full Text Available There is ever increasing data indicating the vmast contribution of oxidative stress to the pathogenesis of numerous diseases (atherosclerosis, hypertension, heart failure, diabetes mellitus, stroke, rheumatoid arthritis, and others. Thus, in the pathogenesis of atherosclerosis the primary role is held by reactive oxygen species that are synthetized by endothelial cells of arterial blood vessels, leukocytes and macrophages. Furthermore, native particles of lipoproteins of small density become atherogenic through oxidation caused by reactive oxygen species. The oxidation of small-density lipoproteins stimulates the inflammatory process, and it in turn steps up adhesion and the inflow of monocytes and affects the synthesis and release of numerous proinflammatory cytokines involved in the further course of the process. One of the reasons for the development of arterial hypertension is the simultaneous activation of NAD(PH oxidase and 12/15-lipoxygenase, since it results in the stepped up production of reactive oxygen species. These stimulate the production of matrix metalloproteinase 2, which lead to vascular remodelling and to increased apoptosis of heart muscle cells. Stepped up apoptosis is linked with myocardial infarction, cardiomyopathies and the development of heart failure. The sensitivity of β-cells of the endocrine part of the pancreas to reactive oxygen species favor the naturally low concentrations of the collectors of free radicals in them, as well as an increase in the concentration of proinflammatory cytokines, glucosis and lipids that induce a reduction in the mass and function of β-cells. Hyperglycemia in diabetes mellitus causes tissue damage through non-enzyme glycosylation of intracellular and extracellular proteins, which results in: reduced enzyme activity, damaged nucleic acid, disrupted natural decomposition of proteins, and activation of cytotoxic pathways. These processes are the basis of the pathogenesis of numerous

  15. Alzheimer's disease: A review of recent developments

    African Journals Online (AJOL)

    2011-06-15

    Jun 15, 2011 ... Keywords:Advancing age, Alzheimer's disease, cognitive dysfunction, dementia, neuropsychological testing, primary ..... of associated behavioral and neurologic problems. ... whether to continue therapy with a particular drug.

  16. Nuclear Positioning in Muscle Development and Disease

    OpenAIRE

    Eric eFolker; Mary eBaylies

    2013-01-01

    Muscle disease as a group is characterized by muscle weakness, muscle loss, and impaired muscle function. Although the phenotype is the same, the underlying cellular pathologies, and the molecular causes of these pathologies, are diverse. One common feature of many muscle disorders is the mispositioning of myonuclei. In unaffected individuals myonuclei are spaced throughout the periphery of the muscle fiber such that the distance between nuclei is maximized. However, in diseased muscles, th...

  17. Nuclear Positioning in Muscle Development and Disease

    Directory of Open Access Journals (Sweden)

    Eric eFolker

    2013-12-01

    Full Text Available Muscle disease as a group is characterized by muscle weakness, muscle loss, and impaired muscle function. Although the phenotype is the same, the underlying cellular pathologies, and the molecular causes of these pathologies, are diverse. One common feature of many muscle disorders is the mispositioning of myonuclei. In unaffected individuals myonuclei are spaced throughout the periphery of the muscle fiber such that the distance between nuclei is maximized. However, in diseased muscles, the nuclei are often clustered within the center of the muscle cell. Although this phenotype has been acknowledged for several decades, it is often ignored as a contributor to muscle weakness. Rather, these nuclei are taken only as a sign of muscle repair. Here we review the evidence that mispositioned myonuclei are not merely a symptom of muscle disease but also a cause. Additionally, we review the working models for how myonuclei move from two different perspectives, from that of the nucleus and from that of the cytoskeleton. We further compare and contrast these mechanisms with the mechanisms of nuclear movement in other cell types both to draw general themes for nuclear movement and to identify muscle-specific considerations. Finally, we focus on factors that can be linked to muscle disease and find that genes that regulate myonuclear movement and positioning have been linked to muscular dystrophy. Although the cause-effect relationship is largely speculative, recent data indicate that the position of nuclei should no longer be considered only a means to diagnose muscle disease.

  18. PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN.

    Science.gov (United States)

    Selleski, Nicole; Almeida, Lucas Malta; Almeida, Fernanda Coutinho de; Pratesi, Claudia Beatriz; Nóbrega, Yanna Karla de Medeiros; Gandolfi, Lenora

    2018-01-01

    Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

  19. PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN

    Directory of Open Access Journals (Sweden)

    Nicole SELLESKI

    Full Text Available ABSTRACT BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100 and non-celiac children (n=110. All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5, DQA1*03-DQB1*03:02 (DQ8 and DQA1*02:01-DQB1*02:02 (DQ2.2. Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78% were positive for DQ2, 13 (13 % were DQ2/DQ8 and 6 (6% were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9% samples, in 2 (1.8 % was positive for DQ2/DQ8 and in 15 (13.6% was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

  20. 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....

  1. Development of a versatile enrichment analysis tool reveals associations between the maternal brain and mental health disorders, including autism

    Science.gov (United States)

    2013-01-01

    Background A recent study of lateral septum (LS) suggested a large number of autism-related genes with altered expression in the postpartum state. However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. Results The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. Conclusions The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. To date, this is the first study to show a significant, quantitative link between the maternal brain and mental health disorders using large scale gene expression data. Thus, the

  2. 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…

  3. Current and investigational non-dopaminergic agents for management of motor symptoms (including motor complications) in Parkinson's disease.

    Science.gov (United States)

    Müller, Thomas

    2017-10-01

    Parkinson's disease is characterized by a heterogeneous combination of motor and non motor symptoms. The nigrostriatal dopamine deficit is one of its essential pathophysiologic features. Areas covered: This invited narrative review provides an overlook over current available and future promising non dopaminergic therapeutics to modulate altered dopaminergic neurotransmission in Parkinson's disease. Current research strategies aim to proof clinical efficacy by amelioration of motor symptoms and preponderant levodopa related movement fluctuations. These so-called motor complications are characterized by involuntary movements as a result of an overstimulation of the nigrostriatal dopaminergic system or by temporary recurrence of motor symptoms, when beneficial effects of dopamine substituting drugs vane. Expert opinion: Non dopaminergic modulation of dopamine replacement is currently mostly investigated in well defined and selected patients with motor complications to get approval. However, the world of daily maintenance of patients with its individually adapted, so-called personalised, therapy will determine the real value of these therapeutics. Here the clinical experience of the treating neurologists and the courage to use unconventional drug combinations are essential preconditions for successful treatments of motor and associated non motor complications in cooperation with the patients and their care giving surroundings.

  4. Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

    Science.gov (United States)

    Barr, Maureen M

    2005-02-01

    The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  7. Development of a Conceptual Model of Disease Progression for Use in Economic Modeling of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Tabberer, Maggie; Gonzalez-McQuire, Sebastian; Muellerova, Hana; Briggs, Andrew H; Rutten-van Mölken, Maureen P M H; Chambers, Mike; Lomas, David A

    2017-05-01

    To develop and validate a new conceptual model (CM) of chronic obstructive pulmonary disease (COPD) for use in disease progression and economic modeling. The CM identifies and describes qualitative associations between disease attributes, progression and outcomes. A literature review was performed to identify any published CMs or literature reporting the impact and association of COPD disease attributes with outcomes. After critical analysis of the literature, a Steering Group of experts from the disciplines of health economics, epidemiology and clinical medicine was convened to develop a draft CM, which was refined using a Delphi process. The refined CM was validated by testing for associations between attributes using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). Disease progression attributes included in the final CM were history and occurrence of exacerbations, lung function, exercise capacity, signs and symptoms (cough, sputum, dyspnea), cardiovascular disease comorbidities, 'other' comorbidities (including depression), body composition (body mass index), fibrinogen as a biomarker, smoking and demographic characteristics (age, gender). Mortality and health-related quality of life were determined to be the most relevant final outcome measures for this model, intended to be the foundation of an economic model of COPD. The CM is being used as the foundation for developing a new COPD model of disease progression and to provide a framework for the analysis of patient-level data. The CM is available as a reference for the implementation of further disease progression and economic models.

  8. 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

  9. 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

  10. 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.

  11. Pulmonary granulomatous diseases and pulmonary manifestations of systemic granulomatous disease. Including tuberculosis and nontuberculous mycobacteriosis; Pulmonale granulomatoese Erkrankungen und pulmonale Manifestationen systemischer Granulomatosen. Inklusive Tuberkulose und nichttuberkuloese Mykobakteriosen

    Energy Technology Data Exchange (ETDEWEB)

    Piel, S. [Universitaet Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Heidelberg (Germany); Kreuter, M.; Herth, F. [Universitaet Heidelberg, Zentrum fuer interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Kauczor, H.U. [Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany); Heussel, C.P. [Universitaet Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie mit Nuklearmedizin, Thoraxklinik, Heidelberg (Germany); Universitaetsklinikum Heidelberg, Translational Lung Research Center (TLRC), Heidelberg (Germany)

    2016-10-15

    Granulomas as signs of specific inflammation of the lungs are found in various diseases with pulmonary manifestations and represent an important imaging finding. The standard imaging modality for the work-up of granulomatous diseases of the lungs is most often thin-slice computed tomography (CT). There are a few instances, e. g. tuberculosis, sarcoidosis and silicosis, where a chest radiograph still plays an important role. Further radiological modalities are usually not needed in the routine work-up of granulomatous diseases of the chest. In special cases magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT scans play an important role, e. g. detecting cardiac sarcoidosis by cardiac MRI or choline C-11 PET-CT in diagnosing lung carcinoma in scar tissue after tuberculosis. The accuracy of thin-slice CT is very high for granulomatous diseases. In cases of chronic disease and fibrotic interstitial lung disease it is important to perform thin-slice CT in order to diagnose a specific disease pattern. Thin-slice CT is also highly sensitive in detecting disease complications and comorbidities, such as malignancies. Given these indications thin-slice CT is generally accepted in the routine daily practice. A thin-slice CT and an interdisciplinary discussion are recommended in many cases with a suspected diagnosis of pulmonary granulomatous disease due to clinical or radiographic findings. (orig.) [German] Granulome als Zeichen der spezifischen Entzuendung im Lungengewebe treten bei zahlreichen Erkrankungen mit pulmonaler Manifestation auf und stellen einen wichtigen Befund in der Bildgebung dar. Das radiologische Standardverfahren bei pulmonalen Granulomatosen ist meistens die Duennschichtcomputertomographie, in wenigen Faellen, wie z. B. bei Tuberkulose, Sarkoidose und Silikose, spielt die Roentgenthoraxuebersicht immer noch eine wichtige Rolle. Bei der Standardabklaerung der meisten Granulomatosen ist die Hinzunahme weiterer Verfahren nicht

  12. 25 CFR 170.807 - What must BIA include when it develops an IRR Transportation Facilities Maintenance Management...

    Science.gov (United States)

    2010-04-01

    ... Transportation Facilities Maintenance Management System? 170.807 Section 170.807 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM BIA Road Maintenance § 170.807 What must BIA include when it develops an IRR Transportation Facilities Maintenance Management System...

  13. Hawaii Energy Resource Overviews. Volume 4. Impact of geothermal resource development in Hawaii (including air and water quality)

    Energy Technology Data Exchange (ETDEWEB)

    Siegel, S.M.; Siegel, B.Z.

    1980-06-01

    The environmental consequences of natural processes in a volcanic-fumerolic region and of geothermal resource development are presented. These include acute ecological effects, toxic gas emissions during non-eruptive periods, the HGP-A geothermal well as a site-specific model, and the geothermal resources potential of Hawaii. (MHR)

  14. 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

  15. 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.

  16. The ATM signaling network in development and disease

    Science.gov (United States)

    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

  17. The ATM signaling network in development and disease

    Directory of Open Access Journals (Sweden)

    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.

  18. Survey indicated that core outcome set development is increasingly including patients, being conducted internationally and using Delphi surveys.

    Science.gov (United States)

    Biggane, Alice M; Brading, Lucy; Ravaud, Philippe; Young, Bridget; Williamson, Paula R

    2018-02-17

    There are numerous challenges in including patients in a core outcome set (COS) study, these can vary depending on the patient group. This study describes current efforts to include patients in the development of COS, with the aim of identifying areas for further improvement and study. Using the COMET database, corresponding authors of COS projects registered or published from 1 January 2013 to 2 February 2017 were invited via a personalised email to participate in a short online survey. The survey and emails were constructed to maximise the response rate by following the academic literature on enhancing survey responses. Personalised reminder emails were sent to non-responders. This survey explored the frequency of patient input in COS studies, who was involved, what methods were used and whether or not the COS development was international. One hundred and ninety-two COS developers were sent the survey. Responses were collected from 21 February 2017 until 7 May 2017. One hundred and forty-six unique developers responded, yielding a 76% response rate and data in relation to 195 unique COSs (as some developers had worked on multiple COSs). Of focus here are their responses regarding 162 COSs at the published, completed or ongoing stages of development. Inclusion of patient participants was indicated in 87% (141/162) of COSs in the published completed or ongoing stages and over 94% (65/69) of ongoing COS projects. Nearly half (65/135) of COSs included patient participants from two or more countries and 22% (30/135) included patient participants from five or more countries. The Delphi survey was reported as being used singularly or in combination with other methods in 85% (119/140) of projects. Almost a quarter (16/65) of ongoing studies reported using a combination of qualitative interviews, Delphi survey and consensus meeting. These findings indicated that the Delphi survey is the most popular method of facilitating patient participation, while the combination of

  19. Axon Development in Health and Disease

    NARCIS (Netherlands)

    Battum, E.Y. van

    2016-01-01

    During embryonic development neurons migrate and grow their protrusions (neurites) over long distances in a strictly orchestrated manner to form complex neuronal networks. Subtle changes in neuronal network formation may lead to various neurological disorders ranging from congenital mirror

  20. Neuromuscular rate of force development deficit in Parkinson disease.

    Science.gov (United States)

    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.

  1. 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...

  2. Development of several data bases related to reactor safety research including probabilistic safety assessment and incident analysis at JAERI

    International Nuclear Information System (INIS)

    Kobayashi, Kensuke; Oikawa, Tetsukuni; Watanabe, Norio; Izumi, Fumio; Higuchi, Suminori

    1986-01-01

    Presented are several databases developed at JAERI for reactor safety research including probabilistic safety assessment and incident analysis. First described are the recent developments of the databases such as 1) the component failure rate database, 2) the OECD/NEA/IRS information retrieval system, 3) the nuclear power plant database and so on. Then several issues are discussed referring mostly to the operation of the database (data input and transcoding) and to the retrieval and utilization of the information. Finally, emphasis is given to the increasing role which artifitial intelligence techniques such as natural language treatment and expert systems may play in improving the future capabilities of the databases. (author)

  3. Studies and analyses of the management of scientific research and development, including implementation and application at NASA centers

    Science.gov (United States)

    Rubenstein, A. H.

    1975-01-01

    Summary results obtained through the Program of Research on the Management of Research and Development (POMRAD) were presented. The nature of the overall program and the specific projects undertaken were described. Statistical data is also given concerning the papers, publications, people, and major program areas associated with the program. The actual list of papers, names of doctoral and masters theses, and other details of the program are included as appendices.

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

    Science.gov (United States)

    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.

  5. The Pleural Mesothelium in Development and Disease

    Directory of Open Access Journals (Sweden)

    Hitesh eBatra

    2014-08-01

    Full Text Available The pleural mesothelium, derived from the embryonic mesoderm, is formed by a metabolically active monolayer of cells that blanket the chest wall and lungs on the parietal and visceral surfaces, respectively. The pleura and lungs are formed as a result of an intricate relationship between the mesoderm and the endoderm during development. Pleural Mesothelial Cells (PMCs are known to express Wilms tumor-1 (Wt1 gene and in lineage labeling studies of the developing embryo, PMCs were found to track into the lung parenchyma and undergo mesothelial-mesenchymal transition (MMT to form α-smooth muscle actin (α-SMA-positive cells of the mesenchyme and vasculature. There is definite evidence that mesothelial cells can differentiate and this seems to play an important role in pleural and parenchymal pathologies. Mesothelial cells can differentiate into adipocytes, chondrocytes and osteoblasts; and have been shown to clonally generate fibroblasts and smooth muscle cells in murine models. This supports the possibility that they may also modulate lung injury-repair by re-activation of developmental programs in the adult reflecting an altered recapitulation of development, with implications for regenerative biology of the lung.

  6. [Role of hepatitis A and E viruses in the development of autoimmune diseases].

    Science.gov (United States)

    Iakimchuk, K S; Malinnikova, E Iu; Poleshchuk, V F; Mikhaĭlov, M I

    2011-01-01

    The mechanisms of development of autoimmune diseases may be associated with a complex of genetic, immune, hormonal, and infectious factors. Autoimmune diseases include a wide range of systemic and organ-specific diseases, including autoimmune hepatitis (AIH). It is currently assumed that the pathogenesis of AIH is due to compromised immune regulation in the presence of an exogenous triggering factor. Exogenous factors, such as viruses, may be triggers of AIH. There may be different ways of initiating an autoimmune response by viruses, which includes nonspecific T-lymphocyte activation and molecular mimicry. There is much evidence supporting the initiating role of hepatitis viruses in the development of AIH and other autoimmune diseases. The development of AIH symptoms during hepatitis A and E virus infections has been described elsewhere. The creation of animal models of viral hepatitis is required to confirm the hypothesis that the viruses trigger the development of AIH and other autoimmune manifestations.

  7. 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

  8. Histone demethylases in development and disease

    DEFF Research Database (Denmark)

    Pedersen, Marianne Terndrup; Helin, Kristian

    2010-01-01

    Histone modifications serve as regulatory marks that are instrumental for the control of transcription and chromatin architecture. Strict regulation of gene expression patterns is crucial during development and differentiation, where diverse cell types evolve from common predecessors. Since...... the first histone lysine demethylase was discovered in 2004, a number of demethylases have been identified and implicated in the control of gene expression programmes and cell fate decisions. Histone demethylases are now emerging as important players in developmental processes and have been linked to human...

  9. Including capabilities of local actors in regional economic development: Empirical results of local seaweed industries in Sulawesi

    Directory of Open Access Journals (Sweden)

    Mark T.J. Vredegoor

    2013-11-01

    Full Text Available Stimson, et al. (2009 developed one of the most relevant and well known model for Regional Economic Development. This model covers the most important factors related to economic development question. However, this model excludes the social components of development. Local community should be included in terms of the development of a region. This paper introduced to the Stimson model “Skills” and “Knowledge” at the individual level for local actors indicating the capabilities at the individual level and introduced “Human Coordination” for the capabilities at the collective level. In our empirical research we looked at the Indonesian seaweed market with a specific focus on the region of Baubau. This region was chosen because there are hardly any economic developments. Furthermore this study focuses on the poorer community who are trying to improve their situation by the cultivation of Seaweed. Eighteen local informants was interviewed besides additional interviews of informants from educational and governmental institutions in the cities of Jakarta, Bandung and Yogyakarta. The informants selected had a direct or indirect relationship with the region of Baubau. With the support of the empirical data from this region we can confirm that it is worthwhile to include the local community in the model for regional economic development.  The newly added variables: at the individual level; Skills and Knowledge and at the level of the collective: Human Coordination was supported by the empirical material. It is an indication that including the new variables can give regional economic an extra dimension.  In this way we think that it becomes more explicit that “endogenous” means that the people, or variables closely related to them, should be more explicitly included in models trying to capture Regional Economic Development or rephrased as Local Economic Development Keywords:Regional and endogenous development; Fisheries and seaweed

  10. 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

  11. 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....

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

    Science.gov (United States)

    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…

  13. 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.

  14. 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...

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

    Science.gov (United States)

    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.

  16. 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.

  17. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Science.gov (United States)

    Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the

  18. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Rocio Martin

    Full Text Available Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to

  19. 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...

  20. Development of Constraint Force Equation Methodology for Application to Multi-Body Dynamics Including Launch Vehicle Stage Seperation

    Science.gov (United States)

    Pamadi, Bandu N.; Toniolo, Matthew D.; Tartabini, Paul V.; Roithmayr, Carlos M.; Albertson, Cindy W.; Karlgaard, Christopher D.

    2016-01-01

    The objective of this report is to develop and implement a physics based method for analysis and simulation of multi-body dynamics including launch vehicle stage separation. The constraint force equation (CFE) methodology discussed in this report provides such a framework for modeling constraint forces and moments acting at joints when the vehicles are still connected. Several stand-alone test cases involving various types of joints were developed to validate the CFE methodology. The results were compared with ADAMS(Registered Trademark) and Autolev, two different industry standard benchmark codes for multi-body dynamic analysis and simulations. However, these two codes are not designed for aerospace flight trajectory simulations. After this validation exercise, the CFE algorithm was implemented in Program to Optimize Simulated Trajectories II (POST2) to provide a capability to simulate end-to-end trajectories of launch vehicles including stage separation. The POST2/CFE methodology was applied to the STS-1 Space Shuttle solid rocket booster (SRB) separation and Hyper-X Research Vehicle (HXRV) separation from the Pegasus booster as a further test and validation for its application to launch vehicle stage separation problems. Finally, to demonstrate end-to-end simulation capability, POST2/CFE was applied to the ascent, orbit insertion, and booster return of a reusable two-stage-to-orbit (TSTO) vehicle concept. With these validation exercises, POST2/CFE software can be used for performing conceptual level end-to-end simulations, including launch vehicle stage separation, for problems similar to those discussed in this report.

  1. The post-millennium development goals agenda: include 'end to all wars' as a public health goal!

    Science.gov (United States)

    Jayasinghe, Saroj

    2014-09-01

    The process of identifying global post-millennium development goals (post-MDGs) has begun in earnest. Consensus is emerging in certain areas (e.g. eliminating poverty) and conflicts and violence are recognized as key factors that retard human development. However, current discussions focus on tackling intra-state conflicts and individual-based violence and hardly mention eliminating wars as a goal. Wars create public health catastrophes. They kill, maim, displace and affect millions. Inter-state wars fuel intra-state conflicts and violence. The peace agenda should not be the monopoly of the UN Security Council, and the current consensus-building process setting the post-MDG agenda is a rallying point for the global community. The human rights approach will not suffice to eliminate wars, because few are fought to protect human rights. The development agenda should therefore commit to eliminating all wars by 2030. Targets to reduce tensions and discourage wars should be included. We should act now. © The Author(s) 2014.

  2. [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.

  3. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. [Geographical differences in clinical characteristics and management of stable outpatients with coronary artery disease: comparison between the Italian and international population included in the Worldwide CLARIFY registry].

    Science.gov (United States)

    Pozzoli, Massimo; Tavazzi, Luigi

    2014-04-01

    Limited data are available regarding specific differences among countries in demographic and clinical characteristics and treatment of patients with stable coronary artery disease. CLARIFY is an international, prospective and longitudinal registry including more than 33 000 patients with stable coronary artery disease enrolled in 45 countries worldwide. Data were used to compare the characteristics of patients enrolled in Italy with those enrolled in Europe and in the rest of the world. Baseline data were available for 33 283 patients, 2112 of whom from Italy and 12 614 from the remaining western European countries. Italian patients were found to be older, more frequently smoker, hypertensive and with sedentary habits. In addition, they presented more frequently a history of myocardial infarction, carotid arterial disease and chronic obstructive pulmonary disease. In addition, when compared with patients of both European and international cohorts, more Italian patients had undergone coronary angiography and angioplasty. As far as treatment was concerned, a greater number of Italian patients were taking ivabradine, angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, nitrates, thienopyridines, while those taking beta-blockers, calcium antagonists and other antianginal medications were fewer. Among ambulatory patients with stable coronary artery disease, there are important geographic differences in terms of risk factors, clinical characteristics, surgical and pharmacological treatment.

  8. Developing an explicit strategy towards social responsibility in the NHS: a case for including NHS managers in this strategy.

    Science.gov (United States)

    Merali, Faruk

    2006-01-01

    To explore the concept of corporate social responsibility (CSR) within the UK National Health Service (NHS) and to examine how it may be developed to positively influence the psyche, behaviour and performance of NHS managers. Primary research based upon semi-structured individual face to face interviews with 20 NHS managers. Theoretical frameworks and concepts relating to organisational culture and CSR are drawn upon to discuss the findings. The NHS managers see themselves as being driven by altruistic core values. However, they feel that the public does not believe that they share the altruistic NHS value system. The study is based on a relatively small sample of NHS managers working exclusively in London and may not necessarily represent the views of managers either London-wide or nation-wide. It is suggested that an explicit recognition by the NHS of the socially responsible commitment of its managers within its CSR strategy would help challenge the existing negative public image of NHS managers and in turn improve the managers' self esteem and morale. This paper addresses the relative lacunae in research relating to public sector organisations (such as the NHS) explicitly including the role and commitment of its staff within the way it publicises its CSR strategy. This paper would be of interest to a wide readership including public sector and NHS policy formulators, NHS practitioners, academics and students.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. ECH system developments including the design of an intelligent fault processor on the DIII-D tokamak

    International Nuclear Information System (INIS)

    Ponce, D.; Lohr, J.; Tooker, J.F.; O'Neill, R.C.; Moeller, C.P.; Doane, J.L.; Noraky, S.; Dubovenko, K.; Gorelov, Y.A.; Cengher, M.; Penaflor, B.G.; Ellis, R.A.

    2011-01-01

    A new generation fault processor is in development which is intended to increase fault handling flexibility and reduce the number of incomplete DIII-D shots due to gyrotron faults. The processor, which is based upon a field programmable gate array device, will analyze signals for aberrant operation and ramp down high voltage to try to avoid hard faults. The processor will then attempt to ramp back up to an attainable operating point. The new generation fault processor will be developed during an expansion of the electron cyclotron heating (ECH) areas that will include the installation of a depressed collector gyrotron and associated equipment. Existing systems will also be upgraded. Testing of real-time control of the ECH launcher poloidal drives by the DIII-D plasma control system will be completed. The ECH control system software will be upgraded for increased scalability and to increase operator productivity. Resources permitting, all systems will receive an extra layer of interlocks for the filament and magnet power supplies, added shielding for the tank electronics, programmable filament boost shape for long pulses, and electronics upgrades for the installation of the advanced fault processor.

  11. Recent developments in epigenetics of acute and chronic kidney diseases.

    Science.gov (United States)

    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.

  12. Development and Implementation of a Battery-Electric Light-Duty Class 2a Truck including Hybrid Energy Storage

    Science.gov (United States)

    Kollmeyer, Phillip J.

    This dissertation addresses two major related research topics: 1) the design, fabrication, modeling, and experimental testing of a battery-electric light-duty Class 2a truck; and 2) the design and evaluation of a hybrid energy storage system (HESS) for this and other vehicles. The work begins with the determination of the truck's peak power and wheel torque requirements (135kW/4900Nm). An electric traction system is then designed that consists of an interior permanent magnet synchronous machine, two-speed gearbox, three-phase motor drive, and LiFePO4 battery pack. The battery pack capacity is selected to achieve a driving range similar to the 2011 Nissan Leaf electric vehicle (73 miles). Next, the demonstrator electric traction system is built and installed in the vehicle, a Ford F150 pickup truck, and an extensive set of sensors and data acquisition equipment is installed. Detailed loss models of the battery pack, electric traction machine, and motor drive are developed and experimentally verified using the driving data. Many aspects of the truck's performance are investigated, including efficiency differences between the two-gear configuration and the optimal gear selection. The remainder focuses on the application of battery/ultracapacitor hybrid energy storage systems (HESS) to electric vehicles. First, the electric truck is modeled with the addition of an ultracapacitor pack and a dc/dc converter. Rule-based and optimal battery/ultracapacitor power-split control algorithms are then developed, and the performance improvements achieved for both algorithms are evaluated for operation at 25°C. The HESS modeling is then extended to low temperatures, where battery resistance increases substantially. To verify the accuracy of the model-predicted results, a scaled hybrid energy storage system is built and the system is tested for several drive cycles and for two temperatures. The HESS performance is then modeled for three variants of the vehicle design, including the

  13. Function and modulation of premotor brainstem parasympathetic cardiac neurons that control heart rate by hypoxia-, sleep-, and sleep-related diseases including obstructive sleep apnea.

    Science.gov (United States)

    Dergacheva, Olga; Weigand, Letitia A; Dyavanapalli, Jhansi; Mares, Jacquelyn; Wang, Xin; Mendelowitz, David

    2014-01-01

    Parasympathetic cardiac vagal neurons (CVNs) in the brainstem dominate the control of heart rate. Previous work has determined that these neurons are inherently silent, and their activity is largely determined by synaptic inputs to CVNs that include four major types of synapses that release glutamate, GABA, glycine, or serotonin. Whereas prior reviews have focused on glutamatergic, GABAergic and glycinergic pathways, and the receptors in CVNs activated by these neurotransmitters, this review focuses on the alterations in CVN activity with hypoxia-, sleep-, and sleep-related cardiovascular diseases including obstructive sleep apnea. © 2014 Elsevier B.V. All rights reserved.

  14. Early determinants of chronic disease in developing countries.

    Science.gov (United States)

    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.

  15. Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers.

    Science.gov (United States)

    Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L

    2012-07-01

    Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (Panaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (Panaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.

  16. DYNAMICS AND INTENSITY OF APLE DISEASE DEVELOPMENT DURING ITS STORAGE

    Directory of Open Access Journals (Sweden)

    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.

  17. Development of seedless fruits mutants in citrus including tangerine (C. reticulata) and pummelo (C. grandis) through induced mutations and biotechnology

    Energy Technology Data Exchange (ETDEWEB)

    Somsri, S. [Horticulture Research Institute, Department of Agriculture (DOA), Chatuchak, Bangkok (Thailand); Jompook, P. [Department of Applied Radiation and Isotopes, Faculty of Science, Kasetsart University, Chatuchak, Bangkok (Thailand); Kanhom, P. [Phare Horticultural Research Center, Muang, Phare (Thailand); Thayamanont, P.; Meecharoen, S. [Pichit Horticultural Research Center, Muang, Pichit (Thailand); Kumcha, U. [Srisaket Horticultural Research Center, Muang, Srisaket (Thailand)

    2009-05-15

    The development of seedless fruit mutants in citrus, including Tangerine (C. reticulata) and Pummelo (C. grandis), through induced mutation and biotechnology was studied at the Gamma Irradiation Service and Nuclear Technology Center, Pichit and Phare Horticultural Research Center for 4 years (August 2000 to September 2004). The results showed successful induction of mutants with gamma irradiation using both chronic and acute procedures for pot plants, scions and in vitro plantlets of tangerine (Citrus reticulata var. Shogun and Sai Nam Puaeng) and pummelo (Citrus grandis viz. Kao Thong Dee). MS medium with 2 mgL{sup -1} of BA was found to be the most suitable medium for shoot proliferation. The seedlings were sub-cultured at least 4 times, and then they were treated with acute and chronic irradiation. Shoot induction from M{sub 1}V{sub 0} to M{sub 1}V{sub 4} generation was performed in basic MS medium with 2 mgL{sup -1} added BA. Rooting was induced in the M{sub 1}V{sub 4} in halfstrength MS enriched with BA 2 mgL{sup -1}. Later, the shoots were excised and grafted on mature plants or the plantlets directly transferred in the field and later the fruits from mature trees were evaluated for seedlessness in M{sub 1}V{sub 4} at Pichit and Phare Horticultural Research Center. (author)

  18. Laboratory Studies of the Reactive Chemistry and Changing CCN Properties of Secondary Organic Aerosol, Including Model Development

    Energy Technology Data Exchange (ETDEWEB)

    Scot Martin

    2013-01-31

    The chemical evolution of secondary-organic-aerosol (SOA) particles and how this evolution alters their cloud-nucleating properties were studied. Simplified forms of full Koehler theory were targeted, specifically forms that contain only those aspects essential to describing the laboratory observations, because of the requirement to minimize computational burden for use in integrated climate and chemistry models. The associated data analysis and interpretation have therefore focused on model development in the framework of modified kappa-Koehler theory. Kappa is a single parameter describing effective hygroscopicity, grouping together several separate physicochemical parameters (e.g., molar volume, surface tension, and van't Hoff factor) that otherwise must be tracked and evaluated in an iterative full-Koehler equation in a large-scale model. A major finding of the project was that secondary organic materials produced by the oxidation of a range of biogenic volatile organic compounds for diverse conditions have kappa values bracketed in the range of 0.10 +/- 0.05. In these same experiments, somewhat incongruently there was significant chemical variation in the secondary organic material, especially oxidation state, as was indicated by changes in the particle mass spectra. Taken together, these findings then support the use of kappa as a simplified yet accurate general parameter to represent the CCN activation of secondary organic material in large-scale atmospheric and climate models, thereby greatly reducing the computational burden while simultaneously including the most recent mechanistic findings of laboratory studies.

  19. Development of a two-dimensional simulation code (koad) including atomic processes for beam direct energy conversion

    International Nuclear Information System (INIS)

    Yamamoto, Y.; Yoshikawa, K.; Hattori, Y.

    1987-01-01

    A two-dimensional simulation code for the beam direct energy conversion called KVAD (Kyoto University Advanced DART) including various loss mechanisms has been developed, and shown excellent agreement with the authors' experiments using the He + beams. The beam direct energy converter (BDC) is the device to recover the kinetic energy of unneutralized ions in the neutral beam injection (NBI) system directly into electricity. The BDC is very important and essential not only to the improvements of NBI system efficiency, but also to the relaxation of high heat flux problems on the beam dump with increase of injection energies. So far no simulation code could have successfully predicted BDC experimental results. The KUAD code applies, an optimized algorithm for vector processing, the finite element method (FEM) for potential calculation, and a semi-automatic method for spatial segmentations. Since particle trajectories in the KVAD code are analytically solved, very high speed tracings of the particle could be achieved by introducing an adjacent element matrix to identify the neighboring triangle elements and electrodes. Ion space charges are also analytically calculated by the Cloud in Cell (CIC) method, as well as electron space charges. Power losses due to atomic processes can be also evaluated in the KUAD code

  20. 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.

  1. 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.

  2. Systematic review with meta-analysis: online psychological interventions for mental and physical health outcomes in gastrointestinal disorders including irritable bowel syndrome and inflammatory bowel disease.

    Science.gov (United States)

    Hanlon, I; Hewitt, C; Bell, K; Phillips, A; Mikocka-Walus, A

    2018-06-14

    Online psychotherapy has been successfully used as supportive treatment in many chronic illnesses. However, there is a lack of evidence on its role in the management of gastrointestinal (GI) diseases. To examine whether online psychological interventions improve mental and physical outcomes in gastrointestinal diseases. We searched CINAHL Plus, MEDLINE, EMBASE, Health Management Information Consortium, PsycINFO, British Nursing Index, Cochrane Library, a specialised register of the IBD/FBD Cochrane Group, MEDLINE (PubMed) WHO International Clinical Trial Registry, ClinicalTrials.gov, and reference lists of all papers included in the review. The Cochrane Risk of Bias Tool was used to assess internal validity. Where possible, data were pooled using random-effects meta-analysis. We identified 11 publications (encompassing nine studies) meeting inclusion criteria. One study had a high risk of selection bias (allocation concealment), all studies had a high risk of performance and detection bias. Eight studies were included in the meta-analyses (6 on irritable bowel syndrome [IBS] and two on inflammatory bowel disease [IBD]). Online cognitive behavioural therapy (CBT) was shown to significantly improve gastrointestinal symptom-specific anxiety (MD: -8.51, 95% CI -12.99 to -4.04, P = 0.0002) and lessen symptom-induced disability (MD: -2.78, 95% CI -5.43 to -0.12, P = 0.04) in IBS post intervention. There was no significant effect of online CBT on any other outcomes in IBS. No significant effect of online psychotherapy was demonstrated in IBD. There is insufficient evidence to demonstrate the effectiveness of online CBT to manage mental and physical outcomes in gastrointestinal diseases. © 2018 John Wiley & Sons Ltd.

  3. 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.

  4. Characterisation of the legume SERK-NIK gene superfamily including splice variants: Implications for development and defence

    Directory of Open Access Journals (Sweden)

    Rose Ray J

    2011-03-01

    Full Text Available Abstract Background SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK genes are part of the regulation of diverse signalling events in plants. Current evidence shows SERK proteins function both in developmental and defence signalling pathways, which occur in response to both peptide and steroid ligands. SERKs are generally present as small gene families in plants, with five SERK genes in Arabidopsis. Knowledge gained primarily through work on Arabidopsis SERKs indicates that these proteins probably interact with a wide range of other receptor kinases and form a fundamental part of many essential signalling pathways. The SERK1 gene of the model legume, Medicago truncatula functions in somatic and zygotic embryogenesis, and during many phases of plant development, including nodule and lateral root formation. However, other SERK genes in M. truncatula and other legumes are largely unidentified and their functions unknown. Results To aid the understanding of signalling pathways in M. truncatula, we have identified and annotated the SERK genes in this species. Using degenerate PCR and database mining, eight more SERK-like genes have been identified and these have been shown to be expressed. The amplification and sequencing of several different PCR products from one of these genes is consistent with the presence of splice variants. Four of the eight additional genes identified are upregulated in cultured leaf tissue grown on embryogenic medium. The sequence information obtained from M. truncatula was used to identify SERK family genes in the recently sequenced soybean (Glycine max genome. Conclusions A total of nine SERK or SERK-like genes have been identified in M. truncatula and potentially 17 in soybean. Five M. truncatula SERK genes arose from duplication events not evident in soybean and Lotus. The presence of splice variants has not been previously reported in a SERK gene. Upregulation of four newly identified SERK genes (in addition to the

  5. 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 ...

  6. Spectral element modelling of seismic wave propagation in visco-elastoplastic media including excess-pore pressure development

    Science.gov (United States)

    Oral, Elif; Gélis, Céline; Bonilla, Luis Fabián; Delavaud, Elise

    2017-12-01

    Numerical modelling of seismic wave propagation, considering soil nonlinearity, has become a major topic in seismic hazard studies when strong shaking is involved under particular soil conditions. Indeed, when strong ground motion propagates in saturated soils, pore pressure is another important parameter to take into account when successive phases of contractive and dilatant soil behaviour are expected. Here, we model 1-D seismic wave propagation in linear and nonlinear media using the spectral element numerical method. The study uses a three-component (3C) nonlinear rheology and includes pore-pressure excess. The 1-D-3C model is used to study the 1987 Superstition Hills earthquake (ML 6.6), which was recorded at the Wildlife Refuge Liquefaction Array, USA. The data of this event present strong soil nonlinearity involving pore-pressure effects. The ground motion is numerically modelled for different assumptions on soil rheology and input motion (1C versus 3C), using the recorded borehole signals as input motion. The computed acceleration-time histories show low-frequency amplification and strong high-frequency damping due to the development of pore pressure in one of the soil layers. Furthermore, the soil is found to be more nonlinear and more dilatant under triaxial loading compared to the classical 1C analysis, and significant differences in surface displacements are observed between the 1C and 3C approaches. This study contributes to identify and understand the dominant phenomena occurring in superficial layers, depending on local soil properties and input motions, conditions relevant for site-specific studies.

  7. 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.

  8. New Theoretical Developments in Exploring Electronically Excited States: Including Localized Configuration Interaction Singles and Application to Large Helium Clusters

    Science.gov (United States)

    Closser, Kristina Danielle

    superpositions of atomic states with surface states appearing close to the atomic excitation energies and interior states being blue shifted by up to ≈2 eV. The dynamics resulting from excitation of He_7 were subsequently explored using ab initio molecular dynamics (AIMD). These simulations were performed with classical adiabatic dynamics coupled to a new state-following algorithm on CIS potential energy surfaces. Most clusters were found to completely dissociate and resulted in a single excited atomic state (90%), however, some trajectories formed bound, He*2 (3%), and a few yielded excited trimers (<0.5%). Comparisons were made with available experimental information on much larger clusters. Various applications of this state following algorithm are also presented. In addition to AIMD, these include excited-state geometry optimization and minimal energy path finding via the growing string method. When using state following we demonstrate that more physical results can be obtained with AIMD calculations. Also, the optimized geometries of three excited states of cytosine, two of which were not found without state following, and the minimal energy path between the lowest two singlet excited states of protonated formaldimine are offered as example applications. Finally, to address large clusters, a local variation of CIS was developed. This method exploits the properties of absolutely localized molecular orbitals (ALMOs) to limit the total number of excitations to scaling only linearly with cluster size, which results in formal scaling with the third power of the system size. The derivation of the equations and design of the algorithm are discussed in detail, and computational timings as well as a pilot application to the size dependence of the helium cluster spectrum are presented.

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

    Science.gov (United States)

    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

  10. 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.

  11. 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.

  12. 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

  13. Congenital Heart Disease and Impacts on Child Development

    Directory of Open Access Journals (Sweden)

    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.

  14. Pattern of renal diseases in children: A developing country experience

    Directory of Open Access Journals (Sweden)

    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.

  15. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model.

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-08-03

    Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015-2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All

  16. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-01-01

    Objectives Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Methods Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015–2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. Findings The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. Conclusions The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. PMID:28775179

  17. Using Intervention Mapping to develop a programme to prevent sexually transmittable infections, including HIV, among heterosexual migrant men

    Science.gov (United States)

    Wolfers, Mireille EG; van den Hoek, Caty; Brug, Johannes; de Zwart, Onno

    2007-01-01

    Background There is little experience with carefully developed interventions in the HIV/STI prevention field aimed at adult heterosexual target groups in the Netherlands. The ability to apply intervention development protocols, like Intervention Mapping, in daily practice outside of academia, is a matter of concern. An urgent need also exists for interventions aimed at the prevention of STI in migrant populations in the Netherlands. This article describes the theory and evidence based development of HIV/STI prevention interventions by the Municipal Public Health Service Rotterdam Area (MPHS), the Netherlands, for heterosexual migrant men with Surinamese, Dutch-Caribbean, Cape Verdean, Turkish and Moroccan backgrounds. Methods First a needs assessment was carried out. Then, a literature review was done, key figures were interviewed and seven group discussions were held. Subsequently, the results were translated into specific objectives ("change objectives") and used in intervention development for two subgroups: men with an Afro-Caribbean background and unmarried men with a Turkish and Moroccan background. A matrix of change objectives was made for each subgroup and suitable theoretical methods and practical strategies were selected. Culturally-tailored interventions were designed and were pre-tested among the target groups. Results This development process resulted in two interventions for specific subgroups that were appreciated by both the target groups and the migrant prevention workers. The project took place in collaboration with a university center, which provided an opportunity to get expert advice at every step of the Intervention Mapping process. At relevant points of the development process, migrant health educators and target group members provided advice and feedback on the draft intervention materials. Conclusion This intervention development project indicates that careful well-informed intervention development using Intervention Mapping is feasible in

  18. 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.

  19. 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)

  20. DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden.

    Science.gov (United States)

    Dun, Karen A; Riley, Louise A; Diano, Giuseppe; Adams, Leanne B; Chiu, Eleanor; Sharma, Archna

    2018-05-01

    Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease. © 2018 Wiley Periodicals, Inc.

  1. 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.

  2. Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin.

    Directory of Open Access Journals (Sweden)

    Melissa K Boles

    2009-12-01

    Full Text Available An accurate and precisely annotated genome assembly is a fundamental requirement for functional genomic analysis. Here, the complete DNA sequence and gene annotation of mouse Chromosome 11 was used to test the efficacy of large-scale sequencing for mutation identification. We re-sequenced the 14,000 annotated exons and boundaries from over 900 genes in 41 recessive mutant mouse lines that were isolated in an N-ethyl-N-nitrosourea (ENU mutation screen targeted to mouse Chromosome 11. Fifty-nine sequence variants were identified in 55 genes from 31 mutant lines. 39% of the lesions lie in coding sequences and create primarily missense mutations. The other 61% lie in noncoding regions, many of them in highly conserved sequences. A lesion in the perinatal lethal line l11Jus13 alters a consensus splice site of nucleoredoxin (Nxn, inserting 10 amino acids into the resulting protein. We conclude that point mutations can be accurately and sensitively recovered by large-scale sequencing, and that conserved noncoding regions should be included for disease mutation identification. Only seven of the candidate genes we report have been previously targeted by mutation in mice or rats, showing that despite ongoing efforts to functionally annotate genes in the mammalian genome, an enormous gap remains between phenotype and function. Our data show that the classical positional mapping approach of disease mutation identification can be extended to large target regions using high-throughput sequencing.

  3. Early-Life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota

    NARCIS (Netherlands)

    Martin, Rocio; Makino, Hiroshi; Yavuz, Aysun Cetinyurek; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with

  4. Social Licence to Operate through a gender lens : The challenges of including women’s interests in development assistance projects

    NARCIS (Netherlands)

    Jijelava, David; Vanclay, Frank

    2014-01-01

    The paper analyses the concept of social licence to operate from a gender perspective. We examine the challenges associated with obtaining a gender-aware social licence for development assistance organizations working in conservative, traditional rural societies. We argue that during project

  5. Geocraft as a means to support the development of smart cities, getting the people of the place involved - youth included -

    NARCIS (Netherlands)

    Scholten, Henk; Fruijtier, Steven; Dias, Eduardo; Hettinga, Sanne; Opmeer, Mark; van Leeuwen, Willemijn S.; Linde, Marianne; Bos, Steven; Vaughan, Rubio; van Kaam, Heidy; van Manen, Niels; Fruijtier, Ceciel

    2017-01-01

    Purpose: In this paper we present Geocraft, a Geo-ICT framework meant to provide the information needed to support the development of smart cities in an accessible and user-friendly way. We explored whether Geocraft could be an effective way to get the people of the place, especially youth, involved

  6. Development of the preparation technology of macroporous sorbent for industrial off-gas treatment including 14C

    International Nuclear Information System (INIS)

    Cho, Il Hoon; Cho, Young Hyun; Park, Guen Il; Kim, In Tae; Kim, June Hyung; Ahn, Byung Kil

    2001-01-01

    For environmental and health effects due to increasing levels of pollution in the atmosphere, it is necessary to develop environmentally sound technologies for the treatment of greenhouse gases (CO 2 , CH 4 , CFC, etc.) and acid gases (SOx, NOx, etc.). Specifically, advanced technology for CO 2 capturing is currently one of the most important environmental issues in worldwide. 14 CO 2 , specially which has been gradually emerging issue in the nuclear facilities, is generated about 330 ppm from the CANDU (Canadian Deuterium Uranium Reactor) nuclear power plant and the DUPIC (Direct Use of spent PWR fuel in CANDU reactors) process which is the process of spent fuel treatment. For this purpose, it is necessary to develop the most efficient treatment technology of CO 2 capture by various lime materials in semi- or dry process, it should be also considering a removal performance, waste recycling and safety of disposal. In order to develop a highly active slaked lime as a sorbent for CO 2 and high temperature desulfurization, macroporous slaked lime is necessarily prepared by modified swelling process and equipment, which was developed under carrying out this project. And also for the optimal removal process of off-gases the removal performance tests of various sorbents and the effects of relative humidity and bed depth on the removal capacity must be considered

  7. A Proposal for a Methodology to Develop a Cyber-Attack Penetration Test Scenario Including NPPs Safety

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Hyo [KAIST, Daejeon (Korea, Republic of); Son, Han Seong [Joongbu Univ., Geumsan (Korea, Republic of); Kim, Si Won [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of); Kang, Hyun Gook [Rensselaer Polytechnic Institute, Troy (United States)

    2016-10-15

    Penetration test is a method to evaluate the cyber security of NPPs; so, this approach was performed in some studies. Because they focused on vulnerability finding or test bed construction, scenario based approach was not performed. However, to test the cyber security of NPPs, a proper test scenario should be needed. Ahn et al. developed cyber-attack scenarios but those scenarios couldn't be applied in penetration test because they developed the scenarios based on past incidents of NPPs induced by cyber-attack. That is, those scenarios only covered scenarios which were happened before; so, they couldn't cover other various scenarios and couldn't reflect them into a penetration test. In this study, a method to develop a cyber-attack penetration test scenario of NPPs especially focused on safety point of view is suggested. To evaluate the cyber security of NPPs, penetration test can be a possible way. In this study, a method to develop a penetration test scenario was explained. Especially, the goal of hacker was focused on nuclear fuel integrity deterioration. So, in the methodology, Level 1 PSA results were utilized to reflect plant safety into the security. From the PSA results, basic event was post processed and possible cyber-attacks were reviewed with vulnerabilities of digital control system.

  8. Development of the preparation technology of macroporous sorbent for industrial off-gas treatment including {sup 14}C

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Il Hoon; Cho, Young Hyun; Park, Guen Il; Kim, In Tae; Kim, June Hyung; Ahn, Byung Kil

    2001-01-01

    For environmental and health effects due to increasing levels of pollution in the atmosphere, it is necessary to develop environmentally sound technologies for the treatment of greenhouse gases (CO{sub 2}, CH{sub 4}, CFC, etc.) and acid gases (SOx, NOx, etc.). Specifically, advanced technology for CO{sub 2} capturing is currently one of the most important environmental issues in worldwide. {sup 14}CO{sub 2}, specially which has been gradually emerging issue in the nuclear facilities, is generated about 330 ppm from the CANDU (Canadian Deuterium Uranium Reactor) nuclear power plant and the DUPIC (Direct Use of spent PWR fuel in CANDU reactors) process which is the process of spent fuel treatment. For this purpose, it is necessary to develop the most efficient treatment technology of CO{sub 2} capture by various lime materials in semi- or dry process, it should be also considering a removal performance, waste recycling and safety of disposal. In order to develop a highly active slaked lime as a sorbent for CO{sub 2} and high temperature desulfurization, macroporous slaked lime is necessarily prepared by modified swelling process and equipment, which was developed under carrying out this project. And also for the optimal removal process of off-gases the removal performance tests of various sorbents and the effects of relative humidity and bed depth on the removal capacity must be considered.

  9. A Proposal for a Methodology to Develop a Cyber-Attack Penetration Test Scenario Including NPPs Safety

    International Nuclear Information System (INIS)

    Lee, In Hyo; Son, Han Seong; Kim, Si Won; Kang, Hyun Gook

    2016-01-01

    Penetration test is a method to evaluate the cyber security of NPPs; so, this approach was performed in some studies. Because they focused on vulnerability finding or test bed construction, scenario based approach was not performed. However, to test the cyber security of NPPs, a proper test scenario should be needed. Ahn et al. developed cyber-attack scenarios but those scenarios couldn't be applied in penetration test because they developed the scenarios based on past incidents of NPPs induced by cyber-attack. That is, those scenarios only covered scenarios which were happened before; so, they couldn't cover other various scenarios and couldn't reflect them into a penetration test. In this study, a method to develop a cyber-attack penetration test scenario of NPPs especially focused on safety point of view is suggested. To evaluate the cyber security of NPPs, penetration test can be a possible way. In this study, a method to develop a penetration test scenario was explained. Especially, the goal of hacker was focused on nuclear fuel integrity deterioration. So, in the methodology, Level 1 PSA results were utilized to reflect plant safety into the security. From the PSA results, basic event was post processed and possible cyber-attacks were reviewed with vulnerabilities of digital control system

  10. 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.

  11. Applying Next Generation Sequencing to Skeletal Development and Disease

    OpenAIRE

    Bowen, Margot Elizabeth

    2013-01-01

    Next Generation Sequencing (NGS) technologies have dramatically increased the throughput and lowered the cost of DNA sequencing. In this thesis, I apply these technologies to unresolved questions in skeletal development and disease. Firstly, I use targeted re-sequencing of genomic DNA to identify the genetic cause of the cartilage tumor syndrome, metachondromatosis (MC). I show that the majority of MC patients carry heterozygous loss-of-function mutations in the PTPN11 gene, which encodes a p...

  12. Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin

    International Nuclear Information System (INIS)

    LaMonte, C.S.; Yeh, S.D.; Straus, D.J.

    1986-01-01

    Among 41 evaluable patients whose first treatment for advanced Hodgkin's disease had consisted of alternating cycles of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to low-dose mediastinal irradiation, 19 underwent retrospective cardiac evaluation by routine posteroanterior and lateral chest x-ray, 12-lead ECG, M-mode echocardiogram, and ECG-gated left ventricular blood pool scan at rest and during exercise. Fifteen patients had unequivocally normal left ventricular function by all these parameters. Two patients had minimally reduced left ventricular ejection fraction (LVEF) at rest with a normal increment with exercise. In two other patients with high normal resting LVEF and subnormal increment with exercise, the elevated resting values implied initial measurement in a nonbasal state. A twentieth patient (the oldest; one of two with active Hodgkin's disease at the time of evaluation and the stimulus for this study) had markedly reduced LVEF as determined by radionuclide cardiac angiography and had developed clinical congestive heart failure shortly before evaluation. Despite this patient, the study indicates that treatment with MOPP/ABVD and low-dose mediastinal irradiation entails low risk for cardiac complications

  13. [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.

  14. Dynamics of waterflooding massive oil deposits in the Chechen Ingush ASSR, including fissured reservoirs in the late stages of development

    Energy Technology Data Exchange (ETDEWEB)

    Tatashev, K.Kh.; Soboleva, G.N.; Tagunova, A.V.

    1979-01-01

    In 1956 in the Chechen Ingush ASSR a number of massive oil deposits located in fissured cavernous Upper Cretaceous limestone were developed. The deposits were developed by water-oil displacement from the edges and pericline toward the dome of the structure using the natural water pressure drive as well as artificial marginal flooding. The great oil-bearing capacity, the good hydrodynamic link with the deposit, the close magnitude of oil viscosity and water under the layer conditions and the significant difference in their density (0.4-0.5 g/cm/sup 3/) practically guarantees pistonlike oil displacement. Based on the deposit's geologic-physical characteristics, the late stage of development may be characterized by noncontinuous time and a sharp increase in well waterflooding to maintain full flooding. However, the data obtained from working the field suggest that a sharp increase in waterflooding will be substituted by a slow increase, by stabilization and possibly even a decrease in the percentage of water over the last 3-6 years. This occurred in a number of cases where measures were taken to limit the liquid flow, to periodically operate the well with isolated waterflooding and pereclinal perforation at intervals. This also occurred in a number of cases where the rate of fluid yield was naturally lowered by decreasing the number of producing wells due to waterflooding and disengagement. To more completely extract the oil from relatively low permeable areas of the deposits and to develop them in the later stages, it is useful to use a slow tempo once all wells have been brought to perclinal interval operation.

  15. A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms.

    Science.gov (United States)

    Lev, Dorit; Weigl, Yuval; Hasan, Mariana; Gak, Eva; Davidovich, Michael; Vinkler, Chana; Leshinsky-Silver, Esther; Lerman-Sagie, Tally; Watemberg, Nathan

    2007-05-01

    Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness and in some cases, mental retardation and deafness. Other neurological complications, particularly epilepsy, are rare. We report on a novel mutation identified in a patient with ND and profound mental retardation. The patient was diagnosed at the age of 6 months due to congenital blindness. At the age of 8 months he developed infantile spasms, which were diagnosed at 11 months as his EEG demonstrated hypsarrhythmia. Mutation analysis of the ND gene (NDP) of the affected child and his mother revealed a novel missense mutation at position c.134T > A resulting in amino acid change at codon V45E. To the best of our knowledge, such severe neurological involvement has not been previously reported in ND patients. The severity of the phenotype may suggest the functional importance of this site of the NDP gene.

  16. 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)

  17. Development and characterisation of a novel composite electrode material consisting of poly(3,4-ethylenedioxythiophene) including Au nanoparticles

    International Nuclear Information System (INIS)

    Zanardi, C.; Terzi, F.; Pigani, L.; Heras, A.; Colina, A.; Lopez-Palacios, J.; Seeber, R.

    2008-01-01

    Composite material consisting of poly(3,4-ethylenedioxythiophene) (PEDOT), including Au nanoparticles encapsulated by N-dodecyl-N,N-dimethyl-3-ammonium-1-propanesulphonate (SB12) is synthesised by constant-current method on ITO glass, in aqueous medium, leading to an electrode coating. The synthesis process is followed by UV-vis spectroelectrochemistry, both in normal-beam and in parallel-beam configurations. Under the same experimental conditions PEDOT is also synthesised by electropolymerisation only in the presence of LiClO 4 supporting electrolyte, as well in solutions also containing SB12. The data relative to the electrosynthesis of the three materials are compared. The composite material based on the conductive polymer matrix including Au nanoparticles has been characterised by SEM, TEM, ICP, Raman and UV-vis spectroscopies. The behaviour of the three different electrode coatings with respect to p-doping process has been studied by conventional electrochemical techniques and by potentiostatic and potentiodynamic UV-vis spectroelectrochemical methods. Conclusions are drawn out about the effect of the presence of the surfactant and of Au nanoparticles on the electrochemical properties of the electrode system

  18. Childhood bladder stones-an endemic disease of developing countries

    International Nuclear Information System (INIS)

    Lal, B.

    2015-01-01

    Bladder calculi are one of the commonest health problems in young children especially in rural and underprivileged areas. Methods: All children of bladder stones operated at District Headquarter Hospital Mithi from July 2009 to June 2012 were included in this cross-sectional study. Data was collected regarding age, sex, address (rural or urban), body weight, duration of breast feeding, weaning, detailed dietary history regarding milk type, volume, amount of water intake, recurrent diarrhoea, urinary tract infection (UTI), family history, and socioeconomic history. Urine analysis, complete blood count (CBC), renal function, ultra sound abdomen, X-ray kidney, ureter, and bladder (KUB) was done in all patients. All patients had cystolithotomy and were followed up till complete recovery. Results: A total of 113 children (97 males and 16 females) operated at District Headquarter Hospital Mithi Tharparker were included in study. All patients belonged to local desert areas of Tharparker. Age ranged from 18 months to 14 year (mean age 8.6 year). Most frequent symptom was difficulty in micturition in 76 (67.25%) patients, urinary retention in 18 (15.9%) and stone with pyuria and fever in 12 (10.6%) patients. Recurrent episodes of diarrhoea (more than 3 episodes per year) in 73(65%) patients, recurrent UTI in 51 (45.6%), family history of stone disease in 6 (5%) and associated rectal prolapse in 3(2.6%) patients. On x-ray KUB 111 (98%) patients had single stone in bladder, 2 (2%) had multiple stones and an associated renal and ureteric stone in 5 (4.5%). Mild anaemia (Hb 7-10 gm%) was seen in 35 (39.55%) patients, moderate anaemia (Hb 5-7 gm %) was seen in 21(24%) and severe anaemia (Hb less than 5 gm%) was seen in 14 (16%) patients. All patients had open cystolithotomy for removal of stones under general anaesthesia. Conclusion: Bladder stones are public health problem. Majority of affected patients were less than 5 years old. Low protein diet, dehydration, use of goat milk

  19. [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.

  20. Stargardt disease: towards developing a model to predict phenotype.

    Science.gov (United States)

    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.

  1. 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.

  2. Development of a fluidized bed agglomeration modeling methodology to include particle-level heterogeneities in ash chemistry and granular physics

    Science.gov (United States)

    Khadilkar, Aditi B.

    The utility of fluidized bed reactors for combustion and gasification can be enhanced if operational issues such as agglomeration are mitigated. The monetary and efficiency losses could be avoided through a mechanistic understanding of the agglomeration process and prediction of operational conditions that promote agglomeration. Pilot-scale experimentation prior to operation for each specific condition can be cumbersome and expensive. So the development of a mathematical model would aid predictions. With this motivation, the study comprised of the following model development stages- 1) development of an agglomeration modeling methodology based on binary particle collisions, 2) study of heterogeneities in ash chemical composition and gaseous atmosphere, 3) computation of a distribution of particle collision frequencies based on granular physics for a poly-disperse particle size distribution, 4) combining the ash chemistry and granular physics inputs to obtain agglomerate growth probabilities and 5) validation of the modeling methodology. The modeling methodology comprised of testing every binary particle collision in the system for sticking, based on the extent of dissipation of the particles' kinetic energy through viscous dissipation by slag-liquid (molten ash) covering the particles. In the modeling methodology developed in this study, thermodynamic equilibrium calculations are used to estimate the amount of slag-liquid in the system, and the changes in particle collision frequencies are accounted for by continuously tracking the number density of the various particle sizes. In this study, the heterogeneities in chemical composition of fuel ash were studied by separating the bulk fuel into particle classes that are rich in specific minerals. FactSage simulations were performed on two bituminous coals and an anthracite to understand the effect of particle-level heterogeneities on agglomeration. The mineral matter behavior of these constituent classes was studied

  3. 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.

  4. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis.

    Science.gov (United States)

    Moraros, John; Nwankwo, Chijioke; Patten, Scott B; Mousseau, Darrell D

    2017-03-01

    To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. © 2016 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  5. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta‐analysis

    Science.gov (United States)

    Moraros, John; Nwankwo, Chijioke; Patten, Scott B.

    2016-01-01

    1 Objective To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). 2 Method We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. 3 Results Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). 4 Conclusions Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention. PMID:28029715

  6. 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

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

    Science.gov (United States)

    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).

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. White Matter Volume Predicts Language Development in Congenital Heart Disease.

    Science.gov (United States)

    Rollins, Caitlin K; Asaro, Lisa A; Akhondi-Asl, Alireza; Kussman, Barry D; Rivkin, Michael J; Bellinger, David C; Warfield, Simon K; Wypij, David; Newburger, Jane W; Soul, Janet S

    2017-02-01

    To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II and the MacArthur-Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P Development-II scores but did correlate positively with MacArthur-Bates Communicative Development Inventory language development. Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. ClinicalTrials.gov: NCT00006183. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 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.

  12. 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...

  13. Pancreatic cyst development: insights from von Hippel-Lindau disease

    Directory of Open Access Journals (Sweden)

    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.

  14. Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals

    Science.gov (United States)

    Islami, Farhad; Nasseri-Moghaddam, Siavosh; Pourshams, Akram; Poustchi, Hossein; Semnani, Shahryar; Kamangar, Farin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Abnet, Christian C.; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    Background Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. Methods We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. Results Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). Conclusion GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere. PMID:24586635

  15. Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- a cross-sectional analysis of 50,000 individuals.

    Science.gov (United States)

    Islami, Farhad; Nasseri-Moghaddam, Siavosh; Pourshams, Akram; Poustchi, Hossein; Semnani, Shahryar; Kamangar, Farin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M; Pharoah, Paul D; Brennan, Paul; Abnet, Christian C; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75) and opium use (OR 1.70, 95% CI 1.55-1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.

  16. Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- a cross-sectional analysis of 50,000 individuals.

    Directory of Open Access Journals (Sweden)

    Farhad Islami

    Full Text Available Gastroesophageal reflux disease (GERD is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time.We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼ 50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn.Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02-1.75 and opium use (OR 1.70, 95% CI 1.55-1.87 were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76-0.99. After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined.GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.

  17. Validation of inverse seasonal peak mortality in medieval plagues, including the Black Death, in comparison to modern Yersinia pestis-variant diseases.

    Science.gov (United States)

    Welford, Mark R; Bossak, Brian H

    2009-12-22

    Recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval Black Death (and subsequent "plagues") and modern empirical Y. pestis plague data, most of which is derived from the Indian and Chinese plague outbreaks of A.D. 1900+/-15 years. Previous works have noted apparent differences in seasonal mortality peaks during Black Death outbreaks versus peaks of bubonic and pneumonic plagues attributed to Y. pestis infection, but have not provided spatiotemporal statistical support. Our objective here was to validate individual observations of this seasonal discrepancy in peak mortality between historical epidemics and modern empirical data. We compiled and aggregated multiple daily, weekly and monthly datasets of both Y. pestis plague epidemics and suspected Black Death epidemics to compare seasonal differences in mortality peaks at a monthly resolution. Statistical and time series analyses of the epidemic data indicate that a seasonal inversion in peak mortality does exist between known Y. pestis plague and suspected Black Death epidemics. We provide possible explanations for this seasonal inversion. These results add further evidence of inconsistency between historical plagues, including the Black Death, and our current understanding of Y. pestis-variant disease. We expect that the line of inquiry into the disputed cause of the greatest recorded epidemic will continue to intensify. Given the rapid pace of environmental change in the modern world, it is crucial that we understand past lethal outbreaks as fully as possible in order to prepare for future deadly pandemics.

  18. Validation of inverse seasonal peak mortality in medieval plagues, including the Black Death, in comparison to modern Yersinia pestis-variant diseases.

    Directory of Open Access Journals (Sweden)

    Mark R Welford

    Full Text Available BACKGROUND: Recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval Black Death (and subsequent "plagues" and modern empirical Y. pestis plague data, most of which is derived from the Indian and Chinese plague outbreaks of A.D. 1900+/-15 years. Previous works have noted apparent differences in seasonal mortality peaks during Black Death outbreaks versus peaks of bubonic and pneumonic plagues attributed to Y. pestis infection, but have not provided spatiotemporal statistical support. Our objective here was to validate individual observations of this seasonal discrepancy in peak mortality between historical epidemics and modern empirical data. METHODOLOGY/PRINCIPAL FINDINGS: We compiled and aggregated multiple daily, weekly and monthly datasets of both Y. pestis plague epidemics and suspected Black Death epidemics to compare seasonal differences in mortality peaks at a monthly resolution. Statistical and time series analyses of the epidemic data indicate that a seasonal inversion in peak mortality does exist between known Y. pestis plague and suspected Black Death epidemics. We provide possible explanations for this seasonal inversion. CONCLUSIONS/SIGNIFICANCE: These results add further evidence of inconsistency between historical plagues, including the Black Death, and our current understanding of Y. pestis-variant disease. We expect that the line of inquiry into the disputed cause of the greatest recorded epidemic will continue to intensify. Given the rapid pace of environmental change in the modern world, it is crucial that we understand past lethal outbreaks as fully as possible in order to prepare for future deadly pandemics.

  19. Risk of Lyme disease development after a tick bite

    Directory of Open Access Journals (Sweden)

    Mladenović Jovan

    2010-01-01

    Full Text Available Background/Aim. Despite numerous research of Lyme disease (LD, there are still many concerns about environmental of infectious agent of LD, as well as its prophylaxis, diagnosis and treatment. The aim of this work was to determine the risk of LD in relation to the way of removing ticks and duration of tick attachment. Methods. In the period from 2000 to 2007 a prospective study was conducted including persons with tick bite referred to the Institute of Epidemiology, Military Medical Academy, and followed for the occurrence of early Lyme disease up to six months after a tick bite. Epidemiological questionnaire was used to collect relevant information about the place and time of tick bites, the way of a removing tick, duration of tick attachment, remnants of a tick left in the skin (parts of the mouth device and the signs of clinical manifestations of LD. Duration of tick attachment was determined on the basis of size of engorged tick and epidemiological data. Removed ticks were determined by the key of Pomerancev. Professional removing of attached tick was considered to be removing of tick with mechanical means by healthcare personnel. Fisher's exact test, Chi squares test and calculation of the relative risk (RR were used for data analysis. Results. Of 3 126 patients with tick bite, clinical manifestations of LD were demonstrated in 19 (0.61%. In the group of subjects (n = 829 in which a tick was not removed professionally there were 17 (2.05% cases with LD, while in the group of respondents (n=2 297 in who a tick was removed professionally there were 2 (0.09% cases with LD after tick bite (RR, 23.55; p < 0.0001. The disease was most frequent in the group of respondents with incompletely and unprofessionally removed ticks (2.46%. In the groups of patients with unprofessionally but completely removed ticks LD occurred in 0.89%, while in the group of subjects with a tick removed by an expert, but incompletely in 0.78% cases. The disease occurred

  20. 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.

  1. How microbial community composition regulates coral disease development.

    Science.gov (United States)

    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.

  2. 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.

  3. Climate change and diarrhoeal disease: Perspectives for development policies

    DEFF Research Database (Denmark)

    Halsnæs, Kirsten; Føyn, Tullik Helene Ystanes

    2010-01-01

    This paper points to the key role of health in development programmes and illustrates through diarrhoeal diseases as a case example, how climate change can impose increasing risks, which particularly will hit young children and the poor. The increased incidence can both be expected to emerge from...... higher temperatures and from more extreme events in particularly flooding. The number of people affected is by WHO projected to be approximately 700,000 dead and 22 mill disability adjusted life years in 2030 without climate change, so it is very important to initiate climate change adaptation measures...... that can help to reduce these risks. An attempt to start such a process i.e. has been done by the Danish Overseas Development Assistance Programme, Danida, which has conducted a climate screening of programme activities in Bangladesh. The paper presents a number of conclusions from this climate screening...

  4. Excessive daytime sleepiness and subsequent development of Parkinson disease.

    Science.gov (United States)

    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.

  5. Growth and development of children with congenital heart disease.

    Science.gov (United States)

    Chen, Chi-Wen; Li, Chung-Yi; Wang, Jou-Kou

    2004-08-01

    Children with congenital heart disease (CHD) commonly experience delayed growth. Because growth and development are closely related, both should be considered when a child's progress is examined. This paper reports a study to evaluate and compare the growth and development of preschool children with CHD to those of normal preschool children. The heights and weights of 42 preschool children with CHD and 116 normal preschool children were compared with standard growth curves. Differences in development of personal and social skills, fine motor skills and adaptability, language, and gross motor skills were evaluated. Developmental skills were assessed using the Denver Developmental Screening Test II. A significant difference was found in both body height (P motor sections (P development. Learning about the growth and developmental differences between children with CHD and normal children may help parents of the former to detect problems associated with delayed growth and development earlier. These children and their families should have the opportunity to participate in a long-term, follow-up programme that provides information and encourages developmental progress. The results could serve as a reference for those in both clinical and community workers who provide nursing care to children with CHD.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Report of two patients with Paget′s disease - one with typical clinical and radiological manifestations including cardiac involvement and the other subclinical but with radiological changes

    Directory of Open Access Journals (Sweden)

    B Sivapatha Sundharam

    2006-01-01

    Full Text Available Osteitis deformans or Paget′s disease of bone, fondly referred to as the ′collage of matrix madness′, is a unique skeletal disease characterized by furious osteoclastic bone resorption followed by a period of hectic bone formation, resulting in again in the bone mass wherein the newly formed bone is disordered and architecturally unsound. A disease of obscure etiology, it usually manifests as progressive enlargement of one or multiple bones of the skeleton. Herewith we present a typical example of a polyostotic form of Paget′s disease with classical clinical features and radiologic changes in one patient and a subclinical form of Paget′s disease with marked radiological changes in the other patient.

  8. 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.

  9. Development of the Paris definition of early Crohn's disease for disease-modification trials: results of an international expert opinion process.

    Science.gov (United States)

    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

    2012-12-01

    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 agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD.

  10. The effects of infographics and several quantitative versus qualitative formats for cardiovascular disease risk, including heart age, on people's risk understanding.

    NARCIS (Netherlands)

    Damman, Olga C; Vonk, Suzanne I; Van den Haak, Maaike J; van Hooijdonk, Charlotte M J; Timmermans, Danielle R M

    2018-01-01

    To study how comprehension of cardiovascular disease (CVD) risk is influenced by: (1) infographics about qualitative risk information, with/without risk numbers; (2) which qualitative risk dimension is emphasized; (3) heart age vs. traditional risk format.

  11. Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves' Disease Study

    DEFF Research Database (Denmark)

    Laurberg, Peter; Nygaard, Birte; Andersen, Stig

    2014-01-01

    Background. Graves' disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel. Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves' disease (hyperthyroidism...... and Sustenance in Graves' Disease (RISG)." Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy. Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three...... manifestations of Graves' disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25-30% had...

  12. Models of simulation and prediction of the behavior of dengue in four Colombian cities, including climate like modulating variable of the disease

    International Nuclear Information System (INIS)

    Garcia Giraldo, Jairo A; Boshell, Jose Francisco

    2004-01-01

    ARIMA-type models are proposed to simulate the behavior of dengue and to make apparent the relations with the climatic variability in four localities of Colombia. The climatic variable was introduced into the models as an index that modulates the behavior of the disease. It was obtained by means of a multivariate analysis of principal components. The investigation was carried out with information corresponding to the epidemiological weeks from January 1997 to December 2000, for both the number of disease cases and the data corresponding to the meteorological variables. The study shows that the variations of the climate between the previous 9 to 14 weeks have influence on the appearance of new cases of dengue. In particular, the precipitation in these weeks was seen to be greater when in later periods the disease presented epidemic characteristics than the precipitation in those weeks preceded the disease within endemic limits

  13. Sirtuins: Novel targets for metabolic disease in drug development

    International Nuclear Information System (INIS)

    Jiang Weijian

    2008-01-01

    Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD + -dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes

  14. 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.

  15. 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.

  16. Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves’ Disease Study

    Directory of Open Access Journals (Sweden)

    Peter Laurberg

    2014-01-01

    Full Text Available Background. Graves’ disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel. Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves’ disease (hyperthyroidism, goiter, and presence of orbitopathy at the time of diagnosis of hyperthyroidism. Methods. We describe a cohort of 208 patients with newly diagnosed Graves’ hyperthyroidism. Patients were enrolled in a multiphase study of antithyroid drug therapy of Graves’ hyperthyroidism, entitled “Remission Induction and Sustenance in Graves’ Disease (RISG.” Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy. Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three manifestations of Graves’ disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25–30% had orbitopathy. Conclusions. A positive but rather weak correlation was found between TSH-receptor antibodies in serum and the major clinical manifestation of Graves’ disease. Only half of the patients had an enlarged thyroid gland at the time of diagnosis.

  17. 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...

  18. Dental Age Estimation (DAE): Data management for tooth development stages including the third molar. Appropriate censoring of Stage H, the final stage of tooth development.

    Science.gov (United States)

    Roberts, Graham J; McDonald, Fraser; Andiappan, Manoharan; Lucas, Victoria S

    2015-11-01

    The final stage of dental development of third molars is usually helpful to indicate whether or not a subject is aged over 18 years. A complexity is that the final stage of development is unlimited in its upper border. Investigators usually select an inappropriate upper age limit or censor point for this tooth development stage. The literature was searched for appropriate data sets for dental age estimation and those that provided the count (n), the mean (x¯), and the standard deviation (sd) for each of the tooth development stages. The Demirjian G and Demirjian H were used for this study. Upper and lower limits of the Stage G and Stage H data were calculated limiting the data to plus or minus three standard deviations from the mean. The upper border of Stage H was limited by appropriate censoring at the maximum value for Stage G. The maximum age at attainment from published data, for Stage H, ranged from 22.60 years to 34.50 years. These data were explored to demonstrate how censoring provides an estimate for the correct maximum age for the final stage of Stage H as 21.64 years for UK Caucasians. This study shows that confining the data array of individual tooth developments stages to ± 3sd provides a reliable and logical way of censoring the data for tooth development stages with a Normal distribution of data. For Stage H this is inappropriate as it is unbounded in its upper limit. The use of a censored data array for Stage H using Percentile values is appropriate. This increases the reliability of using third molar Stage H alone to determine whether or not an individual is over 18 years old. For Stage H, individual ancestral groups should be censored using the same technique. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  19. Transcriptional network systems in cartilage development and disease.

    Science.gov (United States)

    Nishimura, Riko; Hata, Kenji; Nakamura, Eriko; Murakami, Tomohiko; Takahata, Yoshifumi

    2018-04-01

    Transcription factors play important roles in the regulation of cartilage development by controlling the expression of chondrogenic genes. Genetic studies have revealed that Sox9/Sox5/Sox6, Runx2/Runx3 and Osterix in particular are essential for the sequential steps of cartilage development. Importantly, these transcription factors form network systems that are also required for appropriate cartilage development. Molecular cloning approaches have largely contributed to the identification of several transcriptional partners for Sox9 and Runx2 during cartilage development. Although the importance of a negative-feedback loop between Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) in chondrocyte hypertrophy has been well established, recent studies indicate that several transcription factors interact with the Ihh-PTHrP loop and demonstrated that Ihh has multiple functions in the regulation of cartilage development. The most common cartilage disorder, osteoarthritis, has been reported to result from the pathological action of several transcription factors, including Runx2, C/EBPβ and HIF-2α. On the other hand, NFAT family members appear to play roles in the protection of cartilage from osteoarthritis. It is also becoming important to understand the homeostasis and regulation of articular chondrocytes, because they have different cellular and molecular features from chondrocytes of the growth plate. This review summarizes the regulation and roles of transcriptional network systems in cartilage development and their pathological roles in osteoarthritis.

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

    Science.gov (United States)

    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.

  1. Reaching a consensus. "Global issues, including environmental ones, are things to be solved with the cooperation of developed and developing countries".

    Science.gov (United States)

    Hiraiwa, G

    1998-01-01

    This article is an excerpt of a speech given by the Honorary Chairman of the Japan Federation of Economic Organizations at the Common Agenda Roundtable meeting in February 1996. The Common Agenda is a bilateral cooperative effort between the US and Japan, which was established in July 1993, to address common concerns through a public-private partnership. The roundtable membership includes about 50 persons who have a range of expertise and professions including scholars, journalists, civil society organizations, and businesses. There have been about 10 Roundtable meetings over the past 2 years. Each meeting includes a report by the deputy minister of foreign affairs on progress made under the Common Agenda. Members exchange views in lively debate and meet with senior government officials. The US-Japan Partnerships on Environmental Awareness and Education were held in April 1997, in Tokyo. The February 1998 meeting with 60 participants was held in Washington, DC, on the Global Context of Civil Society. The workshops focused on the ways that cooperation with civil society organizations, businesses, and governments can be reinforced in the areas of population, health, and the environment. The workshop resulted in effective proposals. This speaker urges that the US and Japan reach as many agreements as possible; that some of the agreements result quickly in Common Agenda projects; and that each country will produce a private sector organization to support the Common Agenda. This effort is moving in new directions and offers a consensus of concerns for the environment.

  2. Atopic diseases and the risk of developing ulcerative colitis

    NARCIS (Netherlands)

    Azim, Samman; Hak, Eelko; Bos, Jens H.J.; Schuiling-Veninga, Catharina C.M.

    2016-01-01

    Background: Although auto-immune diseases and atopic diseases seem to be caused by different malfunctions in the immunological pathways, there is an increasing body of evidence for cross regulation between the two pathways. Research showed that patients suffering from atopic diseases are at greater

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

    Science.gov (United States)

    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.

  4. Factors Promoting Development of Fibrosis in Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Gerhard Rogler

    2017-07-01

    Full Text Available The concepts on the pathophysiology of intestinal fibrosis in Crohn’s disease (CD have changed in recent years. Some years ago fibrosis was regarded to be a consequence of long-standing inflammation with subsequent destruction of the gut wall matrix followed by scar formation and collagen deposition. Fibrosis in CD patients appeared to be an irreversible process that could hardly be influenced. Therefore, the main target in CD therapy was to control inflammation to avoid fibrosis development. Many of these assumptions seem to be only partially true. Inflammation may be a necessary prerequisite for the initiation of fibrosis. However, when the pathophysiologic processes that lead to fibrosis in CD patients have been initiated fibrosis development may be independent of inflammation and may continue even when inflammation is under good medical control. Fibrosis in CD also may be reversible. After strictureplasty local collagen deposits decrease or even disappear. With new animal models for intestinal fibrosis on the horizon, we need to spend more efforts on understanding the factors influencing fibrosis in CD patients to finally find specific therapies. In this context, it will be as important to find markers and quantitative imaging tools to have reliable endpoints for clinical trials in fibrosing CD.

  5. The hippo pathway in heart development, regeneration, and diseases.

    Science.gov (United States)

    Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

    2015-04-10

    The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. © 2015 American Heart Association, Inc.

  6. Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

    Science.gov (United States)

    McNellis, Emily M.; Mabry, Sherry M.; Taboada, Eugenio; Ekekezie, Ikechukwu I.

    2014-01-01

    Pulmonary lymphatic development in chronic lung disease (CLD) has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD. PMID:24527433

  7. ANALYSIS OF EFFICIENCY OF R&D ACTIVITIES AMONG COUNTRIES WITH DEVELOPED AND DEVELOPING ECONOMIES INCLUDING REPUBLIC OF BELARUS WITH STOCHASTIC FRONTIER APPROACH

    Directory of Open Access Journals (Sweden)

    I. V. Zhukovski

    2016-01-01

    Full Text Available This study evaluates efficiency of R&D activities based on the stochastic frontier analysis across 69 counties with developed and developing economies. Gross domestic expenditures on R&D in purchasing power parity, researchers per million inhabitants, technicians per million inhabitants are treated as inputs while patents granted to residents and scientific and technical journal articles are considered as outputs. According to the analysis results Costa Rica, Israel and Singapore are the most efficient in terms of transformation of available resources into the R&D results. What concerns Belarus it is necessary that additional investments in R&D go together with increasing efficiency of available resources’ usage. 

  8. 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.

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

    Science.gov (United States)

    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.

  10. Cesic: optomechanical technology last development results and new HBCesic highly light weighted space mirror development including corrective function 7th international conference on space optics, october 2008

    Science.gov (United States)

    Devilliers, Christophe; Kroedel, Mathias

    2017-11-01

    Thales-Alenia-Space and ECM has developed a new SiC ceramic composite to produce very lightweight space mirrors and structure. Cesicmade by ECM has been selected for its own intrinsic properties ( high specific Young modulus, high conductivity , low CTE, high strength for a ceramics) and its large manufacturing capabilities. Recently a full monolithic space instrument for earth observation, with a monolithic Cesicstructure and with Cesicmirrors has been designed, manufactured and space qualified and is now ready for launch. The Cesictelescope assembly has been tested under shock environment, vibration loads, and full qualification thermal environment. All these qualification tests were done directly on the flight model. Extensive development has been also performed to design, size, manufacture and test a very light weight reflector shell made as a single part. This 1 meter reflective shell has an areal density of less than 10 Kg/m2 has been manufactured with its surface grounded to the bi parabolic shape. Such challenging areal density has requested a very thin skin associated with a ribs thickness of less than 2mm. In order to demonstrate the high stability and strength of Cesicthe reflector has been tested successfully under very aggressive environment up to 350°C and also an acoustic test with flight representative levels was successfully performed. To produce future very lightweight space mirrors ECM develop with the support of Thales-Alenia-Space since some years an improved version of Cesicceramic, called HB-Cesic©. HB-Cesicmade by ECM is developed for its higher intrinsic properties, Young modulus, strength and especially its direct polishing capabilities down to 3 nm micro-roughness. One of the major targets for this development was also to overcome size limitations of the C/C raw material of currently around 1x1 m to produce mirror up to 3,5 m diameter out of a single C/C raw material block. Under ESA study a 600 mm mirror with a surface density of only

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

    Science.gov (United States)

    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.

  12. 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.

  13. Tetranectin Knockout Mice Develop Features of Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Er-song Wang

    2014-07-01

    Full Text Available Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD. Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN gene (TN-/- and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Stargardt disease: towards developing a model to predict phenotype

    OpenAIRE

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

    2013-01-01

    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...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  20. 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.)

  1. Cardiovascular disease in patients with end-stage renal disease on hemodialysis in a developing country

    Directory of Open Access Journals (Sweden)

    Leila S. V. Silva

    2012-01-01

    Full Text Available Cardiovascular disease is the main cause of death among patients with end-stage renal disease (ESRD. The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on hemodialysis (HD in Brazil. Their mean age was 47 ± 39 years. The main risk factors for cardiovascular diseases were arterial hypertension (89.4%, dyslipidemia (78.3%, low high-density lipoprotein levels (84.2% and low physical activity (64.1%. Family history of coronary insufficiency and high low-density lipoprotein levels were significantly associated with coronary artery disease (P = 0.005 and P = 0.029, respectively. Sedentary life style, diabetes mellitus, secondary hyperparathyroidism and hyperglycemia also showed a significant association with the underlying vascular disease (P = 0.017, P = 0.039, P = 0.037 and P = 0.030, respectively. Hypercalcemia, hypertension and black race were factors significantly associated with left ventricular systolic dysfunction (P = 0.01, P = 0.0013 and P = 0.024, respectively. Our study shows that the most prevalent cardiovascular diseases in patients with ESRD were left ventricular hypertrophy, atherosclerotic disease, valvular disease and coronary artery disease. Hypertension and dyslipidemia were the common risk factors associated with cardiovascular diseases. The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on HD in a single center in Brazil.

  2. Bifurcation in epigenetics: Implications in development, proliferation, and diseases

    Science.gov (United States)

    Jost, Daniel

    2014-01-01

    Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of biochemical marks on chromatin. Here, we develop a stochastic model that describes the dynamics of epigenetic marks along a given DNA region. Through mathematical analysis, we show the emergence of bistable and persistent epigenetic states from the cooperative recruitment of modifying enzymes. We also find that the dynamical system exhibits a critical point and displays, in the presence of asymmetries in recruitment, a bifurcation diagram with hysteresis. These results have deep implications for our understanding of epigenetic regulation. In particular, our study allows one to reconcile within the same formalism the robust maintenance of epigenetic identity observed in differentiated cells, the epigenetic plasticity of pluripotent cells during differentiation, and the effects of epigenetic misregulation in diseases. Moreover, it suggests a possible mechanism for developmental transitions where the system is shifted close to the critical point to benefit from high susceptibility to developmental cues.

  3. Functional Architecture of the Retina: Development and Disease

    Science.gov (United States)

    Hoon, Mrinalini; Okawa, Haruhisa; Santina, Luca Della; Wong, Rachel O.L.

    2014-01-01

    Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. PMID:24984227

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

    Directory of Open Access Journals (Sweden)

    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

  5. Development of RI protein chip system for measurement of ADMA as risk factor of liver disease, cardiovascular disease and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Park, Gil Hong; An, Sin Ae; Choi, Hyun Mi; Cheong, Kyung Ah; Chang, Yeon Soo [Korea University, Seoul (Korea, Republic of)

    2010-05-15

    ADMA (asymmetric dimethylarginine) is an endogenous competitive NOS (nitric oxide synthase) inhibitor. Elevation of ADMA level in body fluid is related to various diseases including diabetes mellitus, atherosclerosis, hypercholesterolemia, chronic heart failure, and hypertension. Our goal was to elucidate the role for ADMA and protein arginine methylation in the pathogenesis of diabetes and develop RI protein chip system for easy determination of ADMA levels in blood or tissues. As a result, ADMA regulated by protein arginine methylation, DDAH1, and NOS was demonstrated to play some role in the pathogenesis of diabetes mellitus, and arginine methylation of some proteins indicated their possible involvement in the change in ADMA levels. The concept of the RI protein chip system was devised such that firstly, ADMA was acylated by radio-labelled succinic acid, and followed by binding of the complex to anti-acyl ADMA-specific antibody coated on chip. Acylation condition of ADMA with radio-labelled succinic acid was established

  6. Development of RI protein chip system for measurement of ADMA as risk factor of liver disease, cardiovascular disease and diabetes

    International Nuclear Information System (INIS)

    Park, Gil Hong; An, Sin Ae; Choi, Hyun Mi; Cheong, Kyung Ah; Chang, Yeon Soo

    2010-05-01

    ADMA (asymmetric dimethylarginine) is an endogenous competitive NOS (nitric oxide synthase) inhibitor. Elevation of ADMA level in body fluid is related to various diseases including diabetes mellitus, atherosclerosis, hypercholesterolemia, chronic heart failure, and hypertension. Our goal was to elucidate the role for ADMA and protein arginine methylation in the pathogenesis of diabetes and develop RI protein chip system for easy determination of ADMA levels in blood or tissues. As a result, ADMA regulated by protein arginine methylation, DDAH1, and NOS was demonstrated to play some role in the pathogenesis of diabetes mellitus, and arginine methylation of some proteins indicated their possible involvement in the change in ADMA levels. The concept of the RI protein chip system was devised such that firstly, ADMA was acylated by radio-labelled succinic acid, and followed by binding of the complex to anti-acyl ADMA-specific antibody coated on chip. Acylation condition of ADMA with radio-labelled succinic acid was established

  7. Development of a molecular test of Paget's disease of bone.

    Science.gov (United States)

    Guay-Bélanger, Sabrina; Simonyan, David; Bureau, Alexandre; Gagnon, Edith; Albert, Caroline; Morissette, Jean; Siris, Ethel S; Orcel, Philippe; Brown, Jacques P; Michou, Laëtitia

    2016-03-01

    Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance with incomplete penetrance. To date, only SQSTM1 gene mutations have been linked to the disease. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in patient non-carriers of SQSTM1 mutations, but they have minor size effects. The current clinical practice guidelines still recommend to measure total serum alkaline phosphatase (sALP) for PDB screening. However, genetic or bone biomarkers alone may lack sensitivity to detect PDB. Thus, the objective of this study was to develop a molecular test of PDB, combining genetic and bone biomarkers, in order to detect PDB, which is frequently asymptomatic. We genotyped 35 SNPs previously associated with PDB in 305 patients, and 292 healthy controls. In addition, serum levels of 14 bone biomarkers were assayed in 51 patients and 151 healthy controls. Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations. First, a combination of five genetic markers gave rise to the highest area under the ROC curve (AUC) with 95% confidence interval [95% CI] of 0.731 [0.688; 0.773], which allowed us to detect 81.5% of patients with PDB. Second, a combination of two bone biomarkers had an AUC of 0.822 [0.726; 0.918], and was present in 81.5% of patients with PDB. Then, the combination of the five genetic markers and the two bone biomarkers increased the AUC up to 0.892 [0.833; 0.951], and detected 88.5% of patients with PDB. These results suggested that an algorithm integrating first a screen for SQSTM1 gene mutations, followed by either a genetic markers combination or a combined genetic and biochemical markers test in patients non-carrier of any SQSTM1 mutation, may detect the PDB

  8. 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

  9. 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.

  10. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. 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

  14. Celiac disease : from basic insight to therapy development

    NARCIS (Netherlands)

    Stępniak, Dariusz Tomasz

    2006-01-01

    Celiac disease (CD) is a common disorder of the small intestine caused by intolerance to gluten, proteins found in wheat and related cereals. In this study two major questions were addressed: i) which specific properties of gluten contribute to its disease-inducing characteristics ii) how can gluten

  15. Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

    Science.gov (United States)

    Steinitz, Michael

    2008-05-01

    Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

  16. Recent developments in the treatment of inflammatory bowel disease

    NARCIS (Netherlands)

    Rietdijk, Svend T.; D'Haens, Geert R.

    2013-01-01

    Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases that have been treated with corticosteroids, 5-aminosalicates and thiopurines, but therapeutic options have been broadened with the arrival of anti-tumor necrosis factor antibodies. In this article we reviewed the current

  17. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  18. The effects of infographics and several quantitative versus qualitative formats for cardiovascular disease risk, including heart age, on people's risk understanding.

    Science.gov (United States)

    Damman, Olga C; Vonk, Suzanne I; van den Haak, Maaike J; van Hooijdonk, Charlotte M J; Timmermans, Danielle R M

    2018-03-11

    To study how comprehension of cardiovascular disease (CVD) risk is influenced by: (1) infographics about qualitative risk information, with/without risk numbers; (2) which qualitative risk dimension is emphasized; (3) heart age vs. traditional risk format. For aim 1, a 2 (infographics versus text) x 2 (risk number versus no risk number) between-subjects design was used. For aim 2, three pieces of information were tested within-subjects. Aim 3 used a simple comparison group. Participants (45-65 yrs old) were recruited through an online access panel; low educated people were oversampled. They received hypothetical risk information (20%/61yrs). Primary outcomes: recall, risk appraisals, subjective/objective risk comprehension. behavioral intentions, information evaluations. Infographics of qualitative risk dimensions negatively affected recall, subjective risk comprehension and information evaluations. No effect of type of risk dimension was found on risk perception. Heart age influenced recall, comprehension, evaluations and affective risk appraisals. Infographics of hypothetical CVD risk information had detrimental effects on measures related to risk perception/comprehension, but effects were mainly seen in undereducated participants. Heart age influenced perceptions/comprehension of hypothetical risk in a way that seemed to support understanding. Heart age seems a fruitful risk communication approach in disease risk calculators. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. 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.

  20. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Building a roadmap for developing combination therapies for Alzheimer's disease.

    Science.gov (United States)

    Perry, Daniel; Sperling, Reisa; Katz, Russell; Berry, Donald; Dilts, David; Hanna, Debra; Salloway, Stephen; Trojanowski, John Q; Bountra, Chas; Krams, Michael; Luthman, Johan; Potkin, Steven; Gribkoff, Val; Temple, Robert; Wang, Yaning; Carrillo, Maria C; Stephenson, Diane; Snyder, Heather; Liu, Enchi; Ware, Tony; McKew, John; Fields, F Owen; Bain, Lisa J; Bens, Cynthia

    2015-03-01

    Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.

  5. 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.

  6. Soil microbiome characteristics and soilborne disease development associated with long-term potato cropping system practices

    Science.gov (United States)

    Potato cropping system practices substantially affect soil microbial communities and the development of soilborne diseases. Cropping systems incorporating soil health management practices, such as longer rotations, disease-suppressive crops, reduced tillage, and/or organic amendments can potentially...

  7. 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

  8. 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 ...

  9. Development of an Advanced Injectable Therapy for Ischemic Vascular Disease

    Science.gov (United States)

    2017-10-01

    14. ABSTRACT Cardiovascular diseases are the most common causes of death for Americans and it is estimated that 20% of the population over 65 years of...therapies due to overall poor health or diffuse vascular disease. A promising approach to this problem is to induce the growth of new vessels using...angiogenic therapy with growth factors to restore flow to the ischemic tissues. Unfortunately, many clinical trials using growth factors for treating

  10. The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx.

    Science.gov (United States)

    Marsh, R L; Kaestli, M; Chang, A B; Binks, M J; Pope, C E; Hoffman, L R; Smith-Vaughan, H C

    2016-07-07

    Invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. This poses substantial challenges to longitudinal study of paediatric airway microbiota. Non-invasive upper airway sampling is an alternative method for monitoring airway microbiota; however, there are limited data describing the relationship of such results with lung microbiota in young children. In this study, we compared the upper and lower airway microbiota in young children to determine whether non-invasive upper airway sampling procedures provide a reliable measure of either lung microbiota or clinically defined differences. The microbiota in oropharyngeal (OP) swabs, nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) from 78 children (median age 2.2 years) with and without lung disease were characterised using 16S rRNA gene sequencing. Permutational multivariate analysis of variance (PERMANOVA) detected significant differences between the microbiota in BAL and those in both OP swabs (p = 0.0001, Pseudo-F = 12.2, df = 1) and NP swabs (p = 0.0001; Pseudo-F = 21.9, df = 1) with the NP and BAL microbiota more different than the OP and BAL, as indicated by a higher Pseudo-F value. The microbiota in combined OP and NP data (upper airways) provided a more comprehensive representation of BAL microbiota, but significant differences between the upper airway and BAL microbiota remained, albeit with a considerably smaller Pseudo-F (PERMANOVA p = 0.0001; Pseudo-F = 4.9, df = 1). Despite this overall difference, paired BAL and upper airway (OP and NP) microbiota were >50 % similar among 69 % of children. Furthermore, canonical analysis of principal coordinates (CAP analysis) detected significant differences between the microbiota from clinically defined groups when analysing either BAL (eigenvalues >0.8; misclassification rate 26.5 %) or the combined OP and NP data (eigenvalues >0

  11. Research in Biological and Medical Sciences, Including Biochemistry, Communicable Disease and Immunology, Internal Medicine, Nuclear Medicine, Physiology, Psychiatry, Surgery and Veterinary Medicine. Volume 2

    Science.gov (United States)

    1975-07-01

    during the past fiscal year include 45 ovario- hysterectomles, one caesarean section, one fracture repair, one patent ductus arteriosus repair, one...Following closure of the thoracotomy, SOD was down by 60% and VQJ was> 80% of control levels. SOD and VQO did not relate to each other in a parallel...tions. Two patents were applied for, one for the Electronic Debubbler Circuit and one for the Improved Flow Cell. A paper on this latest

  12. 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.

  13. Co-operation of the CMEA member countries in the development of different reactor types, including certain aspects of their nuclear fuel cycle

    International Nuclear Information System (INIS)

    Panasenkov, A.; Barbur, I.; Barchenkov, A.; Molnar, L.; Tolpygo, V.; Khake, V.; Shcherbinin, B.

    1977-01-01

    The report gives an account of the problems of the projected development of atomic power and evaluates its role in the fuel and power complex and long-range development of interconnected power systems of the CMEA member countries. The report emphasizes the importance of scientific and technical co-operation in the creation of thermal and fast-neutron power reactors with 1000-1500MW(e) units, and in the elaboration of nuclear plants for heating services. The positive experience of the international scientific and research group of scientists of the CMEA member countries carrying out reactor-physics studies on critical assemblies is mentioned. The report contains basic conclusions from the forecasts for nuclear power in the CMEA member countries up to 1990, including forecasting methodology; the role of nuclear power plants in saving natural and enriched uranium for a projected period; and the impact of nuclear power development rates on its structure (thermal and fast reactor ratio). It lists the impacts of scientific and technical co-operation of the CMEA member countries on the fuel cycle, including the transport of spent nuclear fuel, its recovery, reprocessing and radioactive waste disposal. Particular effects of co-operation of the CMEA member countries on the radiation safety of nuclear power plants and environmental protection are analysed. The report notes the role of the international economic associations Interatomenergo and Interatominstrument in the accelerated development of nuclear power. (author)

  14. 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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease.

    Science.gov (United States)

    Jacobsson, Susanne; Hedberg, Sara Thulin; Mölling, Paula; Unemo, Magnus; Comanducci, Maurizio; Rappuoli, Rino; Olcén, Per

    2009-03-04

    During the recent years, projects are in progress for designing broad-range non-capsular-based meningococcal vaccines, covering also serogroup B isolates. We have examined three genes encoding antigens (NadA, GNA1030 and GNA2091) included in a novel vaccine, i.e. the 5 Component Vaccine against Meningococcus B (5CVMB), in terms of gene prevalence and sequence variations. These data were combined with the results from a similar study, examining the two additional antigens included in the 5CVMB (fHbp and GNA2132). nadA and fHbp v. 1 were present in 38% (n=36), respectively 71% (n=67) of the isolates, whereas gna2132, gna1030 and gna2091 were present in all the Neisseria meningitidis isolates tested (n=95). The level of amino acid conservation was relatively high in GNA1030 (93%), GNA2091 (92%), and within the main variants of NadA and fHbp. GNA2132 (54% of the amino acids conserved) appeared to be the most diversified antigen. Consequently, the theoretical coverage of the 5CVMB antigens and the feasibility to use these in a broad-range meningococcal vaccine is appealing.

  18. 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.

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

    Science.gov (United States)

    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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Co-operation of the CMEA member countries in the developing power reactors of various types, including some aspects of their nuclear fuel cycles

    International Nuclear Information System (INIS)

    Barbur, I.; Barchenkov, A.; Molnar, L; Panasenkov, A.; Tolpygo, V.; Hake, V.; Shcherbinin, B.

    1977-01-01

    The report gives an account of the problems of projected development of atomic power and evaluates its role in the fuel and power complex and long-range development of interconnected power systems of the CMEA member countries. The report emphasizes the importance of scientific and technical co-operation in the creation of power reactors on thermal and fast neutrons with 1000-1500 MW unit electric capacity as well as in the elaboration of nuclear plants for heating services. It notes the positive experience of the International scientific and research group of scientists of the CMEA member countries carrying out reactor-physical studies on the critical assembly and its contribution to the elaboration of power reactors. The report contains basic conclusions from the development forecast for nuclear power of the CMEA member countries up to 1990 including forecasting methodology; role of nuclear power plants in saving natural and enriched uranium for a projected period; impact of nuclear power development rates on its structure (thermal and fast reactor ratio); relation between the beginning of mass commissioning of nuclear power plants with fast reactors and the integral demand for nuclear fuel; scale of required capacities of fuel cycle services; time dependence of fuel cycle on nuclear fuel requirements. It examines the problems and lists the results of scientific and technical co-operation of the CMEA member countries in the field of fuel cycle, including the transport of spent nuclear fuel, its recovery, reprocessing and radioactive waste disposal. Particular questions of co-operation of the CMEA member countries to secure radiation safety of nuclear power plants and environmental protection are analyzed. The report notes the role of international economic associations - ''Interatomenergo'' and ''Interatominstrument'' - in the accelerated development of nuclear power on the basis of cooperation and specialization in the manufacture of equipment for nuclear power

  3. Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Pedersen, C; Thomsen, C; Arlien-Søborg, P

    1991-01-01

    dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS...... dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late...

  4. Fish Vaccine Development and Use to Prevent Streptococcal Diseases

    Science.gov (United States)

    An important pathogen of tilapia, hybrid striped bass and trout raised in intensive aquaculture is Streptococcus sp., a cause of severe economic losses in the fish farming industry. Infected fish experience severe to moderate mortality due to Streptococcus iniae and/or S. agalactiae. The diseased ...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. Multimodal interventions including nutrition in the prevention and management of disease-related malnutrition in adults: a systematic review of randomised control trials.

    Science.gov (United States)

    Thorne, Frances; Baldwin, Christine

    2014-06-01

    There has been a move to improve nutritional status in malnourished patients through the use of multimodal interventions (MI). There are currently no systematic reviews that have examined their effectiveness. This analysis aimed to examine the effects on nutritional, clinical, functional and patient-centred outcomes. A systematic review and meta-analysis using Cochrane methodology. 15 studies were included in the analysis, 13 comparing MI with usual care and 2 comparing MI with a nutrition intervention alone. Quality of studies varied and studies reported few relevant outcomes. Only 3 outcomes were compatible with meta-analysis; weight, mortality and length of stay (LOS). No statistically significant differences between groups were found. Narrative review was inconclusive. There was no evidence of benefit in the intervention groups in relation to body composition, functional status or quality of life (QoL). Intervention groups appeared to show a trend towards increased energy and protein intake however data was provided by only 2 studies (301 participants). No conclusive evidence of benefit for MI on any of the reviewed outcomes was found. Well designed, high quality trials addressing the impact of MI on relevant nutritional, functional and clinical outcomes are required. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

    Science.gov (United States)

    Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

    2014-04-16

    The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.

  9. Treatment approach, delivery, and follow-up evaluation for cardiac rhythm disease management patients receiving radiation therapy: Retrospective physician surveys including chart reviews at numerous centers

    Energy Technology Data Exchange (ETDEWEB)

    Gossman, Michael S., E-mail: MGossman@TSRCC.com [Regulation Directive Medical Physics, Russell, KY (United States); Wilkinson, Jeffrey D. [Medtronic, Inc., Mounds View, MN (United States); Mallick, Avishek [Department of Mathematics, Marshall University, Huntington, WV (United States)

    2014-01-01

    In a 2-part study, we first examined the results of 71 surveyed physicians who provided responses on how they address the management of patients who maintained either a pacemaker or a defibrillator during radiation treatment. Second, a case review study is presented involving 112 medical records reviewed at 18 institutions to determine whether there was a change in the radiation prescription for the treatment of the target cancer, the method of radiation delivery, or the method of radiation image acquisition. Statistics are provided to illustrate the level of administrative policy; the level of communication between radiation oncologists and heart specialists; American Joint Committee on Cancer (AJCC) staging and classification; National Comprehensive Cancer Network (NCCN) guidelines; tumor site; patient's sex; patient's age; device type; manufacturer; live monitoring; and the reported decisions for planning, delivery, and imaging. This survey revealed that 37% of patient treatments were considered for some sort of change in this regard, whereas 59% of patients were treated without regard to these alternatives when available. Only 3% of all patients were identified with an observable change in the functionality of the device or patient status in comparison with 96% of patients with normal behavior and operating devices. Documented changes in the patient's medical record included 1 device exhibiting failure at 0.3-Gy dose, 1 device exhibiting increased sensor rate during dose delivery, 1 patient having an irregular heartbeat leading to device reprogramming, and 1 patient complained of twinging in the chest wall that resulted in a respiratory arrest. Although policies and procedures should directly involve the qualified medical physicist for technical supervision, their sufficient involvement was typically not requested by most respondents. No treatment options were denied to any patient based on AJCC staging, classification, or NCCN practice standards.

  10. 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.

  11. 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...

  12. New developments in foot-and-mouth disease diagnosis

    International Nuclear Information System (INIS)

    Kitching, R.P.; MacKay, D.K.J.

    1998-01-01

    A variety of newer diagnostic procedures based around the use of molecular technologies are now being undertaken to further characterise the foot-and-mouth disease (FMD) virus enabling a deeper understanding to be gained of the pathogenesis and epidemiology of this disease. Such approaches have categorically identified the carrier state and highlighted the importance of carrier animals in control programmes. Use of the polymerase chain reaction provides even further insight into the carrier animal but interpretation of data has to be undertaken with caution. The role of non-structural proteins can provide further insight into an animals response to both vaccination and natural infection and could provide a basis for separation of the carrier state. Finally the pivotal role of monoclonal antibodies in all aspects of FMD research is now clear and these highly specific reagents are now being used for a variety of research and diagnostic purposes within the FMD field. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

  16. Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

    Science.gov (United States)

    New, P W; Currie, K E

    2016-08-01

    Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

  17. Development of new method and protocol for cryopreservation related to embryo and oocytes freezing in terms of fertilization rate: A comparative study including review of literature.

    Science.gov (United States)

    Barik, Mayadhar; Bajpai, Minu; Patnaik, Santosh; Mishra, Pravash; Behera, Priyamadhaba; Dwivedi, Sada Nanda

    2016-01-01

    Cryopreservation is basically related to meritorious thin samples or small clumps of cells that are cooled quickly without loss. Our main objective is to establish and formulate an innovative method and protocol development for cryopreservation as a gold standard for clinical uses in laboratory practice and treatment. The knowledge regarding usefulness of cryopreservation in clinical practice is essential to carry forward the clinical practice and research. We are trying to compare different methods of cryopreservation (in two dozen of cells) at the same time we compare the embryo and oocyte freezing interms of fertilization rate according to the International standard protocol. The combination of cryoprotectants and regimes of rapid cooling and rinsing during warming often allows successful cryopreservation of biological materials, particularly cell suspensions or thin tissue samples. Examples include semen, blood, tissue samples like tumors, histological cross-sections, human eggs and human embryos. Although presently many studies have reported that the children born from frozen embryos or "frosties," show consistently positive results with no increase in birth defects or development abnormalities is quite good enough and similar to our study (50-85%). We ensure that cryopreservation technology provided useful cell survivability, tissue and organ preservation in a proper way. Although it varies according to different laboratory conditions, it is certainly beneficial for patient's treatment and research. Further studies are needed for standardization and development of new protocol.

  18. 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.

  19. 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...

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Elizarova S.Yu.

    2011-03-01

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

  2. 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.

  3. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

    NARCIS (Netherlands)

    M.K. Chan (Man K.); M.-O. Krebs (M-O); D. Cox; P.C. Guest (Paul); R.H. Yolken; H. Rahmoune (Hassan); M. Rothermundt (Matthias); J. Steiner (Johann); F.M. Leweke (Marcus); N.J.M. van Beveren (Nico); D. Niebuhr (David); N. Weber (Natalya); D. Cowan (David); P. Suarez-Pinilla; B. Crespo-Facorro (Benedicto); C. Mam-Lam-Fook; J. Bourgin; R.J. Wenstrup (Richard); R.R. Kaldate; J.D. Cooper (Jason); S. Bahn (Sabine)

    2015-01-01

    markdownabstractRecent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based

  4. Does vitamin C deficiency promote fatty liver disease development?

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    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...

  5. 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

  6. 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

  7. 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...

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

    Science.gov (United States)

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

    2018-05-19

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

  9. Saskatchewan resources. [including uranium

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    The production of chemicals and minerals for the chemical industry in Saskatchewan are featured, with some discussion of resource taxation. The commodities mentioned include potash, fatty amines, uranium, heavy oil, sodium sulfate, chlorine, sodium hydroxide, sodium chlorate and bentonite. Following the successful outcome of the Cluff Lake inquiry, the uranium industry is booming. Some developments and production figures for Gulf Minerals, Amok, Cenex and Eldorado are mentioned.

  10. Valuing and timing R and D using a real options pricing framework; including an application to the development of Lunar Helium-3 fusion

    International Nuclear Information System (INIS)

    Ott, S.H.

    1992-01-01

    This dissertation uses the real options framework to study the valuation and optimal investment policies for R and D projects. The models developed integrate and extend the literature by taking into account the unique characteristics of such projects including uncertain investment in R and D, time-to-build, and multiple investment opportunities. The models were developed to examine the optimal R and D investment policy for the Lunar Helium-3 fusion project but have general applicability. Models are development which model R and D investment as an information gathering process where R and D investment remaining changes as investment is expended. The value of the project increased as the variance of required investment increases. An extension of this model combines a stochastic benefit with stochastic investment. Both the value of the R and D project and the region prescribing continued investment increased. The policy implications are significant: When uncertainty of R and D investment is ignored, the value of the project is underestimated and a tendency toward underinvestment in R and D will result; the existence of uncertainty in R and D investment will cause R and D projects to experience larger declines in value before discontinuation of investment. The model combining stochastic investment with the stochastic benefit is applied to the Lunar Helium-3 fusion project. Investment in fusion should continue at the maximum level of $1 billion annually given current levels of costs of alternative fuels and the perceived uncertainty of R and D investment in the project. A model is developed to examine the valuation and optimal split of funding between R and D projects when there are two competing new technologies. Without interaction between research expenditures and benefits across technologies, the optimal investment strategy is to invest in one or the other technology or neither. The multiple technology model is applied to analyze competing R and D projects, namely

  11. Morphologic Basis for Developing Diverticular Disease, Diverticulitis, and Diverticular Bleeding.

    Science.gov (United States)

    Wedel, Thilo; Barrenschee, Martina; Lange, Christina; Cossais, François; Böttner, Martina

    2015-04-01

    Diverticula of the colon are pseudodiverticula defined by multiple outpouchings of the mucosal and submucosal layers penetrating through weak spots of the muscle coat along intramural blood vessels. A complete prolapse consists of a diverticular opening, a narrowed neck, and a thinned diverticular dome underneath the serosal covering. The susceptibility of diverticula to inflammation is explained by local ischemia, translocation of pathogens due to retained stool, stercoral trauma by fecaliths, and microperforations. Local inflammation may lead to phlegmonous diverticulitis, paracolic/mesocolic abscess, bowel perforation, peritonitis, fistula formation, and stenotic strictures. Diverticular bleeding is due to an asymmetric rupture of distended vasa recta at the diverticular dome and not primarily linked to inflammation. Structural and functional changes of the bowel wall in diverticular disease comprise: i) Altered amount, composition, and metabolism of connective tissue; ii) Enteric myopathy with muscular thickening, deranged architecture, and altered myofilament composition; iii) Enteric neuropathy with hypoganglionosis, neurotransmitter imbalance, deficiency of neurotrophic factors and nerve fiber remodeling; and iv) Disturbed intestinal motility both in vivo (increased intraluminal pressure, motility index, high-amplitude propagated contractions) and in vitro (altered spontaneous and pharmacologically triggered contractility). Besides established etiologic factors, recent studies suggest that novel pathophysiologic concepts should be considered in the pathogenesis of diverticular disease.

  12. 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)

  13. A Study on the quantification of hydration and the strength development mechanism of cementitious materials including amorphous phases by using XRD/Rietveld method

    International Nuclear Information System (INIS)

    Yamada, Kazuo; Hoshino, Seiichi; Hirao, Hiroshi; Yamashita, Hiroki

    2008-01-01

    X-ray diffraction (XRD)/Rietveld method was applied to measure the phase composition of cement. The quantative analysis concerning the progress of hydration was accomplished in an error of about the maximum 2-3% in spite of including amorphous materials such as blast furnace slag, fly ash, silica fume and C-S-H. The influence of the compressive strength on the lime stone fine powder mixture material was studied from the hydration analysis by Rietveld method. The two stages were observed in the strength development mechanism of cement; the hydration promotion of C 3 S in the early stage and the filling of cavities by carbonate hydrate for the longer term. It is useful to use various mixture materials for the formation of the resource recycling society and the durability improvement of concrete. (author)

  14. The development of small, cabled, real-time video based observation systems for near shore coastal marine science including three examples and lessons learned

    Science.gov (United States)

    Hatcher, Gerry; Okuda, Craig

    2016-01-01

    The effects of climate change on the near shore coastal environment including ocean acidification, accelerated erosion, destruction of coral reefs, and damage to marine habitat have highlighted the need for improved equipment to study, monitor, and evaluate these changes [1]. This is especially true where areas of study are remote, large, or beyond depths easily accessible to divers. To this end, we have developed three examples of low cost and easily deployable real-time ocean observation platforms. We followed a scalable design approach adding complexity and capability as familiarity and experience were gained with system components saving both time and money by reducing design mistakes. The purpose of this paper is to provide information for the researcher, technician, or engineer who finds themselves in need of creating or acquiring similar platforms.

  15. Wnt and the Wnt signaling pathway in bone development and disease

    Science.gov (United States)

    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

  16. Technical meeting on lessons learned with respect to SAT implementation, including development of trainers and use of cost effective training methods

    International Nuclear Information System (INIS)

    2002-01-01

    The past years have brought some significant changes in the world energy market, where the nuclear power plants and utilities are operating. Part of NPPs is privatised now; the electricity markets are liberalized and become more and more international. Due to the increase of competition, the power production costs are now monitored more closely than before. The opening of electricity markets has led the nuclear power plants to be under the serious economic pressure with a demand for continuous cost reduction. All these require from NPPs to make their personnel training more cost-effective. In addition, based on modern technology, a great amount of new training tools, aids and technologies have been introduced during the last 2-3 years, these new opportunities can be quite useful for training cost optimization. On the basis of experience gained worldwide in the application of the systematic approach to training (SAT), SAT based training is now a broad integrated approach emphasizing not only technical knowledge and skills but also human factor related knowledge, skills and attitudes. In this way, all competency requirements for attaining and maintaining personnel competence and qualification can be met, thus promoting and strengthening quality culture and safety culture, which should be fostered throughout the initial and continuing training programmes. The subject of the present technical meeting was suggested by the members of the Technical Working Group on Training and Qualification of NPP Personnel (TWG-T and Q) and supported by a number of the IAEA meetings on NPP personnel training. The technical Meeting on 'Lessons Learned with Respect to SAT Implementation, Including Development of Trainers and Use of Cost Effective Training Methods' was organized by the IAEA in co-operation with the Tecnatom A.S. and was held from 21 to 24 October 2002 in San Sebastian de los Reyes/ Madrid, Spain. The main objective of the meeting was to provide an international forum for

  17. 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.

  18. Prediction of preterm birth in multiple pregnancies: development of a multivariable model including cervical length measurement at 16 to 21 weeks' gestation.

    Science.gov (United States)

    van de Mheen, Lidewij; Schuit, Ewoud; Lim, Arianne C; Porath, Martina M; Papatsonis, Dimitri; Erwich, Jan J; van Eyck, Jim; van Oirschot, Charlotte M; Hummel, Piet; Duvekot, Johannes J; Hasaart, Tom H M; Groenwold, Rolf H H; Moons, Karl G M; de Groot, Christianne J M; Bruinse, Hein W; van Pampus, Maria G; Mol, Ben W J

    2014-04-01

    To develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks' gestation and other variables. We used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks' gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures. We studied 507 women, of whom 270 (53%) delivered models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration. In women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

  19. Development of a TaqMan Array Card for Acute-Febrile-Illness Outbreak Investigation and Surveillance of Emerging Pathogens, Including Ebola Virus.

    Science.gov (United States)

    Liu, Jie; Ochieng, Caroline; Wiersma, Steve; Ströher, Ute; Towner, Jonathan S; Whitmer, Shannon; Nichol, Stuart T; Moore, Christopher C; Kersh, Gilbert J; Kato, Cecilia; Sexton, Christopher; Petersen, Jeannine; Massung, Robert; Hercik, Christine; Crump, John A; Kibiki, Gibson; Maro, Athanasia; Mujaga, Buliga; Gratz, Jean; Jacob, Shevin T; Banura, Patrick; Scheld, W Michael; Juma, Bonventure; Onyango, Clayton O; Montgomery, Joel M; Houpt, Eric; Fields, Barry

    2016-01-01

    Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Development of disease animal models using proton beam

    International Nuclear Information System (INIS)

    Nam, K. H.; Kim, E. K.; Kim, H. R.; Seo, Y. W.

    2010-03-01

    To identify proper proton beam dose for mutant mouse development, total 7 times of proton beam were performed. There are too low incidence of mutation in pup mouse which were derived embryos radiated by 1Gy proton beam. Some mutation could be identified in pup mice which were derived embryos radiated by 1.5-2.5Gy proton beam. Mouse embryos irradiated with 1-10Gy of proton beam were inhibited in their in vitro development to 2 cell stage. There was no pups born from embryos which were irradiated with proton beam over 3 Gy. Early mouse development were greatly inhibited by proton beam irradiation of over 10Gy when cultured in vitro. In conclusion, it is efficient to irradiate mouse embryo with 1.5-2.5Gy of proton beam for development of mutant mice

  1. 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

  2. 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

  3. 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

  4. Low hanging fruit in infectious disease drug development.

    Science.gov (United States)

    Kraus, Carl N

    2008-10-01

    Cost estimates for developing new molecular entities (NME) are reaching non-sustainable levels and coupled with increasing regulatory requirements and oversight have led many pharmaceutical sponsors to divest their anti-microbial development portfolios [Projan SJ: Why is big Pharma getting out of anti-bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug development: implications for the future.Clin Infect Dis 2004, 38:1279-1286]. Operational issues such as study planning and execution are significant contributors to the overall cost of drug development that can benefit from the leveraging of pre-randomization data in an evidence-based approach to protocol development, site selection and patient recruitment. For non-NME products there is even greater benefit from available data resources since these data may permit smaller and shorter study programs. There are now many available open source intelligence (OSINT) resources that are being integrated into drug development programs, permitting an evidence-based or 'operational epidemiology' approach to study planning and execution.

  5. Development, validation and clinical assessment of a short questionnaire to assess disease-related knowledge in inflammatory bowel disease patients.

    LENUS (Irish Health Repository)

    Keegan, Denise

    2013-02-01

    Only two inflammatory bowel disease (IBD) knowledge scales are available, both primarily aimed at evaluating the effectiveness of clinical education programs. The aim of this study was to develop and validate a short knowledge questionnaire for clinical and academic research purposes.

  6. 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.

  7. Sci-Fri AM: Quality, Safety, and Professional Issues 01: CPQR Technical Quality Control Suite Development including Quality Control Workload Results

    International Nuclear Information System (INIS)

    Malkoske, Kyle; Nielsen, Michelle; Brown, Erika; Diamond, Kevin; Frenière, Normand; Grant, John; Pomerleau-Dalcourt, Natalie; Schella, Jason; Schreiner, L. John; Tantot, Laurent; Barajas, Eduardo Villareal; Bissonnette, Jean-Pierre

    2016-01-01

    A close partnership between the Canadian Partnership for Quality Radiotherapy (CPQR) and the Canadian Organization of Medical Physicist’s (COMP) Quality Assurance and Radiation Safety Advisory Committee (QARSAC) has resulted in the development of a suite of Technical Quality Control (TQC) Guidelines for radiation treatment equipment, that outline specific performance objectives and criteria that equipment should meet in order to assure an acceptable level of radiation treatment quality. The framework includes consolidation of existing guidelines and/or literature by expert reviewers, structured stages of public review, external field-testing and ratification by COMP. The adopted framework for the development and maintenance of the TQCs ensures the guidelines incorporate input from the medical physics community during development, measures the workload required to perform the QC tests outlined in each TQC, and remain relevant (i.e. “living documents”) through subsequent planned reviews and updates. This presentation will show the Multi-Leaf Linear Accelerator document as an example of how feedback and cross-national work to achieve a robust guidance document. During field-testing, each technology was tested at multiple centres in a variety of clinic environments. As part of the defined feedback, workload data was captured. This lead to average time associated with testing as defined in each TQC document. As a result, for a medium-sized centre comprising 6 linear accelerators and a comprehensive brachytherapy program, we evaluate the physics workload to 1.5 full-time equivalent physicist per year to complete all QC tests listed in this suite.

  8. Sci-Fri AM: Quality, Safety, and Professional Issues 01: CPQR Technical Quality Control Suite Development including Quality Control Workload Results

    Energy Technology Data Exchange (ETDEWEB)

    Malkoske, Kyle; Nielsen, Michelle; Brown, Erika; Diamond, Kevin; Frenière, Normand; Grant, John; Pomerleau-Dalcourt, Natalie; Schella, Jason; Schreiner, L. John; Tantot, Laurent; Barajas, Eduardo Villareal; Bissonnette, Jean-Pierre [Royal Victoria Hospital, Trillium Health Partners, CPQR, Juravinski Cancer Centre, CIUSSS MCQ - CHAUR, Cape Breton Health Care Complex, Centre d’oncologie Dr. Léon-Richard / Dr. Léon Richard Oncology Centre, QEII Health Sciences Centre, Cancer Centre of Southeastern Ontario, Hôpital Maisonneuve-Rosemont, Tom Baker Cancer Centre, Princess Margaret Cancer Centre (Canada)

    2016-08-15

    A close partnership between the Canadian Partnership for Quality Radiotherapy (CPQR) and the Canadian Organization of Medical Physicist’s (COMP) Quality Assurance and Radiation Safety Advisory Committee (QARSAC) has resulted in the development of a suite of Technical Quality Control (TQC) Guidelines for radiation treatment equipment, that outline specific performance objectives and criteria that equipment should meet in order to assure an acceptable level of radiation treatment quality. The framework includes consolidation of existing guidelines and/or literature by expert reviewers, structured stages of public review, external field-testing and ratification by COMP. The adopted framework for the development and maintenance of the TQCs ensures the guidelines incorporate input from the medical physics community during development, measures the workload required to perform the QC tests outlined in each TQC, and remain relevant (i.e. “living documents”) through subsequent planned reviews and updates. This presentation will show the Multi-Leaf Linear Accelerator document as an example of how feedback and cross-national work to achieve a robust guidance document. During field-testing, each technology was tested at multiple centres in a variety of clinic environments. As part of the defined feedback, workload data was captured. This lead to average time associated with testing as defined in each TQC document. As a result, for a medium-sized centre comprising 6 linear accelerators and a comprehensive brachytherapy program, we evaluate the physics workload to 1.5 full-time equivalent physicist per year to complete all QC tests listed in this suite.

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

    DEFF Research Database (Denmark)

    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...

  10. 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

  11. 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.

  12. 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 ...

  13. Dermatomycosis: Conditions that contribute to the disease development

    Directory of Open Access Journals (Sweden)

    Stojanov Igor M.

    2011-01-01

    Full Text Available Skin lesions caused by dermatophytes are classified depending on the infected skin structure: surface layer of cutis, fur layer, clutches or nails. Surface mycoses are caused by dermatophytes: Epidermophyton, Microsporum and Trichophyton species (also important are Malassezia spp., Candida spp., and Trichosporon. Skin is the target tissue for fungal infections if the epithelial layer is damaged and immune system cannot cope with the infection, or if the conditions are favorable for dermatophytes, which spread in the cutis due to the enzyme activities. Dermatophytes can be found on skin surface if they contaminate or colonize epidermis or hair follicles. However, clinical symptoms of lesion on the skin are sometimes absent. According to the literature data 6-9% of skin lesions are caused by dermatophyte in human medicine. Similar situation is in veterinary medicine. Fungus that cause dermatomycosis are widespread in the nature and could be divided into: zoophilic, geophilic and anthrophilic. The goal of this paper is to present the latest knowledge in pathogenesis on dermatomycosis, predisposing factors important for the outcome of the disease, and immunological reaction of organism to the fungal infection. Our intention is to summarize the subject and present the facts related to specific problems in dermatomycosis.

  14. Tachykinin: recent developments and novel roles in health and disease.

    Science.gov (United States)

    Onaga, Takenori

    2014-06-01

    Over 80 years has passed since the discovery of substance P (SP), and a variety of peptides of the tachykinin (TK) family have been found and investigated. SP, neurokinin A (NKA), and neurokinin B (NKB) are representative peptides in mammalian species. SP and NKA are major excitatory neurotransmitters in the peripheral nervous system, while NKB is primarily involved in the central nervous system (CNS). Moreover, TK peptides play roles not only as neurotransmitters but also as local factors and are involved in almost all aspects of the regulation of physiological functions and pathophysiological processes. The role of SP as a mediator of pain processing and inflammation in peripheral tissues in coordination with transient receptor potential channels is well established, while novel aspects of TKs in relation to hematopoiesis, venous thromboembolism, tendinopathy, and taste perception have been clarified. In the CNS, the NKB signaling system in the hypothalamus has been shown to play a crucial role in the regulation of gonadotropin hormone secretion and the onset of puberty, and molecular biological studies have elucidated novel prophylaxic activities of TKs against neurogenic movement disorders based on their molecular structure. This review provides an overview of the novel aspects of TKs reported around the world in the last 5 years, with particular focus on nociception, inflammation, hemopoiesis, gonadotropin secretion, and CNS diseases.

  15. Inoculation message treatments for curbing noncommunicable disease development.

    Science.gov (United States)

    Mason, Alicia M; Miller, Claude H

    2013-07-01

    To study the effect of various types of inoculation message treatments on resistance to persuasive and potentially deceptive health- and nutrition-related (HNR) content claims of commercial food advertisers. A three-phase experiment was conducted among 145 students from a Midwestern U.S. university. Quantitative statistical analyses were used to interpret the results. RESULTS provide clear evidence that integrating regulatory focus/fit considerations enhances the treatment effectiveness of inoculation messages. Inoculation messages that employed a preventative, outcome focus with concrete language were most effective at countering HNR advertising claims. The findings indicate that inoculation fosters resistance equally across the most common types of commercially advertised HNR product claims (e.g., absolute, general, and structure/function claims). As the drive to refine the inoculation process model continues, further testing and application of this strategy in a public health context is needed to counter ongoing efforts by commercial food advertisers to avoid government regulations against deceptive practices such as dubious health/nutrition claims. This research advances inoculation theory by providing evidence that 1) good regulatory fit strengthens the effect of refutational preemption and 2) an inoculation approach is highly effective at fostering resistance to commercial advertisers' HNR content claims. This macro approach appears far superior to education or information-based promotional health campaigns targeted solely at specific populations demonstrating rising rates of noncommunicable disease.

  16. Inoculation message treatments for curbing noncommunicable disease development

    Directory of Open Access Journals (Sweden)

    Alicia M. Mason

    2013-07-01

    Full Text Available OBJECTIVE: To study the effect of various types of inoculation message treatments on resistance to persuasive and potentially deceptive health- and nutrition-related (HNR content claims of commercial food advertisers. METHODS: A three-phase experiment was conducted among 145 students from a Midwestern U.S. university. Quantitative statistical analyses were used to interpret the results. Results: Results provide clear evidence that integrating regulatory focus/fit considerations enhances the treatment effectiveness of inoculation messages. Inoculation messages that employed a preventative, outcome focus with concrete language were most effective at countering HNR advertising claims. The findings indicate that inoculation fosters resistance equally across the most common types of commercially advertised HNR product claims (e.g., absolute, general, and structure/function claims. CONCLUSIONS: As the drive to refine the inoculation process model continues, further testing and application of this strategy in a public health context is needed to counter ongoing efforts by commercial food advertisers to avoid government regulations against deceptive practices such as dubious health/nutrition claims. This research advances inoculation theory by providing evidence that 1 good regulatory fit strengthens the effect of refutational preemption and 2 an inoculation approach is highly effective at fostering resistance to commercial advertisers' HNR content claims. This macro approach appears far superior to education or information-based promotional health campaigns targeted solely at specific populations demonstrating rising rates of noncommunicable disease.

  17. An update on mycobacteria and the development of allergic diseases

    NARCIS (Netherlands)

    Folkerts, G.

    2015-01-01

    Mycobacteria can diminish allergic and asthmatic manifestations. This means that mycobacteria could offer therapeutical opportunities as an 'anti-allergic' vaccine.In humans, the genetic background and the environment probably contribute to the development of allergies. Over the last 20. years, a

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

    Science.gov (United States)

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

    2016-12-01

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

  19. 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...

  20. 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.

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

    Science.gov (United States)

    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

  2. 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.

  3. Exonic variants associated with development of aspirin exacerbated respiratory diseases.

    Directory of Open Access Journals (Sweden)

    Seung-Woo Shin

    Full Text Available Aspirin-exacerbated respiratory disease (AERD is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study was to identify AERD-associated exonic SNPs and examine the diagnostic potential of a combination of these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects with aspirin-tolerant asthma (ATA, and 398 normal controls were subjected to an Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1 were generated from combinations of the top 10 SNPs, selected by the p-values in association with AERD. The area under the curve (AUC of the receiver operating characteristic (ROC curves was calculated for each model. SNP Function Portal and PolyPhen-2 were used to validate the functional significance of candidate SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p = 3.40×10-8 in its association with AERD risk. From the top 10 SNPs, a combination model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237, exm396794, and exm791954 showed the best AUC of 0.75 (asymptotic p-value of 7.94×10-21, with 34% sensitivity and 93% specificity to discriminate AERD from ATA. Amino acid changes due to exm83523 in CHIA were predicted to be "probably damaging" to the structure and function of the protein, with a high score of '1'. A combination model of seven SNPs may provide a useful, non-invasive genetic marker combination for predicting AERD.

  4. Immunisation strategies for viral diseases in developing countries.

    Science.gov (United States)

    Ruff, T A

    1999-01-01

    In just under a quarter of a century, the Expanded Programme on Immunisation has been associated with an increase in infant immunisation coverage from around 5% to 80%, and the prevention of at least 3 million deaths annually, at very low cost. The global target of poliomyelitis eradication by the year 2000 appears feasible. Measles is the next likely target for eradication via immunisation, through 'catch-up', 'keep up' and 'follow-up' strategies which have proven highly effective in the Americas. Yet much needs to be done in order to extend readily achievable immunisation benefits equitably to all the world's people and to realise the potential of existing and soon to be available vaccines for disease control and eradication, as experience with yellow fever and hepatitis B vaccines demonstrates. Unsafe injection practices are widespread, have received inadequate attention, and cause a substantial global burden of blood-borne infections. The risk of increasing global inequity in immunisation highlights the centrality of resource allocation priorities in determining the extent to which the benefits of immunisation will be realised, particularly for new vaccines which are significantly more costly than established EPI vaccines. WHO/UNICEF strategies to target more effectively immunisation support to the neediest countries, to prioritise new vaccines, and to target carefully vaccine procurement and encourage sharply tiered vaccine pricing support both equity and sustainability. However, increasing the resources available to immunisation is vital and requires powerful advocacy on public health, moral, cost-effectiveness and legal grounds. More appropriate resource allocation priorities could readily provide the means necessary to address both technical and operational immunisation challenges.

  5. 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

  6. [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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  12. DEVELOPMENT OF A HYDRODYNAMIC MODEL OF A HYDROCYCLONE INCLUDING THE SIMULATION OF AIR-CORE EFFECT, USING THE FINITE VOLUME METHOD

    Directory of Open Access Journals (Sweden)

    Gabriel Felipe Aguilera

    2014-07-01

    Full Text Available The hydrocyclone is one of the most used classification equipment in industry, particularly in mineral processing. Maybe its main characteristic is to be a hydrodynamic separation equipment, whereby it has a high production capability and different levels of efficiency are depending on the geometrical configuration, operational parameters and the type of material to be processed. Nevertheless, there are a few successful studies regarding the modelling and simulation of its hydrodynamic principles, because the flow behavior inside is quite complex. Most of the current models are empirical and they are not applicable to all cases and types of minerals. One of the most important problems to be solved, besides the cut size and the effect of the physical properties of the particles, is the distribution of the flow inside the hydrocyclone, because if the work of the equipment is at low slurry densities, very clear for small hydrocyclones, its mechanic behavior is a consequence of the kind of liquid used as continuous phase, being water the most common liquid. This work shows the modelling and simulation of the hydrodynamic behavior of a suspension inside a hydrocyclone, including the air core effect, through the use of finite differences method. For the developing of the model, the Reynolds Stress Model (RSM for the evaluation of turbulence, and the Volume of Fluid (VOF to study the interaction between water and air were used. Finally, the model shows to be significant for experimental data, and for different conditions of an industrial plant.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Developing a weighting strategy to include mobile phone numbers into an ongoing population health survey using an overlapping dual-frame design with limited benchmark information.

    Science.gov (United States)

    Barr, Margo L; Ferguson, Raymond A; Hughes, Phil J; Steel, David G

    2014-09-04

    In 2012 mobile phone numbers were included into the ongoing New South Wales Population Health Survey (NSWPHS) using an overlapping dual-frame design. Previously in the NSWPHS the sample was selected using random digit dialing (RDD) of landline phone numbers. The survey was undertaken using computer assisted telephone interviewing (CATI). The weighting strategy needed to be significantly expanded to manage the differing probabilities of selection by frame, including that of children of mobile-only phone users, and to adjust for the increased chance of selection of dual-phone users. This paper describes the development of the final weighting strategy to properly combine the data from two overlapping sample frames accounting for the fact that population benchmarks for the different sampling frames were not available at the state or regional level. Estimates of the number of phone numbers for the landline and mobile phone frames used to calculate the differing probabilities of selection by frame, for New South Wales (NSW) and by stratum, were obtained by apportioning Australian estimates as none were available for NSW. The weighting strategy was then developed by calculating person selection probabilities, selection weights, applying a constant composite factor to the dual-phone users sample weights, and benchmarking to the latest NSW population by age group, sex and stratum. Data from the NSWPHS for the first quarter of 2012 was used to test the weighting strategy. This consisted of data on 3395 respondents with 2171 (64%) from the landline frame and 1224 (36%) from the mobile frame. However, in order to calculate the weights, data needed to be available for all core weighting variables and so 3378 respondents, 2933 adults and 445 children, had sufficient data to be included. Average person weights were 3.3 times higher for the mobile-only respondents, 1.3 times higher for the landline-only respondents and 1.7 times higher for dual-phone users in the mobile frame

  15. 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.

  16. 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

  17. THE FREQUENCY AND ASSOCIATION OF RISK FACTORS IN DEVELOPMENT OF CORONARY HEART DISEASE IN DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Dušan Sokolović

    2003-01-01

    Full Text Available The coronary heart disease (CHD is a leading cause of lethality in both sexes. The risk for development of CHD is 2-4 times higher in non insulin dependent diabetes mellitus (NIDDM than in nondiabetics, and annual rate of fatal and non-fatal cardiovascular diseases in NIDDM is 2-5%. The etiology of CHD is still unknown until the risk factors connected to the development of CHD are well known.The purpose of this research was to establish the frequency and importance of the risk factors in development of CHD in NIDDM.The research included 60 patients with NIDDM who were by presence of CHD classified into two groups. We determined body mass index and waist hip ratio, total and HDL cholesterol, triglicerides, LDL cholesterols, uric acid and fibrinogen.Values of BMI were statistically higher in patients with CHD than in diabetics without CHD 29.67+3.31 vs. 27.87±3.17 kg/m2 (p<0.05. Raised risk levels of cholesterol had90% with CHD and 76% without CHD (Hi2=6.12, p<0.05. Larger percentage of patients in group with CHD had raised lipid risk levels of triglicerides 70% than in patients without CHD 56.5% (Hi2=4.36, p<0.05. The obesity was relatively rare in patients without CHD than in diabetics with CHD (13.6% vs. 76%, p<0.01.The frequency of risk factors was very high in NIDDM patients, which clearly points at their cumulative effect in development of CHD in diabetics.

  18. Air pollution as noxious environmental factor in the development of cardiovascular disease

    NARCIS (Netherlands)

    Hassing, H. C.; Twickler, Th B.; Kastelein, J. J. P.; Cramer, M. J. M.; Cassee, F. R.

    2009-01-01

    A strong epidemiological association has been revealed between air pollution and the occurrence of cardiovascular disease (CVD). Deleterious consequences of such pollution, including myocardial infarction and coronary ischaemia, have occurred after both acute as well as chronic exposure to air

  19. To vigorously and safely develop the interventional therapy for diabetic peripheral vascular diseases

    International Nuclear Information System (INIS)

    Zhao Jungong; Cheng Yongde

    2011-01-01

    Diabetic critical limb ischemia is one of the most severe complications caused by diabetes mellitus, which carries significant morbidity and mortality. The symptoms related to limb ischemia include intermittent claudication, rest pain, refractory ulcers, infections or even gangrene of the foot or toes. Percutaneous transluminal angioplasty (PTA) can be used to treat arterial stenosis or occlusive disease of the iliac and femoropopliteal arteries. However, PTA has a relatively poor outcome for the treatment of infrapopliteal arteries with conventional short coronary balloons. In the past 10 years, infrapopliteal angioplasty with a long over-the-wire (OTW) balloon, subintimal technique, retrograde transdorsal-to-plantar loop, Excimer laser ablation, local delivery of paclitaxel, etc. have been continually developed. The clinical practise has proved that these techniques and devices are feasible and effective for the treatment of severe limb ischemia in diabetic patients. The midterm outcomes seem to be satisfactory and encouraging. (authors)

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

    Science.gov (United States)

    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

  1. New developments in corneal and external disease--LASIK.

    Science.gov (United States)

    Dhaliwal, Deepinder K; Mather, Rookaya

    2003-03-01

    Lamellar refractive surgery has evolved into LASIK, which is a widely performed, versatile procedure with a high patient acceptance. In this chapter, the two main components of LASIK were discussed: flap creation and stromal ablation. In each of these areas, the authors explored current technology and new advances, including the femtosecond laser and wavefront-guided ablations. Expanded indications and therapeutic application of LASIK also have come to the forefront. The treatment of anisomyopic amblyopia in the pediatric population is a prime example and was discussed fully in this chapter. The field of refractive surgery has never been stagnant. Surgeons and scientists continue to explore new modalities to increase safety, to improve results, and to broaden applications that benefit the patient population.

  2. 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.

  3. Nucleic acid toolkit: Potential diagnosis and treatment of major infectious diseases endemic in developing countries

    CSIR Research Space (South Africa)

    Millroy, L

    2011-09-01

    Full Text Available HIV/AIDS and TB are among the major infectious diseases and defining public health problems in developing countries. This book aims to give an overview of the epidemiology and also provide an understanding of the pathology of these diseases. It also...

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Trends in diet and Alzheimer's disease during the nutrition transition in Japan and developing countries.

    Science.gov (United States)

    Grant, William B

    2014-01-01

    Alzheimer's disease (AD) rates in Japan and developing countries have risen rapidly in recent years. Researchers have associated factors such as the Western diet, obesity, alcohol consumption, and smoking with risk of AD. This paper evaluates whether the dietary transition might explain the rising trend of AD prevalence in Japan and in developing countries, evaluating other factors when possible. This study used two approaches to see whether dietary or other changes could explain AD trends in Japan and developing countries. One approach involved comparing trends of AD in Japan with changes in national dietary supply factors, alcohol consumption, and lung cancer mortality rates from zero to 25 years before the prevalence data. The second compared AD prevalence values for eight developing countries with dietary supply factors from zero to 25 years before the prevalence data. For Japan, alcohol consumption, animal product, meat and rice supply, and lung cancer rates correlated highly with AD prevalence data, with the strongest correlation for a lag of 15-25 years. In the eight-country study, total energy and animal fat correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms to explain the findings include increased obesity for the eight countries, and increases in cholesterol, saturated fat, and iron from increases in animal products and meat supply for Japan. Evidently AD rates will continue rising in non-Western countries for some time unless we address major risk factors involving diet, obesity, and smoking.

  8. DNA methylation dynamics in muscle development and disease

    Directory of Open Access Journals (Sweden)

    Elvira eCarrio

    2015-03-01

    Full Text Available DNA methylation is an essential epigenetic modification for mammalian development and is crucial for the establishment and maintenance of cellular identity. Traditionally, DNA methylation has been considered as a permanent repressive epigenetic mark. However, the application of genome-wide approaches has allowed the analysis of DNA methylation in different genomic contexts revealing a more dynamic regulation than originally thought, since active DNA methylation and demethylation occur during cellular differentiation and tissue specification. Satellite cells are the primary stem cells in adult skeletal muscle and are responsible for postnatal muscle growth, hypertrophy, and muscle regeneration. This review outlines the published data regarding DNA methylation changes along the skeletal muscle program, in both physiological and pathological conditions, to better understand the epigenetic mechanisms that control myogenesis

  9. Expanding the Therapeutic Spectrum of Artemisinin: Activity Against Infectious Diseases Beyond Malaria and Novel Pharmaceutical Developments

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2016-08-01

    Full Text Available The interest of Western medicine in Traditional Chinese Medicine (TCM as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin (qinghaosu, which is extracted from the medicinal plant Artemisia annua L. (qinghao. The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives (artemisinins exert profound activities towards other protozoans (Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella, trematodes (Schistosoma, liver flukes, and viruses (human cytomegalovirus, hepatitis B and C viruses. Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives (artesunate, artemether, arteether, novel drug development strategies have been pursued. These included the synthesis of acetal- and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, e.g. artemisinin-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in

  10. 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

  11. 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

  12. SU-E-T-138: Automated Chart Review Module Including Cross-Vendor Data Transfer Verification Developed for IHE-RO Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Brewer, M; Gordon, C [Franciscan St Margaret Health, Hammond, IN (United States); Tien, C [Community Hospital, Munster, IN (United States)

    2015-06-15

    Purpose: To follow the Integrating Healthcare Enterprise - Radiation Oncology (IHE-RO) initiative of proper cross-vendor technology integration, an automated chart checker (ACC) was developed. ACC compares extracted data from an approved patient plan in the Eclipse treatment planning system (TPS) against data existing in the Mosaiq treatment management system (TMS). ACC automatically analyzes these parameters using built-in quality checklists to provide further aid in chart review. Methods: Eclipse TPS data are obtained using Eclipse scripting API (ESAPI) while Mosaiq TMS data are obtained from a radiotherapy-treatment-planning (RTP) file. Using this information, ACC identifies TPS-TMS discrepancies in 18 primary beam parameters including MU, energy, jaw positions, gantry angle, table angle, accessories, and bolus for up to 31 beams. Next, approximately 40 items from traditional quality checklists are evaluated such as prescription consistency, DRR graticule placement, plan approval status, global max dose, and dose tracking coefficients. Parameters were artificially modified to determine if ACC would detect an error in data transfer and to test each component of quality checklists. Results: Using ESAPI scripting and RTP file-processing, ACC was able to properly aggregate data from TPS and TMS for up to 31 beams. Errors were artificially introduced into each plan parameter, and ACC was able to successfully detect all of them within seconds. Next, ACC was able to successfully detect mistakes in the chart by identifying deviations with its quality checklists, within seconds. Conclusion: ACC effectively addresses the potential issue of faulty cross-vendor data transfer, as described by IHE-RO. In addition, ACC was also able to detect deviations from its built-in quality checklists. ACC is already an invaluable tool for efficient and standardized chart review and will continue to improve as its incorporated checklists become more comprehensive.

  13. SU-E-T-138: Automated Chart Review Module Including Cross-Vendor Data Transfer Verification Developed for IHE-RO Initiative

    International Nuclear Information System (INIS)

    Brewer, M; Gordon, C; Tien, C

    2015-01-01

    Purpose: To follow the Integrating Healthcare Enterprise - Radiation Oncology (IHE-RO) initiative of proper cross-vendor technology integration, an automated chart checker (ACC) was developed. ACC compares extracted data from an approved patient plan in the Eclipse treatment planning system (TPS) against data existing in the Mosaiq treatment management system (TMS). ACC automatically analyzes these parameters using built-in quality checklists to provide further aid in chart review. Methods: Eclipse TPS data are obtained using Eclipse scripting API (ESAPI) while Mosaiq TMS data are obtained from a radiotherapy-treatment-planning (RTP) file. Using this information, ACC identifies TPS-TMS discrepancies in 18 primary beam parameters including MU, energy, jaw positions, gantry angle, table angle, accessories, and bolus for up to 31 beams. Next, approximately 40 items from traditional quality checklists are evaluated such as prescription consistency, DRR graticule placement, plan approval status, global max dose, and dose tracking coefficients. Parameters were artificially modified to determine if ACC would detect an error in data transfer and to test each component of quality checklists. Results: Using ESAPI scripting and RTP file-processing, ACC was able to properly aggregate data from TPS and TMS for up to 31 beams. Errors were artificially introduced into each plan parameter, and ACC was able to successfully detect all of them within seconds. Next, ACC was able to successfully detect mistakes in the chart by identifying deviations with its quality checklists, within seconds. Conclusion: ACC effectively addresses the potential issue of faulty cross-vendor data transfer, as described by IHE-RO. In addition, ACC was also able to detect deviations from its built-in quality checklists. ACC is already an invaluable tool for efficient and standardized chart review and will continue to improve as its incorporated checklists become more comprehensive

  14. A reevaluation of the lineage development of Pararotalia and Praepararotalia including new material from the Rupelian of the southern Upper Rhine Graben

    Science.gov (United States)

    Pirkenseer, C.; Spezzaferri, S.

    2009-04-01

    more rapid increase of chamber size. The necessity of a new genus is in discussion. The second group includes the small intermediate species as Pararotalia ishamae, characterized by inflated globular chambers, a general absence of a keel, partial development of small pseudospines and umbilical plugs. This group can be traced up to recent, as is indicated by the occurrence of small sized Pararotalia cananeiaensis (DEBENAY et al. 2001). Material from the research area (PIRKENSEER 2007), though of generally larger size is attributed to the Rupelian P. curryi. It however shows variation in the development of pseudospines, the lateral profile and umbilicus. The latter species may be a synonym of the similar Late Eocene P. parva. The third group consists only of Pararotalia spinigera (Lutetian) and Pararotalia canui (Rupelian) with an inflated angular lateral profile and a relatively large size. Material from the research area attributed to P. canui shows massive well-developed peripheral pseudospines, a strong umbilical plug and a rounded keel. Double pseudospines occur sporadically. The apertural lip is heavily toothed. The fourth group consists of species with a very angular lateral profile, conical chambers, distinct umbilical plug and a moderate to very large size (up to 600µm), ranging from the Thanetian (Pararotalia minimalis) at least to the Pliocene (P. padana, MANCIN et al. 2000). This reevaluation indicates the perseverance of the "primitive" group of Pararotalia macneilli until today. It thus contradicts a gradual development of the genus Pararotalia to more spineous, angular and larger forms. The latter morphogroup exists well defined since the Paleocene with representatives throughout the Paleogene and Neogene. This study was partly funded by the Swiss National Science Foundation projects 109457 and 118025. References: DEBENAY, J. P., DULEBA, W., BONETTI, C., et al. (2001): Pararotalia cananeiaensis n. sp.: indicator of marine influence and water circulation

  15. Cushing's syndrome: epidemiology and developments in disease management

    Directory of Open Access Journals (Sweden)

    Sharma ST

    2015-04-01

    Full Text Available Susmeeta T Sharma,1 Lynnette K Nieman,1 Richard A Feelders2 1Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; 2Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands Abstract: Cushing’s syndrome is a rare disorder resulting from prolonged exposure to excess glucocorticoids. Early diagnosis and treatment of Cushing’s syndrome is associated with a decrease in morbidity and mortality. Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult. Surgery (resection of the pituitary or ectopic source of adrenocorticotropic hormone, or unilateral or bilateral adrenalectomy remains the optimal treatment in all forms of Cushing’s syndrome, but may not always lead to remission. Medical therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic hormone levels or glucocorticoid receptor antagonists and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for optimal control of hypercortisolemia and management of comorbidities. Keywords: Cushing’s syndrome, hypercortisolemia, treatment, epidemiology

  16. APITHERAPEUTICAL FUNDS: NEW DEVELOPMENT AND PROSPECTS OF INFECTIOUS DISEASES IN PERSON (REVIEW

    Directory of Open Access Journals (Sweden)

    Radchenko EA

    2013-03-01

    Full Text Available The analysis of the development, the study of antimicrobialproperties of pharmacological agents that are based onphenolic propolis and hydrophilic drug shows promise forthe use of complex treatment of infectious diseases.

  17. Acknowledgement to Reviewers of the Journal of Cardiovascular Development and Disease in 2014

    Directory of Open Access Journals (Sweden)

    JCDD Editorial Office

    2015-01-01

    Full Text Available The editors of the Journal of Cardiovascular Development and Disease would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2014:[...

  18. Psychosocial factors in the development of heart disease in women: current research and future directions.

    Science.gov (United States)

    Low, Carissa A; Thurston, Rebecca C; Matthews, Karen A

    2010-11-01

    To review the recent (1995-2009) literature on psychosocial risk and protective factors for coronary heart disease (CHD) among women, including negative emotions, stress, social relationships, and positive psychological factors. Articles for the review were identified using PubMed and bibliographies of relevant articles. Eligible studies included at least 100 women and either focused on a) exclusively female participants or b) both men and women, conducting either gender-stratified analyses or examining interactions with gender. Sixty-seven published reports were identified that examined prospective associations with incident or recurrent CHD. In general, evidence suggests that depression, anxiety disorders, anger suppression, and stress associated with relationships or family responsibilities are associated with elevated CHD risk among women, that supportive social relationships and positive psychological factors may be associated with reduced risk, and that general anxiety, hostility, and work-related stress are less consistently associated with CHD among women relative to men. A growing literature supports the significance of psychosocial factors for the development of CHD among women. Consideration of both traditional psychosocial factors (e.g., depression) and factors that may be especially important for women (e.g., stress associated with responsibilities at home or multiple roles) may improve identification of women at elevated risk as well as the development of effective psychological interventions for women with or at risk for CHD.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

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

    Science.gov (United States)

    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

  2. Confronting the effects of smoking and air quality on the development of chronic respiratory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Jedrychowski, W; Krzyzanowski, M W; Wojtyniak, B

    1985-08-01

    The main purpose of the paper was to compare the effects of outdoor and indoor air quality on the development of chronic respiratory diseases measured in the prospective study of chronic chest diseases among the inhabitants of Cracow, Poland. The 5-year follow-up study covered a probability sample of 4355 adult inhabitants. Data on respiratory symptoms and lung function in addition to variables related to environmental and socioeconomic factors were included. To assess the separate and joint effects of the chosen environmental factors on chronic chest problems, the multiple logistic regression analysis has been carried out. As expected, smoking habit was the strongest single of the factors related to the persistence of the respiratory symptoms. The effect of smoking was more marked in men than in women and this can be attributed to longer duration of smoking and more cigarettes smoked daily by men. Out of all considered adverse occupational factors only chemicals increased the risk of chronic bronchitis in men while dust increased the risk of exacerbations in women. The data showed a significant decrease in risk of exacerbations among the women who used a gas stove for cooking. The study also confirmed the harmful effect of smoking on lung function. Against this particular background the importance of variable temperature combined with ambient air pollution appeared to have rather strong detrimental biologic impact.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Genetic and Biological Changes of Newcastle Disease Virus Due to The Development of Chicken Production System

    Directory of Open Access Journals (Sweden)

    Sudarisman

    2009-09-01

    Full Text Available In many countries, Newcastle Disease (ND is one of the most important diseases of poultry. It causes serious economic losses in poultry industry. Newcastle Disease or pseudo-fowl pest is a highly infectious viral disease that causes very high mortality (up to 100% in severe epidemics in poultry and wild birds around the world. Newcastle Disease remains endemic in many regions and continues to severely limit poultry production in some developing countries. The disease is currently being controlled by routine vaccinations in many countries. However, it was reported that outbreaks of ND in vaccinated flocks often occur on the field may not only be due to differences in the antigenicity of the NDV wild field strains and vaccine strains, but could also be as a result of differences in pathogenicity and virulence between different strains used as vaccine seed in NDV vaccine production.

  7. 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...

  8. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. 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.

  10. Epidemiologic transitions: migration and development of obesity and cardiometabolic disease in the developing world.

    Science.gov (United States)

    Forrester, Terrence

    2013-01-01

    For centuries, the challenge has been the maintenance of bodyweight in the face of marginal food availability. Since the industrial revolution, energy expenditure related to economic activity and domestic life has fallen progressively as technological innovation has replaced muscular power with labor-saving devices. This fall in activity energy expenditure however has not been associated over this entire period with population weight gain. In the 1970s and the 1980s, there was an abrupt uptick in the rate of rise of relative weight in industrialized countries followed rapidly by developing countries. This has led to high and increasing rates of overweight and obesity in high-income countries worldwide, but also an alarming inclusion of low- and middle-income populations in this obesity epidemic. The precise drivers of these concurrent epidemics are not agreed, but probably include on the one hand an increase in dietary energy intake resulting from the impact of industrialization and globalization on food availability and price. On the other, there is the facilitating underlying status of a steadily falling activity energy expenditure as muscle power as an input into economic production as well as household and leisure activities has been supplanted. The rise in population weight without accompanying linear growth manifests as obesity. The accretion of fat as well as the response to other environmental exposures during progressive industrialization and modernization has evoked an accompanying epidemic of cardiometabolic pathology that has significant impact on health as well as macroeconomics. Given the power and presumed irreversibility of industrialization and globalization, our ability to reverse these obesity epidemics is heavily dependent on new knowledge being developed which gives insight with prevention and therapeutic implications on the proximal and distal drivers of this progressive positive energy balance. Copyright © 2013 Nestec Ltd., Vevey/S. Karger

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. Kinetic Modeling of the Lif:Mg,Ti TL System including Defect Creation: Implications to, and Development of Track Structure Theory Calculations of Heavy Charged Particle Radiation Effects

    International Nuclear Information System (INIS)

    Eliyahu, Ian

    2015-01-01

    relative OA band HCP induced efficiencies as described in the following. The high fluence region has allowed the determination of the saturation concentration of the F band and 4.77 eV band using the Beer-Lambert and Smakula formulas. The results indicate order of magnitude enhanced concentrations of vii these centers following the proton and He irradiations relative to photon irradiation. 2. Kinetic Analysis: The second focus of investigation was the development of a kinetic model to describe charge carrier transport in the LiF:Mg,Ti system including three features delineated in the following. The primary motivation for the kinetic analysis was the intention to modify track structure theory by taking into account enhanced vacancy/F center creation in the low ionization density kinetic simulations but was expanded in order to simulate the unique features of dose response in LiF:Mg,Ti. The kinetic model includes: c) Estimated electron-hole (e-h) and e-only population of the spatially correlated trapping center/luminescent center responsible for composite glow peak 5 in the glow curve of LiF:Mg,Ti. d) Combined localized and delocalized recombination of the e-h and e-only centers in the recombination stage. These features are shown to be capable of simulating both the linear/supralinear dose response and the dependence of the supralinearity on photon energy as is observed for composite peak 5. Both of these characteristics have previously eluded the predictive powers of kinetic theory based exclusively on delocalized recombination. e) Vacancy/F center creation in the irradiation stage including vacancyinterstitial recombination. The kinetic model with the latter mechanisms attempts to resolve a central question concerning the mechanisms leading to the linear/exponentially saturating dose response of the F band even though Fluorine vacancies are being continuously created during the irradiation. The electron-trapping characteristics of the created vacancies are assumed to

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

    Science.gov (United States)

    Hamajima, N; Hirose, K; Tajima, K; Rohan, T; Calle, E E; Heath, C W; Coates, R J; Liff, J M; Talamini, R; Chantarakul, N; Koetsawang, S; Rachawat, D; Morabia, A; Schuman, L; Stewart, W; Szklo, M; Bain, C; Schofield, F; Siskind, V; Band, P; Coldman, A J; Gallagher, R P; Hislop, T G; Yang, P; Kolonel, L M; Nomura, A M Y; Hu, J; Johnson, K C; Mao, Y; De Sanjosé, S; Lee, N; Marchbanks, P; Ory, H W; Peterson, H B; Wilson, H G; Wingo, P A; Ebeling, K; Kunde, D; Nishan, P; Hopper, J L; Colditz, G; Gajalanski, V; Martin, N; Pardthaisong, T; Silpisornkosol, S; Theetranont, C; Boosiri, B; Chutivongse, S; Jimakorn, P; Virutamasen, P; Wongsrichanalai, C; Ewertz, M; Adami, H O; Bergkvist, L; Magnusson, C; Persson, I; Chang-Claude, J; Paul, C; Skegg, D C G; Spears, G F S; Boyle, P; Evstifeeva, T; Daling, J R; Hutchinson, W B; Malone, K; Noonan, E A; Stanford, J L; Thomas, D B; Weiss, N S; White, E; Andrieu, N; Brêmond, A; Clavel, F; Gairard, B; Lansac, J; Piana, L; Renaud, R; Izquierdo, A; Viladiu, P; Cuevas, H R; Ontiveros, P; Palet, A; Salazar, S B; Aristizabel, N; Cuadros, A; Tryggvadottir, L; Tulinius, H; Bachelot, A; Lê, M G; Peto, J; Franceschi, S; Lubin, F; Modan, B; Ron, E; Wax, Y; Friedman, G D; Hiatt, R A; Levi, F; Bishop, T; Kosmelj, K; Primic-Zakelj, M; Ravnihar, B; Stare, J; Beeson, W L; Fraser, G; Bullbrook, R D; Cuzick, J; Duffy, S W; Fentiman, I S; Hayward, J L; Wang, D Y; McMichael, A J; McPherson, K; Hanson, R L; Leske, M C; Mahoney, M C; Nasca, P C; Varma, A O; Weinstein, A L; Moller, T R; Olsson, H; Ranstam, J; Goldbohm, R A; van den Brandt, P A; Apelo, R A; Baens, J; de la Cruz, J R; Javier, B; Lacaya, L B; Ngelangel, C A; La Vecchia, C; Negri, E; Marubini, E; Ferraroni, M; Gerber, M; Richardson, S; Segala, C; Gatei, D; Kenya, P; Kungu, A; Mati, J G; Brinton, L A; Hoover, R; Schairer, C; Spirtas, R; Lee, H P; Rookus, M A; van Leeuwen, F E; Schoenberg, J A; McCredie, M; Gammon, M D; Clarke, E A; Jones, L; Neil, A; Vessey, M; Yeates, D; Appleby, P; Banks, E; Beral, V; Bull, D; Crossley, B; Goodill, A; Green, J; Hermon, C; Key, T; Langston, N; Lewis, C; Reeves, G; Collins, R; Doll, R; Peto, R; Mabuchi, K; Preston, D; Hannaford, P; Kay, C; Rosero-Bixby, L; Gao, Y T; Jin, F; Yuan, J-M; Wei, H Y; Yun, T; Zhiheng, C; Berry, G; Cooper Booth, J; Jelihovsky, T; MacLennan, R; Shearman, R; Wang, Q-S; Baines, C-J; Miller, A B; Wall, C; Lund, E; Stalsberg, H; Shu, X O; Zheng, W; Katsouyanni, K; Trichopoulou, A; Trichopoulos, D; Dabancens, A; Martinez, L; Molina, R; Salas, O; Alexander, F E; Anderson, K; Folsom, A R; Hulka, B S; Bernstein, L; Enger, S; Haile, R W; Paganini-Hill, A; Pike, M C; Ross, R K; Ursin, G; Yu, M C; Longnecker, M P; Newcomb, P; Bergkvist, L; Kalache, A; Farley, T M M; Holck, S; Meirik, O

    2002-11-18

    Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship

  16. Development of a questionnaire to measure heart disease risk knowledge in people with diabetes: the Heart Disease Fact Questionnaire.

    Science.gov (United States)

    Wagner, Julie; Lacey, Kimberly; Chyun, Deborah; Abbott, Gina

    2005-07-01

    This paper describes a paper and pencil questionnaire that measures heart disease risk knowledge in people with diabetes. The Heart Disease Fact Questionnaire (HDFQ) is a 25-item questionnaire that was developed to tap into respondents' knowledge of major risk factors for the development of CHD. Approximately half of these items specifically address diabetes-related CHD risk factors. Based on extensive pilot data, the current study analyzed responses from 524 people with diabetes to assess the psychometric properties. The HDFQ is readable to an average 13-year old and imposes little burden. It shows good content and face validity. It demonstrates adequate internal consistency, with Kuder-Richardson-20 formula = 0.77 and good item-total correlations. Item analysis showed a desirable range in P-values. In discriminant function analyses, HDFQ scores differentiated respondents by knowledge of their own cardiovascular health, use of lipid lowering medications, health insurance status, and educational attainment, thus indicating good criterion related validity. This measure of heart disease risk knowledge is brief, understandable to respondents, and easy to administer and score. Its potential for use in research and practice is discussed. Future research should establish norms as well as investigate its test-retest reliability and predictive validity.

  17. 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.

  18. Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Paola eGamba

    2015-06-01

    Full Text Available Alzheimer’s disease (AD, the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid β peptides and neurofibrillary tangles within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism.The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier. The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death.This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis.

  19. 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.

  20. Communicable disease policy development in response to changing European political frontiers in Finland, Norway and Sweden.

    Science.gov (United States)

    Bernitz, Brita Kaltenbrunner

    2008-11-01

    The European Union (EU) enlargement of 2004 brings both opportunities and challenges for public health. It is believed that further integration will bring direct health benefits, mainly through improved socioeconomic conditions, but there are also risks associated with the EU expansion, in particular cross-border health risks, such as the impact of the internal EU market policy of free movement and migration on communicable disease patterns. Against this background, this article examines communicable disease policy development in Finland, Norway and Sweden in response to changing European political frontiers, in particular the EU accession of the Baltic States. The emphasis is on HIV/AIDS and tuberculosis. The study is based on a qualitative and quantitative approach, using two complementary methods: documentary analysis and stakeholder analysis. The article identifies a distinct pattern in communicable disease policy development between 1990 and 2005. The turn of the new millennium saw a sharp increase in national attention and the priority assigned to communicable diseases in Finland, Norway and Sweden. The article argues that this development is likely to be related to the rising national, regional and European awareness of the public health challenges associated with communicable diseases in today's borderless Europe. It also shows that the Baltic health situation is a particular concern for Finland. Although there is increasing national and regional activity within the communicable disease area, there is a need for a more effective European approach to tackle the future communicable disease challenges that may follow in an increasingly interdependent and integrated Europe.

  1. 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)

  2. Development of High Spectral Resolution Technique for Registration Quasielastic Light Scattering Spectra Including Rayleigh and Brillouin Scattering as a Diagnostic Tool in Materials Characterization

    National Research Council Canada - National Science Library

    Bairamov, Bakhysh

    2004-01-01

    ...: As detailed in an on-line proposal the contractor will: 1) develop and build an optical device, fitted to a Fabry-Perot interferometer, to perform high-resolution quasieleastic light scattering spectroscopy; 2...

  3. 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.

  4. 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.

  5. Protocol for a qualitative study exploring perspectives on the INternational CLassification of Diseases (11th revision); Using lived experience to improve mental health Diagnosis in NHS England: INCLUDE study.

    Science.gov (United States)

    Hackmann, Corinna; Green, Amanda; Notley, Caitlin; Perkins, Amorette; Reed, Geoffrey M; Ridler, Joseph; Wilson, Jon; Shakespeare, Tom

    2017-09-03

    Developed in dialogue with WHO, this research aims to incorporate lived experience and views in the refinement of the International Classification of Diseases Mental and Behavioural Disorders 11th Revision (ICD-11). The validity and clinical utility of psychiatric diagnostic systems has been questioned by both service users and clinicians, as not all aspects reflect their lived experience or are user friendly. This is critical as evidence suggests that diagnosis can impact service user experience, identity, service use and outcomes. Feedback and recommendations from service users and clinicians should help minimise the potential for unintended negative consequences and improve the accuracy, validity and clinical utility of the ICD-11. The name INCLUDE reflects the value of expertise by experience as all aspects of the proposed study are co-produced. Feedback on the planned criteria for the ICD-11 will be sought through focus groups with service users and clinicians. The data from these groups will be coded and inductively analysed using a thematic analysis approach. Findings from this will be used to form the basis of co-produced recommendations for the ICD-11. Two service user focus groups will be conducted for each of these diagnoses: Personality Disorder, Bipolar I Disorder, Schizophrenia, Depressive Disorder and Generalised Anxiety Disorder. There will be four focus groups with clinicians (psychiatrists, general practitioners and clinical psychologists). This study has received ethical approval from the Coventry and Warwickshire HRA Research Ethics Committee (16/WM/0479). The output for the project will be recommendations that reflect the views and experiences of experts by experience (service users and clinicians). The findings will be disseminated via conferences and peer-reviewed publications. As the ICD is an international tool, the aim is for the methodology to be internationally disseminated for replication by other groups. ClinicalTrials.gov: NCT03131505

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

    Science.gov (United States)

    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.

  7. Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes.

    Science.gov (United States)

    Collins, F A; Murphy, D L; Reiss, A L; Sims, K B; Lewis, J G; Freund, L; Karoum, F; Zhu, D; Maumenee, I H; Antonarakis, S E

    1992-01-01

    Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. The role of industry in the development of a product for control of mycoplasmal plant diseases.

    Science.gov (United States)

    Carroll, V J

    1982-01-01

    A number of mycoplasmal or mycoplasma-like diseases of plants have been treated with an oxytetracycline-based product. Remission of symptoms has generally resulted, and in some instances the local use of this product under temporary governmental registrations has been approved. The use of oxytetracycline for control of many such diseases is not commercially feasible because the potential market is relatively small and the costs of development are relatively high. However, oxytetracycline products may be useful when a disease problem becomes sufficiently serious to arouse academic attention and agricultural or public concern. The commercial use of oxytetracycline hydrochloride for remission and prevention of lethal yellowing of coconut palm was begun in 1974. Use of this product for control of pear decline disease followed shortly thereafter. To date, joint participation and cooperation of the drug and agricultural industries have also resulted in the control of two important mycoplasma-like diseases of peach trees in the United States.

  13. Prenatal Diagnosis of a Case of Norrie Disease with Late Development of Bilateral Ocular Malformation.

    Science.gov (United States)

    Wu, Li Hong; Chen, Li-Hong; Xie, Hongning; Xie, Ying-Jun

    2017-06-01

    We report a case of Norrie disease, diagnosed by prenatal ultrasound, confirmed by Sanger sequencing of the DNP gene from the aborted fetal cord blood and histologically. Prenatal ultrasound revealed no abnormality in either eye at 22 +1 and 31 +4 gestational weeks, but at 36 +5 gestational weeks both eyes had massive vitreous cavity opacities with complete retinal detachment. Norrie disease was initially suspected because of an older male sibling with the disease. To our knowledge, prenatal ultrasound diagnosis of Norrie disease has been previously described only one case in 1993 in a 34-week-old fetus. The normal eye development until after 31 + 4 gestational weeks provides insight into the first manifestation and then the rapid progression of the eye disease.

  14. Including Youth with Intellectual Disabilities in Health Promotion Research: Development and Reliability of a Structured Interview to Assess the Correlates of Physical Activity among Youth

    Science.gov (United States)

    Curtin, Carol; Bandini, Linda G.; Must, Aviva; Phillips, Sarah; Maslin, Melissa C. T.; Lo, Charmaine; Gleason, James M.; Fleming, Richard K.; Stanish, Heidi I.

    2016-01-01

    Background: The input of youth with intellectual disabilities in health promotion and health disparities research is essential for understanding their needs and preferences. Regular physical activity (PA) is vital for health and well-being, but levels are low in youth generally, including those with intellectual disabilities. Understanding the…

  15. 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

  16. Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly.

    Science.gov (United States)

    van der Lely, Aart J; Gomez, Roy; Pleil, Andreas; Badia, Xavier; Brue, Thierry; Buchfelder, Michael; Burman, Pia; Clemmons, David; Ghigo, Ezio; Jørgensen, Jens Otto Lunde; Luger, Anton; van der Lans-Bussemaker, Joli; Webb, Susan M; Strasburger, Christian J

    2017-12-01

    Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.

  17. 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

  18. 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

  19. 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.

  20. Stakeholder analysis for the development of a community pharmacy service aimed at preventing cardiovascular disease.

    Science.gov (United States)

    Franco-Trigo, L; Hossain, L N; Durks, D; Fam, D; Inglis, S C; Benrimoj, S I; Sabater-Hernández, D

    Participatory approaches involving stakeholders across the health care system can help enhance the development, implementation and evaluation of health services. These approaches may be particularly useful in planning community pharmacy services and so overcome challenges in their implementation into practice. Conducting a stakeholder analysis is a key first step since it allows relevant stakeholders to be identified, as well as providing planners a better understanding of the complexity of the health care system. The main aim of this study was to conduct a stakeholder analysis to identify those individuals and organizations that could be part of a leading planning group for the development of a community pharmacy service (CPS) to prevent cardiovascular disease (CVD) in Australia. An experienced facilitator conducted a workshop with 8 key informants of the Australian health care system. Two structured activities were undertaken. The first explored current needs and gaps in cardiovascular care and the role of community pharmacists. The second was a stakeholder analysis, using both ex-ante and ad-hoc approaches. Identified stakeholders were then classified into three groups according to their relative influence on the development of the pharmacy service. The information gathered was analyzed using qualitative content analysis. The key informants identified 46 stakeholders, including (1) patient/consumers and their representative organizations, (2) health care providers and their professional organizations and (3) institutions and organizations that do not directly interact with patients but organize and manage the health care system, develop and implement health policies, pay for health care, influence funding for health service research or promote new health initiatives. From the 46 stakeholders, a core group of 12 stakeholders was defined. These were considered crucial to the service's development because they held positions that could drive or inhibit progress

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

    Directory of Open Access Journals (Sweden)

    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

  2. Swedish children with celiac disease comply well with a gluten-free diet, and most include oats without reporting any adverse effects: a long-term follow-up study.

    Science.gov (United States)

    Tapsas, Dimitrios; Fälth-Magnusson, Karin; Högberg, Lotta; Hammersjö, Jan-Åke; Hollén, Elisabet

    2014-05-01

    The only known treatment for celiac disease is a gluten-free diet (GFD), which initially meant abstention from wheat, rye, barley, and oats. Recently, oats free from contamination with wheat have been accepted in the GFD. Yet, reports indicate that all celiac disease patients may not tolerate oats. We hypothesized that celiac children comply well with a GFD and that most have included oats in their diet. A food questionnaire was used to check our patients; 316 questionnaires were returned. Mean time on the GFD was 6.9 years, and 96.8% of the children reported that they were trying to keep a strict GFD. However, accidental transgressions occurred in 263 children (83.2%). In 2 of 3 cases, mistakes took place when the patients were not at home. Symptoms after incidental gluten intake were experienced by 162 (61.6%) patients, mostly (87.5%) from the gastrointestinal tract. Small amounts of gluten (gluten consumption. Oats were included in the diet of 89.4% of the children for a mean of 3.4 years. Most (81.9%) ate purified oats, and 45.3% consumed oats less than once a week. Among those who did not consume oats, only 5.9% refrained because of symptoms. General compliance with the GFD was good. Only the duration of the GFD appeared to influence adherence to the diet. Most patients did not report adverse effects after long-term consumption of oats. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Development of new method and protocol for cryopreservation related to embryo and oocytes freezing in terms of fertilization rate: A comparative study including review of literature

    Directory of Open Access Journals (Sweden)

    Mayadhar Barik

    2016-01-01

    Conclusions: We ensure that cryopreservation technology provided useful cell survivability, tissue and organ preservation in a proper way. Although it varies according to different laboratory conditions, it is certainly beneficial for patient′s treatment and research. Further studies are needed for standardization and development of new protocol.

  4. Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases.

    Science.gov (United States)

    Cameron, Robert B; Beeson, Craig C; Schnellmann, Rick G

    2016-12-08

    Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors.

  5. 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.

  6. 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.

  7. 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.

  8. Development of a kinetic model, including rate constant estimations, on iodine and caesium behaviour in the primary circuit of LWR's under accident conditions

    International Nuclear Information System (INIS)

    Alonso, A.; Buron, J.M.; Fernandez, S.

    1991-07-01

    In this report, a kinetic model has been developed with the aim to try to reproduce the chemical phenomena that take place in a flowing system containing steam, hydrogen and iodine and caesium vapours. The work is divided into two different parts. The first part consists in the estimation, through the Activited Complex Theory, of the reaction rate constants, for the chosen reactions, and the development of the kinetic model based on the concept of ideal tubular chemical reactor. The second part deals with the application of such model to several cases, which were taken from the Phase B 'Scoping Calculations' of the Phebus-FP Project (sequence AB) and the SFD-ST and SFD1.1 experiments. The main conclusion obtained from this work is that the assumption of instantaneous equilibrium could be inacurrate in order to estimate the iodine and caesium species distribution under severe accidents conditions

  9. Metformin - a Future Therapy for Neurodegenerative Diseases : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.

    Science.gov (United States)

    Markowicz-Piasecka, Magdalena; Sikora, Joanna; Szydłowska, Aleksandra; Skupień, Agata; Mikiciuk-Olasik, Elżbieta; Huttunen, Kristiina M

    2017-12-01

    Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformin's role in the treatment of neurodegenerative diseases, such as AD, amnestic mild cognitive impairment and Parkinson's disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformin's advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Aβ (β-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory. In regard to the beneficial effects of metformin, its anti-inflammatory and anti-oxidative properties cannot be omitted. Numerous in vitro and in vivo studies have confirmed that metformin ameliorates oxidative damage.

  10. 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.

  11. Development of a 2-h suicide prevention program for medical staff including nurses and medical residents: A two-center pilot trial.

    Science.gov (United States)

    Nakagami, Yukako; Kubo, Hiroaki; Katsuki, Ryoko; Sakai, Tomomichi; Sugihara, Genichi; Naito, Chisako; Oda, Hiroyuki; Hayakawa, Kohei; Suzuki, Yuriko; Fujisawa, Daisuke; Hashimoto, Naoki; Kobara, Keiji; Cho, Tetsuji; Kuga, Hironori; Takao, Kiyoshi; Kawahara, Yoko; Matsumura, Yumi; Murai, Toshiya; Akashi, Koichi; Kanba, Shigenobu; Otsuka, Kotaro; Kato, Takahiro A

    2018-01-01

    Suicide is a crucial global health concern and effective suicide prevention has long been warranted. Mental illness, especially depression is the highest risk factor of suicide. Suicidal risk is increased in people not only with mental illness but also with physical illnesses, thus medical staff caring for physically-ill patients are also required to manage people with suicidal risk. In the present study, we evaluated our newly developed suicide intervention program among medical staff. We developed a 2-h suicide intervention program for medical staff, based on the Mental Health First Aid (MHFA), which had originally been developed for the general population. We conducted this program for 74 medical staff members from 2 hospitals. Changes in knowledge, perceived skills, and confidence in early intervention of depression and suicide-prevention were evaluated using self-reported questionnaires at 3 points; pre-program, immediately after the program, and 1 month after program. This suicide prevention program had significant effects on improving perceived skills and confidence especially among nurses and medical residents. These significant effects lasted even 1 month after the program. Design was a single-arm study with relatively small sample size and short-term follow up. The present study suggests that the major target of this effective program is nurses and medical residents. Future research is required to validate the effects of the program with control groups, and also to assess long-term effectiveness and actual reduction in suicide rates. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-12-01

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

  13. Technology Development for Detection of Circulating Disease Biomarkers from Liquid Biopsies Using Multifunctional Nanomaterials

    Science.gov (United States)

    Balcioglu, Mustafa

    detection methods were developed by utilizing nanomaterials as a capture nanoplatform, DNA/RNA as circulating diseases-specific biomarkers and biofluids as minimally invasive sources. The first multi-marker detection approach is to engineer water-soluble two-dimensional nanoassemblies and develop methodologies to detect circulating miRNAs and DNAs in human body fluids for the state-of-the art diagnostics. Nano-graphene oxide in this approach serves as a highly stable and functional template with extraordinary ssDNA adsorption capacity and fast and ultra-efficient fluorescence quenching capability lead us to engineer a fluorescently silent nano-platform. As a first application, we demonstrate the successful utilization of nano-graphene oxide based nanoplatform for the simultaneous detection of circulating prostate cancer biomarkers from various body fluids including blood, urine, and saliva. Later, we advanced nGO-based detection nanoplatform to an easily tunable and very highly controllable stimuli-responsive nano-device by attaching thermo-responsive polymers to advance its applications and minimize the drawbacks. (Abstract shortened by ProQuest.).

  14. Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome

    DEFF Research Database (Denmark)

    Lottrup, G; Nielsen, J E; Maroun, L L

    2014-01-01

    , and in the majority of LCs, it was mutually exclusive of DLK1. LIMITATIONS, REASONS FOR CAUTION: The number of samples was relatively small and no true normal adult controls were available. True stereology was not used for LC counting, instead LCs were counted in three fields of 0.5 µm(2) surface for each sample...... in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. STUDY FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of interest....

  15. Water quality studied in areas of unconventional oil and gas development, including areas where hydraulic fracturing techniques are used, in the United States

    Science.gov (United States)

    Susong, David D.; Gallegos, Tanya J.; Oelsner, Gretchen P.

    2012-01-01

    Domestic oil and gas production and clean water are critical for economic growth, public health, and national security of the United States. As domestic oil and gas production increases in new areas and old fields are enhanced, there is increasing public concern about the effects of energy production on surface-water and groundwater quality. To a great extent, this concern arises from the improved hydraulic fracturing techniques being used today, including horizontal drilling, for producing unconventional oil and gas in low-permeability formations.

  16. Fructose as a key player in the development of fatty liver disease.

    Science.gov (United States)

    Basaranoglu, Metin; Basaranoglu, Gokcen; Sabuncu, Tevfik; Sentürk, Hakan

    2013-02-28

    We aimed to investigate whether increased consumption of fructose is linked to the increased prevalence of fatty liver. The prevalence of nonalcoholic steatohepatitis (NASH) is 3% and 20% in nonobese and obese subjects, respectively. Obesity is a low-grade chronic inflammatory condition and obesity-related cytokines such as interleukin-6, adiponectin, leptin, and tumor necrosis factor-α may play important roles in the development of nonalcoholic fatty liver disease (NAFLD). Additionally, the prevalence of NASH associated with both cirrhosis and hepatocellular carcinoma was reported to be high among patients with type 2 diabetes with or without obesity. Our research group previously showed that consumption of fructose is associated with adverse alterations of plasma lipid profiles and metabolic changes in mice, the American Lifestyle-Induced Obesity Syndrome model, which