WorldWideScience

Sample records for causing variable disease

  1. [Does vaccination cause disease?].

    Science.gov (United States)

    Zingg, W

    2005-10-01

    Not many inventions in medical history have influenced our society as much as vaccination. The concept is old and simple. When Edward Jenner published his work on cowpox, "variolation" was quite common. In this procedure, pus of patients with mild smallpox was transferred to healthy individuals. Meanwhile smallpox has been eradicated worldwide. Diseases such as poliomyelitis, diphtheria or tetanus almost disappeared in industrialized countries. The same happened with epiglottitis and meningitis due to Haemophilus influenzae type b (Hib) after vaccination against Hib was introduced in Switzerland in 1990. This success was possible because of routine vaccination. Immunization is a save procedure and adverse events are much lower than complications in the natural course of the prevented diseases. However vaccinations were accused to cause diseases themselves such as asthma, multiple sclerosis, diabetes mellitus, chronic arthritis or autism. Hitherto no large cohort study or case-control-study was able to proof responsibility of vaccines in any of these diseases. Public media are eager to publish early data from surveillance reports or case reports which are descriptive and never a principle of cause and effect. In large controlled trials there was no proof that vaccination causes asthma, hepatitis-B-vaccination causes multiple sclerosis or macrophagic myofasciitis, Hib-vaccination causes diabetes mellitus, rubella-vaccination causes chronic arthritis, measles-mumps-rubella-vaccination causes gait disturbance or thiomersal causes autism. These results are rarely published in newspapers or television. Thus, many caring parents are left with negative ideas about immunization. Looking for the best for their children they withhold vaccination and give way to resurgence of preventable diseases in our communities. This must be prevented. There is more evidence than expected that vaccination is safe and this can and must be told to parents.

  2. Common Variable Immunodeficiency Caused by FANC Mutations.

    Science.gov (United States)

    Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

    2017-07-01

    Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

  3. Lower blood glucose and variability are associated with earlier recovery from renal injury caused by episodic urinary tract infection in advanced type 2 diabetic chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Ping-Fang Chiu

    Full Text Available In our previous study, type 2 diabetic chronic kidney disease (CKD patients with glomerular filtration rates of 9 days, Group B groups. The differences in the continuous and categorical variables of the two groups were assessed separately. The mean glucose levels and their variability (using the standard deviation and the coefficient of standard deviation were compared at the fasting, midday pre-meal, evening pre-meal, and evening post-meal time points during hospitalization. We have organized the manuscript in a manner compliant with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology statement.Acute kidney injury occurred within the two groups (p = 0.007 and p = 0.001, respectively. The early-morning blood glucose levels (149.7±44.0 mg/dL and average blood glucose levels (185.6±52.0 mg/dL were better in Group A (p = 0.01, p = 0.02. Group A patients also had lower glucose variability than Group B at the different time points (p<0.05. Group A also had earlier renal recovery. More relevant pathogens were identified from blood in Group B (p = 0.038.Early-morning fasting and mean blood glucose levels and their variability can be good indicators of severe infection and predictors of renal outcome in type 2 diabetic patients with CKD and UTI.

  4. Disease Outbreaks Caused by Water.

    Science.gov (United States)

    Craun, Gunther F.

    1978-01-01

    Presents a literature review of the disease outbreaks caused by drinking polluted water, covering publications of 1976-77. Some of the waterborn outbreaks included are: (1) cholera; (2) gastroenteritis; (3) giardiasis; and (4) typhoid fever and salmonellosis. A list of 66 references is also presented. (HM)

  5. Lower blood glucose and variability are associated with earlier recovery from renal injury caused by episodic urinary tract infection in advanced type 2 diabetic chronic kidney disease.

    Science.gov (United States)

    Chiu, Ping-Fang; Wu, Chia-Lin; Huang, Ching-Hui; Liou, Hung-Hsiang; Chang, Chirn-Bin; Chang, Horng-Rong; Chang, Chia-Chu

    2014-01-01

    In our previous study, type 2 diabetic chronic kidney disease (CKD) patients with glomerular filtration rates of 9 days, Group B) groups. The differences in the continuous and categorical variables of the two groups were assessed separately. The mean glucose levels and their variability (using the standard deviation and the coefficient of standard deviation) were compared at the fasting, midday pre-meal, evening pre-meal, and evening post-meal time points during hospitalization. We have organized the manuscript in a manner compliant with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. Acute kidney injury occurred within the two groups (p = 0.007 and p = 0.001, respectively). The early-morning blood glucose levels (149.7±44.0 mg/dL) and average blood glucose levels (185.6±52.0 mg/dL) were better in Group A (p = 0.01, p = 0.02). Group A patients also had lower glucose variability than Group B at the different time points (pdiabetic patients with CKD and UTI.

  6. Meningococcal Disease: Causes and Transmission

    Science.gov (United States)

    ... patient Anyone with direct contact with the patient’s oral secretions, such as a boyfriend or girlfriend Close contacts of someone with meningococcal disease should receive antibiotics to help prevent them from getting the disease. This is known ...

  7. Addison's Disease: Symptoms and Causes

    Science.gov (United States)

    ... to keep your blood pressure normal. Androgens. These male sex hormones are produced in small amounts by the adrenal glands in both men and women. They cause sexual development in men, and influence muscle mass, libido and a sense of well-being in both ...

  8. Symptoms and Causes of Peptic Ulcer Disease

    Science.gov (United States)

    ... by both NSAIDs and H. pylori. How do NSAIDs cause a peptic ulcer? To understand how NSAIDs cause peptic ulcer disease, it is important to understand how NSAIDs work. Nonsteroidal anti-inflammatory drugs reduce pain, fever, ...

  9. Gumboro Disease Outbreaks Cause High Mortality Rates in ...

    African Journals Online (AJOL)

    Infectious bursal disease is a disease of economic importance which affects all types of chickens and causes variable mortality. ... Thirty nine outbreak farms (5 keeping broilers, 19 keeping layers and 15 keeping indigenous flock) were visited; vaccination history collected, clinical signs observed, flock size and number of ...

  10. Some causes of the variable shape of flocks of birds.

    Directory of Open Access Journals (Sweden)

    Charlotte K Hemelrijk

    Full Text Available Flocks of birds are highly variable in shape in all contexts (while travelling, avoiding predation, wheeling above the roost. Particularly amazing in this respect are the aerial displays of huge flocks of starlings (Sturnus vulgaris above the sleeping site at dawn. The causes of this variability are hardly known, however. Here we hypothesise that variability of shape increases when there are larger local differences in movement behaviour in the flock. We investigate this hypothesis with the help of a model of the self-organisation of travelling groups, called StarDisplay, since such a model has also increased our understanding of what causes the oblong shape of schools of fish. The flocking patterns in the model prove to resemble those of real birds, in particular of starlings and rock doves. As to shape, we measure the relative proportions of the flock in several ways, which either depend on the direction of movement or do not. We confirm that flock shape is usually more variable when local differences in movement in the flock are larger. This happens when a flock size is larger, b interacting partners are fewer, c the flock turnings are stronger, and d individuals roll into the turn. In contrast to our expectations, when variability of speed in the flock is higher, flock shape and the positions of members in the flock are more static. We explain this and indicate the adaptive value of low variability of speed and spatial restriction of interaction and develop testable hypotheses.

  11. Body temperature variability (Part 2): masking influences of body temperature variability and a review of body temperature variability in disease.

    Science.gov (United States)

    Kelly, Gregory S

    2007-03-01

    This is the second of a two-part review on body temperature variability. Part 1 discussed historical and modern findings on average body temperatures. It also discussed endogenous sources of temperature variability, including variations caused by site of measurement; circadian, menstrual, and annual biological rhythms; fitness; and aging. Part 2 reviews the effects of exogenous masking agents - external factors in the environment, diet, or lifestyle that can be a significant source of body temperature variability. Body temperature variability findings in disease states are also reviewed.

  12. Root cause of waterborne diseases in Pakistan

    International Nuclear Information System (INIS)

    Hashml, H.N.; Ghumman, A.R.; Malik, N.E.

    2005-01-01

    The waterborne diseases are increasing rapidly at an alarming rate in Pakistan due to poor sanitation and unsafe drinking water supplies. This study shows that about 25 percent of all the illnesses in Lahore are due to severe cases of waterborne diseases. Unhygienic sanitation system is the root cause for this scenario. Drinking water, samples were collected from different zones of the city to find out the root cause of waterborne diseases. The samples from the distribution system serving 'Kachi Abbadies' (Underdeveloped areas) were much more contaminated, may be due to non-chlorination as compared to the water which is regularly chlorinated in posh areas of the city. Contribution of soakage pits in groundwater contamination is more significant at shallow depths. From the laboratory results it is clear that water distribution in underdeveloped areas of the city is highly contaminated and ground water available at shallow depth is also infected by microbial activities. Data collected from the different hospitals to investigate the problem shows that waterborne diseases vary their trend seasonally. Here in Pakistan, rainy season (July-August) reveals maximum number of cases of waterborne diseases. Proper sanitation and water supply systems are more essential to control the influence of waterborne diseases within the country. It is strongly recommended that reputable ways of communications are urgently required to highlight the diseases related to unsafe drinking water. (author)

  13. Celiac Disease and Other Causes of Duodenitis.

    Science.gov (United States)

    Owen, Daniel R; Owen, David A

    2018-01-01

    - Patients who receive an upper gastrointestinal endoscopic examination frequently have biopsies taken from the duodenum. Accurate interpretation of duodenal biopsies is essential for patient care. Celiac disease is a common clinical concern, but pathologists need to be aware of other conditions of the duodenum that mimic celiac disease. - To review the normal histologic features of duodenal mucosa and describe the clinical and histologic findings in celiac disease and its mimics, listing the differentiating features of biopsies with villous atrophy and epithelial lymphocytosis. - The study comprises a literature review of pertinent publications as of November 30, 2016. - Celiac disease is a common cause of abnormal duodenal histology. However, many of the histologic features found in the duodenal biopsy of patients with celiac disease are also present in other conditions that affect the small bowel. Diagnostic precision may be enhanced by obtaining a careful patient history and by ancillary laboratory testing, particularly for the presence of antitissue transglutaminase antibodies.

  14. Invasive Disease Caused by Nontypeable Haemophilus Influenzae

    Centers for Disease Control (CDC) Podcasts

    2015-11-12

    Dr. Elizabeth Briere discusses Nontypeable Haemophilus influenzae which causes a variety of infections in children and adults.  Created: 11/12/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/17/2015.

  15. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  16. An unusual cause of granulomatous disease

    Directory of Open Access Journals (Sweden)

    Higgins Bernard

    2007-03-01

    Full Text Available Abstract Background Chronic granulomatous disease (CGD is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. Case presentation We describe a case of X-linked Chronic granulomatous disease (CGD diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. Conclusion Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection.

  17. Lower limb movement variability in patients with peripheral arterial disease.

    Science.gov (United States)

    Crowther, Robert G; Spinks, Warwick L; Leicht, Anthony S; Quigley, Frank; Golledge, Jonathan

    2008-10-01

    Peripheral arterial disease is a chronic obstructive disease of the arteries of the lower limb caused by atherosclerosis. The resultant decrease in blood flow can result in symptoms of pain in the lower limb on exercise known as intermittent claudication. Exercise induced pain is experienced in the calves, thigh or buttocks restricting activities of daily living and thus reducing quality of life. This study investigated lower limb movement variability in individuals with peripheral arterial disease-intermittent claudication (n=28) compared to individuals without peripheral arterial disease-intermittent claudication (control, n=25). A further aim was to examine the efficacy of various techniques used to describe single joint movement variability. All participants underwent two-dimensional angular kinematics analysis of the lower limb during normal walking. Single joint movement variability was measured using linear (spanning set and coefficient of variation) techniques. Between group differences were examined by one-way ANOVA. The peripheral arterial disease-intermittent claudication participants displayed significantly higher levels of lower limb movement variability in all joints when assessed using the coefficient of variation technique. There were no significant between group differences using the spanning set technique. Individuals with peripheral arterial disease-intermittent claudication have higher levels of lower limb movement variability and reduced walking speed compared to healthy age and mass matched controls. This variability may be an adaptation to the gradual onset of ischaemic pain in this population.

  18. [Cushing's disease caused by pituitary macroadenoma].

    Science.gov (United States)

    Rubatino, Antônio C; Pereira, Rodrigo Ferreira; Benchimol, Isaac; Laun, Ingeborg Christa

    2004-12-01

    Cushing's syndrome comprises the symptoms and signs associated with prolonged exposure to inappropriately elevated levels of free plasma glucocorticoids. When iatrogenic causes are excluded, the commonest cause of Cushing's syndrome is Cushing's disease, accounting for approximately 70% of cases. We present the case of a 20-year-old male patient with central obesity, moon face and purple-red striae, whose diagnostic investigation shows a pituitary macroadenoma. The patient was submitted to transsphenoidal hypophysectomy, but developed early recurrence. He was submitted to a second transsphenoidal intervention followed by pituitary radiation. Presently, the patient is in clinical and laboratory remission.

  19. [Epidemiology and causes of Parkinson's disease].

    Science.gov (United States)

    Lill, C M; Klein, C

    2017-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1). In addition, there are a plethora of genes causing atypical forms of parkinsonism. In contrast, idiopathic PD is of a multifactorial nature. Genome-wide association studies have established a total of 26 genetic loci for this form of the disease; however, for most of these loci the underlying functional genetic variants have not yet been identified and the respective disease mechanisms remain unresolved. Furthermore, there are a number of environmental and life style factors that are associated with idiopathic PD. Exposure to pesticides and possibly a history of head trauma represent genuine risk factors. Other PD-associated factors, such as smoking and intake of coffee and alcohol may not represent risk factors per se and the cause-effect relationship has not yet been elucidated for most of these factors. A patient with a positive family history and/or an early age of disease onset should undergo counseling with respect to a possible monogenic form of the disease. Disease prediction based on genetic, environmental and life style factors is not yet possible for idiopathic PD and potential gene-specific therapies are currently in the development or early testing phase.

  20. ETIOPATHOGENESIS OF DISEASES CAUSED BY CLOSTRIDIUM DIFFICILE

    Directory of Open Access Journals (Sweden)

    Predrag Stojanović

    2015-03-01

    Full Text Available Clostridium (C. difficile is a typical representative of the genus Clostridium. After colonization of the intestinal tract, toxigenic C. difficile strains are capable to produce two exotoxins, enterotoxin (toxin A and cytotoxin (toxin B, which cause diarrhea and colitis. Toxin A binds to specific carbohydrate receptors on the surface of intestinal cells and this is the beginning of damages in the intestinal tract which include destruction of the villi epithelium, limiting membrane, intercellular connections (zonula occludens and surface of the mucosa. If only toxin B is injected into intestinal cells, it does not cause damage nor increased fluids secretion. Probably, the reason for this is the inability of the toxin to bind to the cell membrane receptor in the intestinal tract under normal physiological conditions. Toxigenic strains of C. difficile can be found in the intestines of healthy people, without any symptoms or clinical signs (asymptomatic colonization. However, in people with risk factors, they can cause diarrhea of varying severity and life-threatening pseudomembranous colitis. These diseases are known as C. difficile associated disease - CDAD.

  1. Occupational disease caused by ionizing radiation

    International Nuclear Information System (INIS)

    Kluepfel, H.U.

    1983-01-01

    The study investigates the course of the disease of persons whose occupational exposure to radiation had resulted in impairment of their professional ability and entitled them to damages under the current regulations. 35 receivers of damages were found who by answering the question form and partly giving permission to study their file at the insurance institution under the conditions of data protection made is possible to carry through this investigation. 14 receivers of damages were occupied in the technical industry, 21 in the sector of medicine. The radiation disease acknowledged as professional concerned in 30 cases the skin, in two cases the lungs and in one case each the haematopoietic system, the eyes and the pelvic organs. In 8 indemnified, acute radiation exposure had caused the disease, in 25 the time of exposure had ranged from one year to several decades. The investigation describes when and under what professional circumstances the radiation exposure took place, the course of the disease, what kind of diagnostic and therapeutical measures were carried through and what personal and professional consequences the indemnified sustained. It gives suggestions to set up a future, more effective documentation system on the basis of the experience gathered on the occasion of this investigation with the currently valid registration system, which is unsuitable for further scientific studies, and with the currently practised methods of after-care. (orig./HP) [de

  2. Heart rate variability reactivity and new romance: Cause or consequence?

    Science.gov (United States)

    Bailey, Laura K; Davis, Ron

    2017-09-01

    There are documented physiological differences between single and coupled individuals during the "honeymoon period" of nascent romantic relationships. One such difference is in autonomic reactivity, specifically heart rate variability (HRV) reactivity. This finding had previously been interpreted as evidence of a stress buffering effect of relationship formation. The present study explored among university women two competing longitudinal hypotheses conceptualizing differences in HRV reactivity as either a cause or a consequence of romantic relationship formation. Results did not support the hypothesis that HRV reactivity changes as a consequence of beginning a new romantic relationship. Instead, lower HRV reactivity predicted greater relationship formation amongst women with low BMI and higher resting HRV. The functioning of the heart therefore predicted the likelihood that an individual would find love. These interactions may be the result of differing success rates of various mating strategies for women with low and high BMI and HRV. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Distal and variably proximal causes: education, obesity, and health.

    Science.gov (United States)

    Schafer, Markus H; Ferraro, Kenneth F

    2011-11-01

    Medical sociologists hold that social conditions generate disparities across a host of health conditions through exposure to a variety of more proximate risk factors. Though distal and proximal causes jointly influence disease, the nature of risk accumulation may differ appreciably by the link of a proximal cause to the outcome in question. This paper employs a representative sample of over 3000 American older adults to examine whether position in the educational gradient amplifies the effect of obesity on two health outcomes. Results indicate that educational inequalities amplify the effect of high body mass index on disability (unstandardized coefficients across education groups range from -.05 [ns] to .26 [p obese adults), but fail to amplify the consequences of severe obesity in the case of C-reactive protein (CRP) levels. Instead, educational gradients in CRP are most pronounced at lower levels of body mass. Sex-specific analyses further clarify these patterns, as the connections between CRP and body mass are particularly strong among women. We conclude that risk accumulation processes differ based on the proximity of causes to the health outcome under examination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Legionella (Legionnaires' Disease and Pontiac Fever): Causes and Transmission

    Science.gov (United States)

    ... Program Application CDC Legionella Healthy Swimming CDC Vessel Sanitation Program Unexplained Respiratory Disease Outbreaks (URDO) European Legionnaires’ Disease Surveillance Network (ELDSNet) Causes, How it Spreads, and People at ...

  5. Understanding the variability of magnetic storms caused by ICMEs

    Science.gov (United States)

    Benacquista, Remi; Rochel, Sandrine; Rolland, Guy

    2017-01-01

    In this paper, we study the dynamics of magnetic storms due to interplanetary coronal mass ejections (ICMEs). We used multi-epoch superposed epoch analyses (SEAs) with a choice of epoch times based on the structure of the events. By sorting the events with respect to simple large-scale features (presence of a shock, magnetic structure, polarity of magnetic clouds), this method provides an original insight into understanding the variability of magnetic storm dynamics. Our results show the necessity of seeing ICMEs and their preceding sheaths as a whole since each substructure impacts the other and has an effect on its geoeffectiveness. It is shown that the presence of a shock drives the geoeffectiveness of the sheaths, while both the shock and the magnetic structure impact the geoeffectiveness of the ICMEs. In addition, we showed that the ambient solar wind characteristics are not the same for ejecta and magnetic clouds (MCs). The ambient solar wind upstream magnetic clouds are quieter than upstream ejecta and particularly slower. We also focused on the polarity of magnetic clouds since it drives not only their geoeffectiveness but also their temporal dynamics. South-north magnetic clouds (SN-MCs) and north-south magnetic clouds (NS-MCs) show no difference in geoeffectiveness for our sample of events. Lastly, since it is well-known that sequences of events can possibly induce strong magnetic storms, such sequences have been studied using superposed epoch analysis (SEA) for the first time. We found that these sequences of ICMEs are very usual and concern about 40 % of the ICMEs. Furthermore, they cause much more intense magnetic storms than isolated events do.

  6. Chemotherapy Side Effects: A Cause of Heart Disease?

    Science.gov (United States)

    ... A cause of heart disease? Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including ...

  7. Animal diseases caused by orbiviruses, Algeria.

    Science.gov (United States)

    Madani, Hafsa; Casal, Jordi; Alba, Anna; Allepuz, Alberto; Cêtre-Sossah, Catherine; Hafsi, Leila; Kount-Chareb, Houria; Bouayed-Chaouach, Nadera; Saadaoui, Hassiba; Napp, Sebastian

    2011-12-01

    Antibodies against bluetongue virus were detected in cattle, sheep, goats, and camels in Algeria in 2008. Antibodies against epizootic hemorrhagic disease virus were detected in cattle, but antibodies against African horse sickness virus were not detected in horses and mules. Epizootic hemorrhagic disease in northern Africa poses a major risk for the European Union.

  8. Interindividual variability in social insects - proximate causes and ultimate consequences.

    Science.gov (United States)

    Jeanson, Raphaël; Weidenmüller, Anja

    2014-08-01

    Individuals within social groups often show consistent differences in behaviour across time and context. Such interindividual differences and the evolutionary challenge they present have recently generated considerable interest. Social insects provide some of the most familiar and spectacular examples of social groups with large interindividual differences. Investigating these within-group differences has a long research tradition, and behavioural variability among the workers of a colony is increasingly regarded as fundamental for a key feature of social insects: division of labour. The goal of this review is to illustrate what we know about both the proximate mechanisms underlying behavioural variability among the workers of a colony and its ultimate consequences; and to highlight the many open questions in this research field. We begin by reviewing the literature on mechanisms that potentially introduce, maintain, and adjust the behavioural differentiation among workers. We highlight the fact that so far, most studies have focused on behavioural variability based on genetic variability, provided by e.g. multiple mating of the queen, while other mechanisms that may be responsible for the behavioural differentiation among workers have been largely neglected. These include maturational, nutritional and environmental influences. We further discuss how feedback provided by the social environment and learning and experience of adult workers provides potent and little-explored sources of differentiation. In a second part, we address what is known about the potential benefits and costs of increased behavioural variability within the workers of a colony. We argue that all studies documenting a benefit of variability so far have done so by manipulating genetic variability, and that a direct test of the effect of behavioural variability on colony productivity has yet to be provided. We emphasize that the costs associated with interindividual variability have been largely

  9. Dengue disease outbreak definitions are implicitly variable

    Directory of Open Access Journals (Sweden)

    Oliver J. Brady

    2015-06-01

    Full Text Available Infectious diseases rarely exhibit simple dynamics. Outbreaks (defined as excess cases beyond response capabilities have the potential to cause a disproportionately high burden due to overwhelming health care systems. The recommendations of international policy guidelines and research agendas are based on a perceived standardised definition of an outbreak characterised by a prolonged, high-caseload, extra-seasonal surge. In this analysis we apply multiple candidate outbreak definitions to reported dengue case data from Brazil to test this assumption. The methods identify highly heterogeneous outbreak characteristics in terms of frequency, duration and case burden. All definitions identify outbreaks with characteristics that vary over time and space. Further, definitions differ in their timeliness of outbreak onset, and thus may be more or less suitable for early intervention. This raises concerns about the application of current outbreak guidelines for early warning/identification systems. It is clear that quantitatively defining the characteristics of an outbreak is an essential prerequisite for effective reactive response. More work is needed so that definitions of disease outbreaks can take into account the baseline capacities of treatment, surveillance and control. This is essential if outbreak guidelines are to be effective and generalisable across a range of epidemiologically different settings.

  10. Fibrocystic disease of breast: variable mammographic and sonography appearance

    Energy Technology Data Exchange (ETDEWEB)

    Han, Heon; Cha, Yoo Mi; Yang, Joo Hyun; Song, Ek Hyun; Hwang, Hee Yong; Chung, Hyo Sun; Park, Sung Hye [Chung Ang Gil Hospital, Incheon (Korea, Republic of)

    1993-12-15

    Fibrocystic disease of the breast is a frequent cause of abnormal mammogram and ultrasonogram in patients with breast pain. The differentiation of fibrocystic disease form fibroadenoma or carcinoma is often difficult. The present study was performed to evaluate the mammographic and sonographic features of fibrocystic disease of the breast Mammograms and sonogram s of 45 patients with pathologically proven fibrocystic disease of breast were analyzed and correlated retrospectively with the pathologic specimens. Clinically the patients had palpable breast lumps or focal skin thickening. The patients were aged 19 to 64 years(average, 37 years) Histologic examination of 29 patients with abnormal findings in mammograms and/or sonograms revealed stromal fibrosis in 28(97%), cyst formation in 24(83%), epithelial hyperplasia in 29(90%), apocrine metaplasia in 7 (24%), chronic inflammation in 15 (52%), fibroadenomatous change in 2 (7%), large pseudocyst formation in 2 (7%), calcification in 1 (3%), and/or chondroid maseptol in 1 (3%). Of 43 patients with mammograms, 23 showed no detectable lesion, even in retrospect, because of dense mammograms there were well marginated mass in 7, poorly marginated mass in 4, multiple small nodules in 2, mixed density radio opaque mass in 3, radiolucent mass in one, and asymmetrical dense breast in 3. One case had calcification within the mass, and another one had very high density nodules that showed chondroid metaplasia. In 14 patients with sonograms, the echogenicity was variable; anechoic in 2, hypoechoic in 8, isoechoic in 3, or mixed echoic in one. The shape of the lesion was round in 2, ovoid in 8, tubular in 2, and irregular in 2. The margin was well marginated in 11 and poorly marginated in 3. Fibrocystic breast disease, which is a frequent cause of breast lumps, has variable findings in mammograms and sonograms. Therefore, fibrocystic disease should be included in the differential diagnosis of breast mass when the typical

  11. Fibrocystic disease of breast: variable mammographic and sonography appearance

    International Nuclear Information System (INIS)

    Han, Heon; Cha, Yoo Mi; Yang, Joo Hyun; Song, Ek Hyun; Hwang, Hee Yong; Chung, Hyo Sun; Park, Sung Hye

    1993-01-01

    Fibrocystic disease of the breast is a frequent cause of abnormal mammogram and ultrasonogram in patients with breast pain. The differentiation of fibrocystic disease form fibroadenoma or carcinoma is often difficult. The present study was performed to evaluate the mammographic and sonographic features of fibrocystic disease of the breast Mammograms and sonogram s of 45 patients with pathologically proven fibrocystic disease of breast were analyzed and correlated retrospectively with the pathologic specimens. Clinically the patients had palpable breast lumps or focal skin thickening. The patients were aged 19 to 64 years(average, 37 years) Histologic examination of 29 patients with abnormal findings in mammograms and/or sonograms revealed stromal fibrosis in 28(97%), cyst formation in 24(83%), epithelial hyperplasia in 29(90%), apocrine metaplasia in 7 (24%), chronic inflammation in 15 (52%), fibroadenomatous change in 2 (7%), large pseudocyst formation in 2 (7%), calcification in 1 (3%), and/or chondroid maseptol in 1 (3%). Of 43 patients with mammograms, 23 showed no detectable lesion, even in retrospect, because of dense mammograms there were well marginated mass in 7, poorly marginated mass in 4, multiple small nodules in 2, mixed density radio opaque mass in 3, radiolucent mass in one, and asymmetrical dense breast in 3. One case had calcification within the mass, and another one had very high density nodules that showed chondroid metaplasia. In 14 patients with sonograms, theechogenicity was variable ; anechoic in 2, hypoechoic in 8, isoechoic in 3, or mixed echoic in one. The shape of the lesion was round in 2, ovoid in 8, tubular in 2, and irregular in 2. The margin was well marginated in 11 and poorly marginated in 3. Fibrocystic breast disease, which is a frequent cause of breast lumps, has variable findings in mammograms and sonograms. Therefore, fibrocystic disease should be included in the differential diagnosis of breast mass when the typical

  12. Equine diseases caused by known genetic mutations.

    Science.gov (United States)

    Finno, Carrie J; Spier, Sharon J; Valberg, Stephanie J

    2009-03-01

    The recent development of equine genome maps by the equine genome community and the complete sequencing of the horse genome performed at the Broad Institute have accelerated the pace of genetic discovery. This review focuses on genetic diseases in the horse for which a mutation is currently known, including hyperkalemic periodic paralysis, severe combined immunodeficiency, overo lethal white syndrome, junctional epidermolysis bullosa, glycogen branching enzyme deficiency, malignant hyperthermia, hereditary equine regional dermal asthenia, and polysaccharide storage myopathy. Emphasis is placed on the prevalence, clinical signs, etiology, diagnosis, treatment and prognosis for each disease.

  13. Pathogen Causing Disease of Diagnosis PCR Tecnology

    OpenAIRE

    SEVİNDİK, Emre; KIR, A. Çağrı; BAŞKEMER, Kadir; UZUN, Veysel

    2013-01-01

    Polimerase chain reaction (PCR) with which, the development of recombinant DNA tecnology, a technique commonly used in field of moleculer biology and genetic. Duplication of the target DNA is provided with this technique without the need for cloning. Some fungus species, bacteria, viruses constitutent an important group of pathogenicity in human, animals and plants. There are routinely applied types of PCR in the detection of pathogens infections diseases. These Nested- PCR, Real- Time PCR, M...

  14. Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

    Directory of Open Access Journals (Sweden)

    Stephanie J B Vos

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

  15. The superior vena cava syndrome caused by malignant disease

    International Nuclear Information System (INIS)

    Eren, Suat; Karaman, Adem; Okur, Adnan

    2006-01-01

    Objective: The superior vena cava (SVC) obstruction by malignant diseases is either by direct invasion and compression or by tumour thrombus of the SVC. Whatever is its cause, obstruction of the SVC causes elevated pressure in the veins draining into the SVC and increased or reversed blood flow through collateral vessels. Severity of the syndrome depends on the collateral vascular system development. Therefore, imaging of the collateral veins with variable location and connection is important in determining the extension and management of the disease. Our aims are to describe collateral vessels of the superior vena cava syndrome (SVCS) related with the malignant diseases and to assess the ability of multi-detector row CT with multiplanar and 3D volume rendering techniques in determining and describing collateral circulations. Materials and methods: We present CT angiography findings of seven patients with small cell carcinoma of the lung (n = 2), squamous cell carcinoma of the lung (n = 3), Hodgkin disease of the thorax (n = 1), and squamous cell carcinoma of the oesophagus (n = 1). The patients received contrast-enhanced CT scans of the chest and abdomen on a multi-detector row CT during breath holding at suspended inspiration. Results: CT images revealed the cause and level of the SVC obstruction in all patients with axial and multiplanar reconstructed images. The SVC showed total obstruction in five patients and partial obstruction in two patients. The most common experienced collateral vessels were azygos vein (6), intercostal veins (6), mediastinal veins (6), paravertebral veins (5), hemiazygos vein (5), thoracoepigastric vein (5), internal mammary vein (5), thoracoacromioclavicular venous plexus (5), and anterior chest wall veins (5). While one case showed the portal-systemic shunt, V. cordis media and sinus coronarius with phrenic veins were enlarged in two cases, and the left adrenal vein was enlarged in a patient. In one case, the azygos vein with reversed

  16. Acrolein Can Cause Cardiovascular Disease: A Review.

    Science.gov (United States)

    Henning, Robert J; Johnson, Giffe T; Coyle, Jayme P; Harbison, Raymond D

    2017-07-01

    Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

  17. Mechanisms of Disease and Clinical Features of Mutations of the Gene for Mitofusin 2: An Important Cause of Hereditary Peripheral Neuropathy with Striking Clinical Variability in Children and Adults

    Science.gov (United States)

    Ouvrier, Robert; Grew, Simon

    2010-01-01

    Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial membrane, promotes membrane fusion and is involved in the maintenance of the morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2 ("MFN2") have recently been identified as the cause of approximately one-third of dominantly inherited cases of the…

  18. Chronic heart disease caused by irradiation

    International Nuclear Information System (INIS)

    Horimoto, Masashi; Matsuhashi, Hironobu; Nakano, Hiroshi; Honda, Hajime; Sekiguchi, Morie.

    1988-01-01

    An analysis was made of 5 patients who had chronic heart disease 18 months to 13 years after radiation therapy for breast cancer or rib osteoblastoma. A total dose of X-ray or electron beam was ≥50 Gy for each patient. Computed tomography of the chest and cardiac catheterization led to the diagnosis of constrictive pericarditis with chronic pericardial effusion in one patient and chronic effusive pericarditis in the other three patients. Complete or incomplete right bundle branch block was observed on ECG in 3 patients. Endomyocardial biopsy of the right ventricle for 4 patients revealed nonspecific pathological findings, such as hypertrophy, disarray of cardiac muscle cells, various sized cell nuclei, rarefaction of myofibrils, and slight interstitial fibrosis with infrequent cellular infiltration. The results may implicate radiation-induced myocardial disturbance. Long-term follow-up is mandatory for the management of patients treated with radiation. (Namekawa, K.)

  19. Crustal displacements in Greenland caused by ice mass variability

    DEFF Research Database (Denmark)

    Nielsen, Karina

    Isstrøm and Jakobshavn Isbræ. GIA is an important correction in gravity-based mass balance estimates. It is therefore important to obtain reliable GIA predictions. Observed rates of crustal displacement can be used to constrain the GIA response, assuming that the presentday response, can be accurately....... Gradients of crustal displacement rates near Upernavik Isstrøm and Jakobshavn Isbræ are modeled and compared to observed rates, to assess the mass balance of these glaciers. By considering displacement gradients, contributions from the mass loss of the rest of the ice sheet and GIA are reduced. Hence......The climate of the Earth is changing. A consequence of this is observed at the polar regions such as Greenland, where the ice sheet is melting with an increasing rate. The unloading of ice causes the Earth to respond elastically in terms of uplift and an outward horizontal deformation of the crust...

  20. [A brief history of the natural causes of human disease].

    Science.gov (United States)

    Lips-Castro, Walter

    2015-01-01

    In the study of the causes of disease that have arisen during the development of humankind, one can distinguish three major perspectives: the natural, the supernatural, and the artificial. In this paper we distinguish the rational natural causes of disease from the irrational natural causes. Within the natural and rational causal approaches of disease, we can highlight the Egyptian theory of putrid intestinal materials called "wechdu", the humoral theory, the atomistic theory, the contagious theory, the cellular theory, the molecular (genetic) theory, and the ecogenetic theory. Regarding the irrational, esoteric, and mystic causal approaches to disease, we highlight the astrological, the alchemical, the iatrochemical, the iatromechanical, and others (irritability, solidism, brownism, and mesmerism).

  1. Modelling studies on neurodegenerative disease-causing triplet ...

    Indian Academy of Sciences (India)

    Unknown

    degenerative diseases are caused by expansion of triplet repeats. To date, more than twelve human genetic diseases, including myotonic dystrophy (dystrophia myotonica,. DM), fragile X syndrome (FraX), Huntington disease. (HD), several spinocerebellar ataxias and Friedreich ataxia have been associated with the ...

  2. Does disease cause vaccination? Disease outbreaks and vaccination response.

    Science.gov (United States)

    Oster, Emily

    2017-11-02

    Parental fear of vaccines has limited vaccination rates in the United States. I test whether disease outbreaks increase vaccination using a new dataset of county-level disease and vaccination data. I find that pertussis (whooping cough) outbreaks in a county decrease the share of unvaccinated children entering kindergarten. These responses do not reflect changes in the future disease risk. I argue that these facts are best fit by a model in which individuals are both myopic and irrational. This suggests that better promotion of information about outbreaks could enhance the response. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Mutations that Cause Human Disease: A Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Beernink, P; Barsky, D; Pesavento, B

    2006-01-11

    International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximately half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which

  4. Celiac disease: A missed cause of metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Ashu Rastogi

    2012-01-01

    Full Text Available Introduction: Celiac disease (CD is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002-2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6% of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

  5. Addressing parents' concerns: do vaccines cause allergic or autoimmune diseases?

    Science.gov (United States)

    Offit, Paul A; Hackett, Charles J

    2003-03-01

    Anecdotal case reports and uncontrolled observational studies in the medical literature claim that vaccines cause chronic diseases such as asthma, multiple sclerosis, chronic arthritis, and diabetes. Several biological mechanisms have been proposed to explain how vaccines might cause allergic or autoimmune diseases. For example, allergic diseases might be caused by prevention of early childhood infections (the "hygiene hypothesis"), causing a prolongation of immunoglobulin E-promoting T-helper cell type 2-type responses. However, vaccines do not prevent most common childhood infections, and large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies. Autoimmune diseases might occur after immunization because proteins on microbial pathogens are similar to human proteins ("molecular mimicry") and could induce immune responses that damage human cells. However, wild-type viruses and bacteria are much better adapted to growth in humans than vaccines and much more likely to stimulate potentially damaging self-reactive lymphocytes. Consistent with critical differences between natural infection and immunization, well-controlled epidemiologic studies do not support the hypothesis that vaccines cause autoimmunity. Flaws in proposed biological mechanisms that explain how vaccines might cause chronic diseases are consistent with the findings of many well-controlled large epidemiologic studies that fail to show a causal relationship.

  6. Echinococcal disease of the bone: An unusual cause of a ...

    African Journals Online (AJOL)

    Echinococcosis is caused by the larva of the tapeworm, Echinococcus granulosus or Echinococcus multiloccularis and is endemic in many rural areas of southern Africa. Echinococcosis of the bone is an unusual manifestation of echinococcal disease and a rare cause of a lytic lesion of bone. This report describes a ...

  7. Hereditary Causes of Kidney Stones and Chronic Kidney Disease

    Science.gov (United States)

    Edvardsson, Vidar O.; Goldfarb, David S.; Lieske, John C.; Beara-Lasic, Lada; Anglani, Franca; Milliner, Dawn S.; Palsson, Runolfur

    2013-01-01

    Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC and PH with emphasis on childhood manifestations. PMID:23334384

  8. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    NARCIS (Netherlands)

    J. Aaltonen (Johanna); P. Björses (Petra); L.A. Sandkuijl (Lodewijk); J. Perheentupa (Jaakko); L. Peltonen (Leena Johanna)

    1994-01-01

    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does

  9. Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish

    Directory of Open Access Journals (Sweden)

    Kathryn Bambino

    2018-02-01

    Full Text Available The rapid increase in fatty liver disease (FLD incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD. We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf, including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR caused by endoplasmic reticulum (ER stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin, suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease. This article has an associated First Person interview with the first author of the paper.

  10. Cause-Specific Mortality Among Spouses of Parkinson Disease Patients

    DEFF Research Database (Denmark)

    Nielsen, Malene; Hansen, Jonni; Ritz, Beate

    2014-01-01

    BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson...... disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among...... men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1...

  11. Spontaneous expulsive suprachoroidal hemorrhage caused by decompensated liver disease

    Directory of Open Access Journals (Sweden)

    Krishnagopal Srikanth

    2013-01-01

    Full Text Available Expulsive suprachoroidal hemorrhage can be surgical or spontaneous. Spontaneous expulsive suprachoroidal hemorrhage (SESCH is a rare entity. Most of the reported cases of SESCH were caused by a combination of corneal pathology and glaucoma. We are reporting a rare presentation of SESCH with no pre-existing glaucoma or corneal pathology and caused by massive intra- and peri-ocular hemorrhage due to decompensated liver disease.

  12. Diseases caused by Ganoderma spp. on perennial crops in Pakistan.

    Science.gov (United States)

    Nasir, Nasreen

    2005-01-01

    Ganoderma applanatum (Pres. Wallr) Pat. and G. lucidum (Leyss. ex Fr.) Karst attack species of Pinus, Dalbergia, Artocarpus, Morus, Cedrus, Melia, Quercus, Populus and other trees in Pakistan causing stem, butt and root rot diseases. A research institution to manage the diseases of perennial crops in general and of trees yielding edible oil in particular such as coconut and oil palm needs to be established in Pakistan.

  13. Lipoprotein (a) as a cause of cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Langsted, Anne

    2016-01-01

    Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly supports that elevated lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve...... with very high concentrations to reduce cardiovascular disease are awaited. Recent genetic evidence documents elevated Lp(a) as a cause of myocardial infarction, atherosclerotic stenosis, and aortic valve stenosis....

  14. Lack of exercise is a major cause of chronic diseases

    Science.gov (United States)

    Booth, Frank W.; Roberts, Christian K.; Laye, Matthew J.

    2014-01-01

    Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life

  15. Frequency of causes of chronic liver disease in children

    International Nuclear Information System (INIS)

    Shah, S.Z.; Malik, R.; Shah, S.F.; Idrees, S.; Hameed, S.

    2017-01-01

    Objective: To determine the etiology of chronic liver disease in children. Study Design: Descriptive cross sectional. Place and Duration of Study: Department of Paediatrics, Combined Military Hospital Lahore, from Jun 2014 to Dec 2014. Material and Methods: This is a descriptive cross sectional study conducted at department of Paediatrics, Combined Military Hospital Lahore from 1st June 2014 to 31st December 2014. It included 150 consecutive paediatric patients (1-14 years) with chronic liver disease. Results: Out of 150 children 95 (63.33%) were male and 55 (36.66%) were females. The mean age of the children included in the study was 7.2 +- 4.6 years and the age range was 1 year to 14 years. Viral hepatitis (61, 40.67%) was the commonest cause of the liver disease followed by glycogen storage disease (11, 7.33%) and Wilson's disease in 13 (8.6%). Conclusion: There are various causes of chronic liver disease in children most common being hepatitis B and C infection. The early identification of etiology of chronic liver disease in children is of cardinal importance for optimal management of these cases.

  16. Neuromuscular Electrical Stimulation Therapy for Dysphagia Caused by Wilson's Disease

    Science.gov (United States)

    Lee, Seon Yeong; Yang, Hee Seung; Lee, Seung Hwa; Jeung, Hae Won; Park, Young Ok

    2012-01-01

    Wilson's disease is an autosomal recessive disorder of abnormal copper metabolism. Although dysphagia is a common complaint of patients with Wilson's disease and pneumonia is an important cause of death in these patients, management of swallowing function has rarely been reported in the context of Wilson's disease. Hence, we report a case of Wilson's disease presenting with dysphagia. A 33-year-old man visited our hospital with a complaint of difficulty in swallowing, since about last 7 years and which had worsened since the last 2-3 months. He was diagnosed with Wilson's disease about 13 years ago. On the initial VFSS, reduced hyoid bone movement, impaired epiglottic movement and moderate amount of residue in the valleculae during the pharyngeal phase were noted. After 10 sessions of neuromuscular electrical stimulation for 1 hour per day, decreased amount of residue was observed in the valleculae during the pharyngeal phase on the follow-up VFSS. PMID:22837979

  17. Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Orsted, David Dynnes; Nordestgaard, Børge Grønne

    2014-01-01

    of cancer (p = .002), ischemic heart disease (p = 4 × 10(-99)), chronic obstructive pulmonary disease (p = 6 × 10(-86)), and all-cause mortality (p = .001) examined in the same individuals. CONCLUSIONS: Elevated CRP was associated with increased risk of depression in individuals in the general population......BACKGROUND: Elevated levels of plasma C-reactive protein (CRP) have been associated with many diseases including depression, but it remains unclear whether this association is causal. We tested the hypothesis that CRP is causally associated with depression, and compared these results to those...... for cancer, ischemic heart disease, chronic obstructive pulmonary disease, and all-cause mortality. METHODS: We performed prospective and instrumental variable analyses using plasma CRP levels and four CRP genotypes on 78,809 randomly selected 20- to 100-year-old men and women from the Danish general...

  18. Chemical control of blossom blight disease of sarpagandha caused ...

    African Journals Online (AJOL)

    ONOS

    2010-09-20

    Sep 20, 2010 ... Sarpagandha (Rauvolfia serpentina Benth) is grown in different parts of India and its adjoining countries for its root which is the chief source of ... There are many reports on the chemical control of the diseases caused by the pathogen, .... infection of weed seedlings by H. sativum. J. Agric. Res. 5: 195-217.

  19. Diseases and causes of death among the Popes | Retief | Acta ...

    African Journals Online (AJOL)

    ... terminal kidney disease, gallstones, cancer, dysentery, the plague, lung infection, gangrene of a leg, abscesses, depression or debilitating psychiatric illness. Unnatural causes comprise inter alia assassination, death in prison or in exile, casualties of war or public violence, poisoning and stoning during street violence.

  20. Diseases of pines caused by the pitch canker fungus

    Science.gov (United States)

    L. David Dwinell; Stephen W. Fraedrich; D. Adams

    2001-01-01

    Fusarium subglutinans f. sp. pini, the pitch canker fungus, causes a number of serious diseases of Pinus species. The pathogen infects a variety of vegetative and reproductive pine structures at different stages of maturity and produces a diversity of symptoms. When the pathogen infects the woody vegetative...

  1. Danon’s disease as a cause of hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    I. V. Leontyeva

    2015-01-01

    Full Text Available Hypertrophic cardiomyopathy is the most common inherited disease of the myocardium. The causes of the disease are heterogeneous; its primary form results from mutations in the genes encoding cardiac sarcomeric proteins; its secondary (metabolic and syndromic forms develop due to mutations in the genes encoding non-sarcomeric proteins. Glycogenosis is the most common cause of the metabolic ones of hypertrophic cardiomyopathy. Danon’s disease (lysosome-associated membrane protein 2 (LAMP2-cardiomyopathy is a form of glycogenosis and it is characterized by a typical triad: hypertrophic cardiomyopathy, mental retardation, and skeletal myopathy. The disease occurs with mutations in the LAMP2 gene; X-linked dominant inheritance. LAMP2-cardiomyopathy does not virtually differ in its clinical manifestations from the severe form of hypertrophic cardiomyopathy, which results from mutations in the sarcomeric protein genes. The disease is characterized by a poor progressive course with the high probability of causing sudden death or with the progression of severe heart failure. Implantation of a cardioverter defibrillator is a main method to prevent sudden cardiac death. 

  2. Variability in the clinical expression of Parkinson's disease

    NARCIS (Netherlands)

    Wolters, E.C.

    2008-01-01

    Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo-/akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's disease (PD). Symptoms of PD are due to a progressive loss of nigral neurons causing striatal dopaminergic denervation. However, nigral degeneration

  3. Diagnostics of vascular diseases as a cause for acute abdomen

    International Nuclear Information System (INIS)

    Juchems, M.S.; Aschoff, A.J.

    2010-01-01

    Vascular pathologies are rare causes of an acute abdomen. If the cause is a vascular disease a rapid diagnosis is desired as vascular pathologies are associated with high mortality. A differentiation must be made between arterial and venous diseases. An occlusion of the superior mesenteric artery is the most common reason for acute mesenteric ischemia but intra-abdominal arterial bleeding is also of great importance. Venous pathologies include thrombotic occlusion of the portal vein, the mesenteric vein and the vena cava. Multi-detector computed tomography (MDCT) is predestined for the diagnostics of vascular diseases of the abdomen. Using multiphasic contrast protocols enables reliable imaging of the arterial and venous vessel tree and detection of disorders with high sensitivity and specificity. Although conventional angiography has been almost completely replaced by MDCT as a diagnostic tool, it is still of high importance for minimally invasive interventions, for example in the management of gastrointestinal bleeding. (orig.) [de

  4. Streptococcus mitis Strains Causing Severe Clinical Disease in Cancer Patients

    Science.gov (United States)

    Sahasrabhojane, Pranoti; Saldana, Miguel; Yao, Hui; Su, Xiaoping; Horstmann, Nicola; Thompson, Erika; Flores, Anthony R.

    2014-01-01

    The genetically diverse viridans group streptococci (VGS) are increasingly recognized as the cause of a variety of human diseases. We used a recently developed multilocus sequence analysis scheme to define the species of 118 unique VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68 patients) and S. oralis (22 patients) were the most frequently identified strains. Compared with patients infected with non–S. mitis strains, patients infected with S. mitis strains were more likely to have moderate or severe clinical disease (e.g., VGS shock syndrome). Combined with the sequence data, whole-genome analyses showed that S. mitis strains may more precisely be considered as >2 species. Furthermore, we found that multiple S. mitis strains induced disease in neutropenic mice in a dose-dependent fashion. Our data define the prominent clinical effect of the group of organisms currently classified as S. mitis and lay the groundwork for increased understanding of this understudied pathogen. PMID:24750901

  5. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

    Science.gov (United States)

    Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

  6. [Anaemia as a cause of haemodynamic angina in a patient with chronic ischaemic heart disease].

    Science.gov (United States)

    Miguéns Blanco, I; Bravo Amaro, M

    2014-01-01

    Ischaemic heart disease is the leading cause of mortality and morbidity and one of the primary causes of morbidity in Spain. The variability in the clinical presentation of this condition at both primary care and emergency services level requires a careful history and a thorough physical examination. In the case presented, the main symptoms of angina and dyspnea reported in the anamnesis, and the obvious pallor in the physical examination, were the key data to identify anaemia as a cause of angina. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  7. Controlling disease and creating disparities: a fundamental cause perspective.

    Science.gov (United States)

    Phelan, Jo C; Link, Bruce G

    2005-10-01

    The United States and other developed countries experienced enormous improvements in population health during the 20th century. In the context of this dramatic positive change, health disparities by race and socioeconomic status emerged for several potent killers. Any explanation for current health disparities must take these changing patterns into account. Any explanation that ignores large improvements in population health and fails to account for the emergence of disparities for specific diseases is an inadequate explanation of current disparities. We argue that genetic explanations and some prominent social causation explanations are incompatible with these facts. We propose that the theory of "fundamental causes" can account for both vast improvements in population health and the creation of large socioeconomic and racial disparities in mortality for specific causes of death over time. Specifically, we argue that it is our enormously expanded capacity to control disease and death in combination with existing social and economic inequalities that create health disparities by race and socioeconomic status: When we develop the ability to control disease and death, the benefits of this new-found ability are distributed according to resources of knowledge, money, power, prestige, and beneficial social connections. We present data on changing mortality patterns by race and socioeconomic status for two types of diseases: those for which our capacity to prevent death has increased significantly and those for which we remain largely unable to prevent death. Time trends in mortality patterns are consistent with the fundamental cause explanation.

  8. Helicobacter pylori and autoimmune disease: Cause or bystander

    Science.gov (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  9. Adult Scheuermann’s disease as cause of mechanic dorsalgia

    OpenAIRE

    F.P. Cantatore; N. Santoro; M.F. Soragnese; A. Corrado; A. Trotta

    2011-01-01

    Scheuermann’s disease (SD) or vertebral osteochondrosis is the most frequent cause of non postural kyphosis and one of more frequent cause of adolescent’s dorsalgia. The criteria for the diagnosis are: more than 5° of wedging of at least three adjacent vertebrae at the apex of the kyphosis; a toracic kyphosis of more than 45° of Cobb’s degree; Schmorl’s nodes and endplates irregularities. In addition to classic SD, there are radiological alterations that remain asintomatic for a long time to ...

  10. Management of Measurable Variable Cardiovascular Disease' Risk Factors.

    Science.gov (United States)

    Zaninovic, Sonja Francula; Nola, Iskra A

    2018-02-21

    To summarize the main findings on variable cardiovascular risk factors and their management in everyday practice. A narrative review of the relevant literature known to the authors and incorporation of healthy changes tips in defined variable cardiovascular risk factors. There are known variable cardiovascular risk factors to be claimed as those that should be changed in order to achieve a better prevention of cardiovascular disease development. But, most papers are informative and they didn't incorporate exact measures for each variable risk factor. Our paper shows exact measures for each variable cardiovascular risk factor that should be incorporate in everyday practice of family practitioners and cardiologists as well. The best cardiovascular disease' prevention should include a multidisciplinary team of experts and the entire community with the support of governmental and non-governmental organizations that will contribute to improving the lifestyle of individuals and the entire community through their activities and legal provisions. The most important factors in cardiovascular disease management are: recognizing individual risk factors, monitoring them, and assisting in changes in life-style habits that directly affect the defined risk factors of a patient. The simplest and most practicable guidelines for CV prevention in accordance with the national, cultural and socioeconomic aspects of their country of work are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    African Journals Online (AJOL)

    Administrator

    GENETIC VARIABILITY FOR TUBER YIELD, QUALITY, AND VIRUS DISEASE. COMPLEX TRAITS IN UGANDA SWEETPOTATO GERMPLASM. E. GASURA, A.B. MASHINGAIDZE1 and S.B. MUKASA. Department of Crop Science, Makerere University, P. O. Box 7062 Kampala, Uganda. 1Department of Crop Science, ...

  12. The unresolved puzzle why alanine extensions cause disease.

    Science.gov (United States)

    Winter, Reno; Liebold, Jens; Schwarz, Elisabeth

    2013-08-01

    The prospective increase in life expectancy will be accompanied by a rise in the number of elderly people who suffer from ill health caused by old age. Many diseases caused by aging are protein misfolding diseases. The molecular mechanisms underlying these disorders receive constant scientific interest. In addition to old age, mutations also cause congenital protein misfolding disorders. Chorea Huntington, one of the most well-known examples, is caused by triplet extensions that can lead to more than 100 glutamines in the N-terminal region of huntingtin, accompanied by huntingtin aggregation. So far, nine disease-associated triplet extensions have also been described for alanine codons. The extensions lead primarily to skeletal malformations. Eight of these proteins represent transcription factors, while the nuclear poly-adenylate binding protein 1, PABPN1, is an RNA binding protein. Additional alanines in PABPN1 lead to the disease oculopharyngeal muscular dystrophy (OPMD). The alanine extension affects the N-terminal domain of the protein, which has been shown to lack tertiary contacts. Biochemical analyses of the N-terminal domain revealed an alanine-dependent fibril formation. However, fibril formation of full-length protein did not recapitulate the findings of the N-terminal domain. Fibril formation of intact PABPN1 was independent of the alanine segment, and the fibrils displayed biochemical properties that were completely different from those of the N-terminal domain. Although intranuclear inclusions have been shown to represent the histochemical hallmark of OPMD, their role in pathogenesis is currently unclear. Several cell culture and animal models have been generated to study the molecular processes involved in OPMD. These studies revealed a number of promising future therapeutic strategies that could one day improve the quality of life for the patients.

  13. Causes of chronic kidney disease in Egyptian children

    Directory of Open Access Journals (Sweden)

    Hesham Safouh

    2015-01-01

    Full Text Available There are very few published reports on the causes of chronic kidney disease (CKD in Egyptian children. We reviewed the records of 1018 (males 56.7%, age ranged from 1 to 19 years Egyptian patients suffering from CKD and followed-up at the pediatric nephrology units (outpatient clinics and dialysis units of 11 universities over a period of two years. The mean of the estimated glomerular filtration rate was 12.5 mL/min/1.73 m 2 . Children with CKD stage I and stage II comprised 4.4% of the studied group, while those with stage III, IV and V comprised 19.7%, 18.3% and 57.6%, respectively. The most common single cause of CKD was obstructive uropathy (21.7%, followed by primary glomerulonephritis (15.3%, reflux/urinary tract infection (14.6%, aplasia/hypoplasia (9.8% and familial/metabolic diseases (6.8%; unknown causes accounted for 20.6% of the cases. Of the 587 patients who had reached end-stage renal disease, 93.5% was treated with hemodialysis and only 6.5% were treated with peritoneal dialysis.

  14. Vascular pathology: Cause or effect in Alzheimer disease?

    Science.gov (United States)

    Rius-Pérez, S; Tormos, A M; Pérez, S; Taléns-Visconti, R

    2018-03-01

    Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Prioritizing disease-causing microbes based on random walking on the heterogeneous network.

    Science.gov (United States)

    Shen, Xianjun; Chen, Yao; Jiang, Xingpeng; Hu, Xiaohua; He, Tingting; Yang, Jincai

    2017-07-15

    As we all know, the microbiota show remarkable variability within individuals. At the same time, those microorganisms living in the human body play a very important role in our health and disease, so the identification of the relationships between microbes and diseases will contribute to better understanding of microbes interactions, mechanism of functions. However, the microbial data which are obtained through the related technical sequencing is too much, but the known associations between the diseases and microbes are very less. In bioinformatics, many researchers choose the network topology analysis to solve these problems. Inspired by this idea, we proposed a new method for prioritization of candidate microbes to predict potential disease-microbe association. First of all, we connected the disease network and microbe network based on the known disease-microbe relationships information to construct a heterogeneous network, then we extended the random walk to the heterogeneous network, and used leave-one-out cross-validation and ROC curve to evaluate the method. In conclusion, the algorithm could be effective to disclose some potential associations between diseases and microbes that cannot be found by microbe network or disease network only. Furthermore, we studied three representative diseases, Type 2 diabetes, Asthma and Psoriasis, and finally presented the potential microbes associated with these diseases by ranking candidate disease-causing microbes, respectively. We confirmed that the discovery of the new associations will be a good clinical solution for disease mechanism understanding, diagnosis and therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Identification of a Disease on Cocoa Caused by Fusariumin Sulawesi

    Directory of Open Access Journals (Sweden)

    Ade Rosmana

    2013-12-01

    Full Text Available A disease presumed to be caused by Fusarium was observed in cocoa open fields with few or without shade trees. Within the population of cocoa trees in the field, some trees had died, some had yellowing leaves and dieback, and the others were apparently healthy. In order to demonstrate Fusarium species as the causal pathogen and to obtain information concerning the incidence of the disease, its distribution and its impact on sustainability of cocoa, isolation of the pathogen, inoculation of cocoa seedlings with isolates and a survey of disease has been conducted. Fusarium was isolated from roots and branches, and inoculated onto cocoa seedlings (one month old via soil. Symptoms appeared within 3-4 weeks after infection. These symptoms consisted of yellowing of leaves beginning from the bottom until the leaves falldown, and browning internal of vascular tissue. Darkened vascular traces in the petiole characteristic of vascularstreak dieback infection were absent. The occurrence of Fusarium in the field was characterized by the absence of obvious signs of fungal infestation on root of infected trees, yellowing of leaves on twigs, dieback, and tree mortality in severe infestations. Disease incidence could reach 77% and in this situation it was difficult for trees recover from heavy infections or to be regenerated in the farm. The study proves that Fusarium is a pathogen causing dieback and the disease is called as Fusarium vascular dieback (FVD. Its development is apparently enhanced by dry conditions in the field. Key words: Fusarium sp., vascular disease, dieback, FVD, Theobroma cacao L.

  17. Asthma-like peak flow variability in various lung diseases

    Directory of Open Access Journals (Sweden)

    Virendra Singh

    2012-01-01

    Full Text Available Background and Objectives: Bronchodilator reversibility and diurnal peak flow variability are considered characteristic of asthma patients. Patients with chronic obstructive pulmonary disease (COPD show poor reversibility. But reversibility and variability in other pulmonary diseases manifesting with airflow obstruction in not known. Therefore, we assessed reversibility and peak flow variability in patients with various lung diseases to recognize the pattern. Materials and Methods : Seventy consecutive patients with a diagnosis of lung diseases manifesting with airflow obstruction were recruited in the study. These included 23 patients with asthma, 11 patients with bronchiectasis, 16 patients with post-tubercular lung disease (PTLD, and 20 patients with COPD. Ten healthy matched control subjects were also selected to pair with asthmatic patients. Bronchodilator reversibility test was done initially and peak expiratory flow rate (PEFR was measured for a duration of 1 week by patients themselves on a chart that was given to them. The mean amplitude percentage of these records were analyzed. Results : The mean values of peak flow variability were 14.73% ± 6.1% in asthmatic patients, 11.98% ± 7.5% in patients with bronchiectasis, and 10.54% ± 5.3% in PTLD. The difference in the mean values of peak flow variability between asthma and bronchiectasis, that is, 14.73 (6.1 vs 11.98 (7.5 was not statistically significant (P > 0.05. Forced expiratory volume one second (FEV 1 reversibility values were 14.77% ± 26.93%, 11.24% ± 20.43%, 10.85% ± 13.02%, 16.83% ± 22.84%, and 5.47% ± 4.99% in asthma, COPD, PTLD, bronchiectasis, and healthy subjects, respectively. Conclusion: Both reversibility and diurnal peak flow variability were higher in patients with various lung diseases compared with normal healthy subjects. Although these are characteristic of asthma, some cases of bronchiectasis and PTLD patients may also manifest asthma-like PEFR variability

  18. Documentation of Occupational Accidents and Diseases caused by Ionising Radiation

    International Nuclear Information System (INIS)

    Fehringer, F.; Seitz, G.

    2004-01-01

    . One of the major goals of the institutions for statutory accident insurance is the prevention of occupational diseases. To perform a successful prevention work it is necessary not only to count the number of accidents or diseases in the various working fields but to look for details of the conditions of work and the human response to those conditions. The institutions for statutory accident insurance have engaged the institution for statutory accident insurance in the precision engineering and electrical industry to carry out documentation, in form of a data bank, for all cases of occupational diseases which could be caused by ionising radiation. Those are not only the cases which are accepted as occupational disease but also the cases where a suspicion of an occupational disease is announced but finally rejected. At the moment about 1700 cases are included in the data bank. For preserving the anonymity information to name and residence are deleted. Various data to one single case are linked by a case-specific key-number. Information to occupation and field of working, to details of a possible exposure to ionising radiation like kind of radiation, time and duration of radiation, exposure of the whole body or of parts of the body and whole body or organ doses are collected. Additional information refers to medical aspects like diagnosis and date of diagnosis. (Author)

  19. Opa protein repertoires of disease-causing and carried meningococci.

    Science.gov (United States)

    Callaghan, Martin J; Buckee, Caroline; McCarthy, Noel D; Ibarz Pavón, Ana Belén; Jolley, Keith A; Faust, Saul; Gray, Stephen J; Kaczmarski, Edward B; Levin, Michael; Kroll, J Simon; Maiden, Martin C J; Pollard, Andrew J

    2008-09-01

    The meningococcal Opa proteins play an important role in pathogenesis by mediating invasion of human cells. The aim of this investigation was to determine whether carried and disease-associated meningococci possess different Opa repertoires and whether the diversity of these proteins is associated with clinical severity of disease. Opa repertoires in 227 disease-associated meningococci, isolated in the United Kingdom over a period of 6 years, were compared to the repertoires in 190 asymptomatically carried meningococci isolated in the United Kingdom from a contemporary, nonepidemic period. Multidimensional scaling (MDS) was employed to investigate the association between Opa repertoires and multilocus sequence typing (MLST) genotypes. Associations with clinical severity were also analyzed statistically. High levels of diversity were observed in opa alleles, variable regions, and repertoires, and MDS revealed that MLST genotypes were strongly associated with particular Opa repertoires. Individual Opa proteins or repertoires were not associated with clinical severity, though there was a trend toward an association with the opaD locus. Meningococcal Opa repertoire is strongly linked to MLST genotype irrespective of epidemiological sampling and therefore correlates with invasiveness. It is not, however, strongly associated with severity of meningococcal disease.

  20. Can we control all-cause meningococcal disease in Europe?

    Science.gov (United States)

    Sadarangani, M; Pollard, A J

    2016-12-01

    Invasive disease caused by Neisseria meningitidis is potentially devastating, with a case fatality rate of 5-15% and high rates of significant sequelae among survivors after septicaemia or meningitis. Capsular group C (MenC) conjugate vaccines have been highly successful in achieving control of MenC disease across Europe, and some countries have also introduced quadrivalent MenACWY conjugate vaccines to reduce disease caused by groups A, W and Y in addition to C. These vaccines putatively elicit protective levels of bactericidal antibodies in all age groups, induce immunologic memory and reduce nasopharyngeal carriage, thereby leading to herd protection. Protein-based meningococcal vaccines based on subcapsular components, and designed primarily to target capsular group B (MenB) disease, have recently been licensed. These vaccines are highly immunogenic in infants and adolescents, inducing bactericidal antibodies against strains expressing high levels of vaccine antigens which are identical to the variants present in the vaccines. Effectiveness of these vaccines at a population level will be determined by whether vaccine-induced antibodies provide cross-protection against variants of the vaccine antigens present on the surface of the diverse collection of circulating invasive strains. The level of serum bactericidal activity induced against strains also seems to depend on the level of expression of the vaccine antigens. The duration of protection and the impact on carriage of meningococci will have a major bearing on the overall effectiveness of the programme. In September 2015 the UK became the first country to introduce the multicomponent meningococcal serogroup B vaccine (4CMenB) into a national routine immunization schedule, and data on the effectiveness of this programme are anticipated in the next few years. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Sexual Orientation Disparities in Preventable Disease: A Fundamental Cause Perspective.

    Science.gov (United States)

    Bränström, Richard; Hatzenbuehler, Mark L; Pachankis, John E; Link, Bruce G

    2016-06-01

    To determine whether fundamental cause theory (which posits that, in societal conditions of unequal power and resources, members of higher-status groups experience better health than members of lower-status groups because of their disproportionate access to health-protective factors) might be relevant in explaining health disparities related to sexual orientation. We used 2001 to 2011 morbidity data from the Stockholm Public Health Cohort, a representative general population-based study in Sweden. A total of 66 604 (92.0%) individuals identified as heterosexual, 848 (1.2%) as homosexual, and 806 (1.1%) as bisexual. To test fundamental cause theory, we classified diseases in terms of preventability potential (low vs high). There were no sexual orientation differences in morbidity from low-preventable diseases. By contrast, gay or bisexual men (adjusted odds ratio [OR] = 1.48; 95% confidence interval [CI] = 1.13, 1.93) and lesbian or bisexual women (adjusted OR = 1.64; 95% CI = 1.28, 2.10) had a greater risk of high-preventable morbidity than heterosexual men and women, respectively. These differences were sustained in analyses adjusted for covariates. Our findings support fundamental cause theory and suggest that unequal distribution of health-protective resources, including knowledge, prestige, power, and supportive social connections, might explain sexual orientation health disparities.

  2. Pelvic Hydatid Disease: CT and MRI Findings Causing Sciatica

    Energy Technology Data Exchange (ETDEWEB)

    Sanal, Hatice Tuba; Kocaoglu, Murat; Bulakbasi, Nail; Yildirim, Duzgun [Gulhane Military Medical School, Department of Radiology, 06018, Ankara (Turkmenistan)

    2007-12-15

    Pelvic masses, especially hydatid disease, rarely present with sciatica. We present the computed tomography (CT) and the magnetic resonance imaging (MRI) findings of a 49-year-old female patient with presacral hydatid disease, who was evaluated for her sciatica. We also want to emphasize the importance of assessing the pelvis of patients with symptoms and clinical findings that are inconsistent and that cannot be satisfactorily explained by the spinal imaging findings. isc herniation in the lumbar spine is a well-known etiology of back pains and sciatica, but whenever disc herniation of the lumbar spine is excluded by the employed imaging modalities, then the pelvis should be examined for other possible etiologies of nerve compression. We describe here a patient, who was complaining of sciatica, with no abnormal findings in her lumbar spinal magnetic resonance imaging (MRI). The cause of her sciatica was found to be associated with a pelvic hydatid cyst compressing the lumbosacral nerve plexus. In conclusion, if no pathology is evident for the lumbar discal structures, in connection with the cause of sciatica and lumbar back pains, then the pelvis should also be examined for the possible etiologies of compression of the lumbosacral nerve plexus. Whenever a multiseptated cyst is come across in a patient of an endemic origin with a positive history for hydatid disease like surgery, indicating recurrence, hydatid cyst is the most likely diagnosis.

  3. Structural heart disease as the cause of syncope

    Science.gov (United States)

    Guimarães, R.B.; Essebag, V.; Furlanetto, M.; Yanez, J.P.G.; Farina, M.G.; Garcia, D.; Almeida, E.D.; Stephan, L.; Lima, G.G.; Leiria, T.L.L.

    2018-01-01

    We described the clinical evolution of patients with structural heart disease presenting at the emergency room with syncope. Patients were stratified according to their syncope etiology and available scores for syncope prognostication. Cox proportional hazard models were used to investigate the relationship between etiology of the syncope and event-free survival. Of the 82,678 emergency visits during the study period, 160 (0.16%) patients were there due to syncope, having a previous diagnosis of structural heart disease. During the median follow-up of 33.8±13.8 months, mean age at the qualifying syncope event was 68.3 years and 40.6% of patients were male. Syncope was vasovagal in 32%, cardiogenic in 57%, orthostatic hypotension in 6%, and of unknown causes in 5% of patients. The primary composite endpoint death, readmission, and emergency visit in 30 days was 39.4% in vasovagal syncope and 60.6% cardiogenic syncope (Psyncope (HR=2.97, 95%CI=1.94-4.55; Psyncope causes in patients with structural heart disease is important, because vasovagal and postural hypotension have better survival and less probability of emergency room or hospital readmission. The available scores are not reliable tools for prognosis in this specific patient population. PMID:29513795

  4. Ultrasonographic Findings of Extratesticular Diseases Causing Acute Scrotal Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jae Joon; Lee, Tack; Chang, So Yong; Kim, Myeong Jin; Yoo, Hyung Sik; Lee, Jong Tae [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1996-12-15

    To evaluate the kinds of extratesticular diseases causing acute scrotal disorders by emergent sonography of the scrotum. Scrotal sonography in sixty-five patients, with age ranging from 5months to 82 years (mean : 27.3 years), with acute scrotal pain and swelling, was prospectively carried out by either a 10 or 7.5 MHz transducer. We evaluated the size and echogenicity of the epididymis, the presence of extratesticular solid mass or cyst, testicular involvement by extratesticular diseases, calcification, hydrocele and scrotal wall thickening. The most common cause of acute scrotal disorders was acute epididymitis (n= 50), followed by acute epididymo-orchitis (n = 4), mumps epididymo-orchitis (n = 2), enlarged epididymis secondary to testicular torsion (n = 2), infected hydrocele (n = 2), epididymal cyst (n = 2), rupture of varicocele (n = 1), angioneurotic edema (n = 1), and sperm granuloma (n = 1). Hydrocele was seen in 20 cases, and epididymal calcification was noted in 6 cases. Emergent scrotal sonography was useful for correct diagnosis and proper treatment in patients with acute scrotal disorders, especially in the differentiation of the acute epididymitis from other intrascrotal diseases

  5. Causes of interannual to decadal variability of Gila River streamflow over the past century

    Directory of Open Access Journals (Sweden)

    M.A. Pascolini-Campbell

    2015-03-01

    Full Text Available Study region: The Gila River, New Mexico, is characterized by two peaks in streamflow: one in the winter–spring (December–May, and summer (August–September. The region is influenced both by Pacific SST variability as well as the North American Monsoon. Study focus: The mechanisms responsible for the variability of the winter–spring and summer streamflow peaks are investigated by correlation of streamflow with precipitation and sea surface temperature for 1928–2012. Decadal variability in the flow record is examined for a longer term perspective on Gila River streamflow using tree ring-based reconstructions of the Palmer Drought Severity Index (PDSI and the Standardized Precipitation Index (SPI. New hydrological insights for the region: Results indicate a strong influence of winter–spring precipitation and Pacific SST anomalies on the winter–spring streamflow, with El Niño conditions in the Pacific causing increased precipitation and streamflow. Decadal Pacific variability helps explain the transition from high winter flow in the late 20th century to lower flows in the most recent decade. The summer streamflow has a somewhat weaker correlation with precipitation and Pacific SST than the winter–spring streamflow. Its variability is more likely influenced by local North American Monsoon precipitation variability. PDSI and SPI reconstructions indicate much more severe and extended periods of droughts and pluvials in past centuries as well as periods of concurrent winter and summer drought. Keywords: Streamflow decadal variability, Drought, Pluvials, Treering, Teleconnections, North American Monsoon

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

    African Journals Online (AJOL)

    Administrator

    improvement of yield and quality attributes. Cultivar Munyeera displayed the highest level of SPVD resistance followed by New Kawogo and Polyster as exhibited by relative area under disease progress curves following natural field infection and graft inoculation with SPVD causing viruses, Sweet potato chlorotic stunt virus ...

  7. Multiple myeloma and acquired von Willebrand disease: a combined cause of preanalytical interference causing gel formation?

    Science.gov (United States)

    RicoRios, Natividad; Bowles, Louise; Ayling, Ruth M

    2018-01-01

    We report a patient with acquired von Willebrand disease, associated with multiple myeloma. At one stage in his illness, we were unable to analyse a sample sent in a serum separator tube, due to the presence of a gel within the separated serum layer. We suggest this was due to anomalous position of the gel because of the density of the sample caused by its high total protein concentration, exacerbated by fibrin strand formation because of inhibition of appropriate fibrin clot formation secondary to clotting disorder.

  8. Seeking environmental causes of neurodegenerative disease and envisioning primary prevention.

    Science.gov (United States)

    Spencer, Peter S; Palmer, Valerie S; Kisby, Glen E

    2016-09-01

    Pathological changes of the aging brain are expressed in a range of neurodegenerative disorders that will impact increasing numbers of people across the globe. Research on the causes of these disorders has focused heavily on genetics, and strategies for prevention envision drug-induced slowing or arresting disease advance before its clinical appearance. We discuss a strategic shift that seeks to identify the environmental causes or contributions to neurodegeneration, and the vision of primary disease prevention by removing or controlling exposure to culpable agents. The plausibility of this approach is illustrated by the prototypical neurodegenerative disease amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long-latency disease, once thought to be an inherited genetic disorder but now known to have a predominant or exclusive environmental origin, is in the process of disappearing from the three heavily affected populations, namely Chamorros of Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure via traditional food and/or medicine (the only common exposure in all three geographic isolates) to one or more neurotoxins in seed of cycad plants is the most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at exposure might explain the stratified epidemic of neurodegenerative disease on Guam in which high-incidence ALS peaked and declined before that of PD, only to be replaced today by a dementing disorder comparable to Alzheimer's disease. Exposure to the Guam environment is also linked to the delayed development of ALS among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of which is reported here for the first time. Lessons learned from this study and from 65 years of research on ALS-PDC include the exceptional value of initial, field-based informal investigation of

  9. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  10. Low-density lipoproteins cause atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian

    2017-01-01

    Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from......, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk...

  11. Causes of decadal climate variability over the North Pacific and North America

    International Nuclear Information System (INIS)

    Latif, M.; Barnett, T.P.

    1994-01-01

    The cause of decadal climate variability over the North Pacific and North America is investigated by analyzing data from a multi-decadal integration with a state of the art coupled ocean-atmosphere model and observations. About one third of the low-frequency climate variability in the region of interest can be attributed to a cycle involving unstable air-sea interactions between the subtropical gyre circulation in the North Pacific and the Aleutian low pressure system. The existence of this cycle provides a basis for long-range climate forecasting over the western United States at decadal time scales. (orig.)

  12. Cardiovascular variability in Mexican patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Guillermo Delgado

    2014-10-01

    Full Text Available Cardiovascular variability (CVV has been evaluated in patients with Parkinson's disease (PD in other countries and exhibit ethnic differences. Objective We investigated heart rate variability (HRV and blood pressure variability (BPV in Mexican patients with PD. Method We further compared HRV and BPV between this group and young healthy controls (YHC in order to estimate, for the first time in our country, the magnitude of the difference. Twenty patients were examined. Time- and frequency-domain CVV parameters were studied during supine rest (SR, active standing (AS and controlled breathing. These measurements were compared to those of 20 YHC. Results In the three conditions tested, our study showed a decrease in almost all HRV parameters in PD patients; on the contrary, decreased BPV parameters were found less frequently and only during SR and AS. Conclusion Our results indicate that HRV is impaired in PD. Some BPV parameters are also diminished.

  13. A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

    Directory of Open Access Journals (Sweden)

    Ad de Groof

    2015-08-01

    Full Text Available From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch's postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.

  14. [Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

    Science.gov (United States)

    Dalphin, J-C; Didier, A

    2013-10-01

    Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  15. Adult Scheuermann’s disease as cause of mechanic dorsalgia

    Directory of Open Access Journals (Sweden)

    F.P. Cantatore

    2011-09-01

    Full Text Available Scheuermann’s disease (SD or vertebral osteochondrosis is the most frequent cause of non postural kyphosis and one of more frequent cause of adolescent’s dorsalgia. The criteria for the diagnosis are: more than 5° of wedging of at least three adjacent vertebrae at the apex of the kyphosis; a toracic kyphosis of more than 45° of Cobb’s degree; Schmorl’s nodes and endplates irregularities. In addition to classic SD, there are radiological alterations that remain asintomatic for a long time to reveal in adult age: in that case it speaks of adult Scheuermann’s disease (ASD. We considered the diagnosis of patients came from April 2006 to April 2007 on Day Hospital in our Clinic. ASD was diagnosed, besides, in 10 of these patients. 7 patients had previous diagnosis such as: dorsal Spondiloarthrosis (4 subjects; Osteoporosis with vertebral fractures (3 subjects. All these diagnosis was not confirmed by us. In case of chronic dorsalgia of adult, ASD is rarely considered as differential diagnosis. Besides, the vertebral dorsalgia, even in absence of red flags as fever, astenia, ipersedimetry, functional loss and aching spinal processes to tapping, could hide a serious scene that lead us to be careful in the differential diagnosis, because of similar radiological pictures of the MSA to other pathology as spondylodiscitis, primitive or metastasic spinal tumors, and brittleness vertebral fractures

  16. Unstable mutations: cause of some neurological hereditary diseases

    International Nuclear Information System (INIS)

    Cuenca Berger, P.; Morales Montero, F.

    1999-01-01

    Unstable mutations or amplification of triplets constitute a kind of genetic alteration discovered during the last decade. They had been found inside or near genes important for the normal neurological function of the human being. In some cases, the presence of the amplification causes the inactivation of the gene or the synthesis of a new product which functions different from the original protein. Some common characteristics of diseases caused by the amplification of triplets are that it affects the nervous system and are degenerative in nature. The expression of the manifestations varies according to age. Most of them show genetic anticipation in which the severity of the manifestations increases with each generation and appear at an earlier age. In most cases, the severity of the symptoms is correlated positively to the size of the amplification. The diagnosis of an affected individual in a family may indicate the presence of an altered gene in other relatives. These relatives may not present evident signs of the illness either because it is of late onset or because they carry premutations. The molecular diagnosis of these mutations is important to estimate the risk of developing the disease and/or of transmitting the illness to the descendants and to eliminate the fears of healthy relatives who have inherited normal copies of the gene. (Author) [es

  17. Structural heart disease as the cause of syncope

    Directory of Open Access Journals (Sweden)

    R.B. Guimarães

    2018-03-01

    Full Text Available We described the clinical evolution of patients with structural heart disease presenting at the emergency room with syncope. Patients were stratified according to their syncope etiology and available scores for syncope prognostication. Cox proportional hazard models were used to investigate the relationship between etiology of the syncope and event-free survival. Of the 82,678 emergency visits during the study period, 160 (0.16% patients were there due to syncope, having a previous diagnosis of structural heart disease. During the median follow-up of 33.8±13.8 months, mean age at the qualifying syncope event was 68.3 years and 40.6% of patients were male. Syncope was vasovagal in 32%, cardiogenic in 57%, orthostatic hypotension in 6%, and of unknown causes in 5% of patients. The primary composite endpoint death, readmission, and emergency visit in 30 days was 39.4% in vasovagal syncope and 60.6% cardiogenic syncope (P<0.001. Primary endpoint-free survival was lower for patients with cardiogenic syncope (HR=2.97, 95%CI=1.94-4.55; P<0.001. The scores were analyzed for diagnostic performance with area under the curve (AUC and did not help differentiate patients with an increased risk of adverse events. The differential diagnosis of syncope causes in patients with structural heart disease is important, because vasovagal and postural hypotension have better survival and less probability of emergency room or hospital readmission. The available scores are not reliable tools for prognosis in this specific patient population.

  18. Attributions about cause of illness in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Hoth, Karin F; Wamboldt, Frederick S; Bowler, Russell; Make, Barry; Holm, Kristen E

    2011-05-01

    Patients' beliefs about the causes of their illness have been associated with emotional adjustment and behavioral outcomes in several medical conditions; however, few studies have examined illness attributions among patients with chronic obstructive pulmonary disease (COPD). In the current study, patterns of patients' causal attributions for COPD were identified and examined in relation to health behaviors and symptoms. Three-hundred and ninety-four patients with COPD and >10 pack year history of smoking completed a self-report questionnaire that included the Illness Perception Questionnaire-Revised (IPQ-R). A factor analysis of the IPQ-R cause items using principal axis factoring yielded four individual items (i.e., smoking, heredity, pollution, and personal behavior) and one large factor that was primarily driven by psychological attributions. Ninety-three percent of patients agreed or strongly agreed that smoking was a cause of their COPD. Higher scores on the large IPQ-R factor were associated with reduced quality of life (r=.25, PIPQ-R in other chronic illness populations. This difference may be due to the importance of smoking, environmental exposures, and heredity in the development of COPD. Future research should expand upon these specific attributions in COPD. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Ethnic variability in adiposity and cardiovascular risk: the variable disease selection hypothesis.

    Science.gov (United States)

    Wells, Jonathan C K

    2009-02-01

    Evidence increasingly suggests that ethnic differences in cardiovascular risk are partly mediated by adipose tissue biology, which refers to the regional distribution of adipose tissue and its differential metabolic activity. This paper proposes a novel evolutionary hypothesis for ethnic genetic variability in adipose tissue biology. Whereas medical interest focuses on the harmful effect of excess fat, the value of adipose tissue is greatest during chronic energy insufficiency. Following Neel's influential paper on the thrifty genotype, proposed to have been favoured by exposure to cycles of feast and famine, much effort has been devoted to searching for genetic markers of 'thrifty metabolism'. However, whether famine-induced starvation was the primary selective pressure on adipose tissue biology has been questioned, while the notion that fat primarily represents a buffer against starvation appears inconsistent with historical records of mortality during famines. This paper reviews evidence for the role played by adipose tissue in immune function and proposes that adipose tissue biology responds to selective pressures acting through infectious disease. Different diseases activate the immune system in different ways and induce different metabolic costs. It is hypothesized that exposure to different infectious disease burdens has favoured ethnic genetic variability in the anatomical location of, and metabolic profile of, adipose tissue depots.

  20. Multi-taxa integrated landscape genetics for zoonotic infectious diseases: deciphering variables influencing disease emergence.

    Science.gov (United States)

    Leo, Sarah S T; Gonzalez, Andrew; Millien, Virginie

    2016-05-01

    Zoonotic disease transmission systems involve sets of species interacting with each other and their environment. This complexity impedes development of disease monitoring and control programs that require reliable identification of spatial and biotic variables and mechanisms facilitating disease emergence. To overcome this difficulty, we propose a framework that simultaneously examines all species involved in disease emergence by integrating concepts and methods from population genetics, landscape ecology, and spatial statistics. Multi-taxa integrated landscape genetics (MTILG) can reveal how interspecific interactions and landscape variables influence disease emergence patterns. We test the potential of our MTILG-based framework by modelling the emergence of a disease system across multiple species dispersal, interspecific interaction, and landscape scenarios. Our simulations showed that both interspecific-dependent dispersal patterns and landscape characteristics significantly influenced disease spread. Using our framework, we were able to detect statistically similar inter-population genetic differences and highly correlated spatial genetic patterns that imply species-dependent dispersal. Additionally, species that were assigned coupled-dispersal patterns were affected to the same degree by similar landscape variables. This study underlines the importance of an integrated approach to investigating emergence of disease systems. MTILG is a robust approach for such studies and can identify potential avenues for targeted disease management strategies.

  1. How reflux causes symptoms: reflux perception in gastroesophageal reflux disease.

    Science.gov (United States)

    Weijenborg, Pim W; Bredenoord, Albert J

    2013-06-01

    In gastroesophageal reflux disease (GERD) symptoms arise due to reflux of gastric content into the oesophagus. However, the relation between magnitude and onset of reflux and symptom generation in GERD patients is far from simple; gastroesophageal reflux occurs several times a day in everyone and the majority of reflux episodes remains asymptomatic. This review aims to address the question how reflux causes symptoms, focussing on factors leading to enhanced reflux perception. We will highlight esophageal sensitivity variance between subtypes of GERD, which is influenced by peripheral sensitization of primary afferents, central sensitization of spinal dorsal horn neurons, impaired mucosal barrier function and genetic factors. We will also discuss the contribution of specific refluxate characteristics to reflux perception, including acidity, and the role of bile, pepsin and gas and proximal extent. Further understanding of reflux perception might improve GERD treatment, especially in current partial responders to therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Sleep disorders in Parkinson's disease: many causes, few therapeutic options.

    Science.gov (United States)

    Diederich, Nico J; McIntyre, Deborah J

    2012-03-15

    Sleep symptoms in Parkinson's disease (PD) are frequent and have multifactorial and multilayered causes. Primary involvement of sleep/wake regulating centers in the brainstem, sleep problems caused by the nocturnal manifestation of motor and dysautonomic signs and medication-induced sleep problems are often impossible to disentangle in the individual patient. Two syndromes, hypersomnia and REM sleep behavior disorder (RBD), are increasingly recognized as harbingers of the core PD motor syndrome. RBD, associated with a panoply of other nonmotor symptoms, may predispose to a specific PD phenotype. Long-acting dopaminergic stimulation, when abating nocturnal akinesia, also improves subjective sleep quantity. While this strategy is backed up by several randomized controlled trials (RCT), other treatment recommendations are mostly based on case series or expert opinion. Thus we identified only two other RCT, one treating insomnia with eszopiclone, the other nocturnal behavioral abnormalities in demented PD patients with memantine. While the causal complexity of sleep problems in PD certainly hampers the design of therapeutic studies, multiple general treatment strategies against sleep disorders can however be applied efficiently in PD patients as well. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Hypoxemia in patients with COPD: cause, effects, and disease progression.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation\\/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.

  4. Hypoxemia in patients with COPD: cause, effects, and disease progression

    Directory of Open Access Journals (Sweden)

    Brian D Kent

    2011-03-01

    Full Text Available Brian D Kent1,2, Patrick D Mitchell1, Walter T McNicholas1,21Pulmonary and Sleep Disorders Unit, St. Vincent’s University Hospital, Dublin; 2Conway Institute of Biomolecular and Biomedical Research, University College Dublin, IrelandAbstract: Chronic obstructive pulmonary disease (COPD is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.Keywords: COPD, hypoxia, sleep, inflammation, pulmonary hypertension

  5. Causes of variability in pesticide and PCB concentrations in air near the Great Lakes.

    Science.gov (United States)

    Buehler, Stephanie S; Basu, Ilora; Hites, Ronald A

    2004-01-15

    Data through 2001 from the Integrated Atmospheric Deposition Network (IADN) were used to investigate the causes of variability in gas-phase polychlorinated biphenyl (PCB) and pesticide concentrations measured near Lakes Michigan, Erie, and Superior. A multiple linear regression model that incorporates temperature and time was used explain the variability in the concentrations. Our approach used autocorrelation analyses of the residuals to help us determine the effectiveness of the regression. Autocorrelation plots forthe in-use pesticide lindane indicated that an agricultural application cycle was also present in the regression residual data at all sites. The addition of parameters for this effect to the regression equation accounted for, on average, 16% more of the variability in the data. Similar analyses forthe in-use pesticide endosulfan did not show an agricultural application effect. The banned compounds DDT and chlordane showed that temperature and time correctly accounted for the variability in the atmospheric concentrations of these compounds at all sites. In contrast to the other compounds, PCBs and hexachlorobenzene showed strong residual autocorrelation patterns near Lake Michigan of an unknown origin.

  6. Association of allergic rhinitis, coronary heart disease, cerebrovascular disease, and all-cause mortality.

    Science.gov (United States)

    Crans Yoon, Angelina M; Chiu, Vicki; Rana, Jamal S; Sheikh, Javed

    2016-10-01

    Inflammation is implicated in atherosclerotic cardiovascular disease. Allergic diseases also involve a systemic inflammatory state, which may potentiate cardiovascular disease. To examine the association of allergic rhinitis, coronary heart disease (CHD), cerebrovascular disease (CVD), and all-cause mortality. We conducted a retrospective, population-based, matched cohort study comparing the incidence of CHD, CVD, and all-cause mortality from January 1, 1999, through December 31, 2012, in patients with International Classification of Disease, Ninth Revision, documented allergic rhinitis matched 1:1 by age, sex, and ethnicity to a reference cohort without allergic rhinitis within Kaiser Permanente Southern California. Fully adjusted hazard ratios (HRs) were calculated. Further analyses for those with positive environmental allergen specific IgE (sIgE) test results within the allergic rhinitis cohort were also performed. Patients with physician-diagnosed allergic rhinitis (N = 110, 207 in matched cohort) had significantly lower risk for myocardial infarction (HR, 0.63; 95% confidence interval [CI], 0.59-0.67; P allergic rhinitis was associated with decreased CHD, CVD, and all-cause mortality. This decreased risk was more pronounced after excluding patients with asthma. Patients with positive sIgE test results also had decreased risk of CHD. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Common variable immunodeficiency presenting in a man with recurrent pneumonia caused by Staphylococcus lugdunensis.

    Science.gov (United States)

    Mbaebie, Nkechi Chiugo; Alarcon Velasco, Sylvia Vania; Touhey, Jason

    2018-03-20

    Common variable immunodeficiency (CVID) refers to a group of disorders where differentiation and maturation of B cells into plasma cells are affected, leading to decreased or defective immunoglobulin production and subsequent immunodeficiency. Symptoms may present at any age between 5 and 72 years, although more severe forms often manifest earlier in life. Milder forms may not be detected. We present an intriguing case of a 69-year-old man presenting with recurrent pneumonia caused by a rare organism Staphylococcus lugdunensis , eventually determined to be caused by CVID. The patient had a good clinical outcome after receiving immunoglobulin replacement therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Pathophysiology and spectrum of diseases caused by defects in lymphocyte cytotoxicity.

    Science.gov (United States)

    Meeths, Marie; Chiang, Samuel C C; Löfstedt, Alexandra; Müller, Martha-Lena; Tesi, Bianca; Henter, Jan-Inge; Bryceson, Yenan T

    2014-07-01

    In experimental settings, lymphocyte cytotoxicity has been recognized as a central mechanism for immune defense against infected and neoplastic cells. More recently, molecular determinants of lymphocyte cytotoxicity have been identified through studies of rare, inherited hyperinflammatory and lymphoproliferative syndromes that include hemophagocytic lymphohistiocytosis (HLH). These studies have unraveled a set of genes pivotal for the biogenesis and directed release of perforin-containing lysosomes that mediate target cell killing, in addition to other pathways including Fas that also contribute to induction of cell death. Furthermore, studies of such human primary immunodeficiencies have highlighted non-redundant roles of perforin for maintenance of immune homeostasis. Besides providing mechanistic insights to lymphocyte cytotoxicity, studies of individuals with rare hyperinflammatory diseases are highlighting the relevance of lymphocyte cytotoxicity to more common human diseases. It is increasingly recognized that mutations abrogating lymphocyte cytotoxicity not only cause HLH, but also are associated with susceptibility to cancer and autoimmune syndromes. In addition, patients may initially be present with neurological symptoms or severe infectious disease masquerading as variable immunodeficiency syndrome. Here, we highlight new knowledge regarding the molecular mechanisms regulating lymphocyte cytotoxicity and review how mutations in genes associated with HLH cause disease. We also discuss the wider implications of impairments in lymphocyte cytotoxicity for human disease predisposition. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Geographic Variability in Liver Disease Related Mortality Rates in the United States.

    Science.gov (United States)

    Desai, Archita P; Mohan, Prashanthinie; Roubal, Anne M; Bettencourt, Ricki; Loomba, Rohit

    2018-02-26

    Liver disease is an important cause of morbidity and mortality in the United States (US). Geographic variations in the burden of chronic liver disease may have significant impact on public health policies but have not been explored at the national level. The objective of this study is to examine inter-state variability in liver disease mortality in the US. We compared liver disease mortality from the 2010 National Vital Statistics Report on a state level. States in each quartile of liver disease mortality were compared with regard to viral hepatitis death rates, alcohol consumption, obesity, ethnic and racial composition, and household income. Race, ethnicity, and median household income data was derived from the 2010 US Census. Alcohol consumption and obesity data was obtained from the 2010 Behavioral Risk Factor Surveillance System Survey. We found significant inter-state variability in liver disease mortality, ranging from 6.4 to 17.0 per 100,000. The South and Mid-West carry the highest rates of liver disease mortality. In addition to viral hepatitis death rates, there is a strong correlation between higher percent Hispanic population and a state's liver disease mortality rate (r = 0.538, p< 0.001). Greater racial diversity (p < 0.001) and lower household income (r = 0.405, p=0.003) was associated with the higher liver disease mortality. While there was a trend between higher obesity rates and higher liver disease mortality, the correlation was not strong and there was no clear association between alcohol consumption and liver disease mortality rates. Copyright © 2018. Published by Elsevier Inc.

  10. Mycoplasma genitalium: An Emerging Cause of Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Catherine L. Haggerty

    2011-01-01

    Full Text Available Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID. Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted.

  11. Evaluating disease management programme effectiveness: an introduction to instrumental variables.

    Science.gov (United States)

    Linden, Ariel; Adams, John L

    2006-04-01

    This paper introduces the concept of instrumental variables (IVs) as a means of providing an unbiased estimate of treatment effects in evaluating disease management (DM) programme effectiveness. Model development is described using zip codes as the IV. Three diabetes DM outcomes were evaluated: annual diabetes costs, emergency department (ED) visits and hospital days. Both ordinary least squares (OLS) and IV estimates showed a significant treatment effect for diabetes costs (P = 0.011) but neither model produced a significant treatment effect for ED visits. However, the IV estimate showed a significant treatment effect for hospital days (P = 0.006) whereas the OLS model did not. These results illustrate the utility of IV estimation when the OLS model is sensitive to the confounding effect of hidden bias.

  12. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

    Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

  13. Phenotypic Variability of Childhood Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Cornett, Kayla M D; Menezes, Manoj P; Bray, Paula; Halaki, Mark; Shy, Rosemary R; Yum, Sabrina W; Estilow, Timothy; Moroni, Isabella; Foscan, Maria; Pagliano, Emanuela; Pareyson, Davide; Laurá, Matilde; Bhandari, Trupti; Muntoni, Francesco; Reilly, Mary M; Finkel, Richard S; Sowden, Janet; Eichinger, Katy J; Herrmann, David N; Shy, Michael E; Burns, Joshua

    2016-06-01

    Disease severity of childhood Charcot-Marie-Tooth disease (CMT) has not been extensively characterized, either within or between types of CMT to date. To assess the variability of disease severity in a large cohort of children and adolescents with CMT. A cross-sectional study was conducted among 520 children and adolescents aged 3 to 20 years at 8 universities and hospitals involved in the Inherited Neuropathies Consortium between August 6, 2009, and July 31, 2014, in Australia, Italy, the United Kingdom, and the United States. Data analysis was conducted from August 1, 2014, to December 1, 2015. Scores on the Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS), a well-validated unidimensional clinical outcome measure to assess disease severity. This instrument includes 11 items assessing fine and gross motor function, sensation, and balance to produce a total score ranging from 0 (unaffected) to 44 (severely affected). Among the 520 participants (274 males) aged 3 to 20 years, CMT type 1A (CMT1A) was the most prevalent type (252 [48.5%]), followed by CMT2A (31 [6.0%]), CMT1B (15 [2.9%]), CMT4C (13 [2.5%]), and CMTX1 (10 [1.9%]). Disease severity ranged from 1 to 44 points on the CMTPedS (mean [SD], 21.5 [8.9]), with ankle dorsiflexion strength and functional hand dexterity test being most affected. Participants with CMT1B (mean [SD] CMTPedS score, 24.0 [7.4]), CMT2A (29.7 [7.1]), and CMT4C (29.8 [8.6]) were more severely affected than those with CMT1A (18.9 [7.7]) and CMTX1 (males: 15.3 [7.7]; females: 13.0 [3.6]) (P < .05). Scores on the CMTPedS tended to worsen principally during childhood (ages, 3-10 years) for participants with CMT4C and CMTX1 and predominantly during adolescence for those with CMT1B and CMT2A (ages, 11-20 years), while CMT1A worsened consistently throughout childhood and adolescence. For individual items, participants with CMT4C recorded more affected functional dexterity test scores than did those with all other types of CMT (P

  14. Historical perspectives on music as a cause of disease.

    Science.gov (United States)

    Kennaway, James

    2015-01-01

    The relationship between music and medicine is generally understood in the benign context of music therapy, but, as this chapter shows, there is a long parallel history of medical theories that suggest that music can cause real physical and mental illness. During the seventeenth and eighteenth centuries, the idea of music as an expression of universal harmony was challenged by a more mechanistic model of nervous stimulation. By the 1790s, there was a substantial discourse on the dangers of musical overstimulation to health in medicine, literature, and etiquette books. During the nineteenth century, the sense of music as a pathogenic stimulant gained in influence. It was often linked to fears about sexuality, female gynecological health, and theories of hypnosis and degeneration. In the twentieth century, the debate on the medical perils of the wrong kinds of music became overtly politicized in Germany and the Soviet Union. Likewise, the opponents of jazz, particularly in the United States, often turned to medicine to fend off its supposed social, moral, and physical consequences. The Cold War saw an extensive discourse on the idea of musical "brainwashing," that rumbled on into the 1990s. Today, regular media panics about pathological music are mirrored by alarming evidence of the deliberate use of music to harm listeners in the context of the so-called War on Terror. Can music make you ill? Music therapy is a common if perhaps rather neglected part of medicine, but its diametric opposite, the notion that music might lead to real mental and physical illness, may seem improbable. In fact, over the last two hundred years, there have been many times when as much was written about the medical dangers of music as about its potential benefits. Since the eighteenth century, fears about music's effects on the nerves and the mind have created a remarkably extensive discourse on pathological music based on a view of both music and the causation of disease as matters of

  15. diseases and causes of death among the popes 1. introduction

    African Journals Online (AJOL)

    2.3.1 Causes of death. • Unnatural causes. Only three popes died of unnatural causes during this period. Lucius. III became personally involved in a war against the insurgent Roman population in 1145 and died as a result of injuries sustained when he was stoned. John XX, who had had a special study built in the Vatican,.

  16. Changes in adult neurogenesis in neurodegenerative diseases: Cause or consequence?

    NARCIS (Netherlands)

    Thompson, A.; Boekhoorn, K.; van Dam, A.-M.; Lucassen, P.J.

    2008-01-01

    This review addresses the role of adult hippocampal neurogenesis and stem cells in some of the most common neurodegenerative disorders and their related animal models. We discuss recent literature in relation to Alzheimer's disease and dementia, Parkinson's disease, Huntington's disease, amyotrophic

  17. Changes in adult neurogenesis in neurodegenerative diseases: cause or consequence?

    NARCIS (Netherlands)

    Thompson, A.; Boekhoorn, K.; van Dam, A.M.W.; Lucassen, P.J.

    2008-01-01

    This review addresses the role of adult hippocampal neurogenesis and stem cells in some of the most common neurodegenerative disorders and their related animal models. We discuss recent literature in relation to Alzheimer's disease and dementia, Parkinson's disease, Huntington's disease, amyotrophic

  18. Onychomadesis outbreak in Valencia, Spain associated with hand, foot, and mouth disease caused by enteroviruses.

    Science.gov (United States)

    Davia, Javier López; Bel, Pablo Hernández; Ninet, Violeta Zaragoza; Bracho, María Alma; González-Candelas, Fernando; Salazar, Antonio; Gobernado, Miguel; Bosch, Isabel Febrer

    2011-01-01

    This report evaluates the June 2008 onychomadesis outbreak in Valencia, Spain. The study sample consisted of 221 onychomadesis cases and 77 nonaffected individuals who lived close to those affected. We collected data on dietary variables, hygiene products, and individual pathological histories. Feces and blood specimens were collected from 44 cases and 24 controls to evaluate exposure to infectious agents. Pathological background data revealed a high frequency (61%) of hand, foot, and mouth disease among the onychomadesis cases. Coxsackievirus A10 was the most commonly detected enterovirus in both case and control groups (49%). Other enteroviruses such as coxsackieviruses A5, A6, A16, B1, and B3; echoviruses 3, 4, and 9; and enterovirus 71 were present in low frequencies in the case and control groups (3-9%). The 2008 onychomadesis outbreak in the metropolitan area of Valencia was associated with an outbreak of hand, foot, and mouth disease primarily caused by coxsackievirus A10. © 2010 Wiley Periodicals, Inc.

  19. Climate variability and causes: from the perspective of the Tharaka people of eastern Kenya

    Science.gov (United States)

    Recha, Charles W.; Makokha, George L.; Shisanya, Chris A.

    2017-12-01

    The study assessed community understanding of climate variability in semi-arid Tharaka sub-county, Kenya. The study used four focus group discussions (FGD) ( N = 48) and a household survey ( N = 326) to obtain information from four agro-ecological zones (AEZs). The results were synthesized and descriptively presented. People in Tharaka sub-county are familiar with the term climate change and associate it with environmental degradation. There are, however, misconceptions and gaps in understanding the causes of climate change. There was a mismatch between community and individual perception of onset and cessation of rainfall—evidence that analysis of the impact of climate change should take into account the scale of interaction. To improve climate change knowledge, there is a need for climate change education by scientific institutions—to provide information on local climatic conditions and global and regional drivers of climate change to local communities.

  20. Ataxia and Hypogonadotropic Hypogonadism with Intrafamilial Variability Caused by RNF216 Mutation.

    Science.gov (United States)

    Alqwaifly, Mohammed; Bohlega, Saeed

    2016-06-15

    Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with RNF216 mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in RNF216 that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G>A). We herein report two patients with GHS caused by a novel RNF216 mutation as the first follow up report on RNF216-related GHS, and show interfamilial variability of phenotype supporting the previously reported RNF216-related cases.

  1. Ataxia and hypogonadotropic hypogonadism with intrafamilial variability caused by RNF216 mutation

    Directory of Open Access Journals (Sweden)

    Mohammed Alqwaifly

    2016-06-01

    Full Text Available Gordon Holmes syndrome (GHS is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with RNF216 mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in RNF216 that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G>A. We herein report two patients with GHS caused by a novel RNF216 mutation as the first follow up report on RNF216-related GHS, and show interfamilial variability of phenotype supporting the previously reported RNF216-related cases.

  2. Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis.

    Science.gov (United States)

    Reynolds, Tim

    2013-11-01

    Cholesteryl ester storage disease (CESD) is an autosomal recessive lysosomal storage disorder caused by a variety of mutations of the LIPA gene. These cause reduced activity of lysosomal acid lipase, which results in accumulation of cholesteryl esters in lysosomes. If enzyme activity is very low/absent, presentation is in infancy with failure to thrive, malabsorption, hepatosplenomegaly and rapid early death (Wolman disease). With higher but still low enzyme activity, presentation is later in life with hepatic fibrosis, dyslipidaemia and early atherosclerosis.Identification of this rare disorder is difficult as it is essential to assay leucocyte acid phosphatase activity. An assay using specific inhibitors has now been developed that facilitates measurement in dried blood spots. Treatment of CESD has until now been limited to management of the dyslipidaemia, but this does not influence the liver effects. A new enzyme replacement therapy (Sebelipase) has now been developed that could change treatment options for the future.

  3. Phenotypic Variability of Osteogenesis Imperfecta Type V Caused by an IFITM5 Mutation

    Science.gov (United States)

    Shapiro, Jay R; Lietman, Caressa; Grover, Monica; Lu, James T; Nagamani, Sandesh CS; Dawson, Brian C; Baldridge, Dustin M; Bainbridge, Matthew N; Cohn, Dan H; Blazo, Maria; Roberts, Timothy T; Brennen, Feng-Shu; Wu, Yimei; Gibbs, Richard A; Melvin, Pamela; Campeau, Philippe M; Lee, Brendan H

    2013-01-01

    In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5′ untranslated region (5′UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.–14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation. PMID:23408678

  4. Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective Study.

    Science.gov (United States)

    Sandouk, Zahrae; Johnston, Philip; Bunch, Dustin; Wang, Sihe; Bena, James; Hamrahian, Amir; Kennedy, Laurence

    2018-03-01

    The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. To assess the frequency of variable hormonogenesis in patients presenting with CD. Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

  5. Possibility of biological control of primocane fruiting raspberry disease caused by Fusarium sambucinum.

    Science.gov (United States)

    Shternshis, Margarita V; Belyaev, Anatoly A; Matchenko, Nina S; Shpatova, Tatyana V; Lelyak, Anastasya A

    2015-10-01

    Biological control agents are a promising alternative to chemical pesticides for plant disease suppression. The main advantage of the natural biocontrol agents, such as antagonistic bacteria compared with chemicals, includes environmental pollution prevention and a decrease of chemical residues in fruits. This study is aimed to evaluate the impact of three Bacillus strains on disease of primocane fruiting raspberry canes caused by Fusarium sambucinum under controlled infection load and uncontrolled environmental factors. Bacillus subtilis, Bacillus licheniformis, and Bacillus amyloliquefaciens were used for biocontrol of plant disease in 2013 and 2014 which differed by environmental conditions. The test suspensions were 10(5) CFU/ml for each bacterial strain. To estimate the effect of biological agents on Fusarium disease, canes were cut at the end of vegetation, and the area of outer and internal lesions was measured. In addition to antagonistic effect, the strains revealed the ability to induce plant resistance comparable with chitosan-based formulation. Under variable ways of cane treatment by bacterial strains, the more effective were B. subtilis and B. licheniformis demonstrating dual biocontrol effect. However, environmental factors were shown to impact the strain biocontrol ability; changes in air temperature and humidity led to the enhanced activity of B. amyloliquefaciens. For the first time, the possibility of replacing chemicals with environmentally benign biological agents for ecologically safe control of the raspberry primocane fruiting disease was shown.

  6. On the causes of variability in amounts of airborne grass pollen in Melbourne, Australia

    Science.gov (United States)

    de Morton, Julian; Bye, John; Pezza, Alexandre; Newbigin, Edward

    2011-07-01

    In Melbourne, Australia, airborne grass pollen is the predominant cause of hay fever (seasonal rhinitis) during late spring and early summer, with levels of airborne grass pollen also influencing hospital admissions for asthma. In order to improve predictions of conditions that are potentially hazardous to susceptible individuals, we have sought to better understand the causes of diurnal, intra-seasonal and inter-seasonal variability of atmospheric grass pollen concentrations (APC) by analysing grass pollen count data for Melbourne for 16 grass pollen seasons from 1991 to 2008 (except 1994 and 1995). Some of notable features identified in this analysis were that on days when either extreme (>100 pollen grains m-3) or high (50-100 pollen grains m-3) levels of grass pollen were recorded the winds were of continental origin. In contrast, on days with a low ( 100 pollen grains m-3) during the study period were characterised by an average downward vertical wind anomaly in the surface boundary layer over Melbourne. Together these findings form a basis for a fine resolution atmospheric general circulation model for grass pollen in Melbourne's air that can be used to predict daily (and hourly) APC. This information will be useful to those sectors of Melbourne's population that suffer from allergic problems.

  7. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    OpenAIRE

    Ogrendik, Mesut

    2013-01-01

    Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species...

  8. On the cause of variability of the cosmic ray spectrum in the knee region

    Science.gov (United States)

    Loznikov, V. M.; Erokhin, N. S.; Zol'nikova, N. N.; Mikhailovskaya, L. A.

    2017-09-01

    Cosmic ray (CR) energy spectra for H, He, Si, and Fe nuclei with energy-to-charge number ratios ℰ/ Z in the range from 10 to 5 × 107 GeV are studied using observational data obtained at different times in different energy ranges: AMS-02, CREAM, Tibet ASγ, Tibet (hybrid), GRAPES-3, KASCADE, and KASCADE-Grande. Comparison of the H and He CR fluxes according to the KASCADE and KASCADE-Grande data (for different models of deconvolving CR spectra) with the Tibet ASγ and Tibet (hybrid) data obtained at another time in the range of ℰ/ Z ˜ 3 × 106 GeV demonstrates space weather-caused variability of the CR flux. This feature of CR energy spectra in the Tibet ASγ data is most clearly observed in the spectra of heavier nuclei (Si and Fe) according to the KASCADE-Grande and GRAPES-3 data. The variability in the energy spectra of all CRs in the vicinity of the "knee" is shown in the data of Yakutsk EAS, CASA-BLANCA, and Tibet-III experiments. The variability of the CR flux on a time scale on the order of several years exists only if the source corresponding to the peak in the energy spectrum is situated at a distance of no more than 1 pc from the Sun. Rapid surfatron acceleration of CRs may result from colliding interstellar clouds nearest to the Sun (LIC and G). This acceleration mechanism allows one to explain the variability of the CR spectrum in the range 103 GeV < ℰ/ Z < 108 GeV. Conditions for the trapping of strongly relativistic Fe nuclei by an electromagnetic wave, the dynamics of the components of the particle velocity and momentum, and the dependence of the particle acceleration rate on the initial parameters of the problem are analyzed using numerical calculations. The structure of the phase plane of the accelerated Fe nuclei is examined. Optimal conditions for the implementation of ultrarelativistic surfatron acceleration of Fe nuclei by an electromagnetic wave are formulated.

  9. a potential cause of cardiovascular diseases in chronic kidney ...

    African Journals Online (AJOL)

    Fibroblast growth factor 23 (FGF-23) has been identified as one of the risk factors for the development of cardiovascular diseases (CVDs) in chronic kidney disease (CKD) patients. Although FGF-23 is necessary for the maintenance of phosphate balance, it has been implicated in the pathogenesis of left ventricular ...

  10. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA

    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only

  11. Inflorescence rot disease of date palm caused by Fusarium ...

    African Journals Online (AJOL)

    Date palm is one of the important income sources for many farmers in different parts of several countries, including Iraq, Iran, Saudi Arabia, North Africa etc. Inflorescence rot is a serious disease of date palm which limits its yield. The identification of the causal organism is a key step to tackling this disease, and such studies ...

  12. Biological control of post harvest disease caused by Aspergillus ...

    African Journals Online (AJOL)

    The highest control was obtained by the cell suspension of Pantoea agglomerans RK-153. Erwinia chrysanthemi RK-67 and Bacillus subtilis RK-6 treatments reduced disease severity on both lemon cultivars. Furthermore, both the cell suspension and culture filtrates of Burkholderia cepacia strain RK- 277 reduced disease ...

  13. Causes of Charcot-Marie-Tooth Disease (CMT)

    Science.gov (United States)

    ... for MDA Blog Donate Search MDA.org Close Charcot-Marie-Tooth Disease (CMT) Share print email share facebook twitter ... More than 30 genes have been implicated in Charcot-Marie-Tooth disease (CMT). In different types of CMT, peripheral ...

  14. Living with intestinal failure caused by Crohn disease: not letting the disease conquer life.

    Science.gov (United States)

    Carlsson, Eva; Persson, Eva

    2015-01-01

    This article reports the findings of what it means to live with intestinal failure caused by Crohn disease and how it influences daily life. Ten patients, 7 with an ostomy and 7 on home parenteral nutrition followed up at an outpatient clinic for patients with intestinal failure, were interviewed using a qualitative, phenomenological-hermeneutic method. The analysis of the transcribed data is described thematically and resulted in 3 main themes; (a) struggling to not be controlled by the disease, (b) walking on a thin thread, and (c) being seen as a person, not just as a patient. These themes led to the comprehensive understanding that living with intestinal failure was interpreted as the criticality of maintaining control over one's life and body while maintaining autonomy and not letting the disease conquer life. Life entails a constant struggle with much planning to live as normally as possible and get the most out of life. It was of great importance to be seen as a person and not just as a disease, affirm that life as it is has meaning, there is a state of suffering related to the disease, there are existential issues, and suffering is related to care.

  15. Diseases and causes of death in European bats: dynamics in disease susceptibility and infection rates.

    Directory of Open Access Journals (Sweden)

    Kristin Mühldorfer

    Full Text Available BACKGROUND: Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date. METHODOLOGY/PRINCIPAL FINDINGS: Between 2002 and 2009, 486 deceased bats of 19 European species (family Vespertilionidae were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats.

  16. Variable antibiotic susceptibility patterns among Streptomyces species causing actinomycetoma in man and animals

    Directory of Open Access Journals (Sweden)

    Hamid Mohamed E

    2011-06-01

    Full Text Available Abstract Background Drug therapy is recommended in conjunction with surgery in treatment of actinomycetoma. The specific prescription depends on the type of bacteria (actinomycetoma or fungi (eumycetoma causing the disease and their in vitro antimicrobial susceptibility. Objectives To investigate the antimicrobial susceptibility among isolates of Streptomyces spp. isolated from cases of actinomycetoma in man and animals in Sudan. Methods Streptomyces strains (n = 18 isolated from cases of actinomycetoma were tested in vitro against 15 commonly prescribed antibacterial agents using MIC agar dilution method as per standard guidelines. Results Streptomyces strains isolated from actinomycetoma fall into various phenotypic groups. All of the strains were inhibited by novobiocin (8 μg/mL, gentamycin (8, 32 μg/mL and doxycycline (32 μg/mL. Fusidic acid (64 μg/mL inhibited 94.4% of the strains; bacitracin, streptomycin, cephaloridine, clindamycin, ampicillin, rifampicin and tetracycline (64 μg/mL inhibited between 61.1 and 77.8% of the strains. All strains were found resistant to amphotericin B (64 μg/mL, penicillin (20 μg/mL and sulphamethoxazole (64 μg/mL. Conclusions Saprophytic Streptomyces spp. cause actinomycetoma in man and animal belong to separate phenotypes and have a wide range of susceptibility patterns to antimicrobial agents, which pose a lot of difficulties in selecting effective in vivo treatment for actinomycetoma.

  17. Kimura's Disease: A Rare Cause of Postauricular Swelling

    Directory of Open Access Journals (Sweden)

    Suman Kumar Das

    2017-04-01

    Full Text Available Introduction Kimura’s Disease is a chronic inflammatory disorder of lymph node which is very rare in Indian population. Case Report A 15 year old boy with multiple postauricular swelling for 18 months presenting in OPD and diagnosed having eosinophilia. Then excision biopsy was taken, which indicates Kimura’s Disease. Patient was treated with high dose of corticosteroid. Conclusion Kimura’s disease, though rare should be kept in mind for treating a patient with lymphadenopathy with eosinophilia or high IgE level, because it can spare the patient unnecessary invasive procedure.

  18. Chemical control of blossom blight disease of sarpagandha caused ...

    African Journals Online (AJOL)

    80% in both the years against blossom blight disease and their treatments also produced healthy and highest seed yield per plant. Key words: Blossom blight, Colletotrichum capsici, fungicides, Rauvolfia serpentina, sarpagandha.

  19. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    Directory of Open Access Journals (Sweden)

    Ogrendik M

    2013-05-01

    Full Text Available Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD and systemic diseases has been identified. Rheumatoid arthritis (RA, which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.Keywords: etiopathogenesis, chronic arthritis, periodontitis, Porphyromonas gingivalis, systemic disease, animal models, antibiotics

  20. Pelvic Hydatid Disease: CT and MRI Findings Causing Sciatica

    Science.gov (United States)

    Kocaoglu, Murat; Bulakbasi, Nail; Yildirim, Duzgun

    2007-01-01

    Pelvic masses, especially hydatid disease, rarely present with sciatica (1, 2). We present the computed tomography (CT) and the magnetic resonance imaging (MRI) findings of a 49-year-old female patient with presacral hydatid disease, who was evaluated for her sciatica. We also want to emphasize the importance of assessing the pelvis of patients with symptoms and clinical findings that are inconsistent and that cannot be satisfactorily explained by the spinal imaging findings. PMID:18071287

  1. Parasitic Diseases as a cause of Mortality in Commercial Chicken in ...

    African Journals Online (AJOL)

    ... the role of parasitic diseases as causes of mortalities in chickens brought to the postmortem facility of the veterinary school of the University of Nairobi, Kenya. Parasitic diseases caused deaths in 786(26%) chicken out of 2975 dead from a combination of diseases. The major contributor of mortalities was acute coccidiosis, ...

  2. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  3. Impact of the vibrations on the environment caused by passages of trains at variable speed

    Directory of Open Access Journals (Sweden)

    Kożuch Barbara

    2016-01-01

    Full Text Available The paper deals with negative environmental impact caused by the passages of different kinds of trains at variable speed. The study is based on the measurement results which took place in Poland in 2013 on the railway line no. 4. The effect of the traction unit – Pendolino (EMU 250 on the vibration climate was analysed. The impact of passages of new trains was compared to currently operated rolling stock. The speed of trains was varying between 40 and 250 km/h. Vibration measurements were conducted by stuff of an accredited Laboratory of Structural Mechanics at Cracow University of Technology (Accreditation No. AB 826. The influence of the indicated vibrations due to passages of the trains on the building in the neighbourhood of the line was investigated. The vibration assessment was done for horizontal components of vibrations according to Polish standard code. Assessment of environmental impact was presented by indicator of perceptibility of vibration through construction (WODB, which refers to the Scales of Dynamic Influences (SDI scales. The limits specified by standards in any of the passages have not been exceeded. The change of speed or rolling stock resulted in a change in the characteristic of the vibration spectrum.

  4. Climate variability rather than overstocking causes recent large scale cover changes of Tibetan pastures

    Science.gov (United States)

    Lehnert, L. W.; Wesche, K.; Trachte, K.; Reudenbach, C.; Bendix, J.

    2016-04-01

    The Tibetan Plateau (TP) is a globally important “water tower” that provides water for nearly 40% of the world’s population. This supply function is claimed to be threatened by pasture degradation on the TP and the associated loss of water regulation functions. However, neither potential large scale degradation changes nor their drivers are known. Here, we analyse trends in a high-resolution dataset of grassland cover to determine the interactions among vegetation dynamics, climate change and human impacts on the TP. The results reveal that vegetation changes have regionally different triggers: While the vegetation cover has increased since the year 2000 in the north-eastern part of the TP due to an increase in precipitation, it has declined in the central and western parts of the TP due to rising air temperature and declining precipitation. Increasing livestock numbers as a result of land use changes exacerbated the negative trends but were not their exclusive driver. Thus, we conclude that climate variability instead of overgrazing has been the primary cause for large scale vegetation cover changes on the TP since the new millennium. Since areas of positive and negative changes are almost equal in extent, pasture degradation is not generally proceeding.

  5. Clinical intrafamilial variability in lethal familial neonatal seizure disorder caused by TBC1D24 mutations.

    Science.gov (United States)

    Lozano, Reymundo; Herman, Kristin; Rothfuss, Melanie; Rieger, Hillary; Bayrak-Toydemir, Pinar; Aprile, Davide; Fruscione, Floriana; Zara, Federico; Fassio, Anna

    2016-12-01

    TBC1D24-related disorders include a wide phenotypic ranging from mild to lethal seizure disorders, non-syndromic deafness, and composite syndromes such as DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures). The TBC1D24 gene has a role in cerebral cortex development and in presynaptic neurotransmission. Here, we present a familial case of a lethal early-onset epileptic encephalopathy, associated with two novel compound heterozygous missense variants on the TBC1D24 gene, which were detected by exome sequencing. The detailed clinical data of the three siblings is summarized in order to support the variability of the phenotype, severity, and progression of this disorder among these family members. Functional studies demonstrated that the identified novel missense mutations result in a loss of expression of the protein, suggesting a correlation between residual expression, and the disease severity. This indicates that protein expression analysis is important for interpreting genetic results when novel variants are found, as well as for complementing clinical assessment by predicting the functional impact. Further analysis is necessary to delineate the clinical presentation of individuals with TBC1D24 pathogenic variants, as well as to develop markers for diagnosis, prognosis, and potential targeted treatments. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. An unusual cause of cervical lymphadenopathy: Kikuchi-Fujimoto disease

    Directory of Open Access Journals (Sweden)

    Mehmet Uluğ

    2012-03-01

    Full Text Available Kikuchi-Fujimoto disease (KFD, also known as histiocytic necrotizing lymphadenitis, is an uncommon clinical and pathologicalself-limited feature of benign prognosis that may mimic many other diseases diagnosed chiefly in youngadults. The etiology of the disease is unknown although several investigators postulate viral, parasitic and autoimmuneetiologies. The most common symptoms are cervical lymphadenopathy and fever. Diagnosis is usually rendered withexcisional biopsy of lymph nodes and through histopathological findings. Non-steroidal anti-inflammatory drugs areused for the treatment. In this report, two cases of KFD without any associated infectious and/or non-infectious conditionswere presented. J Microbiol Infect Dis 2012; 2(1: 21-25

  7. Waterborne Exophiala species causing disease in cold-blooded animals

    NARCIS (Netherlands)

    de Hoog, G.S.; Vicente, V.A.; Najafzadeh, M.J.; Harrak, M.J.; Badali, H.; Seyedmousavi, S.

    2011-01-01

    The majority of mesophilic waterborne species of the black yeast genus Exophiala (Chaetothyriales) belong to a single clade judging from SSU rDNA data. Most taxa are also found to cause cutaneous or disseminated infections in cold-blooded, water animals, occasionally reaching epidemic proportions.

  8. Waterborne Exophiala species causing disease in cold-blooded animals

    NARCIS (Netherlands)

    de Hoog, G.S.; Vicente, V.A.; Najafzadeh, M.J.; Harrak, M.J.; Badali, H.; Seyedmousavi, S.

    2012-01-01

    The majority of mesophilic waterborne species of the black yeast genus Exophiala (Chaetothyriales) belong to a single clade judging from SSU rDNA data. Most taxa are also found to cause cutaneous or disseminated infections in cold-blooded, water animals, occasionally reaching epidemic proportions.

  9. Metabolic effects of obesity causing disease in childhood.

    Science.gov (United States)

    Abrams, Pamela; Levitt Katz, Lorraine E

    2011-02-01

    Childhood obesity is rising to epidemic proportions throughout the world, and much emphasis has been placed on the long-term consequences that can result later, in adulthood. This article reviews the metabolic consequences of obesity that can manifest as disease during the childhood years. Obese children suffer from many disease processes once thought to affect only adults. They can have type 2 diabetes mellitus, and potentially early β cell failure with rapid progression to an insulin requirement. There is a high prevalence of fatty liver disease in obese children, and complications such as steatohepatitis and even cirrhosis can develop during childhood. Visceral fat has been shown to have many different properties than subcutaneous fat, and children with central adiposity can develop the metabolic syndrome with insulin resistance, hypertension, and dyslipidemia. Hyperandrogenism, sleep disturbances, and many types of orthopedic complications can also develop in young children. Physicians should not only warn obese children and their families about the long-term consequences of obesity for which they are at risk in adulthood, they should also screen for the many diseases that may already be present.

  10. Inflorescence rot disease of date palm is caused by Fusarium ...

    African Journals Online (AJOL)

    Zulfiqar-Ali

    2012-05-01

    May 1, 2012 ... inflorescence rot disease in southern part of Iraq is Fusarium proliferatum. Pathogenecity test confirmed the ... Key words: Fusarium proliferatum, ITS1, ITS4, pathogenecity, PCR, isolates, phylogeny. INTRODUCTION ..... ITS rRNA Region for Identification of Fusarium spp. from Ocular. Sources. Investigative ...

  11. Fabry disease: a rare cause of neuropathic pain

    NARCIS (Netherlands)

    Biegstraaten, Marieke; Linthorst, Gabor E.; van Schaik, Ivo N.; Hollak, Carla E. M.

    2013-01-01

    Fabry disease is characterized by burning or shooting pains in hands and feet, which have a severe impact on the quality of life of patients. It is therefore of importance that Fabry patients receive adequate diagnosis, counseling, treatment and follow up. This review describes neuropathic pain in

  12. A Novel Virus Causes Scale Drop Disease in Lates calcarifer

    NARCIS (Netherlands)

    Groof, A.; Guelen, L.; Deijs, M.; Wal, van der Y.; Miyata, M.; Ng, K.S.; Grinsven, van L.; Simmelink, B.; Biermann, Y.; Grisez, L.; Lent, van J.W.M.; Ronde, de A.; Chang, S.F.; Schrier, C.; Hoek, L.

    2015-01-01

    From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained

  13. Prevalence And Disabilities Caused By Guinea-Worm Disease ...

    African Journals Online (AJOL)

    A survey was carried out in 2001 to ascertain the status of Guinea worm disease infection among farm households in Ebonyi Local Government Area (LGA) of Ebonyi State. A total of 3,777 respondents were randomly sampled from 15 communities that comprised the LGA. The sample respondents were clinically examined ...

  14. Foot-and-Mouth Disease Virus Serotype O Phylodynamics: Genetic Variability Associated with Epidemiological Factors in Pakistan

    DEFF Research Database (Denmark)

    Brito, B. P.; Perez, A. M.; Jamal, S. M.

    2013-01-01

    One of the most challenging aspects of foot-and-mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating...... outbreaks in disease-free areas. In countries trying to control and eradicate FMD using vaccination strategies, the constantly evolving and wide diversity of field FMDV strains is an obstacle for identifying vaccine strains that are successful in conferring protection against infection with field viruses...... from this study will contribute to the understanding of FMDV variability and to the design of FMD control strategies in Pakistan. Viruses sequenced here also provide the earliest reported isolate from the Pan Asia IIANT-10 sublineage, which has caused several outbreaks in the Middle East and spread...

  15. Albedo Spatial Variability and Causes on the Western Greenland Ice Sheet Percolation Zone

    Science.gov (United States)

    Lewis, G.; Osterberg, E. C.; Hawley, R. L.; Koffman, B. G.; Marshall, H. P.; Birkel, S. D.; Dibb, J. E.

    2016-12-01

    Many recent studies have concluded that Greenland Ice Sheet (GIS) mass loss has been accelerating over recent decades, but spatial and temporal variations in GIS mass balance remain poorly understood due to a complex relationship among precipitation and temperature changes, increasing melt and runoff, ice discharge, and surface albedo. Satellite measurements from MODerate resolution Imaging Spectroradiometer (MODIS) indicate that albedo has been declining over the past decade, but the cause and extent of GIS albedo change remains poorly constrained by field data. As fresh snow (albedo > 0.85) warms and melts, its albedo decreases due to snow grain growth, promoting solar absorption, higher snowpack temperatures and further melt. However, dark impurities like soot and dust can also significantly reduce snow albedo, even in the dry snow zone. While many regional climate models (e.g. the Regional Atmospheric Climate MOdel - RACMO2) calculate albedo spatial resolutions on the order of 10-30 km, and MODIS averages albedo over 500 m, surface features like sastrugi can affect albedo on much smaller scales. Here we assess the relative importance of grain size and shape vs. impurity concentrations on albedo in the western GIS percolation zone. We collected broadband albedo measurements (300-2500 nm at 3-8 nm resolution) at 35 locations using an ASD FieldSpec4 spectroradiometer to simultaneously quantify radiative fluxes and spectral reflectance. Measurements were collected on 10 x 10 m, 1 x 1 km, 5 x 5 km, and 10 x 10 km grids to determine the spatial variability of albedo as part of the 850-km Greenland Traverse for Accumulation and Climate Studies (GreenTrACS) traverse from Raven/Dye 2 to Summit. Additionally, we collected shallow (0-50 cm) snow pit samples every 5 cm at ASD measurement sites to quantify black carbon and mineral dust concentrations and size distributions using a Single Particle Soot Photometer and Coulter Counter, respectively. Preliminary results

  16. Preventing fatal diseases increases healthcare costs: cause elimination life table approach

    NARCIS (Netherlands)

    L.G.A. Bonneux (Luc); J.J.M. Barendregt (Jan); W.J. Nusselder (Wilma); P.J. van der Maas (Paul)

    1998-01-01

    textabstractOBJECTIVES: To examine whether elimination of fatal diseases will increase healthcare costs. DESIGN: Mortality data from vital statistics combined with healthcare spending in a cause elimination life table. Costs were allocated to specific diseases through

  17. Ending versus controlling versus employing addiction in the tobacco-caused disease endgame: moral psychological perspectives

    OpenAIRE

    Kozlowski, Lynn T

    2013-01-01

    Even though interest in reducing or eliminating tobacco-caused diseases is a common goal in tobacco control, many experts hold different views on addiction as a target of intervention. Some consider tobacco-caused addiction as a tobacco-caused disease to be eliminated alongside the other diseases. Some consider tobacco-caused addiction as a much lower priority disease to be eliminated, and a subset of this group is prepared to employ addiction to tobacco (nicotine) as a tool to reduce other t...

  18. An amalgam tattoo causing local and systemic disease?

    Science.gov (United States)

    Weaver, T; Auclair, P L; Taybos, G M

    1987-01-01

    Amalgam tattoos are common oral lesions. The case presented here involved a 33-year-old woman who had had an amalgam tattoo for 2 years and complained of localized soreness and occasional swelling as well as systemic symptoms of weight loss, fatigue, sinusitis, and headaches. After excisional biopsy of the lesion, the patient's complaints ceased dramatically. It is suggested that alterations in healing due to the presence of amalgam particles led to systemic as well as local disease.

  19. RNA Viruses that Cause Hemorrhagic, Encephalitic, and Febrile Disease

    Science.gov (United States)

    1990-01-01

    commercial priority. Further, fund- - The views of the authors do not purport to reflect ing for studying many of these viruses is the position of the...tion of headache, meningismus, vertigo , mated 200,000 cases occurred with 598 re- confusion, hallucinations, and recrudes- ported deaths. Most cases...latter. Patients surviving this disease require several weeks for conva- Clinical Features lescence, and paroxysmal and orthostatic hypotension

  20. Important causes of chronic kidney disease in South Africa | Moosa ...

    African Journals Online (AJOL)

    In hypertensive patients without chronic kidney disease (CKD) the goal is to keep blood pressure (BP) at ≤140/90 mmHg. When CKD is present, especially where there is proteinuria of ≥0.5 g/day, the goal is a BP of ≤130/80 mmHg. Lifestyle measures are mandatory, especially limitation of salt intake, ingestion of ...

  1. Ribbing disease: Uncommon cause of a common symptom

    International Nuclear Information System (INIS)

    Damle, Nishikant Avinash; Patnecha, Manish; Kumar, Praveen; Gadodia, Ankur; Subbarao, Kiran; Bal, Chandrasekhar

    2011-01-01

    Ribbing disease is a rare form of sclerosing dysplasia characterized by benign endosteal and periosteal bone growth confined to the diaphyses of the long bones, usually the tibiae and femora. It occurs after puberty and is more commonly seen in women. The most common presenting symptom is pain that is usually self-limited; however, progression is known. The etiology and optimal treatment for the disease are as yet undefined. We present here the case of a 31-year-old woman with clinical, radiological and bone scan manifestations of Ribbing disease corroborated by bone biopsy. Radiographs demonstrated cortical thickening of the diaphyses of both tibiae. 99mTc-methylene diphosphonate bone scan revealed intense irregular uptake in diaphyseal region of both tibiae. Magnetic resonance imaging showed cortical thickening with bone marrow edema in bilateral tibial diaphysis with minimal adjacent soft tissue edema. Bone biopsy revealed predominantly dense lamellar bone with irregular sized and spaced haversian systems. Serum and urine markers of bone metabolism were within normal limits. The patient was treated with analgesics, and had partial relief from pain. Medullary rimming is the next treatment option in case pain progresses. This report emphasizes the role of bone scan in the diagnosis of this rare condition

  2. Biological Control of Plant Disease Caused by Bacteria

    Directory of Open Access Journals (Sweden)

    Triwidodo Arwiyanto

    2014-07-01

    Full Text Available Bacterial diseases in plants are difficult to control. The emphasis is on preventing the spread of the bacteria rather than curing the diseased plant. Integrated management measures for bacterial plant pathogens should be applied for successfull control. Biological control is one of the control measures viz. through the use of microorganisms to suppress the growth and development of bacterial plant pathogen and ultimately reduce the possibility of disease onset. The study of biological control of bacterial plant pathogen was just began compared with of fungal plant pathogen. The ecological nature of diverse bacterial plant pathogens has led scientists to apply different approach in the investigation of its biological control. The complex process of entrance to its host plant for certain soil-borne bacterial plant pathogens need special techniques and combination of more than one biological control agent. Problem and progress in controlling bacterial plant pathogens biologically will be discussed in more detail in the paper and some commercial products of biological control agents (biopesticides will be introduced.     Penyakit tumbuhan karena bakteri sulit dikendalikan. Penekanan pengendalian adalah pada pencegahan penyebaran bakteri patogen dan bukan pada penyembuhan tanaman yang sudah sakit. Untuk suksesnya pengendalian bakteri patogen tumbuhan diperlukan cara pengelolaan yang terpadu. Pengendalian secara biologi merupakan salah satu cara pengendalian dengan menggunakan mikroorganisme untuk menekan pertumbuhan dan perkembangan bakteri patogen tumbuhan dengan tujuan akhir menurunkan kemungkinan timbulnya penyakit. Sifat ekologi bakteri patogen tumbuhan yang berbeda-beda mengharuskan pendekatan yang berbeda pula dalam pengendaliannya secara biologi. Masalah dan perkembangan dalam pengendalian bakteri patogen tumbuhan secara biologi didiskusikan secara detail dalam makalah ini.

  3. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    Directory of Open Access Journals (Sweden)

    Alice Ossoli

    Full Text Available Human familial lecithin:cholesterol acyltransferase (LCAT deficiency (FLD is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.

  4. Causes and consequences of endoplasmic reticulum stress in rheumatic disease.

    Science.gov (United States)

    Navid, Fatemeh; Colbert, Robert A

    2017-01-01

    Rheumatic diseases represent a heterogeneous group of inflammatory conditions, many of which involve chronic activation of both innate and adaptive immune responses by multiple genetic and environmental factors. These immune responses involve the secretion of excessive amounts of cytokines and other signalling mediators by activated immune cells. The endoplasmic reticulum (ER) is the cellular organelle that directs the folding, processing and trafficking of membrane-bound and secreted proteins, including many key components of the immune response. Maintaining homeostasis in the ER is critical to cell function and survival. Consequently, elaborate mechanisms have evolved to sense and respond to ER stress through three main signalling pathways that together comprise the unfolded protein response (UPR). Activation of the UPR can rapidly resolve the accumulation of misfolded proteins, direct permanent changes in the size and function of cells during differentiation, and critically influence the immune response and inflammation. Recognition of the importance of ER stress and UPR signalling pathways in normal and dysregulated immune responses has greatly increased in the past few years. This Review discusses several settings in which ER stress contributes to the pathogenesis of rheumatic diseases and considers some of the therapeutic opportunities that these discoveries provide.

  5. Environmental chemicals and autoimmune disease: cause and effect

    International Nuclear Information System (INIS)

    Hess, Evelyn V.

    2002-01-01

    Many important clues have been provided by the relationship of certain medications to lupus and other autoimmune syndromes. These are temporary conditions that resolve when the medication is removed. There are now over 70 such medications which have been reported related to these autoimmune conditions. Interest continues to grow in the potential for environmental substances to cause these syndromes. Among those under suspicion are hydrazines, tartrazines, hair dyes, trichloroethylene, industrial emissions and hazardous wastes. Other possible associations include silica, mercury, cadmium, gold and L canavanine. Two recognised outbreaks include 'toxic oil syndrome' related to contaminated rape seed oil in Spain in 1981 and exposure to a contaminated environmental substance associated with an autoimmune attack on muscle tissue in 1989. Recently, there have been proposals made for the definition and identification of environmentally associated immune disorders. The World Health Organisation (WHO) has also provided recent publications for other environmentally related problems. All these aspects will be presented and reviewed in detail

  6. Contemporary Approaches for Identifying Rare Bone Disease Causing Genes.

    Science.gov (United States)

    Farber, Charles R; Clemens, Thomas L

    Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisticated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.

  7. Inflammatory spine disease as a cause of back pain

    International Nuclear Information System (INIS)

    Schlossbauer, T.; Panteleon, A.; Becker-Gaab, C.

    2006-01-01

    The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-α antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-α antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the effectiveness of anti-inflammatory therapy. (orig.) [de

  8. Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases.

    Science.gov (United States)

    Afrin, Lawrence B; Pöhlau, Dieter; Raithel, Martin; Haenisch, Britta; Dumoulin, Franz L; Homann, Juergen; Mauer, Uwe M; Harzer, Sabrina; Molderings, Gerhard J

    2015-11-01

    Neurologists and psychiatrists frequently encounter patients whose central and/or peripheral neurologic and/or psychiatric symptoms (NPS) are accompanied by other symptoms for which investigation finds no unifying cause and for which empiric therapy often provides little to no benefit. Systemic mast cell activation disease (MCAD) has rarely been considered in the differential diagnosis in such situations. Traditionally, MCAD has been considered as just one rare (neoplastic) disease, mastocytosis, generally focusing on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, MC activation syndrome (MC), has been recognized, featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. There also has developed greater appreciation for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic themes--including very wide arrays of central and peripheral NPS. Significantly helpful treatment--including for neuropsychiatric issues--usually can be identified once MCAD is accurately diagnosed. We describe MCAD's pathogenesis, presentation (focusing on NPS), and therapy, especially vis-à-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Mapping global potential risk of mango sudden decline disease caused by fungus Ceratocystis fimbriata

    Science.gov (United States)

    Mango Sudden Decline (MSD), sometimes referred to as mango wilt, is an important disease of mango caused by one of the most significant fungal species causing disease in woody plants, Ceratocystis fimbriata. This species is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Steb...

  10. Tight Bra in a 34-Year-Old Woman: An Unusual Cause of Mondor's Disease.

    Science.gov (United States)

    Vincenza Polito, Maria; De Cicco, Pierluigi; Apicella, Rosa

    2014-01-01

    Mondor's disease is characterized by thrombophlebitis of the superficial veins of the breast and the chest wall. The list of causes is long. Various types of clothing, mainly tight bras and girdles, have been postulated as causes. We report a case of a 34-year-old woman who referred typical symptoms and signs of Mondor's disease, without other possible risk factors, and showed the cutaneous findings of the tight bra. Therefore, after distinguishing benign causes of Mondor's disease from hidden malignant causes, the clinicians should consider this clinical entity.

  11. Pathological gambling caused by drugs used to treat Parkinson disease.

    Science.gov (United States)

    Dodd, M Leann; Klos, Kevin J; Bower, James H; Geda, Yonas E; Josephs, Keith A; Ahlskog, J Eric

    2005-09-01

    Pathological gambling is a rare potential complication related to treatment of Parkinson disease (PD). However, the etiology of this behavior is poorly understood. To examine the relationship between medical therapy for PD and pathological gambling. In our routine movement disorders practice (2002-2004), we encountered 11 patients with idiopathic PD who had recently developed pathological gambling. We assessed the relationship to their medical therapy and compared them with cases identified by systematic review of the existing literature on pathological gambling and PD. All 11 patients with PD and pathological gambling were taking therapeutic doses of a dopamine agonist; 3 of these patients were not treated with levodopa. In 7 patients, pathological gambling developed within 3 months of starting to take or escalating the dose of the agonist; in the other 4 with a longer latency, gambling resolved after the agonist use was discontinued. Pramipexole dihydrochloride was the agonist in 9 of 11 cases in our series and 10 of 17 in the literature (68% in total). Dopamine agonist therapy was associated with potentially reversible pathological gambling, and pramipexole was the medication predominantly implicated. This may relate to disproportionate stimulation of dopamine D(3) receptors, which are primarily localized to the limbic system.

  12. Psychological disorders in gastrointestinal disease: epiphenomenon, cause or consequence?

    Science.gov (United States)

    Shah, Eric; Rezaie, Ali; Riddle, Mark; Pimentel, Mark

    2014-01-01

    Psychological disorders have been associated with irritable bowel syndrome (IBS) for decades in the absence of other objective etiology. However, such associations are also evident in other chronic diseases with more clearly defined pathogenesis such as ulcerative colitis. In this study, we examined the prevalence and severity of psychological disorders among IBS and ulcerative colitis (UC) patients relative to healthy controls. A review was conducted of English-language literature to identify case-control studies reporting the prevalence of depression or anxiety in IBS and UC populations relative to healthy controls. Our primary endpoint was the pooled prevalence or average score of depression or anxiety in an IBS or UC population relative to healthy control. Seven case-control studies evaluating IBS and three evaluating UC were included. All IBS and UC studies reported excess prevalence and severity of depression as well as anxiety, relative to healthy controls. The prevalence of depression in excess of healthy controls was 39% in UC case-control trials and 33% in IBS studies, and excess anxiety was present in UC (42%) and IBS (19%) case-control trials as well. Anxiety and depression scores were higher (representing more severe symptoms) in both UC and IBS patients compared to healthy controls. Anxiety and depressive disorders are associated with both IBS and UC. The non-specific association between these psychological and gastrointestinal disorders could suggest that chronic gastrointestinal illness might affect psychosocial behavior.

  13. Heart rate variability predicts 30-day all-cause mortality in intensive ...

    African Journals Online (AJOL)

    HRV), has shown promise in predicting clinically important outcomes in the critical care setting; however, there is debate concerning its utility. ... Keywords: APACHE II, autonomic nervous system, critical care, heart rate variability, mortality ...

  14. Gender-based variability in disease presentation in pemphigus vulgaris.

    Science.gov (United States)

    Naseer, Sahar Y; Gill, Liza; Shah, Jay; Sinha, Animesh A

    2014-10-01

    Pemphigus vulgaris is a chronic autoimmune blistering disorder of the skin. As with many autoimmune diseases, a female predominance in pemphigus vulgaris is well established. The genetic and physiological basis for this gender bias is not well understood. Moreover, it is unclear whether the affect of gender extends beyond disease susceptibility to influence disease presentation. To address this issue, we performed a comprehensive analysis of 72 male and 125 female pemphigus vulgaris patients across a set of defined demographic (HLA type, ethnicity) and clinical (age at disease onset, anti-desmoglein antibody levels, site of lesions, and history of autoimmune disease) factors. We find that male patients are more likely to present with disease onset before age 40 than females. Additionally, we find that males have increased cutaneous involvement and display greater co-expression of anti-Dsg1 and anti-Dsg3 antibodies, while females tend to have mucosal predominance and stronger personal and family histories of autoimmunity. We do not find any differences in the distribution of HLA type or ethnicity between male and female pemphigus vulgaris patients. Our findings establish that gender does influence disease presentation in pemphigus vulgaris, supporting a role for genetic and hormonal factors in immune dysregulation and perpetuation of the autoimmune phenotype.

  15. Effects of Host Variability on the Spread of Invasive Forest Diseases

    Directory of Open Access Journals (Sweden)

    Simone Prospero

    2017-03-01

    Full Text Available Biological invasions, resulting from deliberate and unintentional species transfers of insects, fungal and oomycete organisms, are a major consequence of globalization and pose a significant threat to biodiversity. Limiting damage by non-indigenous forest pathogens requires an understanding of their current and potential distributions, factors affecting disease spread, and development of appropriate management measures. In this review, we synthesize innate characteristics of invading organisms (notably mating system, reproduction type, and dispersal mechanisms and key factors of the host population (namely host diversity, host connectivity, and host susceptibility that govern spread and impact of invasive forest pathogens at various scales post-introduction and establishment. We examine spread dynamics for well-known invasive forest pathogens, Hymenoscyphus fraxineus (T. Kowalski Baral, Queloz, Hosoya, comb. nov., causing ash dieback in Europe, and Cryphonectria parasitica, (Murr. Barr, causing chestnut blight in both North America and Europe, illustrating the importance of host variability (diversity, connectivity, susceptibility in their invasion success. While alien pathogen entry has proven difficult to control, and new biological introductions are indeed inevitable, elucidating the key processes underlying host variability is crucial for scientists and managers aimed at developing effective strategies to prevent future movement of organisms and preserve intact ecosystems.

  16. Solar Irradiance Variability is Caused by the Magnetic Activity on the Solar Surface

    Science.gov (United States)

    Yeo, K. L.; Solanki, S. K.; Norris, C. M.; Beeck, B.; Unruh, Y. C.; Krivova, N. A.

    2017-09-01

    The variation in the radiative output of the Sun, described in terms of solar irradiance, is important to climatology. A common assumption is that solar irradiance variability is driven by its surface magnetism. Verifying this assumption has, however, been hampered by the fact that models of solar irradiance variability based on solar surface magnetism have to be calibrated to observed variability. Making use of realistic three-dimensional magnetohydrodynamic simulations of the solar atmosphere and state-of-the-art solar magnetograms from the Solar Dynamics Observatory, we present a model of total solar irradiance (TSI) that does not require any such calibration. In doing so, the modeled irradiance variability is entirely independent of the observational record. (The absolute level is calibrated to the TSI record from the Total Irradiance Monitor.) The model replicates 95% of the observed variability between April 2010 and July 2016, leaving little scope for alternative drivers of solar irradiance variability at least over the time scales examined (days to years).

  17. Solar Irradiance Variability is Caused by the Magnetic Activity on the Solar Surface.

    Science.gov (United States)

    Yeo, Kok Leng; Solanki, Sami K; Norris, Charlotte M; Beeck, Benjamin; Unruh, Yvonne C; Krivova, Natalie A

    2017-09-01

    The variation in the radiative output of the Sun, described in terms of solar irradiance, is important to climatology. A common assumption is that solar irradiance variability is driven by its surface magnetism. Verifying this assumption has, however, been hampered by the fact that models of solar irradiance variability based on solar surface magnetism have to be calibrated to observed variability. Making use of realistic three-dimensional magnetohydrodynamic simulations of the solar atmosphere and state-of-the-art solar magnetograms from the Solar Dynamics Observatory, we present a model of total solar irradiance (TSI) that does not require any such calibration. In doing so, the modeled irradiance variability is entirely independent of the observational record. (The absolute level is calibrated to the TSI record from the Total Irradiance Monitor.) The model replicates 95% of the observed variability between April 2010 and July 2016, leaving little scope for alternative drivers of solar irradiance variability at least over the time scales examined (days to years).

  18. Modelling the economic impact of three lameness causing diseases using herd and cow level evidence

    DEFF Research Database (Denmark)

    Ettema, Jehan Frans; Østergaard, Søren; Kristensen, Anders Ringgaard

    2010-01-01

    Diseases to the cow's hoof, interdigital skin and legs are highly prevalent and of large economic impact in modern dairy farming. In order to support farmer's decisions on preventing and treating lameness and its underlying causes, decision support models can be used to predict the economic...... horn diseases. Secondly, the existing simulation model was set-up inwaythat it uses hyper-distributions describing diseases risk of the three lameness causing diseases. By combining information on herd level risk factors with prevalence of lameness or prevalence of underlying diseases among cows...

  19. Hemolytic disease of the fetus and newborn caused by anti-Lan.

    Science.gov (United States)

    Brooks, Sarah; Squires, Jerry E

    2014-05-01

    Antibodies to the high-incidence red blood cell (RBC) antigen Lan (Langereis) are typically immunoglobulin G and have been shown to fix complement and cause hemolysis of Lan antigen-positive RBCs. Only three cases of hemolytic disease of the fetus and newborn (HDFN) have been reported involving anti-Lan and all have been characterized as "mild." A 26-year-old Hispanic female presented in her fifth pregnancy for routine obstetric care. Due to progressively rising anti-Lan titers, middle cerebral artery (MCA) Dopplers were performed. At 32 weeks of gestation, the antibody titer had reached 128; the MCA Doppler indicated that fetal anemia was severe. An intrauterine transfusion with Lan antigen-negative RBCs was performed and a viable infant was delivered 25 days later. Three cases of HDFN associated with anti-Lan have been previously reported. While these cases have been associated with somewhat variable serologic findings, none have resulted in fetal demise or severe symptomatology requiring pre- or postnatal intervention other than routine phototherapy. The current report, however, suggests that in some instances anti-Lan can result in a more severe form of HDFN requiring more aggressive prenatal therapy. In spite of previous case reports suggesting that anti-Lan is associated with relatively mild HDFN, this case suggests that in some instances, this antibody can cause severe HDFN requiring prenatal intervention. © 2013 American Association of Blood Banks.

  20. Alcohol Consumption and Risk of All-Cause and Cardiovascular Disease Mortality in Men

    Directory of Open Access Journals (Sweden)

    Erin K. Howie

    2011-01-01

    Full Text Available This study examined the association between consumption of alcoholic beverages and all-cause and cardiovascular disease (CVD mortality in a cohort of men (n=31,367. In the Cox proportional hazards model adjusted for age, year of examination, body mass index (BMI, smoking, family history of CVD, and aerobic fitness, there were no significant differences in risk of all-cause mortality across alcohol intake groups. Risk of CVD mortality was reduced 29% in quartile 1 (HR = 0.71, 95% confidence interval (CI: 0.53, 0.95 and 25% in quartile 2 (HR = 0.75, 95% CI: 0.58, 0.98. The amount of alcohol consumed to achieve this risk reduction was <6 drinks/week; less than the amount currently recommended. The addition of other potential confounders and effect modifiers including blood pressure, insulin sensitivity, lipid levels, and psychological variables did not affect the magnitude of association. Future research is needed to validate the current public health recommendations for alcohol consumption.

  1. An investigation in InGaO3(ZnO)m pellets as cause of variability in ...

    Indian Academy of Sciences (India)

    An investigation in InGaO3(ZnO)m pellets as cause of variability in thin film transistor characteristics. SONACHAND ADHIKARI†, RAJEEV GUPTA†,††, ASHISH GARG††† ..... and aids in the final phase formation. 3.3 Applicability of sintering process for various compositions. After optimizing to two-stage sintering process at.

  2. Evaluating the Contribution of the Cause of Kidney Disease to Prognosis in CKD

    DEFF Research Database (Denmark)

    Haynes, Richard; Staplin, Natalie; Emberson, Jonathan

    2014-01-01

    BACKGROUND: The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain. STUDY DESIGN: Observational study. SETTINGS & PARTICIPANTS: 6,245 nondialysis participants in the Study of Heart and Renal Protection (SHARP). PREDICTOR: Baseline cause...... of kidney disease was categorized into 4 groups: cystic kidney disease, diabetic nephropathy, glomerulonephritis, and other recorded diagnoses. OUTCOMES: End-stage renal disease (ESRD; dialysis or transplantation) and death. RESULTS: During an average 4.7 years' follow-up, 2,080 participants progressed...... to ESRD, including 454 with cystic kidney disease (23% per year), 378 with glomerulonephritis (10% per year), 309 with diabetic nephropathy (12% per year), and 939 with other recorded diagnoses (8% per year). By comparison with patients with cystic kidney disease, other disease groups had substantially...

  3. Variable complementary combined radiologic imaging methods for breast diseases

    International Nuclear Information System (INIS)

    Oh, Ki Keun; Lee, Kyong Sik; Sohn, Seing Kook

    1985-01-01

    Radiographic examination of the breast has been so improved that it became a routine complement to physical examination. From November 1, 1983 through September 30, 1984, 684 patients with complains of various breast problem were examined by low-dose film mammography at Yong Dong Hospital, Yonsei University. Among them, a comparative studies, independently conducted physical examination, 97 cases of film mammography, 35 cases of ultrasound mammography, 16 cases of aspiration cytology, and 3 cases of galactography were performed for our pathologically proven 98 cases of breast diseases. Combined and complementary studies for breast diseases were analyzed in 37 proven cases and authors found that specificity of those combined immediate complementary study techniques for breast diseases were 94% under close cooperation with surgeon in Yong Dong Hospital, Yonsei University

  4. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Sevilla, Teresa; Lupo, Vincenzo; Martínez-Rubio, Dolores; Sancho, Paula; Sivera, Rafael; Chumillas, María J; García-Romero, Mar; Pascual-Pascual, Samuel I; Muelas, Nuria; Dopazo, Joaquín; Vílchez, Juan J; Palau, Francesc; Espinós, Carmen

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a

  5. Rare Central Pacific El Niño Events Caused by Interdecadal Tropical Pacific Variability

    Science.gov (United States)

    Zhong, Wenxiu; Zheng, Xiaotong; Cai, Wenju

    2017-04-01

    The frequency of Central Pacific (CP) El Niño events displays strong decadal-variability but the associated dynamics is still not clear. The Inter-decadal Pacific Oscillation (IPO) and the Tropical Pacific Decadal Variability (TPDV) are two dominant modes of the Pacific low-frequency variability that can modify high-frequency behaviors. Using a 500-year control integration of Geophysical Fluid Dynamics Laboratory Earth System Model simulation, we find that the mean state, determined by the two independent modes of tropical Pacific decadal variability, strongly affects CP El Niño frequency and the associated developing processes. A positive TPDV features a shallow thermocline and cool sea surface temperature anomalies (SSTAs) across the central-to-western tropical Pacific, and a negative IPO features cool SSTAs and strong trade winds along the equatorial Pacific. The combination of a positive TPDV and a negative IPO generates a decadal mean state, in which the climatological zonal temperature gradient is reduced, equatorward and westward current anomalies are harder to be generated over the central-to-western tropical Pacific, resulting in the lack of CP El Niño.

  6. Heart rate variability predicts 30-day all-cause mortality in intensive ...

    African Journals Online (AJOL)

    inotrope/vasopressor therapy, and need for renal replacement therapy we conducted logistic regression as detailed above to determine the strength of association between the HRV parameters and these outcomes. We compared HRV variables identified as significantly predictive of the primary outcome with the APACHE II ...

  7. Mosaicism for dominant collagen 6 mutations as a cause for intrafamilial phenotypic variability

    NARCIS (Netherlands)

    Donkervoort, S.; Hu, Y.; Stojkovic, T.; Voermans, N.C.; Foley, A.R.; Leach, M.E.; Dastgir, J.; Bolduc, V.; Cullup, T.; Becdelievre, A. de; Yang, L.; Su, H.; Meilleur, K.; Schindler, A.B.; Kamsteeg, E.J.; Richard, P.; Butterfield, R.J.; Winder, T.L.; Crawford, T.O.; Weiss, R.B.; Muntoni, F.; Allamand, V.; Bonnemann, C.G.

    2015-01-01

    Collagen 6-related dystrophies and myopathies (COL6-RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter- and intrafamilial variable expressivity are commonly

  8. Variable virulence factors in Burkholderia pseudomallei (melioidosis associated with human disease.

    Directory of Open Access Journals (Sweden)

    Derek S Sarovich

    Full Text Available Burkholderia pseudomallei is a Gram-negative environmental bacterium that causes melioidosis, a potentially life-threatening infectious disease affecting mammals, including humans. Melioidosis symptoms are both protean and diverse, ranging from mild, localized skin infections to more severe and often fatal presentations including pneumonia, septic shock with multiple internal abscesses and occasionally neurological involvement. Several ubiquitous virulence determinants in B. pseudomallei have already been discovered. However, the molecular basis for differential pathogenesis has, until now, remained elusive. Using clinical data from 556 Australian melioidosis cases spanning more than 20 years, we identified a Burkholderia mallei-like actin polymerization bimA(Bm gene that is strongly associated with neurological disease. We also report that a filamentous hemagglutinin gene, fhaB3, is associated with positive blood cultures but is negatively correlated with localized skin lesions without sepsis. We show, for the first time, that variably present virulence factors play an important role in the pathogenesis of melioidosis. Collectively, our study provides a framework for assessing other non-ubiquitous bacterial virulence factors and their association with disease, such as candidate loci identified from large-scale microbial genome-wide association studies.

  9. NDRC: A Disease-Causing Genes Prioritized Method Based on Network Diffusion and Rank Concordance.

    Science.gov (United States)

    Fang, Minghong; Hu, Xiaohua; Wang, Yan; Zhao, Junmin; Shen, Xianjun; He, Tingting

    2015-07-01

    Disease-causing genes prioritization is very important to understand disease mechanisms and biomedical applications, such as design of drugs. Previous studies have shown that promising candidate genes are mostly ranked according to their relatedness to known disease genes or closely related disease genes. Therefore, a dangling gene (isolated gene) with no edges in the network can not be effectively prioritized. These approaches tend to prioritize those genes that are highly connected in the PPI network while perform poorly when they are applied to loosely connected disease genes. To address these problems, we propose a new disease-causing genes prioritization method that based on network diffusion and rank concordance (NDRC). The method is evaluated by leave-one-out cross validation on 1931 diseases in which at least one gene is known to be involved, and it is able to rank the true causal gene first in 849 of all 2542 cases. The experimental results suggest that NDRC significantly outperforms other existing methods such as RWR, VAVIEN, DADA and PRINCE on identifying loosely connected disease genes and successfully put dangling genes as potential candidate disease genes. Furthermore, we apply NDRC method to study three representative diseases, Meckel syndrome 1, Protein C deficiency and Peroxisome biogenesis disorder 1A (Zellweger). Our study has also found that certain complex disease-causing genes can be divided into several modules that are closely associated with different disease phenotype.

  10. Glycogen Storage Disease type 1a – a secondary cause for hyperlipidemia: report of five cases

    Science.gov (United States)

    2013-01-01

    Background and aims Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Hyperlipidemia and hyperuricemia are almost always present and hepatocellular adenomas and renal dysfunction frequent late complications. Methods The authors present a report of five adult patients with GSD Ia followed in internal medicine appointments and subspecialties. Results Four out of five patients were diagnosed in the first 6 months of life, while the other one was diagnosed in adult life after the discovery of hepatocellular adenomas. In two cases genetic tests were performed, being identified the missense mutation R83C in one, and the mutation IVS4-3C > G in the intron 4 of glucose-6-phosphatase gene, not previously described, in the other. Growth retardation was present in 3 patients, and all of them had anemia, increased bleeding tendency and hepatocellular adenomas; osteopenia/osteoporosis was present in three cases. All but one patient had marked hyperlipidemia and hyperuricemia, with evidence of endothelial dysfunction in one case and of brain damage with refractory epilepsy in another case. Proteinuria was present in two cases and end-stage renal disease in another case. There was a great variability in the dietary measures; in one case, liver transplantation was performed, with correction of the metabolic derangements. Conclusions Hyperlipidemia is almost always present and only partially responds to dietary and drug therapy; liver transplantation is the only definitive solution. Although its association with premature atherosclerosis is rare, there have been reports of endothelial dysfunction, raising the possibility for increased cardiovascular risk in this group of

  11. Prediction of Disease Causing Non-Synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

    DEFF Research Database (Denmark)

    Johansen, Morten Bo; Gonzalez-Izarzugaza, Jose Maria; Brunak, Søren

    2013-01-01

    We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features...

  12. Molecular characterization of an Enterovirus 71 causing neurological disease in Germany.

    Science.gov (United States)

    Kehle, Johannes; Roth, Bernhard; Metzger, Christoph; Pfitzner, Artur; Enders, Gisela

    2003-02-01

    Enterovirus 71 (EV71) is mainly known as a cause of hand-foot-and-mouth disease (HFMD) but sometimes associated with neurological disease, even as fatal brainstem encephalitis. In Europe, EV71 infections are extremely rare, in contrast to the worldwide situation. This is the first report of molecular characterization of an EV71 strain isolated in Europe that had caused neurological disease. The german strain is closest related to sublineage B2 strains isolated in the United States, which where mainly associated with neurological disease. Phylogenetic analysis also showed that the strain must have been imported to Germany several years ago, and continues to circulate since then.

  13. Quality problems root cause identification and variability reduction in casting processes

    Directory of Open Access Journals (Sweden)

    G. Furgał

    2009-01-01

    Full Text Available Increasing customer requirements and production costs force casting manufacturers to adopt a methodological approach to manufacturingprocesses, in order to deliver increasingly more repeatable, predictable and competitive products. One of the methods of achieving such results is the reduction of variability of manufacturing processes and the optimization of their control. This paper presents the possibilities granted by the Six Sigma methodology in efficient identification of special factors influencing pre-heat of ceramic moulds and castingparameters, in the minimization of the frequency at which they occur, and in the reduction of key process parameters variability. This paper also shows the usability of the method in achieving measurable business advantages for the company using the example of one DMAIC methodology based project realized in the Investment Foundry Department of WSK “PZL-Rzeszow” S.A.

  14. Absenteeism due to Functional Limitations Caused by Seven Common Chronic Diseases in US Workers.

    Science.gov (United States)

    Vuong, Tam D; Wei, Feifei; Beverly, Claudia J

    2015-07-01

    The study examined the relationship between functional limitation due to chronic diseases and absenteeism among full-time workers. The studied chronic diseases include arthritis/rheumatism, cancer, diabetes, heart disease, hypertension, lung disease, and stroke. We analyzed data from the 2011 to 2013 National Health Interview Survey. Economic impact was determined by workdays lost and lost income. Increase in absenteeism was observed for each studied condition. Employees with multiple conditions also saw increase absenteeism. Employers lose 28.2 million workdays annually ($4.95 billion in lost income) due to functional limitation caused by chronic diseases. The results show a burden on society due to functional limitation caused by studied chronic diseases. Employers should look into implementing intervention/prevention programs, such as the Chronic Disease Self-Management Programs, to help reduce the cost associated with absenteeism.

  15. Comparison of cardiopulmonary exercise testing variables in COPD patients with and without coronary artery disease.

    Science.gov (United States)

    Thirapatarapong, Wilawan; Armstrong, Hilary F; Bartels, Matthew N

    2014-01-01

    Coronary artery disease (CAD) is a common concomitant condition and an important cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Since COPD and CAD can both independently cause reduced exercise capacity, it is reasonable to hypothesize that the combination of these diseases may compound the abnormalities observed during cardiopulmonary exercise testing (CPET). However, little is known about the impact of CAD on the CPET response in COPD patients. The aim of this study is to compare exercise capacity and gas exchange variables in COPD patients with and without CAD. Fifty-four COPD subjects without CAD (COPDnoCAD) were matched to 54 COPD subjects diagnosed with CAD (COPD/CAD) according to age, gender, body mass index and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET. Comparing COPDnoCAD patients with COPD/CAD patients revealed that exercise capacity, as measured by % peak oxygen consumption (42 ± 16% vs 53 ± 19%, p = 0.002) and % peak wattage (23 ± 13% vs 32 ± 16%, p = 0.001), was significantly lower in COPD/CAD. Ventilatory response, as measured by VE/VCO2 nadir (36 ± 9 vs 32 ± 5, p = 0.001), was significantly higher in COPD/CAD, with % peak VO2 and VE/VCO2 nadir correlating to % FEV1 and inversely correlating with %DLCO. COPD patients with CAD have significantly impaired CPET responses with lower exercise capacity and impaired gas exchange compared to COPD patients without CAD. These findings may affect the clinical interpretation of CPET data in COPD patients who have concomitant CAD. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Protein-truncating mutations in ASPM cause variable reduction in brain size

    NARCIS (Netherlands)

    Bond, Jacquelyn; Scott, Sheila; Hampshire, Daniel J.; Springell, Kelly; Corry, Peter; Abramowicz, Marc J.; Mochida, Ganesh H.; Hennekam, Raoul C. M.; Maher, Eamonn R.; Fryns, Jean-Pierre; Alswaid, Abdulrahman; Jafri, Hussain; Rashid, Yasmin; Mubaidin, Ammar; Walsh, Christopher A.; Roberts, Emma; Woods, C. Geoffrey

    2003-01-01

    Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed

  17. Differing Relationship of Psycho-Social Variables with Active Ulcerative Colitis or Crohn's Disease.

    Science.gov (United States)

    Sarid, Orly; Slonim-Nevo, Vered; Schwartz, Doron; Friger, Michael; Sergienko, Ruslan; Pereg, Avihu; Vardi, Hillel; Chernin, Elena; Singer, Terri; Greenberg, Dan; Odes, Shmuel

    2018-03-09

    How psycho-social variables affect the degree of disease activity in patients with ulcerative colitis (UC) or Crohn's disease (CD) is incompletely understood. Therefore, we measured and compared the impact of psycho-social variables on the active disease state in UC and CD. One hundred and twenty-two UC and 305 CD patients with active disease completed questionnaires detailing their psychological symptoms, threatening experiences, disease-coping strategies, satisfaction with life, quality of life, and demographics. UC and CD patients were aged (mean, SD) 38.6 ± 14.0 and 45.2 ± 15.1 years, respectively. The psychological symptom index (median, IQR) was greater in UC 1.24 (0.8) than CD 0.9 (0.8), p psycho-social variables on the active disease state differs between UC and CD, thus indicating a need for specifically tailored psychotherapies.

  18. Sleep duration and ischemic heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Garde, Anne Helene; Hansen, Åse Marie; Holtermann, Andreas

    2013-01-01

    This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association.......This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association....

  19. Ileitis caused by Yersinia enterocolitica - X-ray differential diagnosis of Crohn's disease

    International Nuclear Information System (INIS)

    Lingg, G.; Hering, L.; Tanneberger, D.

    1981-01-01

    The article gives a brief description of the characteristic features of the clinical and roentgenological course and the various stages of enteritis caused by Yersinia. Basing on three cases of ileitis caused by Yersinia, the far-reaching similarity with the early changes and even the advanced stages of Crohn's diseases are demonstrated. Attention is drawn to the possibilities of differentiating between the two disease patterns. (orig.) [de

  20. Ileitis caused by Yersinia enterocolitica - X-ray differential diagnosis of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lingg, G.; Hering, L.; Tanneberger, D.

    1981-12-01

    The article gives a brief description of the characteristic features of the clinical and roentgenological course and the various stages of enteritis caused by Yersinia. Basing on three cases of ileitis caused by Yersinia, the far-reaching similarity with the early changes and even the advanced stages of Crohn's diseases are demonstrated. Attention is drawn to the possibilities of differentiating between the two disease patterns.

  1. Age of oil palm plantations causes a strong change in surface biophysical variables

    Science.gov (United States)

    Sabajo, Clifton; le Maire, Guerric; Knohl, Alexander

    2016-04-01

    Over the last decades, Indonesia has experienced dramatic land transformations with an expansion of oil palm plantations at the expense of tropical forests. As vegetation is a modifier of the climate near the ground these large-scale land transformations are expected to have major impacts on the surface biophysical variables i.e. surface temperature, albedo, and vegetation indices, e.g. the NDVI. Remote sensing data are needed to assess such changes at regional scale. We used 2 Landsat images from Jambi Province in Sumatra/Indonesia covering a chronosequence of oil palm plantations to study the 20 - 25 years life cycle of oil palm plantations and its relation with biophysical variables. Our results show large differences between the surface temperature of young oil palm plantations and forest (up to 9.5 ± 1.5 °C) indicating that the surface temperature is raised substantially after the establishment of oil palm plantations following the removal of forests. During the oil palm plantation lifecycle the surface temperature differences gradually decreases and approaches zero around an oil palm plantation age of 10 years. Similarly, NDVI increases and the albedo decreases approaching typical values of forests. Our results show that in order to assess the full climate effects of oil palm expansion biophysical processes play an important role and the full life cycle of oil palm plantations need to be considered.

  2. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality

    NARCIS (Netherlands)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A.; Gijsbers, Lieke; Givens, David I.; Soedamah-Muthu, Sabita S.

    2017-01-01

    With a growing number of prospective cohort studies, an updated dose–response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to

  3. First report of mango malformation disease caused by Fusarium pseudocircinatum in Mexico

    Science.gov (United States)

    Mango (Mangifera indica L.) malformation disease (MMD) is one of the most important diseases affecting this crop worldwide, causing severe economic loss due to reduction of yield. Subsequent to the first report in India in 1891 (3), MMD has spread worldwide to most mango-growing regions. Several spe...

  4. First report of laurel wilt disease caused by Raffaelea lauricola on pondspice in Florida

    Science.gov (United States)

    M. Hughes; J.A. Smith; A.E. Mayfield III; M.C. Minno; K. Shin

    2011-01-01

    Laurel wilt is a fungal vascular disease of redbay (Persea borbonia (L.) Spreng) and other plants in the family Lauraceae in the southeastern United States (1). The disease is caused by Raffaelea lauricola T. C. Harr., Fraedrich & Aghayeva, which is vectored by the exotic redbay ambrosia beetle (Xyleborus glabratus...

  5. Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency

    NARCIS (Netherlands)

    Lemmens, R.; Maugeri, A.; Niessen, H.W.M.; Goris, A.; Tousseyn, T.; Demaerel, P.; Corveleyn, A.; Robberecht, W.; van der Knaap, M.S.; Thijs, V.N.; Zwijnenburg, P.J.G.

    2013-01-01

    Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused

  6. MOSAIC DISEASE OF MAIZE CAUSED BY SUGARCANE MOSAIC POTYVIRUS IN SULAWESI

    Directory of Open Access Journals (Sweden)

    W. Wakmana

    2016-10-01

    Full Text Available Mosaic disease of maize and grasses is commonly found in Sulawesi. The symptoms resemble the common mosaic symptoms of virus infection, but the pathogen has not been identified. The objective of this study was to identify the causal agent of the mosaic disease of maize and grasses in Sulawesi. Transmissions of the virus were studied by mechanical inoculation and the insect vector aphid. Serological study was done by using enzyme linked immunosorbent assay (ELISA. Results of mechanical inoculation showed that the disease was caused by a virus which was transmitted from diseased maize and grasses to healthy sweet corn seedlings. The disease was also transmitted by aphid (Rhopalosiphum maidis. Serological study indicated that the virus was closely related to the sugarcane mosaic virus (SCMV. Based on these results, it can be concluded that the maize and grass mosaic disease was caused by SCMV.

  7. Immunoglobulin G4-related Kidney Disease as a Cause of Acute Renal Insufficiency.

    Science.gov (United States)

    Li, Cai; Du, Xiao-Gang

    2015-09-01

    Immunoglobulin G4 (IgG4)-related kidney disease is a systemic autoimmune disease which characterized by elevated serum IgG4 and dense infiltration of IgG4-positive plasma cells into tubular interstitium. It can be a mimicker of acute renal insufficiency. We herein report a rare case of IgG4-related kidney disease as a cause of acute renal insufficiency.

  8. Causes of intraseasonal diabatic heating variability over and near the Tibetan Plateau in boreal summer

    Science.gov (United States)

    Yang, Shuangyan; Li, Tim

    2017-10-01

    The structure and evolution features of the first two leading modes of the intraseasonal diabatic heating variability over the Tibetan Plateau (TP) during northern summer are investigated using reanalysis and observational data. Both of the leading modes present a dominant 10-30-day intraseasonal oscillation (ISO). The first mode is characterized by a perturbation center over the southern TP (STP), which remains quasi-stationary and is closely related to the low-latitude ISO. The associated low-latitude ISO is originated from the tropical western Pacific (WP) and propagates westward/northwestward toward northwestern India along the mean monsoon trough. The westward propagation near the South China Sea is mainly attributed to anomalous meridional vorticity advection and the advection of the planetary vorticity by ISO flow. The stationary feature of the perturbation over the STP is ascribed to the topographical features around the STP. The intraseasonal heating variability over the STP is attributed to the alternation of anticyclonic and cyclonic flow associated with the westward-propagating ISO perturbation originated from the tropical WP. The second leading mode is characterized by an east-west asymmetric structure over the TP. The intraseasonal diabatic heating anomaly propagates clockwise from the northwestern to eastern TP, while a heating anomaly with an opposite sign propagates from the southeastern to western TP. The mid-latitude Rossby wave trains play an essential role in forming the dipole structure. The wave trains propagate southeastward before reaching the TP and then eastward as they cross the TP. The source of anomalous water vapor over the TP is originated from lower latitudes. The upper- and lower-level wave trains are well coupled over the TP, exhibiting a baroclinic structure.

  9. Disease and predation: sorting out causes of a bighorn sheep (Ovis canadensis decline.

    Directory of Open Access Journals (Sweden)

    Joshua B Smith

    Full Text Available Estimating survival and documenting causes and timing of mortality events in neonate bighorn sheep (Ovis canadensis improves understanding of population ecology and factors influencing recruitment. During 2010-2012, we captured and radiocollared 74 neonates in the Black Hills, South Dakota, of which 95% (70 died before 52 weeks of age. Pneumonia (36% was the leading cause of mortality followed by predation (30%. We used known fate analysis in Program MARK to estimate weekly survival rates and investigate the influence of intrinsic variables on 52-week survival. Model {S1 wk, 2-8 wks, >8 wks} had the lowest AIC c (Akaike's Information Criterion corrected for small sample size value, indicating that age (3-stage age-interval: 1 week, 2-8 weeks, and >8 weeks best explained survival. Weekly survival estimates for 1 week, 2-8 weeks, and >8 weeks were 0.81 (95% CI = 0.70-0.88, 0.86 (95% CI = 0.81-0.90, and 0.94 (95% CI = 0.91-0.96, respectively. Overall probability of surviving 52 weeks was 0.02 (95% CI = 0.01-0.07. Of 70 documented mortalities, 21% occurred during the first week, 55% during weeks 2-8, and 23% occurred >8 weeks of age. We found pneumonia and predation were temporally heterogeneous with lambs most susceptible to predation during the first 2-3 weeks of life, while the greatest risk from pneumonia occurred from weeks 4-8. Our results indicated pneumonia was the major factor limiting recruitment followed by predation. Mortality from predation may have been partly compensatory to pneumonia and its effects were less pronounced as alternative prey became available. Given the high rates of pneumonia-caused mortality we observed, and the apparent lack of pneumonia-causing pathogens in bighorn populations in the western Black Hills, management activities should be geared towards eliminating contact between diseased and healthy populations.

  10. Disease and predation: Sorting out causes of a bighorn sheep (Ovis canadensis) decline

    Science.gov (United States)

    Smith, Joshua B.; Jenks, Jonathan A.; Grovenburg, Troy W.; Klaver, Robert W.

    2014-01-01

    Estimating survival and documenting causes and timing of mortality events in neonate bighorn sheep (Ovis canadensis) improves understanding of population ecology and factors influencing recruitment. During 2010–2012, we captured and radiocollared 74 neonates in the Black Hills, South Dakota, of which 95% (70) died before 52 weeks of age. Pneumonia (36%) was the leading cause of mortality followed by predation (30%). We used known fate analysis in Program MARK to estimate weekly survival rates and investigate the influence of intrinsic variables on 52-week survival. Model {S1 wk, 2–8 wks, >8 wks} had the lowest AICc (Akaike’s Information Criterion corrected for small sample size) value, indicating that age (3-stage age-interval: 1 week, 2–8 weeks, and >8 weeks) best explained survival. Weekly survival estimates for 1 week, 2–8 weeks, and >8 weeks were 0.81 (95% CI = 0.70–0.88), 0.86 (95% CI = 0.81–0.90), and 0.94 (95% CI = 0.91–0.96), respectively. Overall probability of surviving 52 weeks was 0.02 (95% CI = 0.01–0.07). Of 70 documented mortalities, 21% occurred during the first week, 55% during weeks 2–8, and 23% occurred >8 weeks of age. We found pneumonia and predation were temporally heterogeneous with lambs most susceptible to predation during the first 2–3 weeks of life, while the greatest risk from pneumonia occurred from weeks 4–8. Our results indicated pneumonia was the major factor limiting recruitment followed by predation. Mortality from predation may have been partly compensatory to pneumonia and its effects were less pronounced as alternative prey became available. Given the high rates of pneumonia-caused mortality we observed, and the apparent lack of pneumonia-causing pathogens in bighorn populations in the western Black Hills, management activities should be geared towards eliminating contact between diseased and healthy populations.

  11. Independent and competing disease risks: Implications for host Populations in variable environments

    NARCIS (Netherlands)

    Jolles, A.E.; Etienne, R.S.

    2006-01-01

    Disease models usually assume disease to act independently of other mortality- and morbidity-causing factors. Alternatively, disease may function as a competing risk factor, for example, killing already moribund hosts. Using tuberculosis (TB) in African buffalo as a model system, we explore

  12. Independent and competing disease risks : Implications for host Populations in variable environments

    NARCIS (Netherlands)

    Jolles, AE; Etienne, RS; Olff, H; Jolles, Anna E.; DeAngelis, Donald L.; Michalakis, Yannis

    Disease models usually assume disease to act independently of other mortality- and morbidity-causing factors. Alternatively, disease may function as a competing risk factor, for example, killing already moribund hosts. Using tuberculosis (TB) in African buffalo as a model system, we explore

  13. Low Residual CBF Variability in Alzheimer's Disease after Correction for CO(2) Effect

    DEFF Research Database (Denmark)

    Rodell, Anders Bertil; Aanerud, Joel; Braendgaard, Hans

    2012-01-01

    We tested the claim that inter-individual CBF variability in Alzheimer's disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO(2)). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age...

  14. A rat model of Charcot-Marie-Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients.

    Science.gov (United States)

    Fledrich, Robert; Schlotter-Weigel, Beate; Schnizer, Tuuli J; Wichert, Sven P; Stassart, Ruth M; Meyer zu Hörste, Gerd; Klink, Axel; Weiss, Bernhard G; Haag, Uwe; Walter, Maggie C; Rautenstrauss, Bernd; Paulus, Walter; Rossner, Moritz J; Sereda, Michael W

    2012-01-01

    Charcot-Marie-Tooth disease is the most common inherited neuropathy and a duplication of the peripheral myelin protein 22 gene causes the most frequent subform Charcot-Marie-Tooth 1A. Patients develop a slowly progressive dysmyelinating and demyelinating peripheral neuropathy and distally pronounced muscle atrophy. The amount of axonal loss determines disease severity. Although patients share an identical monogenetic defect, the disease progression is strikingly variable and the impending disease course can not be predicted in individual patients. Despite promising experimental data, recent therapy trials have failed. Established clinical outcome measures are thought to be too insensitive to detect amelioration within trials. Surrogate biomarkers of disease severity in Charcot-Marie-Tooth 1A are thus urgently needed. Peripheral myelin protein 22 transgenic rats harbouring additional copies of the peripheral myelin protein 22 gene ('Charcot-Marie-Tooth rats'), which were kept on an outbred background mimic disease hallmarks and phenocopy the variable disease severity of patients with Charcot-Marie-Tooth 1A. Hence, we used the Charcot-Marie-Tooth rat to dissect prospective and surrogate markers of disease severity derived from sciatic nerve and skin tissue messenger RNA extracts. Gene set enrichment analysis of sciatic nerve transcriptomes revealed that dysregulation of lipid metabolism associated genes such as peroxisome proliferator-activated receptor gamma constitutes a modifier of present and future disease severity. Importantly, we directly validated disease severity markers from the Charcot-Marie-Tooth rats in 46 patients with Charcot-Marie-Tooth 1A. Our data suggest that the combination of age and cutaneous messenger RNA levels of glutathione S-transferase theta 2 and cathepsin A composes a strong indicator of disease severity in patients with Charcot-Marie-Tooth 1A, as quantified by the Charcot-Marie-Tooth Neuropathy Score. This translational approach

  15. Motor output variability, deafferentation, and putative deficits in kinesthetic reafference in Parkinson’s disease

    Science.gov (United States)

    Torres, Elizabeth B.; Cole, Jonathan; Poizner, Howard

    2014-01-01

    Parkinson’s disease (PD) is a neurodegenerative disorder defined by motor impairments that include rigidity, systemic slowdown of movement (bradykinesia), postural problems, and tremor. While the progressive decline in motor output functions is well documented, less understood are impairments linked to the continuous kinesthetic sensation emerging from the flow of motions. There is growing evidence in recent years that kinesthetic problems are also part of the symptoms of PD, but objective methods to readily quantify continuously unfolding motions across different contexts have been lacking. Here we present evidence from a deafferented subject (IW) and a new statistical platform that enables new analyses of motor output variability measured as a continuous flow of kinesthetic reafferent input. Systematic increasing similarities between the patterns of motor output variability in IW and the participants with increasing degrees of PD severity suggest potential deficits in kinesthetic sensing in PD. We propose that these deficits may result from persistent, noisy, and random motor patterns as the disorder progresses. The stochastic signatures from the unfolding motions revealed levels of noise in the motor output fluctuations of these patients bound to decrease the kinesthetic signal’s bandwidth. The results are interpreted in light of the concept of kinesthetic reafference ( Von Holst and Mittelstaedt, 1950). In this context, noisy motor output variability from voluntary movements in PD leads to a returning stream of noisy afference caused, in turn, by those faulty movements themselves. Faulty efferent output re-enters the CNS as corrupted sensory motor input. We find here that severity level in PD leads to the persistence of such patterns, thus bringing the statistical signatures of the subjects with PD systematically closer to those of the subject without proprioception. PMID:25374524

  16. Motor output variability, deafferentation, and putative deficits in kinesthetic reafference in Parkinson's disease.

    Science.gov (United States)

    Torres, Elizabeth B; Cole, Jonathan; Poizner, Howard

    2014-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder defined by motor impairments that include rigidity, systemic slowdown of movement (bradykinesia), postural problems, and tremor. While the progressive decline in motor output functions is well documented, less understood are impairments linked to the continuous kinesthetic sensation emerging from the flow of motions. There is growing evidence in recent years that kinesthetic problems are also part of the symptoms of PD, but objective methods to readily quantify continuously unfolding motions across different contexts have been lacking. Here we present evidence from a deafferented subject (IW) and a new statistical platform that enables new analyses of motor output variability measured as a continuous flow of kinesthetic reafferent input. Systematic increasing similarities between the patterns of motor output variability in IW and the participants with increasing degrees of PD severity suggest potential deficits in kinesthetic sensing in PD. We propose that these deficits may result from persistent, noisy, and random motor patterns as the disorder progresses. The stochastic signatures from the unfolding motions revealed levels of noise in the motor output fluctuations of these patients bound to decrease the kinesthetic signal's bandwidth. The results are interpreted in light of the concept of kinesthetic reafference ( Von Holst and Mittelstaedt, 1950). In this context, noisy motor output variability from voluntary movements in PD leads to a returning stream of noisy afference caused, in turn, by those faulty movements themselves. Faulty efferent output re-enters the CNS as corrupted sensory motor input. We find here that severity level in PD leads to the persistence of such patterns, thus bringing the statistical signatures of the subjects with PD systematically closer to those of the subject without proprioception.

  17. Motor output variability, deafferentation, and putative deficits in kinesthetic reafference in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Elizabeth B Torres

    2014-10-01

    Full Text Available Parkinson’s disease is a neurodegenerative disorder defined by motor impairments that include rigidity, systemic slowdown of movement (bradykinesia, postural problems and tremor. While the progressive decline in motor output functions is well documented, less understood are impairments linked to the continuous kinesthetic sensation emerging from the flow of motions. There is growing evidence in recent years that kinesthetic problems are also part of the symptoms of PD, but objective methods to readily quantify continuously unfolding motions across different contexts have been lacking. Here we present evidence from a deafferented subject (IW and a new statistical platform that enables new analyses of motor output variability measured as a continuous flow of kinesthetic reafferent input. Systematic increasing similarities between the patterns of motor output variability in IW and the participants with increasing degrees of PD severity suggest potential deficits in kinesthetic sensing in PD. We propose that these deficits may result from persistent, noisy and random motor patterns as the disorder progresses. The stochastic signatures from the unfolding motions revealed levels of noise in the motor output fluctuations of these patients bound to decrease the kinesthetic signal’s bandwidth. The results are interpreted in light of the concept of kinesthetic reafference (von Holst and Mittelstaedt, 1950. In this context, noisy motor output variability from voluntary movements in PD leads to a returning stream of noisy afference caused, in turn, by those faulty movements themselves. Faulty efferent output re-enters the CNS as corrupted sensory motor input. We find here that severity level in PD leads to the persistence of such patterns, thus bringing the statistical signatures of the subjects with PD systematically closer to those of the subject without proprioception.

  18. Causes of Greenland temperature variability over the past 4000 yr: implications for northern hemispheric temperature changes

    Directory of Open Access Journals (Sweden)

    T. Kobashi

    2013-10-01

    Full Text Available Precise understanding of Greenland temperature variability is important in two ways. First, Greenland ice sheet melting associated with rising temperature is a major global sea level forcing, potentially affecting large populations in coming centuries. Second, Greenland temperatures are highly affected by North Atlantic Oscillation/Arctic Oscillation (NAO/AO and Atlantic multidecadal oscillation (AMO. In our earlier study, we found that Greenland temperature deviated negatively (positively from northern hemispheric (NH temperature trend during stronger (weaker solar activity owing to changes in atmospheric/oceanic changes (e.g. NAO/AO over the past 800 yr (Kobashi et al., 2013. Therefore, a precise Greenland temperature record can provide important constraints on the past atmospheric/oceanic circulation in the region and beyond. Here, we investigated Greenland temperature variability over the past 4000 yr reconstructed from argon and nitrogen isotopes from trapped air in a GISP2 ice core, using a one-dimensional energy balance model with orbital, solar, volcanic, greenhouse gas, and aerosol forcings. The modelled northern Northern Hemisphere (NH temperature exhibits a cooling trend over the past 4000 yr as observed for the reconstructed Greenland temperature through decreasing annual average insolation. With consideration of the negative influence of solar variability, the modelled and observed Greenland temperatures agree with correlation coefficients of r = 0.34–0.36 (p = 0.1–0.04 in 21 yr running means (RMs and r = 0.38–0.45 (p = 0.1–0.05 on a centennial timescale (101 yr RMs. Thus, the model can explain 14 to 20% of variance of the observed Greenland temperature in multidecadal to centennial timescales with a 90–96% confidence interval, suggesting that a weak but persistent negative solar influence on Greenland temperature continued over the past 4000 yr. Then, we estimated the distribution of multidecadal NH and northern high

  19. Wilson′s disease - A rare cause of renal tubular acidosis with metabolic bone disease

    Directory of Open Access Journals (Sweden)

    D. K. S. Subrahmanyam

    2014-01-01

    Full Text Available We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson′s disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease.

  20. Multiple opportunistic pathogens can cause a bleaching disease in the red seaweed Delisea pulchra.

    Science.gov (United States)

    Kumar, Vipra; Zozaya-Valdes, Enrique; Kjelleberg, Staffan; Thomas, Torsten; Egan, Suhelen

    2016-11-01

    While macroalgae (or seaweeds) are increasingly recognized to suffer from disease, in most cases the causative agents are unknown. The model macroalga Delisea pulchra is susceptible to a bleaching disease and previous work has identified two epiphytic bacteria, belonging to the Roseobacter clade, that cause bleaching under laboratory conditions. However, recent environmental surveys have shown that these in vitro pathogens are not abundant in naturally bleached D. pulchra, suggesting the presence of other pathogens capable of causing this algal disease. To test this hypothesis, we cultured bacteria that were abundant on bleached tissue across multiple disease events and assessed their ability to cause bleaching disease. We identified the new pathogens Alteromonas sp. BL110, Aquimarina sp. AD1 and BL5 and Agarivorans sp BL7 that are phylogenetically diverse, distinct from the previous two pathogens and can also be found in low abundance in healthy individuals. Moreover, we found that bacterial communities of diseased individuals that were infected with these pathogens were less diverse and more divergent from each other than those of healthy algae. This study demonstrates that multiple and opportunistic pathogens can cause the same disease outcome for D. pulchra and we postulate that such pathogens are more common in marine systems than previously anticipated. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  1. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome.

    Science.gov (United States)

    Brown, Kyla; Selfridge, Jim; Lagger, Sabine; Connelly, John; De Sousa, Dina; Kerr, Alastair; Webb, Shaun; Guy, Jacky; Merusi, Cara; Koerner, Martha V; Bird, Adrian

    2016-02-01

    Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise ∼25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilizing effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account for the divergent clinical impact of the mutations. Overall, this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies and provides a valuable resource in the search for personalized therapeutic interventions. © The Author 2015. Published by Oxford University Press.

  2. The Nature and Cause of Spectral Variability in LMC X-1

    Science.gov (United States)

    Ruhlen, L.; Smith, D. M.; Scank, J. H.

    2011-01-01

    We present the results of a long-term observation campaign of the extragalactic wind-accreting black-hole X-ray binary LMC X-1, using the Proportional Counter Array on the Rossi X-Ray Timing Explorer (RXTE). The observations show that LMC X-1's accretion disk exhibits an anomalous temperature-luminosity relation. We use deep archival RXTE observations to show that large movements across the temperature-luminosity space occupied by the system can take place on time scales as short as half an hour. These changes cannot be adequately explained by perturbations that propagate from the outer disk on a viscous timescale. We propose instead that the apparent disk variations reflect rapid fluctuations within the Compton up-scattering coronal material, which occults the inner parts of the disk. The expected relationship between the observed disk luminosity and apparent disk temperature derived from the variable occultation model is quantitatively shown to be in good agreement with the observations. Two other observations support this picture: an inverse correlation between the flux in the power-law spectral component and the fitted inner disk temperature, and a near-constant total photon flux, suggesting that the inner disk is not ejected when a lower temperature is observed.

  3. Paget's disease of the skull causing hyperprolactinemia and erectile dysfunction: a case report

    Directory of Open Access Journals (Sweden)

    Hepherd Rachel

    2008-07-01

    Full Text Available Abstract Introduction Hyperprolactinemia is an uncommon cause of erectile dysfunction in men. Paget's disease of the skull is a relatively common disease. This case proposes a rare example of a causative link between the two and how treatment of the Paget's disease with bisphosphonates helped the patient regain erectile function. Case presentation A 67-year-old man with Paget's disease of the skull presented with prostatitis, erectile dysfunction, and hyperprolactinemia. Radio-isotope scanning showed increased vascularity around the sphenoid bone. Treatment with intravenous bisphosphonates improved the active Paget's disease as indicated by declining alkaline phosphatase levels and the patient's erectile function while serum prolactin levels became normal and serum testosterone levels remained unchanged. Conclusion It is possible that hyperprolactinemia is unrecognised in other patients with Paget's disease of the skull. Normalizing elevated prolactin levels by using bisphosphonates in treating Paget's disease appears to be more appropriate than traditional treatment for hyperprolactinemia.

  4. Phenotypic variability in patients with osteogenesis imperfecta caused by BMP1 mutations.

    Science.gov (United States)

    Pollitt, Rebecca C; Saraff, Vrinda; Dalton, Ann; Webb, Emma A; Shaw, Nick J; Sobey, Glenda J; Mughal, M Zulf; Hobson, Emma; Ali, Farhan; Bishop, Nicholas J; Arundel, Paul; Högler, Wolfgang; Balasubramanian, Meena

    2016-12-01

    Osteogenesis Imperfecta (OI) is an inherited bone fragility disorder most commonly associated with autosomal dominant mutations in the type I collagen genes. Autosomal recessive mutations in a number of genes have also been described, including the BMP1 gene that encodes the mammalian Tolloid (mTLD) and its shorter isoform bone morphogenic protein-1 (BMP1). To date, less than 20 individuals with OI have been identified with BMP1 mutations, with skeletal phenotypes ranging from mild to severe and progressively deforming. In the majority of patients, bone fragility was associated with increased bone mineral density (BMD); however, the full range of phenotypes associated with BMP1 remains unclear. Here, we describe three children with mutations in BMP1 associated with a highly variable phenotype: a sibship homozygous for the c.2188delC mutation that affects only the shorter BMP1 isoform and a further patient who is compound heterozygous for a c.1293C>G nonsense mutation and a c.1148G>A missense mutation in the CUB1 domain. These individuals had recurrent fractures from early childhood, are hypermobile and have no evidence of dentinogenesis imperfecta. The homozygous siblings with OI had normal areal BMD by dual energy X-ray absorptiometry whereas the third patient presented with a high bone mass phenotype. Intravenous bisphosphonate therapy was started in all patients, but discontinued in two patients and reduced in another due to concerns about increasing bone stiffness leading to chalk-stick fractures. Given the association of BMP1-related OI with very high bone material density, concerns remain whether anti-resorptive therapy is indicated in this ultra-rare form of OI.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Experimental observations of deformation caused by mineral dissolution in variable-aperture fractures

    Science.gov (United States)

    Detwiler, Russell L.

    2008-08-01

    Problems such as CO2 sequestration, petroleum production and nuclear waste isolation involve the potential for rock-water reactions. Mineral alteration resulting from reactive fluid flow can lead to significant changes to fracture transport properties. At depth, these processes are further influenced by stresses in the host rock. To quantitatively explore these coupled processes, we built a new experimental apparatus designed to directly measure changes in fracture aperture in analog fractures subjected to the combined influence of a reactive fluid and an applied normal stress. Light transmission techniques provided direct measurements of the changing fracture aperture at high spatial resolution during two experiments in identical fractures with an initial mean fracture aperture of 95 μm. The two experiments were carried out at values of the dimensionless Damkohler number (Da = reaction rate/advection rate) that differed by a factor of 2. The high-Da experiment resulted in the formation of a large-scale dissolution channel in the middle of the fracture and regions with little dissolution and slow closure of the fracture surfaces. By contrast, the low-Da experiment exhibited relatively uniform dissolution across the width of the fracture, with locally enhanced dissolution in small aperture regions. This resulted in increased stresses in contacting asperities and eventual damage of the asperities accompanied by large (up to 50 μm), instantaneous displacements of the surfaces and corresponding reductions in fracture aperture. The results demonstrate the importance of the spatial variability of dissolution rates, which are controlled by both local reaction kinetics and hydrodynamics, in fractures deforming because of combined dissolution and mechanical stress.

  6. Causes of interannual variability over the southern hemispheric tropospheric ozone maximum

    Science.gov (United States)

    Liu, Junhua; Rodriguez, Jose M.; Steenrod, Stephen D.; Douglass, Anne R.; Logan, Jennifer A.; Olsen, Mark A.; Wargan, Krzysztof; Ziemke, Jerald R.

    2017-03-01

    We examine the relative contribution of processes controlling the interannual variability (IAV) of tropospheric ozone over four sub-regions of the southern hemispheric tropospheric ozone maximum (SHTOM) over a 20-year period. Our study is based on hindcast simulations from the National Aeronautics and Space Administration Global Modeling Initiative chemistry transport model (NASA GMI-CTM) of tropospheric and stratospheric chemistry, driven by assimilated Modern Era Retrospective Analysis for Research and Applications (MERRA) meteorological fields. Our analysis shows that over SHTOM region, the IAV of the stratospheric contribution is the most important factor driving the IAV of upper tropospheric ozone (270 hPa), where ozone has a strong radiative effect. Over the South Atlantic region, the contribution from surface emissions to the IAV of ozone exceeds that from stratospheric input at and below 430 hPa. Over the South Indian Ocean, the IAV of stratospheric ozone makes the largest contribution to the IAV of ozone with little or no influence from surface emissions at 270 and 430 hPa in austral winter. Over the tropical South Atlantic region, the contribution from IAV of stratospheric input dominates in austral winter at 270 hPa and drops to less than half but is still significant at 430 hPa. Emission contributions are not significant at these two levels. The IAV of lightning over this region also contributes to the IAV of ozone in September and December. Over the tropical southeastern Pacific, the contribution of the IAV of stratospheric input is significant at 270 and 430 hPa in austral winter, and emissions have little influence.

  7. Association between NOx exposure and deaths caused by respiratory diseases in a medium-sized Brazilian city

    Directory of Open Access Journals (Sweden)

    A. C. G. César

    2015-12-01

    Full Text Available Exposure to nitrogen oxides (NOx emitted by burning fossil fuels has been associated with respiratory diseases. We aimed to estimate the effects of NOx exposure on mortality owing to respiratory diseases in residents of Taubaté, São Paulo, Brazil, of all ages and both sexes. This time-series ecological study from August 1, 2011 to July 31, 2012 used information on deaths caused by respiratory diseases obtained from the Health Department of Taubaté. Estimated daily levels of pollutants (NOx, particulate matter, ozone, carbon monoxide were obtained from the Centro de Previsão de Tempo e Estudos Climáticos Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System. These environmental variables were used to adjust the multipollutant model for apparent temperature. To estimate association between hospitalizations owing to asthma and air pollutants, generalized additive Poisson regression models were developed, with lags as much as 5 days. There were 385 deaths with a daily mean (±SD of 1.05±1.03 (range: 0-5. Exposure to NOx was significantly associated with mortality owing to respiratory diseases: relative risk (RR=1.035 (95% confidence interval [CI]: 1.008-1.063 for lag 2, RR=1.064 (95%CI: 1.017-1.112 lag 3, RR=1.055 (95%CI: 1.025-1.085 lag 4, and RR=1.042 (95%CI: 1.010-1.076 lag 5. A 3 µg/m3 reduction in NOx concentration resulted in a decrease of 10-18 percentage points in risk of death caused by respiratory diseases. Even at NOx concentrations below the acceptable standard, there is association with deaths caused by respiratory diseases.

  8. Association between NOx exposure and deaths caused by respiratory diseases in a medium-sized Brazilian city.

    Science.gov (United States)

    César, A C G; Carvalho, J A; Nascimento, L F C

    2015-12-01

    Exposure to nitrogen oxides (NOx) emitted by burning fossil fuels has been associated with respiratory diseases. We aimed to estimate the effects of NOx exposure on mortality owing to respiratory diseases in residents of Taubaté, São Paulo, Brazil, of all ages and both sexes. This time-series ecological study from August 1, 2011 to July 31, 2012 used information on deaths caused by respiratory diseases obtained from the Health Department of Taubaté. Estimated daily levels of pollutants (NOx, particulate matter, ozone, carbon monoxide) were obtained from the Centro de Previsão de Tempo e Estudos Climáticos Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System. These environmental variables were used to adjust the multipollutant model for apparent temperature. To estimate association between hospitalizations owing to asthma and air pollutants, generalized additive Poisson regression models were developed, with lags as much as 5 days. There were 385 deaths with a daily mean (±SD) of 1.05±1.03 (range: 0-5). Exposure to NOx was significantly associated with mortality owing to respiratory diseases: relative risk (RR)=1.035 (95% confidence interval [CI]: 1.008-1.063) for lag 2, RR=1.064 (95%CI: 1.017-1.112) lag 3, RR=1.055 (95%CI: 1.025-1.085) lag 4, and RR=1.042 (95%CI: 1.010-1.076) lag 5. A 3 µg/m3 reduction in NOx concentration resulted in a decrease of 10-18 percentage points in risk of death caused by respiratory diseases. Even at NOx concentrations below the acceptable standard, there is association with deaths caused by respiratory diseases.

  9. Application of Whole Exome Sequencing to Identify Disease-Causing Variants in Inherited Human Diseases

    Directory of Open Access Journals (Sweden)

    Gerald Goh

    2012-12-01

    Full Text Available The recent advent of next-generation sequencing technologies has dramatically changed the nature of biomedical research. Human genetics is no exception-it has never been easier to interrogate human patient genomes at the nucleotide level to identify disease-associated variants. To further facilitate the efficiency of this approach, whole exome sequencing (WES was first developed in 2009. Over the past three years, multiple groups have demonstrated the power of WES through robust disease-associated variant discoveries across a diverse spectrum of human diseases. Here, we review the application of WES to different types of inherited human diseases and discuss analytical challenges and possible solutions, with the aim of providing a practical guide for the effective use of this technology.

  10. Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia.

    Science.gov (United States)

    Shao, Yi-Hong; Choquet, Karine; La Piana, Roberta; Tétreault, Martine; Dicaire, Marie-Josée; Boycott, Kym M; Majewski, Jacek; Brais, Bernard

    2016-04-01

    Mutations in GALC cause Krabbe disease. This autosomal recessive leukodystrophy generally presents in early infancy as a severe disorder, but sometimes manifests as a milder adult-onset disease with spastic paraplegia as the main symptom. We recruited a family with five affected individuals presenting with adult-onset predominant cerebellar ataxia with mild spasticity. Whole exome sequencing (WES) revealed one novel and one previously reported compound heterozygous variants in GALC. Magnetic resonance imaging (MRI) confirmed the presence of typical Krabbe features. Our findings expand the phenotypic spectrum of adult-onset Krabbe disease and demonstrate the usefulness of combining WES and pattern-specific MRI for the diagnosis of neurodegenerative diseases.

  11. [Disease burden caused by violence in the Chinese population, in 1990 and 2013].

    Science.gov (United States)

    Yang, L; Gao, X; Jin, Y; Ye, P P; Er, Y L; Deng, X; Wang, Y; Duan, L L

    2017-10-10

    Objective: To analyze the disease burden of violence in the Chinese population, in 1990 and 2013. Methods: Indicators including mortality rate, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted of life years (DALY) related to violence, were extracted from the Global Burden of Disease 2013 and used to describe the burden of disease caused by violence in the Chinese population. Data related to corresponding parameters on disease burden of violence in 1990 and 2013 were described. Results: In 2013, a total of 20 500 people died of violent events, with the death rate as 1.44 per 100 000, in China. DALY caused by violence was 1.08 million person years in 2013. DALY caused by sharp violence was 0.47 million person years, with 0.09 million person years lost due to firearm violence. Disease burden caused by violence appeared higher in males than in females. When comparing with data from the 1990s, reductions were seen by 67.35 % on the standardized death rate of violence, by 68.07 % on the DALY attributable to violence, and by 70.47 % on the standardized DALY rate attributable to violence, respectively, in 2013. Disease burden of violence among young adults and elderly was among the highest. When comparing with data from the 1990, DALY in 2013 decreased among all the age groups except for the 70-year-old showed an increase of 9.36 % . The standardized DALY rate in 2013 showed a declining trend in all the age groups, mostly in the 0-4-year-old group. The standardized DALY rates caused by sharp violence or firearm decreased by75.11 % and 83.20 % in the 0-4-year-old group. Conclusion: In recent years, the disease burden caused by violence showed a decreasing trend but appeared higher in males however with the increase of DALY in the elder population.

  12. Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations.

    Science.gov (United States)

    Adebali, Ogun; Reznik, Alexander O; Ory, Daniel S; Zhulin, Igor B

    2016-10-01

    Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism's fitness. Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well.Genet Med 18 10, 1029-1036.

  13. Prevalence of G class antibodies to antigens of lyme disease causes in dogs in Vojvodina, Serbia

    Directory of Open Access Journals (Sweden)

    Potkonjak Aleksandar

    2013-01-01

    Full Text Available Lyme disease is a multisystemic disease, zoonotic in nature, caused by the Borrelia burgdorferi sensu lato complex. In the continent of Europe, these spirochetes are predominantly transmitted by ticks of the genus Ixodes. Small mammals and birds have particular significance as reservoirs of the cause of lyme disease. The objective of these epidemiological investigations was to determine the value of IgG seroprevalence to Borrelia burgdorferi and to secure the geographic distribution of seropositive dogs in Vojvodina. The investigations covered 135 dogs that were not vaccinated against lyme disease. The indirect ELISA test was used to determine IgG prevalence to Borrelia burgdorferi antigens. Reactive blood serums of dogs were tested again using the rapid immunochromatographic and immunoblot test. A seroprevalence of G class antibodies to antigens of lyme disease causes of 8.1% (11/135 was established in the examined dog population of Vojvodina. The biggest number of positive results was recorded for the South Bačka District. The presented value for the seroprevalence of anti-Borrelia burgdorferi antibodies in the dog population indicates the exhistence of a significant risk of humans becoming infected with the cause of lyme disease in Vojvodina.

  14. Causes of daily cycle variability of atmospheric pollutants in a western Mediterranean urban site (DAURE campaign)

    Science.gov (United States)

    Reche, Cristina; Moreno, Teresa; Viana, Mar; Querol, Xavier; Alastuey, Andrés.; Jimenez, Jose L.; Pandolfi, Marco; Amato, Fulvio; Pérez, Noemí; Moreno, Natalia

    2010-05-01

    The 2009 DAURE Aerosol Campaign (23-February-2009 to 27-March-2009 and 1-July to 31-July) (see Presentation: Pandolfi et al., section AS3.2) had the objective of characterising the main sources and chemical processes controlling atmospheric pollution due to particulate matter in the Mediterranean site of Barcelona (Spain). An urban and a rural background site were selected in order to describe both kinds of pollution setting. Several parameters were taken into consideration, including the variability of mass concentration in the coarse and fine fractions, particle number, amount of black carbon and the concentration of gaseous pollutants (SO2, H2S, NO, NO2, CO, O3) present. Comparisons between the chemical composition of ambient atmospheric particles during day versus night were made using twelve-hour PM samples. The data shown here are focused on results obtained for the urban site where two main atmospheric settings were distinguishable in winter, namely Atlantic advection versus local air mass recirculation. During the warmer months Saharan dust intrusions added a third important influence on PM background. The data demonstrate that superimposed upon these background influences on city air quality are important local contributions from road traffic, construction-demolition works and shipping. There is also a major local contribution of secondary aerosols, with elevated number of particles occurring at midday (and especially in summer) when nucleation processes are favoured by photochemistry. Concentrations of SO2 peak at different times to the other gaseous pollutants due to regular daytime onshore south-easterly breezes bringing harbour emissions into the city. Road traffic in Barcelona also has a great impact on air quality, as demonstrated by daily and weekly cycles of gaseous pollutants, black carbon and the finer fraction of PM, with peaks being coincident with traffic rush-hours (8-10h and 20-22h), levels of pollution increasing from Monday to Friday, and

  15. Atypical Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 in Denmark:

    DEFF Research Database (Denmark)

    Horsten, Hans-Henrik; Kemp, Michael; Fischer, Thea K

    2018-01-01

    Since 2008, outbreaks of atypical hand, foot, and mouth disease (HFMD) in children and adults have been reported worldwide. The majority of these outbreaks are caused by a new lineage of Coxsackie virus A6 (CV-A6) presenting a more severe clinical phenotype than the classical childhood HFMD caused...... by CV-A16. Between June 2014 and January 2016, 23 cases of atypical HFMD disease presented at a Dermatology Department at a regional University Hospital in Denmark. Patients were referred by general practitioners and dermatologists with a variety of clinical diagnoses, including eczema herpeticum...... caused by CV-A6 in the Region of Southern Denmark and that atypical HFMD can be difficult to diagnose clinically as it may mimic other severe skin diseases....

  16. Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables

    Directory of Open Access Journals (Sweden)

    Rodrigo Andrade Alves

    Full Text Available CONTEXT AND OBJECTIVES:Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1 determine the prevalence of anemia among patients with inflammatory bowel disease; 2 investigate whether routine laboratory markers are useful for diagnosing anemia; and 3 evaluate whether any association exists between anemia and clinical/laboratory variables.DESIGN AND SETTING:Cross-sectional at a federal university.METHODS:44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid were investigated.RESULTS:Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6% and ulcerative colitis (76.7%. Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index.CONCLUSIONS:Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index.

  17. Pulmonary Hypertension Due to Left Ventricular Cardiomyopathy: Is it the Result or Cause of Disease Progression?

    Science.gov (United States)

    Adusumalli, Srinath; Mazurek, Jeremy A

    2017-12-01

    The purpose of this review is to define pulmonary hypertension in the setting of left heart disease (PH-LHD), discuss its epidemiology and pathophysiology, and highlight the cause and effect relationship it has with disease progression in the setting of cardiomyopathy. Both pulmonary hypertension (PH) and heart failure are becoming increasingly common. As such, PH-LHD is now the most common form of PH. The pathophysiology of the condition relates to backward transmission of elevated left ventricular filling pressures into the pulmonary circulation and, ultimately, right ventricular (RV) strain/dysfunction. It is evident that these pathophysiologic processes are both the effect and cause of left heart disease progression. In this review, we describe the complex relationship between disease progression in left ventricular cardiomyopathy and PH-LHD. Clinicians and researchers should take note of the importance of PH-LHD and RV dysfunction to appropriately risk stratify patients and develop therapies for the condition.

  18. Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    Nearly 200 mutations in the gene coding for presenilin 1 (PSEN1) cause early-onset Alzheimer's Disease, yet the molecular mechanism remains obscure. As a meta-analysis, we compiled available clinical and biochemical data for PSEN1 variants and correlated these to chemical properties of the mutants...... protein stability. This explains why the many mutations that spread out across the protein and far from the catalytic aspartates can cause disease. The identified molecular determinants of clinical age of symptom onset may be relevant to future presenilin-modulating therapies specifically directed towards...

  19. First results of investigations into causes of diseases of cultivated chamomile (Matricaria recutita L.) in Germany

    OpenAIRE

    Gärber, Ute; Sommerfeld, Katja

    2016-01-01

    Diseases on cultivated chamomile have occurred in Germany since 2007, which have severely been affecting the crop yields. The causes of damage are very complex and have not been identified yet. Additionally to the damage in the stems caused by larvae, fungal pathogens are of relevance. Tests of the Julius Kühn-Institute first revealed that a new, not yet identified fungus is pathogenic to chamomile. Symptoms observed in infection tests like chlorosis, browning and black coloration of stems an...

  20. Echinococcal disease of the bone: An unusual cause of a pathological fracture

    Directory of Open Access Journals (Sweden)

    Matthew Goodier

    2010-12-01

    Full Text Available Echinococcosis is caused by the larva of the tapeworm, Echinococcus granulosus or Echinococcus multiloccularis and is endemic in many rural areas of Southern Africa. Echinococcosis of the bone is an unusual manifestation of echinococcal disease and a rare cause of a lytic lesion of bone. This report describes a 30-yr old female who presented with an Echinococcal cyst of the right radius complicated by a pathological fracture.

  1. Genotypes of the Enterovirus Causing Hand Foot and Mouth Disease in Shanghai, China, 2012-2013

    OpenAIRE

    Xu, Menghua; Su, Liyun; Cao, Lingfeng; Zhong, Huaqing; Dong, Niuniu; Dong, Zuoquan; Xu, Jin

    2015-01-01

    Sporadic HFMD (hand foot and mouth disease, HFMD) cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic...

  2. Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia.

    Directory of Open Access Journals (Sweden)

    Nmn NikNadia

    2016-03-01

    Full Text Available Enterovirus A71 (EV-A71 is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2-3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence. Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance. A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24-1.69; P<0.001. Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01-1.34 P<0.034. In summary, the 2-3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs.

  3. The use of organic certified compost to control soilborne diseases caused by Phytophthora spp.

    OpenAIRE

    Pugliese, Massimo; Gullino, M. Lodovica; Garibaldi, Angelo

    2008-01-01

    Soilborne pathogens can cause serious damages to economically important crops. Control of these diseases has traditionally depended upon rotations and soil quality improvement strategies. Compost has shown a suppressive activity against soilborne pathogens, and its use may decrease the severity of root rot diseases, optimize waste recycling and increase yields in organic farming. An organic certified compost produced from biowaste, green and yard wastes in a composting plant in the North-West...

  4. An Examination of the Demographic and Environmental Variables Correlated with Lyme Disease Emergence in Virginia.

    Science.gov (United States)

    Seukep, Sara E; Kolivras, Korine N; Hong, Yili; Li, Jie; Prisley, Stephen P; Campbell, James B; Gaines, David N; Dymond, Randel L

    2015-12-01

    Lyme disease is the United States' most significant vector-borne illness. Virginia, on the southern edge of the disease's currently expanding range, has experienced an increase in Lyme disease both spatially and temporally, with steadily increasing rates over the past decade and disease spread from the northern to the southwestern part of the state. This study used a Geographic Information System and a spatial Poisson regression model to examine correlations between demographic and land cover variables, and human Lyme disease from 2006 to 2010 in Virginia. Analysis indicated that herbaceous land cover is positively correlated with Lyme disease incidence rates. Areas with greater interspersion between herbaceous and forested land were also positively correlated with incidence rates. In addition, income and age were positively correlated with incidence rates. Levels of development, interspersion of herbaceous and developed land, and population density were negatively correlated with incidence rates. Abundance of forest fragments less than 2 hectares in area was not significantly correlated. Our results support some findings of previous studies on ecological variables and Lyme disease in endemic areas, but other results have not been found in previous studies, highlighting the potential contribution of new variables as Lyme disease continues to emerge southward.

  5. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.

    Science.gov (United States)

    Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte

    2015-01-01

    Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy

  6. Effects of Parkinson’s Disease on Fundamental Frequency Variability in Running Speech

    Science.gov (United States)

    Bowen, Leah K.; Hands, Gabrielle L.; Pradhan, Sujata; Stepp, Cara E.

    2013-01-01

    In Parkinson’s Disease (PD), qualitative speech changes such as decreased variation in pitch and loudness are common, but quantitative vocal changes are not well documented. The variability of fundamental frequency (F0) in 32 individuals (23 male) with PD both ON and OFF levodopa medication was compared with 32 age-matched healthy controls (23 male). Participants read a single paragraph and estimates of fundamental frequency (F0) variability were determined for the entire reading passage as well as for the first and last sentences of the passage separately. F0 variability was significantly increased in controls relative to both PD groups and PD patients showed significantly higher F0 variability while ON medication relative to OFF. No significant effect of group was seen in the change in F0 variability from the beginning to the end of the reading passage. Female speakers were found to have higher F0 variability than males. F0 variability was both significantly reduced in PD relative to controls and significantly increased in patients with PD during use of dopaminergic medications. F0 variability changes over the course of reading a paragraph may not be indicative of PD but rather dependent on non-disease factors such as the linguistic characteristics of the text. PMID:25838754

  7. Strength of Occipital Hair as an Explanation for Pilonidal Sinus Disease Caused by Intruding Hair.

    Science.gov (United States)

    Doll, Dietrich; Bosche, Friederike D; Stauffer, Verena K; Sinicina, Inga; Hoffmann, Sebastian; van der Zypen, Dominic; Luedi, Markus M

    2017-09-01

    Pilonidal sinus disease is thought to be caused by intrusion of hair into healthy skin; loose hair in the intergluteal fold is thought to promote disease. However, compelling evidence to support these postulates is lacking; the cause of pilonidal sinus disease remains uncertain. To determine whether particular properties of hair are associated with susceptibility to pilonidal sinus disease, we compared physical properties of hairs of patients with pilonidal sinus disease with hairs from control subjects who were matched for sex, BMI, and age. This was an experimental study with establishment of a mechanical strength test for single hairs to quantify the maximum vertical force that a hair could exert, following tests of strength of occipital, lumbar, and intergluteal hair. Hair from patients with pilonidal sinus disease and matched control subjects were harvested from patients of the St. Marienhospital Vechta Department of Procto-Surgery. A total of 17 adult patients with pilonidal sinus disease and 217 control subjects were included. ANOVA and intraclass and interclass variations of data gained from mechanical strength tests of occipital, lumbar, and intergluteal hair were included. Vertical hair strength was significantly greater in patients with pilonidal sinus disease. Occipital hair exhibited 20% greater, glabella sacralis 1.1 times greater, and intergluteal hair 2 times greater strength in patients with pilonidal sinus disease than in matched control subjects (all p = 0.0001). In addition, patients with pilonidal sinus disease presented with significantly more hair at the glabella sacralis and in the intergluteal fold. The study was limited by its relatively small number of patients from a specific cohort of European patients. Occipital hair exhibited considerable vertical strength. Because occipital hair exerted the greatest force and cut hair fragments were found in the pilonidal nest in large quantities, these data suggest that pilonidal sinus disease is

  8. Myocardial performance and perfusion during exercise in patients with coronary artery disease caused by Kawasaki disease

    International Nuclear Information System (INIS)

    Paridon, S.M.; Ross, R.D.; Kuhns, L.R.; Pinsky, W.W.

    1990-01-01

    For a study of the natural history of coronary artery lesions after Kawasaki disease and their effect on myocardial blood flow reserve with exercise, five such patients underwent exercise testing on a bicycle. Oxygen consumption, carbon dioxide production, minute ventilation, and electrocardiograms were monitored continuously. Thallium-201 scintigraphy was performed for all patients. One patient stopped exercise before exhaustion of cardiovascular reserve but had no evidence of myocardial perfusion abnormalities. Four patients terminated exercise because of exhaustion of cardiovascular reserve; one had normal cardiovascular reserve and thallium scintiscans, but the remaining patients had diminished cardiovascular reserve. Thallium scintigrams showed myocardial ischemia in two and infarction in one. No patient had exercise-induced electrocardiographic changes. These results indicate that patients with residual coronary artery lesions after Kawasaki disease frequently have reduced cardiovascular reserve during exercise. The addition of thallium scintigraphy and metabolic measurements to exercise testing improved the detection of exercise-induced abnormalities of myocardial perfusion

  9. Assessing the variability of Red Stripe Disease in Louisiana sugarcane using precision agriculture methods

    Science.gov (United States)

    Symptoms of red stripe disease caused by Acidovorax avenae subsp. avenae in Louisiana between 1985 and 2010 were limited to the leaf stripe form which caused no apparent yield loss. During 2010, the more severe top rot form was observed, and a study was initiated to investigate the distribution of r...

  10. Offer acceptance practices and geographic variability in allocation model for end-stage liver disease at transplant.

    Science.gov (United States)

    Wey, Andrew; Pyke, Joshua; Schladt, David P; Gentry, Sommer E; Weaver, Tim; Salkowski, Nicholas; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

    2018-04-01

    Offer acceptance practices may cause geographic variability in allocation Model for End-Stage Liver Disease (aMELD) score at transplant and could magnify the effect of donor supply and demand on aMELD variability. To evaluate these issues, offer acceptance practices of liver transplant programs and donation service areas (DSAs) were estimated using offers of livers from donors recovered between January 1, 2016, and December 31, 2016. Offer acceptance practices were compared with liver yield, local placement of transplanted livers, donor supply and demand, and aMELD at transplant. Offer acceptance was associated with liver yield (odds ratio, 1.32; P offer acceptance (r = 0.09; P = 0.50). Additionally, the association between DSA-level donor-to-candidate ratios and aMELD at transplant did not change after adjustment for offer acceptance. The average squared difference in median aMELD at transplant across DSAs was 24.6; removing the effect of donor-to-candidate ratios reduced the average squared differences more than removing the effect of program-level offer acceptance (33% and 15% reduction, respectively). Offer acceptance practices and donor-to-candidate ratios independently contributed to geographic variability in aMELD at transplant. Thus, neither offer acceptance nor donor-to-candidate ratios can explain all of the geographic variability in aMELD at transplant. Liver Transplantation 24 478-487 2018 AASLD. © 2018 by the American Association for the Study of Liver Diseases.

  11. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

    Science.gov (United States)

    Wiseman, Frances K.; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Strydom, André

    2015-01-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) — an Alzheimer disease risk factor — although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population. PMID:26243569

  12. Complete staghorn calculus in polycystic kidney disease: infection is still the cause.

    Science.gov (United States)

    Mao, Zhiguo; Xu, Jing; Ye, Chaoyang; Chen, Dongping; Mei, Changlin

    2013-08-01

    Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.

  13. [Coeliac disease as a possible cause of some gynecological and obstetric abnormalities].

    Science.gov (United States)

    Fiolková, K; Biringer, K; Hrtánková, M; Fiolka, R; Danko, J

    To bring a review of available literature sources on the prevalence of coeliac disease and its possible impact on gynecological and obstetric disorders. Review article. Gynecology and Obstetrics Clinic, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia. Analysis of literary sources. Coeliac disease is an autoimmune enteropathy caused by abnormal immune system response to gluten. Over the last decade when the prevalence of the disease increases rapidly confirming the relationship between coeliac disease and a range of reproductive disorders. Problems in this area are mostly confirmed in untreated women. Among the atypical symptoms of coeliac disease also include infertility such as delayed onset of menstruation, early menopause, secondary amenorrhea, infertility and pregnancy complications, such as recurrent abortions, intrauterine fetal growth restriction, small fetus for gestational age, low birth weight and premature birth.

  14. Some Pathogenic Bacteria of Livestock Origin as a Cause of Foodborne Diseases

    Directory of Open Access Journals (Sweden)

    Anni Kusumaningsih

    2010-09-01

    Full Text Available Food are essentialy required for cell metabolism in human physiologyc. Food should be free from biological, chemical, and physical contamination and also hazardous substances. All of them are able to disrupt physiological homeostatis resulting disorder or diseases. Diseases resulted by those contaminant are called food borne disease. One of the important contaminants is biological contaminant especially pathogenic bacterias. Some pathogenic bacteria such as Salmonella spp., Escherichia coli, Bacillus anthracis, Clostridium spp., Listeria monocytogenes, Campylobacter spp., Vibrio cholerae, Enterobacter sakazakii, Shigella, are able to cause symptomatic diseases. Overall, the general symptoms of the diseases due to pathogenic bacterial infection are gastric pain, nausea, vomit, headache, loss of appetite, fever, and also dehydration.

  15. Developmental Abnormalities, Blood Pressure Variability and Renal Disease In Riley Day Syndrome

    Science.gov (United States)

    Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B.; Kaufmann, Horacio

    2011-01-01

    Riley Day syndrome, commonly referred to as familial dysautonomia (FD), is a genetic disease with extremely labile blood pressure due to baroreflex deafferenation. Chronic renal disease is very frequent in these patients and was attributed to recurrent arterial hypotension and renal hypoperfusion. Aggressive treatment of hypotension, however, has not reduced its prevalence. We evaluated the frequency of kidney malformations as well as the impact of hypertension, hypotension and blood pressure variability on the severity of renal impairment. We also investigated the effect of fludrocortisone treatment on the progression of renal disease. Patients with FD appeared to have an increased incidence of hydronephrosis/reflux and patterning defects. Patients younger than 4 years old had hypertension and normal eGFR. Patients with more severe hypertension and greater variability in their blood pressure had worse renal function (both, p<0.01). In contrast, there was no relationship between eGFR and the lowest blood pressure recorded during upright tilt. The progression of renal disease was faster in patients receiving fludrocortisone (p<0.02). Hypertension precedes kidney disease in these patients. Moreover, increased blood pressure variability as well as mineralocorticoid treatment accelerate the progression of renal disease. No association was found between hypotension and renal disease in patients with FD. PMID:22129610

  16. Alexander disease as a cause of nocturnal vomiting in a 7-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Niinikoski, Harri [University of Turku, Department of Paediatrics, Turku (Finland); Haataja, Leena [University of Turku, Department of Paediatrics, Turku (Finland); University of Turku, Department of Pediatric Neurology, Turku (Finland); Brander, Antti [University of Tampere, Department of Radiology, Tampere (Finland); Valanne, Leena [University of Helsinki, Department of Radiology, Helsinki (Finland); Blaser, Susan [Hospital for Sick Children, Department of Radiology, Toronto (Canada)

    2009-08-15

    Alexander disease is a rare form of leukodystrophy with a highly variable clinical course. Occasionally night-time nausea and vomiting are the first symptoms of juvenile Alexander disease. A 7-year-old girl had recurrent night-time vomiting and her growth and weight gain had deteriorated after her sixth birthday. Cranial MRI demonstrated two small, symmetrical focal areas of abnormally high signal intensity in the dorsal medulla oblongata on T2-W and FLAIR images. These were suggestive of juvenile Alexander disease, and subsequent sequencing of the glial fibrillary acidic protein (GFAP) gene revealed a heterogeneous missense mutation in the GFAP gene in exon 6. Alexander disease should be considered in young patients with atypical anorexia nervosa-type symptoms. (orig.)

  17. Alexander disease as a cause of nocturnal vomiting in a 7-year-old girl

    International Nuclear Information System (INIS)

    Niinikoski, Harri; Haataja, Leena; Brander, Antti; Valanne, Leena; Blaser, Susan

    2009-01-01

    Alexander disease is a rare form of leukodystrophy with a highly variable clinical course. Occasionally night-time nausea and vomiting are the first symptoms of juvenile Alexander disease. A 7-year-old girl had recurrent night-time vomiting and her growth and weight gain had deteriorated after her sixth birthday. Cranial MRI demonstrated two small, symmetrical focal areas of abnormally high signal intensity in the dorsal medulla oblongata on T2-W and FLAIR images. These were suggestive of juvenile Alexander disease, and subsequent sequencing of the glial fibrillary acidic protein (GFAP) gene revealed a heterogeneous missense mutation in the GFAP gene in exon 6. Alexander disease should be considered in young patients with atypical anorexia nervosa-type symptoms. (orig.)

  18. Latent variable modelling of risk factors associated with childhood diseases: Case study for Nigeria

    Directory of Open Access Journals (Sweden)

    Khaled Khatab

    2011-09-01

    Full Text Available Objective: To investigate the impact of various bio-demographic and socio-economic variables on joint childhood diseases in Nigeria with flexible geoadditive probit models. Methods: Geoadditive latent variable model (LVM was applied where the three observable disease (diarrhea, cough, fever variables were modelled as indicators for the latent individual variable "health status" or "frailty" of a child. This modelling approach allowed us to investigate the common influence of risk factors on individual frailties of children, thereby automatically accounting for association between diseases as indicators for health status. The LVM extended to analyze the impact of risk factors and the spatial effects on the unobservable variable “health status ” of a child less than 5 years of age using the 2003 Demographic and Health Surveys (DHS data for Nigeria. Results: The results suggest some strong underlying spatial patterns of the three ailments with a clear southeastern divide of childhood morbidities and this might be the results in the overlapping of the various risk factors. Conclusions: Comorbidity with conditions such as cough, diarrhoea and fever is common in Nigeria. However, little is known about common risk factors and geographical overlaps in these illnesses. The search for overlapping common risk factors and their spatial effects may improve our understanding of the etiology of diseases for efficient and cost-effective control and planning of the three ailments.

  19. [Causes of diabetic patients' indifference towards treatment, diet and monitoring and possible factors associated with such disease].

    Science.gov (United States)

    De La Cruz-Maldonado, María G; Vargas-Morales, Juan M; Ledezma-Tristán, Erika S; Holguín-Carrillo, Mariana C; Martínez-Castellanos, Alan Y; Fragoso-Morales, Lilia E

    2013-01-01

    Analyze the causes of detachment to diet and treatment of patients with diabetes and factors associated with disease such as family history of diabetes and hypertension, in patients from one municipality of San Luis Potosi, Mexico, and surrounding areas. Descriptive study of variables such as age, sex, schooling level, occupation, family history of diabetes and hypertension, causes of detachment to diet and treatment; analytic for groups in terms of the risk of diabetes according to socio demographic and family history. Of the 156 patients included main causes of detachment or abandonment of the indicated treatment and/or were the oblivion and insistence on restricted food intake. Patients with a family history of hypertension in both parents had 5.8 times the risk of Diabetes Mellitus, compared to those without this history (ppatients with a maternal history of diabetes had 4.76 times the risk of suffering it too, compared to those with only paternal history (ppatients with a history of obesity, they had 2.4 times higher risk of developing diabetes than those who had not (ppatients, for detachment to treatment and diet were the oblivion and the insistence on restricted food intake, and the degree of association of Diabetes Mellitus with family history of this disease and hypertension is 2.4 to 5.8 times, with p<0.05.

  20. Inherited Cardiac Diseases Caused by Mutations in the Nav1.5 Sodium Channel

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Jacob; Winkel, Bo Gregers; Grunnet, Morten

    2009-01-01

    Cardiac Diseases Caused by SCN5A Mutations. A prerequisite for a normal cardiac function is a proper generation and propagation of electrical impulses. Contraction of the heart is obtained through a delicate matched transmission of the electrical impulses. A pivotal element of the impulse...

  1. Causes of Death Data in the Global Burden of Disease Estimates for Ischemic and Hemorrhagic Stroke

    DEFF Research Database (Denmark)

    Truelsen, Thomas; Krarup, Lars-Henrik; Iversen, Helle K

    2015-01-01

    BACKGROUND: Stroke mortality estimates in the Global Burden of Disease (GBD) study are based on routine mortality statistics and redistribution of ill-defined codes that cannot be a cause of death, the so-called 'garbage codes' (GCs). This study describes the contribution of these codes to stroke...

  2. Tobacco blue mould disease caused by Peronospora hyoscyami f. sp. tabacina

    NARCIS (Netherlands)

    Borrás-Hidalgo, O.; Thomma, B.P.H.J.; Silva, Y.; Chacón, O.; Pujol, M.

    2010-01-01

    Blue mould [Peronospora hyoscyami f. sp. tabacina (Adam) Skalicky 1964] is one of the most important foliar diseases of tobacco that causes significant losses in the Americas, south-eastern Europe and the Middle East. This review summarizes the current knowledge of the mechanisms employed by this

  3. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015

    DEFF Research Database (Denmark)

    Roth, Gregory A; Johnson, Catherine; Abajobir, Amanuel

    2017-01-01

    -income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0...

  4. MRPL44 mutations cause a slowly progressive multisystem disease with childhood-onset hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Distelmaier, F.; Haack, T.B.; Catarino, C.B.; Gallenmuller, C.; Rodenburg, R.J.T.; Strom, T.M.; Baertling, F.; Meitinger, T.; Mayatepek, E.; Prokisch, H.; Klopstock, T.

    2015-01-01

    Defects in mitochondrial translation may lead to combined respiratory chain deficiency and typically cause childhood-onset multisystem disease. Only recently, a homozygous missense mutation (c.467T > G, p.Leu156Arg) in MRPL44, encoding a protein of the large subunit of the mitochondrial ribosome,

  5. Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

    NARCIS (Netherlands)

    van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

    2016-01-01

    Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic

  6. The haematocrit – an important factor causing impaired haemostasis in patients with cyanotic congenital heart disease

    DEFF Research Database (Denmark)

    Jensen, A S; Johansson, P I; Idorn, L

    2013-01-01

    BACKGROUND: Patients with cyanotic congenital heart disease(CCHD) have haemostatic abnormalities, which result in an increased risk of bleeding. The cause is unknown, but recent studies have indicated that an elevated haematocrit, which is present in cyanotic patients, could be an important factor...

  7. Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics

    DEFF Research Database (Denmark)

    Roca, Xavier; Olson, Andrew J; Rao, Atmakuri R

    2008-01-01

    Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5'-splice-site (5'ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies...

  8. ANIMAL PATHOGENS THAT MAY CAUSE HUMAN DISEASE THAT ORIGINATE FROM FARM OPERATIONS

    Science.gov (United States)

    The recent increase in concentrated animal feeding operations in the United States has caused renewed concern regarding the infectious diseases that may be passed from farm animals to humans via the environment. It is also known that more than 20 recent epidemics among humans cou...

  9. An emergent disease causes directional changes in forest species composition in coastal California

    Science.gov (United States)

    Margaret Metz; Kerri Frangioso; Allison Wickland; Ross Meentemeyer; David Rizzo

    2012-01-01

    Non-native forest pathogens can cause dramatic and long-lasting changes to the composition of forests, and these changes may have cascading impacts on community interactions and ecosystem functioning. Phytophthora ramorum, the causal agent of the emergent forest disease sudden oak death (SOD), has a wide host range, but mortality is concentrated in...

  10. The suggestion of common cause of disease, characteristics of human body, and medical treatment

    Directory of Open Access Journals (Sweden)

    Byung-Jun Cho

    2011-06-01

    Full Text Available Objectives & Methods: This suggestion was attempted to be elevated the recognition of common characteristics in disease. So, we performed to analyze the correlation of common cause of disease, characteristics of human body, and medical treatment. And the results are as follows. Results: 1. The cause of disease is consist of genetic factor, aging, habit, food of not good in health, weather, environment, deficit of the physical activity, stress and so on. 2. Generally, human has common and individual weakness. Individual weakness is appeared similar to the occurrence of volcano and lapse. 3. The correlation of disease and medical treatments is possible to explain using the quotation of the law of motion made by Isaac Newton, the great physicist. 4. When the process of the medical treatment was not progressed, the prognosis is determined by the correlation of the homeostasis(H' in human body and the homeostasis(H of disease. 5. The prognosis of disease is determined by the relationship between the energy of disease(F and medical treatment(F'. 6. The exact diagnosis is possible to predict the treatment sequence, and the facts that homeostasis in human body and disease, relationship between the energy of disease(F and medical treatment(F', action and reaction are important to determine the prognosis. 7. The careful observation of improving response and worsening action of disease becomes available for exact prognosis. Conclusion: The above described contents may be useful in clinical studies, and the concrete clinical reports about this will be made afterward.

  11. Haptoglobin Phenotype Predicts a Low Heart Rate Variability in Patients with Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Svensson, My; Strandhave, Charlotte; Krarup, H.B.

    to a phenotype-dependent antioxidant capacity where Hp 2-2 exhibits a low antioxidant ability, increasing the risk of cardiovascular disease. An attenuated heart rate variability (HRV) may be an important predictor of mortality in patients with chronic kidney disease (CKD). In the present study, we examined......F-PO1096 Haptoglobin Phenotype Predicts a Low Heart Rate Variability in Patients with Chronic Kidney Disease My Svensson,1 Charlotte Strandhave,1 Henrik My Svensson,1 Charlotte Strandhave,1 HenrikKrarup,2 Jeppe H. Christensen.1 1Department of Nephrology, Aalborg Hospital, Aalborg, Denmark; 2......Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark. Introduction Three major phenotypes for the haptoglobin (Hp) gene has been identified: Hp 1-1, Hp 2-2, and the heterozygous Hp 2-1. Hp 2-2 is associated with a poor outcome in patients with cardiovascular disease. This may be due...

  12. Haptoglobin Phenotype Predicts a Low Heart Rate Variability in Patients with Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Svensson, My; Strandhave, Charlotte; Krarup, H.B.

    2009-01-01

    F-PO1096 Haptoglobin Phenotype Predicts a Low Heart Rate Variability in Patients with Chronic Kidney Disease My Svensson,1 Charlotte Strandhave,1 Henrik My Svensson,1 Charlotte Strandhave,1 HenrikKrarup,2 Jeppe H. Christensen.1 1Department of Nephrology, Aalborg Hospital, Aalborg, Denmark; 2...... to a phenotype-dependent antioxidant capacity where Hp 2-2 exhibits a low antioxidant ability, increasing the risk of cardiovascular disease. An attenuated heart rate variability (HRV) may be an important predictor of mortality in patients with chronic kidney disease (CKD). In the present study, we examined......Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark. Introduction Three major phenotypes for the haptoglobin (Hp) gene has been identified: Hp 1-1, Hp 2-2, and the heterozygous Hp 2-1. Hp 2-2 is associated with a poor outcome in patients with cardiovascular disease. This may be due...

  13. Heart Rate Variability in Cavalier King Charles Spaniels with Different Degree of Myxomatous Mitral Valve Disease

    DEFF Research Database (Denmark)

    Rasmussen, Caroline Elisabeth; Falk, Bo Torkel; Zois, Nora Elisabeth

    2010-01-01

    Heart Rate Variability in Cavalier King Charles Spaniels with Different Degree of Myxomatous Mitral Valve Disease Rasmussen, C.E. 1, Falk, T. 1, Zois, N.E. 1, Moesgaard, S.G. 1, Häggström, J. 2, Pedersen, H.D. 3 and Olsen, L.H1. 1Department of Basic Animal and Veterinary Sciences, Faculty of Life...... Sciences, University of Copenhagen, Frederiksberg, Denmark, 2Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden; and 3Novo Nordic A/S, Maaloev, Denmark. Introduction: Modulation of heart rate by the autonomic nervous system can indirectly be measured by heart rate...... variability (HRV). Reduced HRV is seen in dogs with heart failure secondary to myxomatous mitral valve disease (MMVD). However, HRV is suggested to increase with disease progression in dogs with early stages of MMVD. Comparable results are found in people with primary mitral valve prolapse, a disease...

  14. Public funding for medical research in relation to the burden of disease caused by cardiovascular diseases and neoplasms in Germany.

    Science.gov (United States)

    Krone, Manuel; Dufner, Vera; Wagner, Martin; Gelbrich, Götz; Ertl, Georg; Heuschmann, Peter U

    2018-04-13

    Public funding for medical research in Germany is primarily provided by the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF). The aim of this study was to analyze the amount of national public funding for medical research on predominant causes of death in Germany, cardiovascular diseases and neoplasms, in relation to the burden of these diseases in Germany. Three evaluators categorized medical research projects funded by the DFG or BMBF between 2010 and 2012 into the categories "Diseases of the circulatory system" (with subgroups "Ischemic heart diseases", "Heart failure" and "Cerebrovascular diseases") and "Neoplasms". The total amount of public funding by the national agencies was analyzed in relation to the burden of disease for the respective disease condition. Information on national public funding for medical research of 2091 million euros was available; of those, 246.8 million euros (11.8%) were categorized being spent for research on "Neoplasms", 118.4 million euros (5.7%) for research on "Diseases of the circulatory system". This results in 362.08 euros per case of death, 16.58 euros per year of life lost (YLL) and 16.04 euros per disability-adjusted life year (DALY) for "Neoplasms" and in 113.44 euros per case of death, 8.05 euros per YLL and 7.17 euros per DALY for "Diseases of the circulatory system". In Germany, research on cardiovascular diseases receives a lower share of national public funding for medical research compared to oncological research. These results are comparable to other European countries.

  15. A systematic review and meta-analysis of clinical variables used in Huntington disease research.

    Science.gov (United States)

    Franciosi, Sonia; Shim, Yaein; Lau, Margaret; Hayden, Michael R; Leavitt, Blair R

    2013-12-01

    Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these measures have limited sensitivity, particularly in pre- to early stages of the disease. We performed a systematic review of HD clinical studies to identify endpoints that correlate with disease severity. Using standard HD keywords and terms, we identified 749 published studies from 1993 to 2011 based on the availability of demographic, biochemical, and clinical measures. The average and variability of each measure was abstracted and stratified according to pre-far, pre-close, early, mild, moderate, and severe HD stages. A fixed-effect meta-analysis on selected variables was conducted at various disease stages. A total of 1,801 different clinical variables and treatment outcomes were identified. Unified Huntington Disease Rating Scale (UHDRS) Motor, UHDRS Independence, and Trail B showed a trend toward separation between HD stages. Other measures, such as UHDRS Apathy, Verbal Fluency, and Symbol Digit, could only distinguish between pre- and early stages of disease and later stages, whereas other measures showed little correlation with increasing HD stages. Using cross-sectional data from published HD clinical trials, we have identified potential endpoints that could be used to track HD disease progression and treatment effect. Longitudinal studies, such as TRACK-HD, are critical for assessing the value of potential markers of disease progression for use in future HD therapeutic trials. A list of variables, references used in this meta-analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications. © 2013 Movement Disorder Society.

  16. Regional differences in determining cardiovascular diseases as the cause of death in Poland: time for change.

    Science.gov (United States)

    Wojtyniak, Bogdan; Jankowski, Krzysztof; Zdrojewski, Tomasz; Opolski, Grzegorz

    2012-01-01

    Data regarding deaths in many countries is a reliable source of information on population health status, due to the legal obligation to register the fact of a death and its cause. Such data is widely used to analyse regional health differences, changes in health over time, and to pursue and monitor the effects of health policies. Therefore, it is extremely important that the data is reliable and comparable across the country. To analyse death rates from cardiovascular diseases in 2007-2009 among residents of large Polish cities, where medical universities are located, in order to assess the magnitude of differences in mortality in those populations. The information on deaths was collected from a routine death registration system run by the Central Statistical Office. We analysed mortality by accessing individual death records of the residents of the following cities: Bialystok, Bydgoszcz, Gdansk, Katowice, Krakow, Lublin, Lodz, Poznan, Szczecin, Warsaw and Wroclaw. The following causes of death were taken into account: diseases of the circulatory system in total (ICD-10: I00-I99); ischaemic heart disease (I20-I25) including myocardial infarction (I21-I22); pulmonary heart disease and other heart diseases (I26-I51) including cardiac arrest (I46); heart failure (I50); complications and ill-defined descriptions of heart disease (I51); cerebrovascular diseases (I60-I69); and atherosclerosis (I70). The death rates were age-standardised by the direct method, taking as a standard the so-called 'European age structure'. Comparison of mortality rates in the studied cities revealed substantial and unjustified differences in the values of the rates for individual groups of diseases. The death rate from myocardial infarction in Katowice was nearly three times higher than those in Wroclaw and Krakow (74.8/100,000 against 25.2 and 25.7/100,000). Mortality rates from pulmonary heart disease and other heart diseases in Warsaw, Lodz, Bydgoszcz, and Szczecin were in the range of 12

  17. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

    LENUS (Irish Health Repository)

    Arsov, Todor

    2011-05-13

    The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.

  18. Snoring Is Not Associated With All-Cause Mortality, Incident Cardiovascular Disease, or Stroke in the Busselton Health Study

    Science.gov (United States)

    Marshall, Nathaniel S.; Wong, Keith K.H.; Cullen, Stewart R.J.; Knuiman, Matthew W.; Grunstein, Ronald R.

    2012-01-01

    Study Objectives: To ascertain whether objectively measured snoring increases mortality, cardiovascular disease, or stroke risk over the effects of obstructive sleep apnea and other established risk factors. Design: Community-based cohort. Participants: 400 residents of the Western Australian town of Busselton. Interventions: N/A. Measurements: Snoring and obstructive sleep apnea were quantified via the percentage of the night spent snoring and the respiratory disturbance index as measured by a single night recording in November-December 1990 by a home sleep apnea monitoring device (MESAM IV), along with a range of cardiovascular disease risk factors. Follow-up for deaths and cardiovascular hospitalizations was ascertained via record linkage until the end of 2007. Results: Our analytical sample of 380 people was made up of the 397 people for whom the authors had follow-up data, minus 17 people who reported a previous stroke or heart attack at baseline (n = 380/400 = 95% of cohort). Snoring was observed for a mean/median of 32.0/27.4% of the night (standard deviation = 23.9%; range = 0-97.2%). There were 46 deaths, 68 cardiovascular events, and 24 strokes during 17 yr of follow-up. Snoring as either a categoric or continuous variable was not significantly associated with death, incident cardiovascular disease, or stroke in both unadjusted Cox regression models and in models that adjusted for obstructive sleep apnea and other risk factors. Conclusions: No measure of snoring was associated with all-cause mortality, or incident cardiovascular disease or stroke over 17 yr in this community-based sample. Citation: Marshall NS; Wong KKH; Cullen SRJ; Knuiman MW; Grunstein RR. Snoring is not associated with all-cause mortality, incident cardiovascular disease, or stroke in the Busselton Health Study. SLEEP 2012;35(9):1235–1240. PMID:22942501

  19. A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease.

    Science.gov (United States)

    Mass, Elvira; Jacome-Galarza, Christian E; Blank, Thomas; Lazarov, Tomi; Durham, Benjamin H; Ozkaya, Neval; Pastore, Alessandro; Schwabenland, Marius; Chung, Young Rock; Rosenblum, Marc K; Prinz, Marco; Abdel-Wahab, Omar; Geissmann, Frederic

    2017-09-21

    The pathophysiology of neurodegenerative diseases is poorly understood and there are few therapeutic options. Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss, and chronic glial activation. Whether microglial activation, which is generally viewed as a secondary process, is harmful or protective in neurodegeneration remains unclear. Late-onset neurodegenerative disease observed in patients with histiocytoses, which are clonal myeloid diseases associated with somatic mutations in the RAS-MEK-ERK pathway such as BRAF(V600E), suggests a possible role of somatic mutations in myeloid cells in neurodegeneration. Yet the expression of BRAF(V600E) in the haematopoietic stem cell lineage causes leukaemic and tumoural diseases but not neurodegenerative disease. Microglia belong to a lineage of adult tissue-resident myeloid cells that develop during organogenesis from yolk-sac erythro-myeloid progenitors (EMPs) distinct from haematopoietic stem cells. We therefore hypothesized that a somatic BRAF(V600E) mutation in the EMP lineage may cause neurodegeneration. Here we show that mosaic expression of BRAF(V600E) in mouse EMPs results in clonal expansion of tissue-resident macrophages and a severe late-onset neurodegenerative disorder. This is associated with accumulation of ERK-activated amoeboid microglia in mice, and is also observed in human patients with histiocytoses. In the mouse model, neurobehavioural signs, astrogliosis, deposition of amyloid precursor protein, synaptic loss and neuronal death were driven by ERK-activated microglia and were preventable by BRAF inhibition. These results identify the fetal precursors of tissue-resident macrophages as a potential cell-of-origin for histiocytoses and demonstrate that a somatic mutation in the EMP lineage in mice can drive late-onset neurodegeneration. Moreover, these data identify activation of the MAP kinase pathway in microglia as a cause of neurodegeneration and this offers

  20. Test-retest repeatability of cardiopulmonary exercise test variables in patients with cardiac or respiratory disease.

    Science.gov (United States)

    Barron, Anthony; Dhutia, Niti; Mayet, Jamil; Hughes, Alun D; Francis, Darrel P; Wensel, Roland

    2014-04-01

    The test-retest reliability for multiple cardiopulmonary exercise test (CPX) variables has not been compared in a single study and the influence of different diseases on test-retest reliability has not been examined. We investigated different measures of test-retest reliability for multiple variables and compared them by category of cardiac or respiratory disease. Patients with chronic obstructive airways disease (n = 24), heart failure (n = 43), or severe mitral valve disease (n = 26) were recruited into a prospective study. Each patient underwent two bicycle ergometer tests; the first, a familiarization test, with a 10 W/min ramp, and the second a personalized ramp based on the results of the familiarization test to elicit maximal effort within 8-10 min. Intraclass correlation coefficients (ICC) and coefficients of variation between the two tests were calculated. Influence of potential modifiers was assessed using repeated measures analysis of variance. Peak VO2 (ICC 0.95, 95% CI 0.94-0.97), oxygen uptake efficiency slope (ICC 0.93, 95% CI 0.90-0.95), O2 pulse (ICC 0.96, 95% CI 0.94-0.97), and the VE/VCO2 ratio at the nadir (ICC 0.92, 95% CI 0.89-0.95) all showed excellent test-retest reliability, with within-subject coefficients of variation test-retest reliability, although inferior to peak VO2. Age, gender, body mass index, disease aetiology, protocol change, and intertest interval did not affect the reliability of most variables. CPX showed high test-retest reliability; certain variables such as peak VO2 and oxygen uptake efficiency slope outperform others. These results identify which variables are most suitable for serial testing of patients with three common disease aetiologies owing to their superior reproducibility.

  1. Inhaled anticholinergic use and all-cause mortality among elderly Medicare beneficiaries with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ajmera M

    2013-06-01

    Full Text Available Mayank Ajmera,1 Chan Shen,2 Xiaoyun Pan,1 Patricia A Findley,3 George Rust,4 Usha Sambamoorthi1 1Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, WV, USA; 2Department of Biostatistics, MD Anderson Cancer Center, University of Texas, Houston, TX, USA; 3School of Social Work, Rutgers University, New Brunswick, NJ, USA; 4Department of Family Medicine, Morehouse School of Medicine, Atlanta, GA, USA Background: The purpose of this study was to examine the association between use of inhaled anticholinergics and all-cause mortality among elderly individuals with chronic obstructive pulmonary disease (COPD, after controlling for demographic, socioeconomic, health, functional status, smoking, and obesity. Methods: We used a retrospective longitudinal panel data design. Data were extracted for multiple years (2002–2009 of the Medicare Current Beneficiary Survey (MCBS linked with fee-for-service Medicare claims. Generic and brand names of inhaled anticholinergics were used to identify inhaled anticholinergic utilization from the self-reported prescription medication files. All-cause mortality was assessed using the vital status variable. Unadjusted group differences in mortality rates were tested using the chi-square statistic. Multivariable logistic regressions with independent variables entered in separate blocks were used to analyze the association between inhaled anticholinergic use and all-cause mortality. All analyses accounted for the complex design of the MCBS. Results: Overall, 19.4% of the elderly Medicare beneficiaries used inhaled anticholinergics. Inhaled anticholinergic use was significantly higher (28.5% among those who reported poor health compared with those reporting excellent or very good health (12.7%. Bivariate analyses indicated that inhaled anticholinergic use was associated with significantly higher rates of all-cause mortality (18.7% compared with nonusers (13.6%. However

  2. Experimental infection with chamois border disease virus causes long-lasting viraemia and disease in Pyrenean chamois (Rupicapra pyrenaica).

    Science.gov (United States)

    Cabezón, Oscar; Velarde, Roser; Mentaberre, Gregorio; Fernández-Sirera, Laura; Casas-Díaz, Encarna; López-Olvera, Jorge; Serrano, Emmanuel; Rosell, Rosa; Riquelme, Cristina; Lavín, Santiago; Segalés, Joaquim; Marco, Ignasi

    2011-11-01

    Since 2001, severe outbreaks of disease associated with border disease virus (BDV) infection have been reported in Pyrenean chamois. The disease is characterized by variable degrees of cachexia, alopecia and neurological manifestations prior to death. The aim of this study was to investigate this disease under experimental conditions. To assess viral virulence, humoral immune response, dissemination and probable routes of transmission, seven chamois (five seronegative and two seropositive for BDV) were inoculated with a BDV isolated from a naturally infected chamois. A group of three chamois were maintained as uninfected controls. The five seronegative chamois became viraemic from day 2 post-inoculation (p.i.) until their death (three animals) or the end of the experiment (on day 34 p.i.) and developed neutralizing antibodies from day 18 p.i. until the end of the study. Continuous shedding of the virus was detected by RT-PCR in oral, nasal and rectal swabs in viraemic chamois from day 5 p.i. Despite none of the viraemic chamois showing obvious neurological signs, all of them had a non-suppurative meningoencephalitis as seen in naturally infected chamois. The two inoculated BDV-seropositive chamois did not become viraemic. This study confirms that BDV is the primary agent of the disease that has been affecting chamois populations in recent years in the Pyrenees and that previously acquired humoral immunity is protective.

  3. Analysis of Causes of Non-Uniform Flow Distribution in Manifold Systems with Variable Flow Rate along Length

    Science.gov (United States)

    Zemlyanaya, N. V.; Gulyakin, A. V.

    2017-11-01

    The uniformity of flow distribution in perforated manifolds is a relevant task. The efficiency of water supply, sewerage and perflation systems is determined by hydraulics of the flow with a variable mass. The extensive study of versatile available information showed that achieving a uniform flow distribution through all of the outlets is almost impossible. The analysis of the studies conducted by other authors and our numerical experiments performed with the help of the software package ANSYS 16.1 were made in this work. The results allowed us to formulate the main causes of non-uniform flow distribution. We decided to suggest a hypothesis to explain the static pressure rise problem at the end of a perforated manifold.

  4. Analysis of complications in thyroid arterial embolization for hyperthyroidism caused by Graves' disease

    International Nuclear Information System (INIS)

    Gao Bulang; Zhao Wei; Huang Jianqiang; Xiang Shutian; Li Liyuan; Li Minghua

    2006-01-01

    Objective: To investigate complications and causes of thyroid arterial embolization for hyperthyroidism caused by Graves' disease. Methods: Twenty-eight patients with hyperthyroidism caused by Graves' disease had been treated through transcathter arterial embolization with mid-term follow up. The thyroid angiography, interventional treatment, complications and causes were investigated. Results Followed up for over one year (12-24 months), mid-term rate of efficiency was 78.6% with recurrent rate of one year being 14.2%. Two patients (7.1%) had brain infarction with one partially recovered after proper therapy and the other died due to subsequent hyperthyroidism crisis. One case had temporary hypothyroidism, and another hypoparathyroidism but no permanent hypothyroidism or hypoparathyroidism occurred. One patient suffered relatively severe post-embolization syndrome. All the other complications disappeared after proper treatment. Followed up for more than a year, no other complications occurred. Conclusion: Misembolization due to regurgitation of embolized agent is one of the most important factors leading to complications of arterial embolization for Graves' disease. In order to reduce complications and improve therapeutic efficacy, it is essential to superselectively catheterize the thyroid, avoid dangerous anastomose, prevent regurgitation misembolization and strictly operate under fluoroscopy. (authors)

  5. Alterations and diseases of the gastrointestinal tract caused by old age

    International Nuclear Information System (INIS)

    Bayerl, F.

    1981-01-01

    The dissertation reviews the publications on 'The gastrointestinal tract in old age' since 1941. As in the 1941 publication by Heinrich, particular interest is taken in diagnostic radiology. The lower age limit of the cases described was set at 55 to 60 years. Oesophageal changes ranged from functional disturbances (e.g. atonia, changes in peristalsis, or dilatation) to chronic inflammation, displacement caused by the surrounding organs, and tumours (mainly carcinoma). Formation of diverticula takes an intermediate position. Of the gastric and duodenal changes, hiatal hermia and chronic atrophic gastritis were the most frequent. Ulcers caused by old age differ from 'common' ulcers in some respects, and the symptoms may be confused with those of gastric carcinoma. Early gastric carcinoma is another disease whose incidence increases with age. Thoracic and spinal changes may cause impressions on the stomach. The effects of old age on the time of passage of contrast media, on gastric tone, and on the shape of the stomach remain unclear. Changes caused by old age in the small and large intestine range from formation of diverticula and vascular diseases (e.g. ischaemic colitis and obstruction of the mesenteric vessels) to the frequent carcinoma of the large intestine and rectum. According to this study it has to be supposed that the degenerative atrophic processes of aging and previous diseases occurring increasingly in old age, favour the provocation of ratrogenic injuries. (orig./MG) [de

  6. How the factoid of wind turbines causing 'vibroacoustic disease' came to be 'irrefutably demonstrated'.

    Science.gov (United States)

    Chapman, Simon; St George, Alexis

    2013-06-01

    In recent years, claims have proliferated in cyberspace that wind turbines cause a large variety of symptoms and diseases. One of these, "vibroacoustic disease" (VAD) is frequently mentioned. The aim of this study is to examine the quality of the evidence on how VAD came to be associated with wind turbine exposure by wind farm opponents. Searches of the web (Google advanced) and major research databases for papers on VAD and wind turbines. Self-citation analysis of research papers on VAD. Google returned 24,700 hits for VAD and wind turbines. Thirty-five research papers on VAD were found, none reporting any association between VAD and wind turbines. Of the 35 papers, 34 had a first author from a single Portuguese research group. Seventy-four per cent of citations to these papers were self-citations by the group. Median self-citation rates in science are around 7%. Two unpublished case reports presented at conferences were found asserting that VAD was "irrefutably demonstrated" to be caused by wind turbines. The quality of these reports was abject. VAD has received virtually no scientific recognition beyond the group who coined and promoted the concept. There is no evidence of even rudimentary quality that vibroacoustic disease is associated with or caused by wind turbines. The claim that wind turbines cause VAD is a factoid that has gone 'viral' in cyberspace and may be contributing to nocebo effects among those living near turbines. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

  7. Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle.

    Science.gov (United States)

    Miyamoto, Yasunori; Miyazaki, Teruo; Honda, Akira; Shimohata, Homare; Hirayama, Kouichi; Kobayashi, Masaki

    2016-11-01

    Insulin resistance occurs frequently in patients with chronic kidney disease. However, the mechanisms of insulin resistance associated with chronic kidney disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a cause of insulin resistance in chronic kidney disease patients. Serum acetylcarnitine concentrations were measured in chronic kidney disease patients, and were significantly increased with reduction of renal function. The effects of excess extracellular acetylcarnitine on insulin resistance were studied in cultured skeletal muscle cells (C2C12 and human myotubes), and insulin-dependent glucose uptake was significantly and dose-dependently inhibited by addition of acetylcarnitine. The added acetylcarnitine was converted to carnitine via reverse carnitine acetyltransferase reaction, and thus the AcCoA concentration and AcCoA/CoA ratio in mitochondria were significantly elevated. The results suggest that increased serum acetylcarnitine in CKD patients causes AcCoA accumulation in mitochondria by stimulating reverse carnitine acetyltransferase reaction, which leads to insulin resistance in skeletal muscle.

  8. Opinions in Denmark on the causes of peptic ulcer disease. A survey among Danish physicians and patients

    DEFF Research Database (Denmark)

    Christensen, A H; Gjørup, T; Andersen, I B

    1994-01-01

    The aim of the study was to investigate opinions among Danish patients and physicians on causes of peptic ulcer disease. Fifty-nine patients with an ulcer history and 77 physicians with a special interest in gastroenterology participated. They were given a questionnaire listing 16 possible causes...... of peptic ulcer and indicated for each whether they believed it was a contributory cause of the disease. The patients stated 0-10 causes each (median, 4), and the physicians 3-12 causes (median, 6) (p ... stated more causes than did their male colleagues (p peptic ulcer disease, whereas only around 40% believed that coffee/tea, alcohol, smoking, side effects...

  9. Hyperspectral imaging for small-scale analysis of symptoms caused by different sugar beet diseases

    Directory of Open Access Journals (Sweden)

    Mahlein Anne-Katrin

    2012-01-01

    Full Text Available Abstract Hyperspectral imaging (HSI offers high potential as a non-invasive diagnostic tool for disease detection. In this paper leaf characteristics and spectral reflectance of sugar beet leaves diseased with Cercospora leaf spot, powdery mildew and leaf rust at different development stages were connected. Light microscopy was used to describe the morphological changes in the host tissue due to pathogen colonisation. Under controlled conditions a hyperspectral imaging line scanning spectrometer (ImSpector V10E with a spectral resolution of 2.8 nm from 400 to 1000 nm and a spatial resolution of 0.19 mm was used for continuous screening and monitoring of disease symptoms during pathogenesis. A pixel-wise mapping of spectral reflectance in the visible and near-infrared range enabled the detection and detailed description of diseased tissue on the leaf level. Leaf structure was linked to leaf spectral reflectance patterns. Depending on the interaction with the host tissue, the pathogens caused disease-specific spectral signatures. The influence of the pathogens on leaf reflectance was a function of the developmental stage of the disease and of the subarea of the symptoms. Spectral reflectance in combination with Spectral Angle Mapper classification allowed for the differentiation of mature symptoms into zones displaying all ontogenetic stages from young to mature symptoms. Due to a pixel-wise extraction of pure spectral signatures a better understanding of changes in leaf reflectance caused by plant diseases was achieved using HSI. This technology considerably improves the sensitivity and specificity of hyperspectrometry in proximal sensing of plant diseases.

  10. Incidence and causes of end-stage renal disease among Aboriginal children and young adults.

    Science.gov (United States)

    Samuel, Susan M; Foster, Bethany J; Hemmelgarn, Brenda R; Nettel-Aguirre, Alberto; Crowshoe, Lynden; Alexander, R Todd; Soo, Andrea; Tonelli, Marcello A

    2012-10-02

    Although Aboriginal adults have a higher risk of end-stage renal disease than non-Aboriginal adults, the incidence and causes of end-stage renal disease among Aboriginal children and young adults are not well described. We calculated age- and sex-specific incidences of end-stage renal disease among Aboriginal people less than 22 years of age using data from a national organ failure registry. Incidence rate ratios were used to compare rates between Aboriginal and white Canadians. To contrast causes of end-stage renal disease by ethnicity and age, we calculated the odds of congenital diseases, glomerulonephritis and diabetes for Aboriginal people and compared them with those for white people in the following age strata: 0 to less than 22 years, 22 to less than 40 years, 40 to less than 60 years and older than 60 years. Incidence rate ratios of end-stage renal disease for Aboriginal children and young adults (age diseases were less common among Aboriginal people aged less than 22 years (odds ratio [OR] 0.56, 95% CI 0.36-0.86), and glomerulonephritis was more common (OR 2.18, 95% CI 1.55-3.07). An excess of glomerulonephritis, but not diabetes, was seen among Aboriginal people aged 22 to less than 40 years. The converse was true (higher risk of diabetes, lower risk of glomerulonephritis) among Aboriginal people aged 40 years and older. The incidence of end-stage renal disease is higher among Aboriginal children and young adults than among white children and young adults. This higher incidence may be driven by an increased risk of glomerulonephritis in this population.

  11. Non-melanoma skin cancer and risk of Alzheimer's disease and all-cause dementia.

    Directory of Open Access Journals (Sweden)

    Sigrun A J Schmidt

    Full Text Available Cancer patients may be at decreased risk of Alzheimer's disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC, but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer's disease (main outcome and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221 and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097. We followed individuals from the time of diagnosis, or corresponding date for matched comparators, until a dementia diagnosis, death, emigration, or 30 November 2013, whichever came first. We used stratified Cox regression adjusted for comorbidities to compute hazard ratios (HRs associating NMSC with dementia. We computed cumulative risks of dementia, treating death as a competing risk. NMSC was associated with a HR of 0.95 (95% confidence interval [CI]: 0.92-0.98 for Alzheimer's disease and 0.92 (95% CI: 0.90-0.94 for all-cause dementia. HRs were similar for basal cell and squamous cell carcinoma, the two most common forms of NMSC. Estimates of risk reduction were more pronounced in the beginning of follow-up, reaching null after 5-10 years. At the end of follow-up (34 years, cumulative risk of Alzheimer's disease was 4.6% (95% CI: 4.4%-4.8% among patients with NMSC vs. 4.7% (95% CI: 4.6%-4.9% in the comparison cohort. In conclusion, NMSC was associated with 2%-10% reductions in relative risks of Alzheimer's disease and all-cause dementia. However, these small inverse associations may have been caused by ascertainment bias due to decreased awareness of NMSC tumors in persons with undiagnosed early cognitive impairment or by confounding from a more neuroprotective lifestyle among persons with NMSC.

  12. Heart Rate Variability in Cavalier King Charles Spaniels with Different Degree of Myxomatous Mitral Valve Disease

    DEFF Research Database (Denmark)

    Rasmussen, Caroline Elisabeth; Falk, Bo Torkel; Zois, Nora Elisabeth

    2010-01-01

    variability (HRV). Reduced HRV is seen in dogs with heart failure secondary to myxomatous mitral valve disease (MMVD). However, HRV is suggested to increase with disease progression in dogs with early stages of MMVD. Comparable results are found in people with primary mitral valve prolapse, a disease......dogs; even prior to the development of overt congestive heart failure....... into 4 groups: 1) no or minimal mitral regurgitation (MR) (MR jet=15% of the left atrial area) and no murmur, 2) mild MR (20%50%) and no clinical signs of heart failure, 4) left atrium to aortic root ratio >1.5, clinical signs of heart failure and furosemide...

  13. Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden.

    Science.gov (United States)

    Musso, Mandi; Westervelt, Holly James; Long, Jeffrey D; Morgan, Erin; Woods, Steven Paul; Smith, Megan M; Lu, Wenjing; Paulsen, Jane S

    2015-01-01

    The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (F ICV(3,877)=11.25; pdisease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample.

  14. How Do the Virulence Factors of Shigella Work Together to Cause Disease?

    Science.gov (United States)

    Mattock, Emily; Blocker, Ariel J.

    2017-01-01

    Shigella is the major cause of bacillary dysentery world-wide. It is divided into four species, named S. flexneri, S. sonnei, S. dysenteriae, and S. boydii, which are distinct genomically and in their ability to cause disease. Shigellosis, the clinical presentation of Shigella infection, is characterized by watery diarrhea, abdominal cramps, and fever. Shigella's ability to cause disease has been attributed to virulence factors, which are encoded on chromosomal pathogenicity islands and the virulence plasmid. However, information on these virulence factors is not often brought together to create a detailed picture of infection, and how this translates into shigellosis symptoms. Firstly, Shigella secretes virulence factors that induce severe inflammation and mediate enterotoxic effects on the colon, producing the classic watery diarrhea seen early in infection. Secondly, Shigella injects virulence effectors into epithelial cells via its Type III Secretion System to subvert the host cell structure and function. This allows invasion of epithelial cells, establishing a replicative niche, and causes erratic destruction of the colonic epithelium. Thirdly, Shigella produces effectors to down-regulate inflammation and the innate immune response. This promotes infection and limits the adaptive immune response, causing the host to remain partially susceptible to re-infection. Combinations of these virulence factors may contribute to the different symptoms and infection capabilities of the diverse Shigella species, in addition to distinct transmission patterns. Further investigation of the dominant species causing disease, using whole-genome sequencing and genotyping, will allow comparison and identification of crucial virulence factors and may contribute to the production of a pan-Shigella vaccine. PMID:28393050

  15. How Do the Virulence Factors ofShigellaWork Together to Cause Disease?

    Science.gov (United States)

    Mattock, Emily; Blocker, Ariel J

    2017-01-01

    Shigella is the major cause of bacillary dysentery world-wide. It is divided into four species, named S. flexneri, S. sonnei, S. dysenteriae , and S. boydii , which are distinct genomically and in their ability to cause disease. Shigellosis, the clinical presentation of Shigella infection, is characterized by watery diarrhea, abdominal cramps, and fever. Shigella 's ability to cause disease has been attributed to virulence factors, which are encoded on chromosomal pathogenicity islands and the virulence plasmid. However, information on these virulence factors is not often brought together to create a detailed picture of infection, and how this translates into shigellosis symptoms. Firstly, Shigella secretes virulence factors that induce severe inflammation and mediate enterotoxic effects on the colon, producing the classic watery diarrhea seen early in infection. Secondly, Shigella injects virulence effectors into epithelial cells via its Type III Secretion System to subvert the host cell structure and function. This allows invasion of epithelial cells, establishing a replicative niche, and causes erratic destruction of the colonic epithelium. Thirdly, Shigella produces effectors to down-regulate inflammation and the innate immune response. This promotes infection and limits the adaptive immune response, causing the host to remain partially susceptible to re-infection. Combinations of these virulence factors may contribute to the different symptoms and infection capabilities of the diverse Shigella species, in addition to distinct transmission patterns. Further investigation of the dominant species causing disease, using whole-genome sequencing and genotyping, will allow comparison and identification of crucial virulence factors and may contribute to the production of a pan- Shigella vaccine.

  16. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates.

    Science.gov (United States)

    O'Brien, Katherine L; Wolfson, Lara J; Watt, James P; Henkle, Emily; Deloria-Knoll, Maria; McCall, Natalie; Lee, Ellen; Mulholland, Kim; Levine, Orin S; Cherian, Thomas

    2009-09-12

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years. We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b. In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449,000 [316,000-501,000]) occurred in ten African and Asian countries. S pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in

  17. Selective processing and metabolism of disease-causing mutant prion proteins.

    Directory of Open Access Journals (Sweden)

    Aarthi Ashok

    2009-06-01

    Full Text Available Prion diseases are fatal neurodegenerative disorders caused by aberrant metabolism of the cellular prion protein (PrP(C. In genetic forms of these diseases, mutations in the globular C-terminal domain are hypothesized to favor the spontaneous generation of misfolded PrP conformers (including the transmissible PrP(Sc form that trigger downstream pathways leading to neuronal death. A mechanistic understanding of these diseases therefore requires knowledge of the quality control pathways that recognize and degrade aberrant PrPs. Here, we present comparative analyses of the biosynthesis, trafficking, and metabolism of a panel of genetic disease-causing prion protein mutants in the C-terminal domain. Using quantitative imaging and biochemistry, we identify a misfolded subpopulation of each mutant PrP characterized by relative detergent insolubility, inaccessibility to the cell surface, and incomplete glycan modifications. The misfolded populations of mutant PrPs were neither recognized by ER quality control pathways nor routed to ER-associated degradation despite demonstrable misfolding in the ER. Instead, mutant PrPs trafficked to the Golgi, from where the misfolded subpopulation was selectively trafficked for degradation in acidic compartments. Surprisingly, selective re-routing was dependent not only on a mutant globular domain, but on an additional lysine-based motif in the highly conserved unstructured N-terminus. These results define a specific trafficking and degradation pathway shared by many disease-causing PrP mutants. As the acidic lysosomal environment has been implicated in facilitating the conversion of PrP(C to PrP(Sc, our identification of a mutant-selective trafficking pathway to this compartment may provide a cell biological basis for spontaneous generation of PrP(Sc in familial prion disease.

  18. IDENTIFICATION AND PATHOGENICITY OF ISOLATE OF BACTERIUM CAUSED LEAF BLIGHT DISEASE ON Maranta arundinacea

    Directory of Open Access Journals (Sweden)

    Supriadi Supriadi

    2018-01-01

    Full Text Available Arrowroot (Maranta arundinacea L is a multi-functional plant used as a source of medicinal, carbohydrate (especially the green leaf type and also as ornamental plant (the streaked white leaf type. A leaf blight disease is recently found on the streaked white type in Bogor. Preliminary observation indicated that the disease was associated with bacterial infection. The cause of the disease has not been studied. This study was aimed to identify the cause of bacterial leaf blight disease. Experiments were conducted in the laboratory of Research Institute for Spice and Medicinal Crops in Bogor. Suspected bacteria were isolated from diseased leaves. The results showed that the bacterium produced white to brownish colonies on rich agar media containing peptone or cassamino acid. 3-5 mm in diameter, circular, and did not yield fluorescent pigment on King’s B medium. The bacterium formed rod cells, Gram negative, accumulated poly β hydroxybutyrate, utilized glucose under aerobic condition, not hydrolyse arginine and starch, positive catalase, insensitive to tetrazolium salt (0.1%, and grew at 35oC. The bacterium neither producted xanthomonadin pigment nor reduced nitrate to nitrite. The pathogen was tolerant to penicillin and oxolinic acid, but sensitive to streptomycin and oxytetracycline at high concentration (1.000 ppm. These characteristics met to those of Pseudomonas cepacia. Pathogenicity test on detached leaves showed that the typical symptom of blight was similar to that of natural infection on arrowroot. This is the first report on occurrence of P cepacia on arrowroot plant.

  19. Hyposplenism as a cause of pneumococcal meningoencephalitis in an adult patient with coeliac disease

    Directory of Open Access Journals (Sweden)

    Paolo Caraceni

    2013-03-01

    Full Text Available Introduction: Coeliac disease can be associated with hyposplenism and splenic atrophy, which may increase the patient’s risk for fatal infections caused by Streptococcus pneumoniae or Pneumococcus. It is general opinion that many more patients with coeliac disease have died from hyposplenism-related infections than those reported in literature. Case report: A 62-year-old woman with recently diagnosed coeliac disease was hospitalized with high fever, disorientation, and nuchal rigidity. Cerebral computed tomography was negative. Laboratory tests showed an elevated leukocyte count and very high levels of C reactive protein. The cerebrospinal fluid (CSF contained an increased number of mononuclear cells associated with a low glucose level and high protein concentrations. The CSF culture was positive for Streptococcus pneumoniae. Neurological conditions rapidly deteriorated with the onset of coma, and magnetic resonance imaging of the brain revealed initial signs of encephalitis extending above and below the tentorium. Abdominal ultrasonography disclosed splenic hypotrophy that raised the suspicion of hyposplenism. The diagnosis of hyposplenism was confirmed by demonstration of Howell-Jolly bodies in a peripheral blood smear. Discussion: This is the first reported case of pneumococcal meningoencephalitis caused by splenic hypofunction in a patient with coeliac disease. When coeliac disease is diagnosed with a marked delay in an elderly patient, spleen function should always be assessed. If impaired, the patient should undergo vaccination with pneumococcal conjugate vaccine to prevent pneumococcal infections.

  20. Using network theory to identify the causes of disease outbreaks of unknown origin.

    Science.gov (United States)

    Bogich, Tiffany L; Funk, Sebastian; Malcolm, Trent R; Chhun, Nok; Epstein, Jonathan H; Chmura, Aleksei A; Kilpatrick, A Marm; Brownstein, John S; Hutchison, O Clyde; Doyle-Capitman, Catherine; Deaville, Robert; Morse, Stephen S; Cunningham, Andrew A; Daszak, Peter

    2013-04-06

    The identification of undiagnosed disease outbreaks is critical for mobilizing efforts to prevent widespread transmission of novel virulent pathogens. Recent developments in online surveillance systems allow for the rapid communication of the earliest reports of emerging infectious diseases and tracking of their spread. The efficacy of these programs, however, is inhibited by the anecdotal nature of informal reporting and uncertainty of pathogen identity in the early stages of emergence. We developed theory to connect disease outbreaks of known aetiology in a network using an array of properties including symptoms, seasonality and case-fatality ratio. We tested the method with 125 reports of outbreaks of 10 known infectious diseases causing encephalitis in South Asia, and showed that different diseases frequently form distinct clusters within the networks. The approach correctly identified unknown disease outbreaks with an average sensitivity of 76 per cent and specificity of 88 per cent. Outbreaks of some diseases, such as Nipah virus encephalitis, were well identified (sensitivity = 100%, positive predictive values = 80%), whereas others (e.g. Chandipura encephalitis) were more difficult to distinguish. These results suggest that unknown outbreaks in resource-poor settings could be evaluated in real time, potentially leading to more rapid responses and reducing the risk of an outbreak becoming a pandemic.

  1. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation.

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P; Luthi-Carter, Ruth; Lowdell, Mark W; Björkqvist, Maria; Ostroff, Gary R; Aronin, Neil; Tabrizi, Sarah J

    2014-03-01

    Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.

  2. Cushing's disease as a cause of severe osteoporosis: a clinical challenge.

    Science.gov (United States)

    Abdel-Kader, Nadia; Cardiel, Mario H; Navarro Compan, Victoria; Piedra Priego, Juan; González, Ana

    2012-01-01

    Secondary osteoporosis is a frequently underestimated bone disorder. It is a secondary cause of bone loss that affects more than half of men and premenopausal and perimenopausal women, and about one-fitfth of postmenopausal women. We herein report an uncommon case of multiple fractures due to secondary osteoporosis caused by Cushing's disease. In this case the appearance of fractures in a 41 years old woman was the sign of alarm that ultimately lead us to the diagnosis. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  3. Hemolytic disease of the fetus and newborn caused by anti-E

    OpenAIRE

    Usman, Adiyyatu Sa?idu; Mustaffa, Rapiaah; Ramli, Noraida; Diggi, Sirajo A.

    2013-01-01

    Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting wit...

  4. Vitamin D status and incident cardiovascular disease and all-cause mortality

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Pisinger, Charlotta

    2013-01-01

    Low vitamin D status has been associated with cardiovascular disease (CVD) and mortality primarily in selected groups, smaller studies, or with self-reported vitamin D intake. We investigated the association of serum vitamin D status with the incidence of a registry-based diagnosis of ischemic...... heart disease (IHD), stroke, and all-cause mortality in a large sample of the general population. A total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, were included. Measurements of serum 25-hydroxyvitamin D at baseline were carried out using the IDS ISYS immunoassay...

  5. Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease Type 1a

    Energy Technology Data Exchange (ETDEWEB)

    Lei, K.J.; Shelly, L.L.; Pan, C.J.; Sidbury, J.B.; Chou, J.Y. (National Institutes of Health, Bethesda, MD (United States))

    1993-10-22

    Glycogen storage disease (GSD) type 1a is caused by the deficiency of d-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.

  6. Spot Anthracnose Disease Caused by Colletotrichum gloeosporioides on Tulip Tree in Korea.

    Science.gov (United States)

    Choi, Okryun; Choi, Okhee; Kwak, Youn-Sig; Kim, Jinwoo; Kwon, Jin-Hyeuk

    2012-03-01

    The tulip tree (Liriodendron chinense) has been widely cultivated in Korea as a street or garden tree for its large flowers, which have a superficial resemblance to tulips. Occurrence of anthracnose disease on the leaves of tulip trees growing on the campus of Gyeongsang National University, Jinju, Korea, has been observed. Based on mycological characteristics, pathogenicity, and internal transcribed spacer sequence, the causal fungus was identified as Colletotrichum gloeosporioides. This is the first report on anthracnose disease caused by C. gloeosporioides on tulip trees in Korea.

  7. Heart rate and heart rate variability in dogs with different degrees of myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Rasmussen, Caroline Elisabeth; Falk, Bo Torkel; Zois, Nora Elisabeth

    2011-01-01

    HEART RATE AND HEART RATE VARIABILITY IN DOGS WITH DIFFERENT DEGREES OF MYXOMATOUS MITRAL VALVE DISEASE. CE Rasmussen1, T Falk1, NE Zois1, SG Moesgaard1, HD Pedersen2, J Häggström3 and LH Olsen1. 1. Department of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University...... of Copenhagen, Frederiksberg, Denmark. 2. Novo Nordic A/S, Maaloev, Denmark. 3. Department of Clinical Sciences, Swedish University of Agricultural Science, Uppsala, Sweden. Heart rate variability (HRV) is an indirect measurement of the autonomic modulation of heart rate (HR). Reduced HRV measured from short......-time electrocardiography is seen in dogs with heart failure (HF) secondary to myxomatous mitral valve disease (MMVD). However, HRV is suggested to increase with disease severity at early stages of MMVD. The aims of this study were 1) to associate HR and HRV with severity of MMVD in Cavalier King Charles Spaniels (CKCS...

  8. Heart rate variability in leucine-rich repeat kinase 2-associated Parkinson's disease.

    Science.gov (United States)

    Visanji, Naomi P; Bhudhikanok, Grace S; Mestre, Tiago A; Ghate, Taneera; Udupa, Kaviraj; AlDakheel, Amaal; Connolly, Barbara S; Gasca-Salas, Carmen; Kern, Drew S; Jain, Jennifer; Slow, Elizabeth J; Faust-Socher, Achinoam; Kim, Sam; Azhu Valappil, Ruksana; Kausar, Farah; Rogaeva, Ekaterina; William Langston, J; Tanner, Caroline M; Schüle, Birgitt; Lang, Anthony E; Goldman, Samuel M; Marras, Connie

    2017-04-01

    Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine-rich repeat kinase 2-associated PD. This study investigated heart rate variability in LRRK2-associated PD. Resting electrocardiograms were obtained from 20 individuals with LRRK2-associated PD, 37 nonmanifesting carriers, 48 related noncarriers, 26 idiopathic PD patients, and 32 controls. Linear regression modelling compared time and frequency domain values, adjusting for age, sex, heart rate, and disease duration. Low-frequency power and the ratio of low-high frequency power were reduced in idiopathic PD versus controls (P Heart rate variability may remain intact in LRRK2-associated PD, adding to a growing literature supporting clinical-pathologic differences between LRRK2-associated and idiopathic PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  9. Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children.

    Science.gov (United States)

    Bhatnagar, Shinjini; Gupta, Sidhartha Datta; Mathur, Meera; Phillips, Alan D; Kumar, Ramesh; Knutton, Stuart; Unsworth, David J; Unsworth, Joe; Lock, Robert J; Lock, Bob; Natchu, Uma C M; Mukhopadhyaya, Sanjay; Saini, Savita; Bhan, Maharaj K

    2005-08-01

    In developed countries, small bowel histology in coeliac disease is a spectrum, ranging from normal with increased intraepithelial lymphocytes to the classic flat mucosa. In developing countries, mild to moderate enteropathies in children with chronic diarrhea and growth failure are assumed to be caused by tropical sprue, persistent infections, or malnutrition with bacterial overgrowth. We report the prevalence and histology of coeliac disease in children with chronic diarrhea at a tertiary referral hospital in North India. Two hundred fifty-nine children with symptoms indicating coeliac disease attended the All India Institute of Medical Sciences. Histology was graded after a modified Marsh classification. Serum immunoglobulin A anti-endomysial antibodies (AEA) were assayed using indirect immunofluorescence. Subjects with abnormal histology and positive AEA were put on a gluten free diet (GFD). Coeliac disease was diagnosed on small intestinal biopsy changes and a clinical response to a GFD. Severe enteropathies were present in 63 (24%) subjects, and 58 (92%) responded to a GFD. Sixty-six (25%) had moderate histologic changes, 61 responding to a GFD. AEA was positive in 56 of 63 patients with severe and 65 of 66 with moderate enteropathies. Fifty-seven children had mild enteropathies, and 19 of 20 with positive AEA responded clinically to a GFD. Coeliac disease is more common than previously believed. It presents a variable histology, and diagnoses may be missed or delayed if based only on severe enteropathies. Serology is a useful adjunct to diagnosis, and diagnostic criteria need to be developed appropriately for coeliac disease in developing countries despite limited facilities.

  10. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Bhutta, Zulfiqar A.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Pullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Huynh, Chantal; Johnson, Catherine; Kassebaum, Nicholas J.; Kinfu, Yohannes; Kulikoff, Xie Rachel; Kutz, Michael; Kyu, Hmwe H.; Larson, Heidi J.; Leung, Janni; Liang, Xiaofeng; Lim, Stephen S.; Lind, Margaret; Lozano, Rafael; Marquez, Neal; Mensah, George A.; Mikesell, Joe; Mokdad, Ali H.; Mooney, Meghan D.; Nguyen, Grant; Nsoesie, Elaine; Pigott, David M.; Pinho, Christine; Roth, Gregory A.; Salomon, Joshua A.; Sandar, Logan; Silpakit, Naris; Sligar, Amber; Sorensen, Reed J. D.; Stanaway, Jeffrey; Steiner, Caitlyn; Teeple, Stephanie; Thomas, Bernadette A.; Troeger, Christopher; VanderZanden, Amelia; Vollset, Stein Emil; Wanga, Valentine; Whiteford, Harvey A.; Wolock, Timothy; Zoeckler, Leo; Abate, Kalkidan Hassen; Abbafati, Cristiana; Abbas, Kaja M.; Abd-Allah, Foad; Abera, Semaw Ferede; Abreu, Daisy M. X.; Abu-Raddad, Laith J.; Abyu, Gebre Yitayih; Achoki, Tom; Adelekan, Ademola Lukman; Ademi, Zanfina; Adou, Arsene Kouablan; Adsuar, Jose C.; Afanvi, Kossivi Agbelenko; Afshin, Ashkan; Agardh, Emilie Elisabet; Agarwal, Arnav; Agrawal, Anurag; Kiadaliri, Aliasghar Ahmad; Ajala, Oluremi N.; Akanda, All Shafqat; Akinyemi, Rufus Olusola; Akinyemiju, Tomi F.; Akseer, Nadia; Al Lami, Faris Hasan; Alabed, Samer; Al-Aly, Ziyad; Alam, Khurshid; Alam, Noore K. M.; Alasfoor, Deena; Aldhahri, Saleh Fahed; Aldridge, Robert William; Alegretti, Miguel Angel; Aleman, Alicia V.; Alemu, Zewdie Aderaw; Alexander, Lily T.; Alhabib, Samia; Ali, Raghib; Alkerwi, Ala'a; Alla, Francois; Allebeck, Peter; Al-Raddadi, Rajaa; Alsharif, Ubai; Altirkawi, Khalid A.; Martin, Elena Alvarez; Alvis-Guzman, Nelson; Amare, Azmeraw T.; Amegah, Adeladza Kofi; Ameh, Emmanuel A.; Amini, Heresh; Ammar, Walid; Amrock, Stephen Marc; Andersen, Hjalte H.; Anderson, Benjamin; Anderson, Gregory M.; Antonio, Carl Abelardo T.; Aregay, Atsede Fantahun; Arnlov, Johan; Arsenijevic, Valentina S. Arsic; Al Artaman, Ali; Asayesh, Hamid; Asghar, Rana Jawad; Atique, Suleman; Arthur Avokpaho, Euripide Frinel G.; Awasthi, Ashish; Azzopardi, Peter; Bacha, Umar; Badawi, Alaa; Bahit, Maria C.; Balakrishnan, Kalpana; Banerjee, Amitava; Barac, Aleksandra; Barker-Collo, Suzanne L.; Barnighausen, Till; Barregard, Lars; Barrero, Lope H.; Basu, Arindam; Basu, Sanjay; Bayou, Yibeltal Tebekaw; Bazargan-Hejazi, Shahrzad; Beardsley, Justin; Bedi, Neeraj; Beghi, Ettore; Belay, Haileeyesus Adamu; Bell, Brent; Bell, Michelle L.; Bello, Aminu K.; Bennett, Derrick A.; Bensenor, Isabela M.; Berhane, Adugnaw; Bernabe, Eduardo; Betsu, Balem Demtsu; Beyene, Addisu Shunu; Bhala, Neeraj; Bhalla, Ashish; Biadgilign, Sibhatu; Bikbov, Boris; Bin Abdulhak, Aref A.; Biroscak, Brian J.; Biryukov, Stan; Bjertness, Espen; Blore, Jed D.; Blosser, Christopher D.; Bohensky, Megan A.; Borschmann, Rohan; Bose, Dipan; Bourne, Rupert R. A.; Brainin, Michael; Brayne, Carol E. G.; Brazinova, Alexandra; Breitborde, Nicholas J. K.; Brenner, Hermann; Brewer, Jerry D.; Brown, Alexandria; Brown, Jonathan; Brugha, Traolach S.; Buckle, Geoffrey Colin; Butt, Zahid A.; Calabria, Bianca; Campos-Novato, Ismael Ricardo; Campuzano, Julio Cesar; Carapetis, Jonathan R.; Cardenas, Rosario; Carpenter, David; Carrero, Juan Jesus; Castaneda-Oquela, Carlos A.; Rivas, Jacqueline Castillo; Catala-Lopez, Ferran; Cavalleri, Fiorella; Cercy, Kelly; Cerda, Jorge; Chen, Wanqing; Chew, Adrienne; Chiang, Peggy Pei -Chia; Chibalabala, Mirriam; Chibueze, Chioma Ezinne; Chimed-Ochir, Odgerel; Chisumpa, Vesper Hichilombwe; Choi, Jee-Young Jasmine; Chowdhury, Rajiv; Christensen, Hanne; Christopher, Devasahayam Jesudas; Ciobanu, Liliana G.; Cirillo, Massimo; Cohen, Aaron J.; Colistro, Valentina; Colomar, Mercedes; Colquhoun, Samantha M.; Cooper, Cyrus; Cooper, Leslie Trumbull; Cortinovis, Monica; Cowie, Benjamin C.; Crump, John A.; Damsere-Derry, James; Danawi, Hadi; Dandona, Rakhi; Daoud, Farah; Darby, Sarah C.; Dargan, Paul I.; das Neves, Jose; Davey, Gail; Davis, Adrian C.; Davitoiu, Dragos V.; de Castro, E. Filipa; de Jager, Pieter; De Leo, Diego; Degenhardt, Louisa; Dellavalle, Robert P.; Deribe, Kebede; Deribew, Amare; Dharmaratne, Samath D.; Dhillon, Preet K.; Diaz-Torne, Cesar; Ding, Eric L.; dos Santos, Kadine Priscila Bender; Dossou, Edem; Driscoll, Tim R.; Duan, Leilei; Dubey, Manisha; Bartholow, Bruce; Ellenbogen, Richard G.; Lycke, Christian; Elyazar, Iqbal; Endries, Aman Yesuf; Ermakov, Sergey Petrovich; Eshrati, Babak; Esteghamati, Alireza; Estep, Kara; Faghmous, Imad D. A.; Fahimi, Saman; Jose, Emerito; Farid, Talha A.; Sa Farinha, Carla Sofia e; Faro, Andre; Farvid, Maryam S.; Farzadfar, Farshad; Feigin, Valery L.; Fereshtehnejad, Seyed-Mohammad; Fernandes, Jefferson G.; Fernandes, Joao C.; Fischer, Florian; Fitchett, Joseph R. A.; Flaxman, Abraham; Foigt, Nataliya; Fowkes, F. Gerry R.; Franca, Elisabeth Barboza; Franklin, Richard C.; Friedman, Joseph; Frostad, Joseph; Hirst, Thomas; Futran, Neal D.; Gall, Seana L.; Gambashidze, Ketevan; Gamkrelidze, Amiran; Ganguly, Parthasarathi; Gankpe, Fortune Gbetoho; Gebre, Teshome; Gebrehiwot, Tsegaye Tsewelde; Gebremedhin, Amanuel Tesfay; Gebru, Alemseged Aregay; Geleijnse, Johanna M.; Gessner, Bradford D.; Ghoshal, Aloke Gopal; Gibney, Katherine B.; Gillum, Richard F.; Gilmour, Stuart; Giref, Ababi Zergaw; Giroud, Maurice; Gishu, Melkamu Dedefo; Giussani, Giorgia; Glaser, Elizabeth; Godwin, William W.; Gomez-Dantes, Hector; Gona, Philimon; Goodridge, Amador; Gopalani, Sameer Vali; Gosselin, Richard A.; Gotay, Carolyn C.; Goto, Atsushi; Gouda, Hebe N.; Greaves, Felix; Gugnani, Harish Chander; Gupta, Rahul; Gupta, Rajeev; Gupta, Vipin; Gutierrez, Reyna A.; Hafezi-Nejad, Nima; Haile, Demewoz; Hailu, Alemayehu Desalegne; Hailu, Gessessew Bugssa; Halasa, Yara A.; Hamadeh, Randah Ribhi; Hamidi, Samer; Hancock, Jamie; Handal, Alexis J.; Hankey, Graeme J.; Hao, Yuantao; Harb, Hilda L.; Harikrishnan, Sivadasanpillai; Haro, Josep Maria; Havmoeller, Rasmus; Heckbert, Susan R.; Heredia-Pi, Ileana Beatriz; Heydarpour, Pouria; Hilderink, Henk B. M.; Hoek, Hans W.; Hogg, Robert S.; Horino, Masako; Horita, Nobuyuki; Hosgood, H. Dean; Hotez, Peter J.; Hoy, Damian G.; Hsairi, Mohamed; Htet, Aung Soe; Than Htike, Maung Maung; Hu, Guoqing; Huang, Cheng; Huang, Hsiang; Huiart, Laetitia; Husseini, Abdullatif; Huybrechts, Inge; Huynh, Grace; Iburg, Kim Moesgaard; Innos, Kaire; Inoue, Manami; Iyer, Veena J.; Jacobs, Troy A.; Jacobsen, Kathryn H.; Jahanmehr, Nader; Jakovljevic, Mihajlo B.; James, Peter; Javanbakht, Mehdi; Jayaraman, Sudha P.; Jayatilleke, Achala Upendra; Jeemon, Panniyammakal; Jensen, Paul N.; Jha, Vivekanand; Jiang, Guohong; Jiang, Ying; Jibat, Tariku; Jimenez-Corona, Aida; Jonas, Jost B.; Joshi, Tushar Kant; Kabir, Zubair; Karnak, Ritul; Kan, Haidong; Kant, Surya; Karch, Andre; Karema, Corine Kakizi; Karimkhani, Chante; Karletsos, Dimitris; Karthikeyan, Ganesan; Kasaeian, Amir; Katibeh, Marzieh; Kaul, Anil; Kawakami, Norito; Kayibanda, Jeanne Francoise; Keiyoro, Peter Njenga; Kemmer, Laura; Kemp, Andrew Haddon; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Kesavachandran, Chandrasekharan Nair; Khader, Yousef Saleh; Khalil, Ibrahim A.; Khan, Abdur Rahman; Khan, Ejaz Ahmad; Khang, Young-Ho; Khera, Sahil; Muthafer Khoja, Tawfik Ahmed; Kieling, Christian; Kim, Daniel; Kim, Yun Jin; Kissela, Brett M.; Kissoon, Niranjan; Knibbs, Luke D.; Knudsen, Ann Kristin; Kokubo, Yoshihiro; Kolte, Dhaval; Kopec, Jacek A.; Kosen, Soewarta; Koul, Parvaiz A.; Koyanagi, Ai; Krog, Norun Hjertager; Defo, Barthelemy Kuate; Bicer, Burcu Kucuk; Kudom, Andreas A.; Kuipers, Ernst J.; Kulkarni, Veena S.; Kumar, G. Anil; Kwan, Gene F.; Lal, Aparna; Lal, Dharmesh Kumar; Lalloo, Ratilal; Lam, Hilton; Lam, Jennifer O.; Langan, Sinead M.; Lansingh, Van C.; Larsson, Anders; Laryea, Dennis Odai; Latif, Asma Abdul; Lawrynowicz, Alicia Elena Beatriz; Leigh, James; Levi, Miriam; Li, Yongmei; Lindsay, M. Patrice; Lipshultz, Steven E.; Liu, Patrick Y.; Liu, Shiwei; Liu, Yang; Lo, Loon-Tzian; Logroscino, Giancarlo; Lotufo, Paulo A.; Lucas, Robyn M.; Lunevicius, Raimundas; Lyons, Ronan A.; Ma, Stefan; Pedro Machado, Vasco Manuel; Mackay, Mark T.; MacLachlan, Jennifer H.; Abd El Razek, Hassan Magdy; Abd El Razek, Mohammed Magdy; Majdan, Marek; Majeed, Azeem; Malekzadeh, Reza; Ayele Manamo, Wondimu Ayele; Mandisarisa, John; Mangalam, Srikanth; Mapoma, Chabila C.; Marcenes, Wagner; Margolis, David Joel; Martin, Gerard Robert; Martinez-Raga, Jose; Marzan, Melvin Barrientos; Masiye, Felix; Mason-Jones, Amanda J.; Massano, Joao; Matzopoulos, Richard; Mayosi, Bongani M.; McGarvey, Stephen Theodore; McGrath, John J.; Mckee, Martin; McMahon, Brian J.; Meaney, Peter A.; Mehari, Alem; Mehndiratta, Man Mohan; Mena-Rodriguez, Fabiola; Mekonnen, Alemayehu B.; Melaku, Yohannes Adama; Memiah, Peter; Memish, Ziad A.; Mendoza, Walter; Meretoja, Atte; Meretoja, Tuomo J.; Mhimbira, Francis Apolinary; Micha, Renata; Miller, Ted R.; Mirarefin, Mojde; Misganaw, Awoke; Mock, Charles N.; Abdulmuhsin Mohammad, Karzan; Mohammadi, Alireza; Mohammed, Shafiu; Mohan, Viswanathan; Mola, Glen Liddell D.; Monasta, Lorenzo; Montanez Hernandez, Julio Cesar; Montero, Pablo; Montico, Marcella; Montine, Thomas J.; Moradi-Lakeh, Maziar; Morawska, Lidia; Morgan, Katherine; Mori, Rintaro; Mozaffarian, Dariush; Mueller, Ulrich; Satyanarayana Murthy, Gudlavalleti Venkata; Murthy, Srinivas; Musa, Kamarul Imran; Nachega, Jean B.; Nagel, Gabriele; Naidoo, Kovin S.; Naik, Nitish; Naldi, Luigi; Nangia, Vinay; Nash, Denis; Nejjari, Chakib; Neupane, Subas; Newton, Charles R.; Newton, John N.; Ng, Marie; Ngalesoni, Frida Namnyak; Ngirabega, Jean de Dieu; Quyen Le Nguyen, [Unknown; Nisar, Muhammad Imran; Nkamedjie Pete, Patrick Martial; Nomura, Marika; Norheim, Ole F.; Norman, Paul E.; Norrving, Bo; Nyakarahuka, Luke; Ogbo, Felix Akpojene; Ohkubo, Takayoshi; Ojelabi, Foluke Adetola; Olivares, Pedro R.; Olusanya, Bolajoko Olubukunola; Olusanya, Jacob Olusegun; Opio, John Nelson; Oren, Eyal; Ortiz, Alberto; Osman, Majdi; Ota, Erika; Ozdemir, Raziye; Pa, Mahesh; Pandian, Jeyaraj D.; Pant, Puspa Raj; Papachristou, Christina; Park, Eun-Kee; Park, Jae-Hyun; Parry, Charles D.; Parsaeian, Mahboubeh; Caicedo, Angel J. Paternina; Patten, Scott B.; Patton, George C.; Paul, Vinod K.; Pearce, Neil; Pedro, Joao Mario; Stokic, Ljiljana Pejin; Pereira, David M.; Perico, Norberto; Pesudovs, Konrad; Petzold, Max; Phillips, Michael Robert; Piel, Frederic B.; Pillay, Julian David; Plass, Dietrich; Platts-Mills, James A.; Polinder, Suzanne; Pope, C. Arden; Popova, Svetlana; Poulton, Richie G.; Pourmalek, Farshad; Prabhakaran, Dorairaj; Qorbani, Mostafa; Quame-Amaglo, Justice; Quistberg, D. Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Mahfuzar; Rahman, Mohammad Hifz Ur; Rahman, Sajjad Ur; Rai, Rajesh Kumar; Rajavi, Zhale; Rajsic, Sasa; Raju, Murugesan; Rakovac, Ivo; Rana, Saleem M.; Ranabhat, Chhabi L.; Rangaswamy, Thara; Rao, Puja; Rao, Sowmya R.; Refaat, Amany H.; Rehm, Jurgen; Reitsma, Marissa B.; Remuzzi, Giuseppe; Resnikofff, Serge; Ribeiro, Antonio L.; Ricci, Stefano; Blancas, Maria Jesus Rios; Roberts, Bayard; Roca, Anna; Rojas-Rueda, David; Ronfani, Luca; Roshandel, Gholamreza; Rothenbacher, Dietrich; Roy, Ambuj; Roy, Nawal K.; Ruhago, George Mugambage; Sagar, Rajesh; Saha, Sukanta; Sahathevan, Ramesh; Saleh, Muhammad Muhammad; Sanabria, Juan R.; Sanchez-Nino, Maria Dolores; Sanchez-Riera, Lidia; Santos, Itamar S.; Sarmiento-Suarez, Rodrigo; Sartorius, Benn; Satpathy, Maheswar; Savic, Miloje; Sawhney, Monika; Schaub, Michael P.; Schmidt, Maria Ines; Schneider, Ione J. C.; Schottker, Ben; Schutte, Aletta E.; Schwebel, David C.; Seedat, Soraya; Sepanlou, Sadaf G.; Servan-Mori, Edson E.; Shackelford, Katya A.; Shaddick, Gavin; Shaheen, Amira; Shahraz, Saeid; Shaikh, Masood Ali; Shakh-Nazarova, Marina; Sharma, Rajesh; She, Jun; Sheikhbahaei, Sara; Shen, Jiabin; Shen, Ziyan; Shepard, Donald S.; Sheth, Kevin N.; Shetty, Balakrishna P.; Shi, Peilin; Shibuya, Kenji; Shin, Min-Jeong; Shiri, Rahman; Shiue, Ivy; Shrime, Mark G.; Sigfusdottir, Inga Dora; Silberberg, Donald H.; Silva, Diego Augusto Santos; Silveira, Dayane Gabriele Alves; Silverberg, Jonathan I.; Simard, Edgar P.; Singh, Abhishek; Singh, Gitanjali M.; Singh, Jasvinder A.; Singh, Om Prakash; Singh, Prashant Kumar; Singh, Virendra; Soneji, Samir; Soreide, Kjetil; Soriano, Joan B.; Sposato, Luciano A.; Sreeramareddy, Chandrashekhar T.; Stathopoulou, Vasiliki; Stein, Dan J.; Stein, Murray B.; Stranges, Saverio; Stroumpoulis, Konstantinos; Sunguya, Bruno F.; Sur, Patrick; Swaminathan, Soumya; Sykes, Bryan L.; Szoeke, Cassandra E. I.; Tabares-Seisdedos, Rafael; Tabb, Karen M.; Takahashi, Ken; Takala, Jukka S.; Talongwa, Roberto Tchio; Tandon, Nikhil; Tavakkoli, Mohammad; Taye, Bineyam; Taylor, Hugh R.; Ao, Braden J. Te; Tedla, Bemnet Amare; Tefera, Worku Mekonnen; Ten Have, Margreet; Terkawi, Abdullah Sulieman; Tesfay, Fisaha Haile; Tessema, Gizachew Assefa; Thomson, Alan J.; Thorne-Lyman, Andrew L.; Thrift, Amanda G.; Thurston, George D.; Tillmann, Taavi; Tirschwell, David L.; Tonelli, Marcello; Topor-Madry, Roman; Topouzis, Fotis; Nx, Jeffrey Allen Towb; Traebert, Jefferson; Tran, Bach Xuan; Truelsen, Thomas; Trujillo, Ulises; Tura, Abera Kenay; Tuzcu, Emin Murat; Uchendu, Uche S.; Ukwaja, Kingsley N.; Undurraga, Eduardo A.; Uthman, Olalekan A.; Van Dingenen, Rita; Van Donkelaar, Aaron; Vasankari, Tommi; Vasconcelos, Ana Maria Nogales; Venketasubramanian, Narayanaswamy; Vidavalur, Ramesh; Vijayakumar, Lakshmi; Villalpando, Salvador; Violante, Francesco S.; Vlassov, Vasiliy Victorovich; Wagner, Joseph A.; Wagner, Gregory R.; Wallin, Mitchell T.; Wang, Linhong; Watkins, David A.; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G.; Werdecker, Andrea; Westerman, Ronny; White, Richard A.; Wijeratne, Tissa; Wilkinson, James D.; Williams, Hywel C.; Wiysonge, Charles Shey; Woldeyohannes, Solomon Meseret; Wolfe, Charles D. A.; Won, Sungho; Wong, John Q.; Woolf, Anthony D.; Xavier, Denis; Xiao, Qingyang; Xu, Gelin; Yakob, Bereket; Yalew, Ayalnesh Zemene; Yan, Lijing L.; Yano, Yuichiro; Yaseri, Mehdi; Ye, Pengpeng; Yebyo, Henock Gebremedhin; Yip, Paul; Yirsaw, Biruck Desalegn; Yonemoto, Naohiro; Yonga, Gerald; Younis, Mustafa Z.; Yu, Shicheng; Zaidi, Zoubida; Zaki, Maysaa El Sayed; Zannad, Faiez; Zavala, Diego E.; Zeeb, Hajo; Zeleke, Berihun M.; Zhang, Hao; Zodpey, Sanjay; Zonies, David; Zuhlke, Liesl Joanna; Vos, Theo; Lopez, Alan D.; Murray, Christopher J. L.

    2016-01-01

    Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes

  11. Distribution of clinical phenotypes in patients with chronic obstructive pulmonary disease caused by biomass and tobacco smoke.

    Science.gov (United States)

    Golpe, Rafael; Sanjuán López, Pilar; Cano Jiménez, Esteban; Castro Añón, Olalla; Pérez de Llano, Luis A

    2014-08-01

    Exposure to biomass smoke is a risk factor for chronic obstructive pulmonary disease (COPD). It is unknown whether COPD caused by biomass smoke has different characteristics to COPD caused by tobacco smoke. To determine clinical differences between these two types of the disease. Retrospective observational study of 499 patients with a diagnosis of COPD due to biomass or tobacco smoke. The clinical variables of both groups were compared. There were 122 subjects (24.4%) in the biomass smoke group and 377 (75.5%) in the tobacco smoke group. In the tobacco group, the percentage of males was higher (91.2% vs 41.8%, P<.0001) and the age was lower (70.6 vs 76.2 years, P<.0001). Body mass index and FEV1% values were higher in the biomass group (29.4±5.7 vs 28.0±5.1, P=.01, and 55.6±15.6 vs 47.1±17.1, P<.0001, respectively). The mixed COPD-asthma phenotype was more common in the biomass group (21.3% vs 5%, P<.0001), although this difference disappeared when corrected for gender. The emphysema phenotype was more common in the tobacco group (45.9% vs 31.9%, P=.009). The prevalence of the chronic bronchitis and exacerbator phenotypes, the comorbidity burden and the rate of hospital admissions were the same in both groups. Differences were observed between COPD caused by biomass and COPD caused by tobacco smoke, although these may be attributed in part to uneven gender distribution between the groups. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  12. Acute pelvic inflammatory disease as a rare cause of acute small bowel obstruction.

    Science.gov (United States)

    Haumann, Alexandre; Ongaro, Sarah; Detry, Olivier; Meunier, Paul; Meurisse, Michel

    2018-03-21

    Small bowel obstruction (SBO) is a common presentation to emergency abdominal surgery. The most frequent causes of SBO are congenital, postoperative adhesions, abdominal wall hernia, internal hernia and malignancy. A 27-year-old woman was hospitalized because of acute abdominal pain, blockage of gases and stools associated with vomiting. Abdominal computed tomography showed an acute small bowel obstruction without any obvious etiology. In view of important abdominal pain and the lack of clear diagnosis, an explorative laparoscopy was performed. Diagnostic of pelvic inflammatory disease was established and was comforted by positive PCR for Chlamydia Trachomatis. Acute small bowel obstruction resulting from acute pelvic inflammatory disease, emerging early after infection, without any clinical or X-ray obvious signs was not described in the literature yet. This infrequent acute SBO etiology but must be searched especially when there is no other evident cause of obstruction in female patients. Early laparoscopy is mostly advised when there are some worrying clinical or CT scan signs.

  13. No Reported Species, Botrytis aclada Causing Gray Mold Neck Rot Disease on Onion Bulbs in Korea

    OpenAIRE

    Hwang, Sun–Kyoung; Lee, Seung–Yeol; Back, Chang–Gi; Kang, In–Kyu; Lee, Hyang–Burm; Jung, Hee-Young; Ohga, Shoji; Oga, Shoji

    2016-01-01

    Gray mold neck rot was observed on onion bulbs (Allium cepa L.) in low–temperature warehouses in Changnyeong–gun, Korea. The causative pathogen was isolated from rotted onion bulb lesions and identified as Botrytis aclada based on morphological and culture characteristics, the sequences of three nuclear genes (G3PDH, HSP60, and RPB2), and polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) for Botrytis spp. identification. Although onion gray mold disease caused by B...

  14. The role of positive selection in determining the molecular cause of species differences in disease

    Directory of Open Access Journals (Sweden)

    Foord Steven M

    2008-10-01

    Full Text Available Abstract Background Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. Results We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog. We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Conclusion Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences

  15. Clinical Signs, Causes, and Risk Factors of Pediatric Chronic Kidney Diseases: a Hospital-based Case-control Study

    Directory of Open Access Journals (Sweden)

    Parsa Yousefichaijan

    2016-06-01

    Full Text Available Background This retrospective study aimed to determine the epidemiologic characteristics and risk factors of chronic kidney diseases (CKD in patients < 18 years old at a single referral center. Materials and Methods In a hospital-based case control study, 66 CKD patients less than 18 years old were compared to 81 control patients (also under 18 without CKD. A patient was defined as a CKD case with renal injury and/or had a glomerular filtration rate (GFR of Results Fever, chills, and urinary tract infections were the most common clinical signs in the referred patients. Urinary tract infection (39.5% and growth failure (12.9% were the most important causes in referred pediatric CKD. After controlling the effect of confounding variables, household income, using packed water for drinking, percentile of body mass index (BMI, and gestational age were the significant predictors of pediatric CKD (P

  16. Simulation study of the mechanisms underlying outbreaks of clinical disease caused by Actinobacillus pleuropneumoniae in finishing pigs

    NARCIS (Netherlands)

    Klinkenberg, D; Tobias, T J; Bouma, A; van Leengoed, L A M G; Stegeman, J A

    2014-01-01

    Actinobacillus pleuropneumoniae is a major cause of respiratory disease in pigs. Many farms are endemically infected without apparent disease, but occasionally severe outbreaks of pleuropneumonia occur. To prevent and control these outbreaks without antibiotics, the underlying mechanisms of these

  17. Variability in Cadence During Forced Cycling Predicts Motor Improvement in Individuals With Parkinson’s Disease

    Science.gov (United States)

    Ridgel, Angela L.; Abdar, Hassan Mohammadi; Alberts, Jay L.; Discenzo, Fred M.; Loparo, Kenneth A.

    2014-01-01

    Variability in severity and progression of Parkinson’s disease symptoms makes it challenging to design therapy interventions that provide maximal benefit. Previous studies showed that forced cycling, at greater pedaling rates, results in greater improvements in motor function than voluntary cycling. The precise mechanism for differences in function following exercise is unknown. We examined the complexity of biomechanical and physiological features of forced and voluntary cycling and correlated these features to improvements in motor function as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Heart rate, cadence, and power were analyzed using entropy signal processing techniques. Pattern variability in heart rate and power were greater in the voluntary group when compared to forced group. In contrast, variability in cadence was higher during forced cycling. UPDRS Motor III scores predicted from the pattern variability data were highly correlated to measured scores in the forced group. This study shows how time series analysis methods of biomechanical and physiological parameters of exercise can be used to predict improvements in motor function. This knowledge will be important in the development of optimal exercise-based rehabilitation programs for Parkinson’s disease. PMID:23144045

  18. Evidence for Autoinduction and Quorum Sensing in White Band Disease-Causing Microbes on Acropora cervicornis

    Science.gov (United States)

    Certner, Rebecca H.; Vollmer, Steven V.

    2015-06-01

    Coral reefs have entered a state of global decline party due to an increasing incidence of coral disease. However, the diversity and complexity of coral-associated bacterial communities has made identifying the mechanisms underlying disease transmission and progression extremely difficult. This study explores the effects of coral cell-free culture fluid (CFCF) and autoinducer (a quorum sensing signaling molecule) on coral-associated bacterial growth and on coral tissue loss respectively. All experiments were conducted using the endangered Caribbean coral Acropora cervicornis. Coral-associated microbes were grown on selective media infused with CFCF derived from healthy and white band disease-infected A. cervicornis. Exposure to diseased CFCF increased proliferation of Cytophaga-Flavobacterium spp. while exposure to healthy CFCF inhibited growth of this group. Exposure to either CFCF did not significantly affect Vibrio spp. growth. In order to test whether disease symptoms can be induced in healthy corals, A. cervicornis was exposed to bacterial assemblages supplemented with exogenous, purified autoinducer. Incubation with autoinducer resulted in complete tissue loss in all corals tested in less than one week. These findings indicate that white band disease in A. cervicornis may be caused by opportunistic pathogenesis of resident microbes.

  19. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71.

    Science.gov (United States)

    Zhang, Yu-Feng; Deng, Hui-Ling; Fu, Jia; Zhang, Yu; Wei, Jian-Qiang

    2016-02-14

    Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.

  20. Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide.

    Science.gov (United States)

    Bian, Lianlian; Wang, Yiping; Yao, Xin; Mao, Qunying; Xu, Miao; Liang, Zhenglun

    2015-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the predominant pathogens causing outbreaks of hand, foot and mouth disease (HFMD) worldwide. Other human enterovirus A (HEV-A) serotypes tend to cause only sporadic HFMD cases. However, since a HFMD caused by coxsackievirus A6 broke out in Finland in 2008, CA6 has been identified as the responsible pathogen for a series of HFMD outbreaks in Europe, North America and Asia. Because of the severity of the clinical manifestations and the underestimated public health burden, the epidemic of CA6-associated HFMD presents a new challenge to the control of HFMD. This article reviewed the epidemic characteristics, molecular epidemiology, clinical features and laboratory diagnosis of CA6 infection. The genetic evolution of CA6 strains associated with HFMD was also analyzed. It indicated that the development of a multivalent vaccine combining EV71, CA16 and CA6 is an urgent necessity to control HFMD.

  1. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study.

    Science.gov (United States)

    Raaschou-Nielsen, Ole; Andersen, Zorana Jovanovic; Jensen, Steen Solvang; Ketzel, Matthias; Sørensen, Mette; Hansen, Johnni; Loft, Steffen; Tjønneland, Anne; Overvad, Kim

    2012-09-05

    Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993-1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO₂) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders. Mean levels of NO₂ at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06-1.51, per doubling of NO₂ concentration) and all causes (MRR, 1.13; 95% CI, 1.04-1.23, per doubling of NO₂ concentration) after adjustment for potential confounders. For participants who ate causes. Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.

  2. Landscape of Pleiotropic Proteins Causing Human Disease: Structural and System Biology Insights.

    Science.gov (United States)

    Ittisoponpisan, Sirawit; Alhuzimi, Eman; Sternberg, Michael J E; David, Alessia

    2017-03-01

    Pleiotropy is the phenomenon by which the same gene can result in multiple phenotypes. Pleiotropic proteins are emerging as important contributors to rare and common disorders. Nevertheless, little is known on the mechanisms underlying pleiotropy and the characteristic of pleiotropic proteins. We analyzed disease-causing proteins reported in UniProt and observed that 12% are pleiotropic (variants in the same protein cause more than one disease). Pleiotropic proteins were enriched in deleterious and rare variants, but not in common variants. Pleiotropic proteins were more likely to be involved in the pathogenesis of neoplasms, neurological, and circulatory diseases and congenital malformations, whereas non-pleiotropic proteins in endocrine and metabolic disorders. Pleiotropic proteins were more essential and had a higher number of interacting partners compared with non-pleiotropic proteins. Significantly more pleiotropic than non-pleiotropic proteins contained at least one intrinsically long disordered region (P human disease. They represent a biologically different class of proteins compared with non-pleiotropic proteins and a better understanding of their characteristics and genetic variants can greatly aid in the interpretation of genetic studies and drug design. © 2016 WILEY PERIODICALS, INC.

  3. Epidemiology and Control of Strawberry Bacterial Angular Leaf Spot Disease Caused by Xanthomonas fragariae

    Directory of Open Access Journals (Sweden)

    Da-Ran Kim

    2016-08-01

    Full Text Available Strawberry bacterial angular leaf spot (ALS disease, caused by Xanthomonas fragariae has become increasingly problematic in the strawberry agro-industry. ALS causes small angular water-soaked lesions to develop on the abaxial leaf surface. Studies reported optimum temperature conditions for X. fragariae are 20°C and the pathogen suffers mortality above 32°C. However, at the nursery stage, disease symptoms have been observed under high temperature conditions. In the present study, results showed X. fragariae transmission was via infected maternal plants, precipitation, and sprinkler irrigation systems. Systemic infections were detected using X. fragariae specific primers 245A/B and 295A/B, where 300-bp and 615-bp were respectively amplified. During the nursery stage (from May to August, the pathogen was PCR detected only in maternal plants, but not in soil or irrigation water through the nursery stage. During the cultivation period, from September to March, the pathogen was detected in maternal plants, progeny, and soil, but not in water. Additionally, un-infected plants, when planted with infected plants were positive for X. fragariae via PCR at the late cultivation stage. Chemical control for X. fragariae with oxolinic acid showed 87% control effects against the disease during the nursery period, in contrast to validamycin-A, which exhibited increased efficacy against the disease during the cultivation stage (control effect 95%. To our knowledge, this is the first epidemiological study of X. fragariae in Korean strawberry fields.

  4. A derangement of the brain wound healing process may cause some cases of Alzheimer's disease.

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2016-08-01

    A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process.

  5. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease : a report of the Surgeon General

    National Research Council Canada - National Science Library

    2010-01-01

    .... This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke...

  6. [Body composition and heart rate variability in patients with chronic obstructive pulmonary disease pulmonary rehabilitation candidates].

    Science.gov (United States)

    Curilem Gatica, Cristian; Almagià Flores, Atilio; Yuing Farías, Tuillang; Rodríguez Rodríguez, Fernando

    2014-07-01

    Body composition is a non-invasive method, which gives us information about the distribution of tissues in the body structure, it is also an indicator of the risk of mortality in patients with chronic obstructive pulmonary disease. The heart rate variability is a technique that gives us information of autonomic physiological condition, being recognized as an indicator which is decreased in a number of diseases. The purpose of this study was to assess body composition and heart rate variability. The methodology used is that of Debora Kerr (1988) endorsed by the International Society for advances in Cineantropometría for body composition and heart rate variability of the guidelines described by the American Heart Association (1996). Roscraff equipment, caliper Slimguide and watch Polar RS 800CX was used. , BMI 26.7 ± 3.9 kg / m²; Muscle Mass 26.1 ± 6.3 kg ; Bone Mass 1.3 kg ± 8.1 76 ± 9.9 years Age : 14 candidates for pulmonary rehabilitation patients were evaluated , Adipose mass 16.4 ± 3.6 kg ; FEV1 54 ± 14%. Increased waist circumference and waist hip ratio was associated with a lower overall heart rate variability. The bone component was positively related to the variability of heart rate and patients with higher forced expiratory volume in one second had lower high frequency component in heart rate variability. In these patients, the heart rate variability is reduced globally and is associated with cardiovascular risk parameters. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  7. Prognostic value of the oxygen uptake efficiency slope and other exercise variables in patients with coronary artery disease.

    Science.gov (United States)

    Coeckelberghs, Ellen; Buys, Roselien; Goetschalckx, Kaatje; Cornelissen, Véronique A; Vanhees, Luc

    2016-02-01

    Peak exercise capacity is an independent predictor for mortality in patients with coronary artery disease. However, sometimes cardiopulmonary exercise tests are stopped prematurely. Therefore, submaximal exercise measures such as the oxygen uptake efficiency slope have been introduced. The aim of this study was to assess the prognostic value of the oxygen uptake efficiency slope and other exercise parameters, in patients with coronary artery disease. Between 2000 and 2011, 1409 patients with coronary artery disease (age 60.7 ± 9.9 years; 1205 males) underwent cardiopulmonary exercise tests. A maximal effort was not reached in 161 (11.5%) patients. The oxygen uptake efficiency slope was calculated and information on mortality was obtained. Cox proportional hazards regression analyses were used to assess the relation of oxygen uptake efficiency slope and other gas exchange variables with all-cause and cardiovascular mortality. Receiver operating characteristic curve analyses was performed to define optimal cut-off values. During an average follow-up of 7.45 ± 3.20 years (range 0.16-13.95 years), 158 patients died, among which 68 patients for cardiovascular reasons. The oxygen uptake efficiency slope was related to all-cause (hazard ratio: 0.568, p exercise parameters were added to the model, oxygen uptake efficiency slope and minute ventilation/carbon dioxide production slope also remained significantly related to mortality. The oxygen uptake efficiency slope is an independent predictor for all-cause and cardiovascular mortality in patients with coronary artery disease, irrespective of a truly maximal effort during cardiopulmonary exercise tests. Furthermore, the oxygen uptake efficiency slope provides prognostic information, complementary to the minute ventilation/carbon dioxide production slope and peak exercise capacity. © The European Society of Cardiology 2015.

  8. Fitness, work, and leisure-time physical activity and ischaemic heart disease and all-cause mortality among men with pre-existing cardiovascular disease

    DEFF Research Database (Denmark)

    Holtermann, Andreas; Mortensen, Ole Steen; Burr, Hermann

    2010-01-01

    Our aim was to study the relative impact of physical fitness, physical demands at work, and physical activity during leisure time on ischaemic heart disease (IHD) and all-cause mortality among employed men with pre-existing cardiovascular disease (CVD).......Our aim was to study the relative impact of physical fitness, physical demands at work, and physical activity during leisure time on ischaemic heart disease (IHD) and all-cause mortality among employed men with pre-existing cardiovascular disease (CVD)....

  9. Immunodeficiencies and autoimmune diseases: common variable immunodeficiency and Crohn-like

    Directory of Open Access Journals (Sweden)

    Cristina Saldaña-Dueñas

    Full Text Available Background: Common variable immunodeficiency (CVI gives a major risk of principally respiratory and digestive infections. It is associated with autoimmune diseases, granulomatous process and neoplasias. The digestive clinic is common, in 10% of patients it is the only symptom, and 60% present chronic diarrhea. Clinically it can be confused and related with other pathologies such as inflammatory bowel disease which is infrequent (2-13%. Case report: We present the case of a patient with CVI with digestive symptoms being diagnosed of Crohn-like disease with extent ileal affectation. The main treatment of these patients is the same as classical Crohn disease although in the most severe cases, as this one, the use of immunosupresors is necessary. At this time the patient remains on clinical remmision with infliximab. She presented a previous adverse reaction with adalimumab. Discussion: The few case series in this pathology makes the treatment with immunomodulators in this immunodeficiency a real diagnostic and therapeutic challenge.

  10. Napier grass stunt disease prevalence, incidence, severity and genetic variability of the associated phytoplasma in Uganda

    DEFF Research Database (Denmark)

    Kawube, Geofrey; Talwana, Herbert; Nicolaisen, Mogens

    2015-01-01

    The prevalence, incidence and severity of Napier grass stunt disease (NGSD) caused by phytoplasma on Pennisetum purpureum, the main fodder for livestock under intensive and semi-intensive management systems in Uganda were determined following a field survey carried out in 17 districts. A total of...

  11. Prognostic value of biochemical variables for survival after surgery for metastatic bone disease of the extremities.

    Science.gov (United States)

    Sørensen, Michala Skovlund; Hovgaard, Thea Bechman; Hindsø, Klaus; Petersen, Michael Mørk

    2017-03-01

    Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables. In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C-reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses. Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 10 9 /L, neutrophil 5.68 × 10 9 /L, lymphocyte 1.37 × 10 9 /L, C-reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors. We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex. © 2016 Wiley Periodicals, Inc.

  12. Climate variability, weather and enteric disease incidence in New Zealand: time series analysis.

    Directory of Open Access Journals (Sweden)

    Aparna Lal

    Full Text Available BACKGROUND: Evaluating the influence of climate variability on enteric disease incidence may improve our ability to predict how climate change may affect these diseases. OBJECTIVES: To examine the associations between regional climate variability and enteric disease incidence in New Zealand. METHODS: Associations between monthly climate and enteric diseases (campylobacteriosis, salmonellosis, cryptosporidiosis, giardiasis were investigated using Seasonal Auto Regressive Integrated Moving Average (SARIMA models. RESULTS: No climatic factors were significantly associated with campylobacteriosis and giardiasis, with similar predictive power for univariate and multivariate models. Cryptosporidiosis was positively associated with average temperature of the previous month (β =  0.130, SE =  0.060, p <0.01 and inversely related to the Southern Oscillation Index (SOI two months previously (β =  -0.008, SE =  0.004, p <0.05. By contrast, salmonellosis was positively associated with temperature (β  = 0.110, SE = 0.020, p<0.001 of the current month and SOI of the current (β  = 0.005, SE = 0.002, p<0.050 and previous month (β  = 0.005, SE = 0.002, p<0.05. Forecasting accuracy of the multivariate models for cryptosporidiosis and salmonellosis were significantly higher. CONCLUSIONS: Although spatial heterogeneity in the observed patterns could not be assessed, these results suggest that temporally lagged relationships between climate variables and national communicable disease incidence data can contribute to disease prediction models and early warning systems.

  13. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  14. Cancer in Machado-Joseph disease patients-low frequency as a cause of death.

    Science.gov (United States)

    Souza, Gabriele Nunes; Kersting, Nathália; Gonçalves, Thomaz Abramsson; Pacheco, Daphne Louise Oliveira; Saraiva-Pereira, Maria-Luiza; Camey, Suzi Alves; Saute, Jonas Alex Morales; Jardim, Laura Bannach

    2017-04-01

    Since polyglutamine diseases have been related to a reduced risk of cancer, we aimed to study the 15 years cumulative incidence of cancer (CIC) (arm 1) and the proportion of cancer as a cause of death (arm 2) in symptomatic carriers of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). SCA3/MJD and control individuals from our state were invited to participate. A structured interview was performed. CIC as published by the Brazilian National Institute of Cancer, was used as populational control. Causes of death were obtained from the Public Information System on Mortality. We interviewed 154 SCA3/MJD patients and 80 unrelated controls: CIC was 7/154 (4.5%) and 5/80 (6.3%), respectively. The interim analysis for futility showed that the number of individuals required to detect a significant difference between groups (1938) would be three times larger than the existing local SCA3/MJD population (625), for an absolute risk reduction of 1.8%. Then this study arm was discontinued due to lack of power. In the same period, cancer was a cause of death in 9/101 (8.9%) SCA3/MJD and in 52/202 (26.2%) controls, with an absolute reduction risk of 17.3% (OR 0.27, 95%CI 0.13 to 0.58, p = 0.01). A significant reduction of cancer as cause of death was observed in SCA3/MJD, suggesting a common effect to all polyglutamine diseases. Copyright © 2017. Published by Elsevier Inc.

  15. Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 2012.

    Science.gov (United States)

    Säll, O; Stenmark, B; Glimåker, M; Jacobsson, S; Mölling, P; Olcén, P; Fredlund, H

    2017-07-01

    Over the period 1995-2012, the incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y (NmY) increased significantly in Sweden. This is mainly due to the emergence of a predominant cluster named strain type YI subtype 1, belonging to the ST-23 clonal complex (cc). The aim of this study was to examine the clinical picture of patients with invasive disease caused by NmY and to analyse whether the predominant cluster exhibits certain clinical characteristics that might explain the increased incidence. In this retrospective observational study, the medical records available from patients with IMD caused by Nm serogroup Y in Sweden between 1995 and 2012 were systematically reviewed. Patient characteristics, in-hospital findings and outcome were studied and differences between the dominating cluster and other isolates were analysed. Medical records from 175 of 191 patients were retrieved. The median age was 62 years. The all-cause mortality within 30 days of admission was 9% (15/175) in the whole material; 4% (2/54) in the cohort with strain type YI subtype 1 and 11% (12/121) among patients with other isolates. Thirty-three per cent of the patients were diagnosed with meningitis, 19% with pneumonia, 10% with arthritis and 35% were found to have bacteraemia but no apparent organ manifestation. This survey included cases with an aggressive clinical course as well as cases with a relatively mild clinical presentation. There was a trend towards lower mortality and less-severe disease in the cohort with strain type YI subtype 1 compared with the group with other isolates.

  16. High phenotypic variability in Gerstmann-Sträussler-Scheinker disease

    Directory of Open Access Journals (Sweden)

    Jerusa Smid

    Full Text Available ABSTRACT Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

  17. [Disease burden caused by suicide in the Chinese population, in 1990 and 2013].

    Science.gov (United States)

    Gao, X; Wang, L H; Jin, Y; Ye, P P; Yang, L; Er, Y L; Deng, X; Wang, Y; Duan, L L

    2017-10-10

    Objective: To provide basic suicide prevention strategy through analyzing the disease burden of suicide in the Chinese population, in 1990 and 2013. Methods: Indicators including mortality rate, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted of life years (DALY) on suicide, were from the results of Global Burden of Disease 2013 and used to describe the burden of disease caused by suicide in Chinese population. Data described the disease burden of suicide in China by comparing the corresponding parameters in 1990 and 2013. Results: In 2013, the standard mortality on suicide was 9.08 per 100 000, and 73.39 per 100 000 in the 80 and above year-old, with the highest rates on DALY and YLL seen in the 75-79-year-old. Each parameter related to suicide burden in males appeared higher than that in females. Compare to data in the 1990s, these parameters declined in 2013, especially seen in females. The rate of YLLs/YLDs on suicide was 90.03 in 2013, 89.83 in males and 89.00 in females. Conclusion: The disease burden of suicide decreased sharply between 1990 and 2013 but was still a serious issue in the elderly that called for more attention.

  18. Intravenous Immunoglobulin Monotherapy for Granulomatous Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

    Science.gov (United States)

    Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko

    2017-11-01

    Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

  19. Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission.

    Science.gov (United States)

    Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet

    2015-01-01

    Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

  20. Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata

    Science.gov (United States)

    Oliveira, Leonardo S. S.; Alfenas, Acelino C.; Neven, Lisa G.; Al-Sadi, Abdullah M.

    2016-01-01

    The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs. PMID:27415625

  1. Self-reported habitual snoring and risk of cardiovascular disease and all-cause mortality.

    Science.gov (United States)

    Li, Dongmei; Liu, Debao; Wang, Xiuming; He, Dongdong

    2014-07-01

    Inconsistent findings have reported the association between self-reported habitual snoring and risk of cardiovascular disease (CVD) and all-cause mortality. We conducted a meta-analysis to investigate whether self-reported habitual snoring was an independent predictor for CVD and all-cause mortality using prospective observational studies. Electronic literature databases (PubMed, Medline, Embase, Cochrane Library, Wanfang database, and China National Knowledge Infrastructure) were searched for publications prior to September 2013. Only prospective studies evaluating baseline habitual snoring and subsequent risk of CVD and all-cause mortality were selected. Pooled adjust hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates. Eight studies with 65,037 subjects were analyzed. Pooled adjust HR was 1.26 (95% CI 0.98-1.62) for CVD, 1.15 (95% CI 1.05-1.27) for coronary heart disease (CHD), and 1.26 (95% CI 1.11-1.43) for stroke comparing habitual snoring to non-snorers. Pooled adjust HR was 0.98 (95% CI 0.78-1.23) for all-cause mortality in a random effect model comparing habitual snoring to non-snorers. Habitual snoring appeared to increase greater stroke risk among men (HR 1.54; 95% CI: 1.09-2.17) than those in women (HR 1.22; 95% CI: 1.05-1.41). Self-reported habitual snoring is a mild but statistically significant risk factor for stroke and CHD, but not for CVD and all-cause mortality. However, whether the risk is attributable to obstructive sleep apnea syndrome or snoring alone remains controversial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Biliary diseases as main causes of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.

    Science.gov (United States)

    Shi, Shao-Hua; Feng, Xiao-Ning; Lai, Ming-Chun; Kong, Hai-Shen; Zheng, Shu-Sen

    2017-05-01

    Little is known about aetiology and morbidity and clinical characteristics of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. An analysis between pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates and those caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae was performed. Among 817 pyogenic liver abscess patients, there were 176 patients (21.5%) with pyogenic liver abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (mainly Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess patients related to biliary disorders, there were 48 pyogenic liver abscess patients (27.3%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by Enterobacteriaceae expressing extended-spectrum beta-lactamases, the occurrences of 48 pyogenic liver abscess patients (71.6%) were associated with biliary disorders. When compared with pyogenic liver abscess patients caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae, there were significantly greater incidences of polymicrobial infections, bacteremia, pulmonary infection, recurrence and death in pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Carbapenems remain mainstay drugs against extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae. Independent risk factors for occurrence of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae were biliary disorders including extra- and intrahepatic cholangiolithiasis and an abnormal bilioenteric communication between bile and gut, a treatment history of malignancy such as operation and chemotherapy, pulmonary infection, and diabetes mellitus

  3. Clinical analysis of 22 patients with hepatobiliary disease caused by liver fluke

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    ZHANG Hui

    2013-07-01

    Full Text Available ObjectiveTo clinically analyze the hepatobiliary disease caused by the liver fluke and to increase the knowledge of this disease and reduce misdiagnosis. MethodsA retrospective analysis was performed on the clinical data of 22 patients who had a confirmed diagnosis of clonorchiasis after being admitted to our hospital due to hepatobiliary disease over the past 20 years. ResultsOf the 22 patients, who had a mean age of 45.41 years, 19 were males, and 3 were females. When admitted to the hospital, 8 cases were diagnosed with cholecystitis or gallstones, 7 cases with clonorchiasis, and 7 cases with other diseases. Alanine aminotransferase elevation was found in 14 cases (6363%, aspartate aminotransferase elevation in 16 cases (72.72%, total bilirubin elevation in 11 cases (5000%, gamma-glutamyl transpeptidase elevation in 17 cases (77.27%, and increased eosinophils in 14 cases (63.63%. Ten cases (45.45% were diagnosed by fecal examination, 7 cases (31.82% by bile smears, 2 cases (9.09% by liver fluke antibody detection, and 3 cases (1364% according to the history of clonorchiasis. Deworming and comprehensive treatment produced a good outcome in these patients. ConclusionClonorchiasis is endemic and clinically rare, without specific clinical features, and it is easily confused with other hepatobiliary diseases, resulting in a high rate of misdiagnosis. Therefore, for the patients with abdominal pain, jaundice, and liver damage of unknown causes, we should inquire whether they or their family have a special dietary history and need to perform relevant examinations to confirm the diagnosis, so as to provide timely treatment.

  4. Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci▿

    Science.gov (United States)

    Norheim, Gunnstein; Aseffa, Abraham; Yassin, Mohammed Ahmed; Mengistu, Getahun; Kassu, Afework; Fikremariam, Dereje; Tamire, Wegene; Merid, Yared; Høiby, E. Arne; Caugant, Dominique A.; Fritzsønn, Elisabeth; Tangen, Torill; Melak, Berhanu; Berhanu, Degu; Harboe, Morten; Kolberg, Jan; Rosenqvist, Einar

    2008-01-01

    Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease. PMID:18337382

  5. Lyme disease as an underlying cause of supraspinatus tendinopathy in an overhead athlete.

    Science.gov (United States)

    Coulon, Christian L; Landin, Dennis

    2012-05-01

    Supraspinatus tendinopathy is a common cause of shoulder pain seen in overhead athletes, but there appear to be no published cases that present Lyme disease as the underlying cause of tendinopathy. Lyme disease is diagnosed primarily by clinical signs and symptoms and then supported by laboratory tests, including enzyme-linked immunosorbant assay (ELISA) and Western blot testing. This case demonstrates the importance of a physical therapist's input and clinical role in reaching the correct diagnosis in an athlete with Lyme disease who had a diagnosis of rotator cuff impingement and tendinitis. A 34-year-old male tennis player was seen for physical therapy for right shoulder impingement and tendinitis diagnosed by an orthopedic surgeon. He was unable to participate in sporting activities due to impairments in strength and pain. Initial examination revealed distal supraspinatus impingement and tendinopathy. The patient was not progressing with commonly accepted interventions and began to have "arthritis-like" shoulder pain in the uninvolved left shoulder. Suspicious of an underlying condition, the physical therapist informed the physician of the patient's updated status and referred the patient to the physician to discuss the current symptoms in therapy. After testing, the patient was diagnosed with chronic Lyme disease and underwent antibiotic therapy. Many active patients spend time in the outdoors, increasing their risk of exposure to a vector for Borrelia burgdorferi. Physical therapists spend a larger portion of time with patients than other health care professionals and due to this extended contact and musculoskeletal knowledge are able to recognize atypical musculoskeletal disorders or musculoskeletal manifestations of unusual pathologies, including Lyme disease.

  6. Force variability during dexterous manipulation in individuals with mild to moderate Parkinson’s disease

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    Na-hyeon eKo

    2015-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disease affecting about 1-2% of the population over the age of 65. Individuals with PD experience gradual deterioration of dexterous manipulation for activities of daily living, however, current clinical evaluations are mostly subjective and do not quantify changes in dynamic control of fingertip force that is critical for manual dexterity. Thus, there is a need to develop clinical measures to quantify those changes with aging and disease progression. We investigated the dynamic control of fingertip forces in both hands of 20 individuals with PD (69.0 ± 7.4 years using the Strength-Dexterity test. The test requires low forces (< 3N to compress a compliant and slender spring prone to buckling. A maximal level of sustained compression is informative of the greatest instability the person can control, and thus is indicative of the integrity of the neuromuscular system for dexterous manipulation. Miniature sensors recorded fingertip force (F during maximal sustained compressions. The force variability during sustained compression was quantified in two frequency bands: low (<4 Hz, F_LF and high (4-12 Hz, F_HF. F_LF characterizes variability in voluntary fluctuations while F_HF characterizes variability in involuntary fluctuations including tremor. The more-affected hand exhibited significantly lower F and lower F_LF than those in the less-affected hand. The more-affected hand showed significant negative correlations between F_LF and the UPDRS motor scores for both total and hand-only, suggesting that greater force variability in the voluntary range was associated with less clinical motor impairment. We conclude the nature of force variability in the voluntary range during this dynamic and dexterous task may be a biomarker of greater motor capability/flexibility/adaptability in PD. This approach may provide a more quantitative clinical assessment of changes of sensorimotor control in

  7. Physical disorders and causes of death in relatives of Alzheimer's disease patients.

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    Kockler, M; Nitardy, A; Papassotiropoulos, A; Ptok, U; Maier, W; Heun, R

    2002-04-01

    Genetic risk factors are important in Alzheimer's disease (AD). These risk factors might also predispose for other disorders. This might lead to a familial coaggregation of AD and other disorders, e.g. Down's syndrome or Parkinson's disease. In the present study the risk of physical disorders in relatives of AD patients, of depressed patients and of control subjects were compared. Family history and, if possible, interview information on physical disorders and causes of death in relatives of 146 patients with AD, 168 patients with major depression (MD) and 136 controls was collected. Statistical comparisons were performed using chi-square tests and, if necessary, logistic regression analysis accounting for age, gender and interview status. In contrast to our hypotheses, there was no increased risk of cerebrovascular disease, Down's syndrome, haematological malignancies or Parkinson's disease in relatives of AD patients compared with relatives of patients with MD and of controls. The explorative analysis revealed that congenital malformations, i.e. malformations of the heart or of the extremities, were slightly increased in relatives of AD patients. Relatives of patients with AD or MD were at increased risk of dying as a result of accidents, in most cases falls in advanced age, and relatives of patients with MD were at slightly increased risk of dying from gastroenterologic diseases, in most cases complications of peptic ulcers. The results do not support a major overlap between the genetic risk of AD and the genetic risk of cerebrovascular disease, Down's syndrome, haematological malignancies or Parkinson's disease. The finding of an increased risk of congenital malformations in relatives of AD patients needs further replication before it can be stated. The increased risk of dementia or depression with cognitive impairment in elderly relatives of patients with AD or MD increases the risk of accidents like falls. The genetic risk of depression in relatives of

  8. Whipple's disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure.

    Science.gov (United States)

    Glaser, Cornelia; Rieg, Siegbert; Wiech, Thorsten; Scholz, Christine; Endres, Dominique; Stich, Oliver; Hasselblatt, Peter; Geißdörfer, Walter; Bogdan, Christian; Serr, Annerose; Häcker, Georg; Voll, Reinhard E; Thiel, Jens; Venhoff, Nils

    2017-05-25

    Whipple's disease, a rare chronic infectious disorder caused by Tropheryma whipplei, may present with predominant joint manifestations mimicking rheumatoid arthritis (RA). A retrospective single-center cohort study of seven patients was performed. Clinical symptoms were assessed by review of medical charts and Whipple's disease was diagnosed by periodic-acid-Schiff-stain and/or Tropheryma whipplei-specific polymerase-chain-reaction. Median age at disease onset was 54 years, six patients were male. Median time to diagnosis was 5 years. All patients presented with polyarthritis with a predominantly symmetric pattern. Three had erosive arthritis. Affected joints were: wrists (5/7), metacarpophalangeal joints (MCPs) (5/7), knees (5/7), proximal interphalangeal joints (PIPs) (3/7), hips (2/7), elbow (2/7), shoulder (2/7). All patients had increased C-reactive-protein concentrations, while rheumatoid factor and anti-CCP-antibodies were absent, and were initially (mis)classified as RA-patients according to EULAR/ACR-criteria (median DAS28 4.3). Six patients received antirheumatic treatment consisting of prednisone with methotrexate and/or leflunomide, three were additionally treated with at least one biologic agent (abatacept, adalimumab, etanercept, rituximab, tocilizumab). Most patients showed insufficient treatment response. In all patients Tropheryma whipplei was detected in synovial fluid by polymerase-chain-reaction; in three patients the diagnosis of Whipple's disease was further ascertained by periodic-acid-Schiff-staining. Gastrointestinal symptoms and other extra-articular manifestations were absent, mild or non-specific. Treatment was initiated with trimethoprin/sulfamethoxazole in five and doxycycline/hydroxychloroquine in two patients and had to be adapted in five patients. Finally, all patients had good treatment responses with improvement of arthritis and extra-articular manifestations. Whipple's disease is rare and can mimic rheumatoid arthritis

  9. Physiological variability and in vitro antifungal activity against Botrytis cinerea causing botrytis gray mold of chickpea (Cicer arietinum L.)

    Energy Technology Data Exchange (ETDEWEB)

    Hosen, M. I.; Ahmed, A. U.; Islam, M. R.

    2010-07-01

    Physiological variability was studied in 10 isolates of Botrytis cinerea causing botrytis gray mold of chickpea, collected from diverse agro climatic areas in Bangladesh. The optimum temperature and pH for the best mycelial radial growth of B. cinerea were 20 degree centigrade and 4.5, respectively. The mycelial radial growth increased with the temperature up to 20 degree centigrade thereafter it decreased gradually up to 30 degree centigrade and no growth was observed at 35 degree centigrade. Chickpea dextrose agar (CDA) medium supported the highest mycelial radial growth (79.17 mm). The quickest (in 5 days) sclerotia initiation was recorded on chickpea destrose agar and lentil dextrose agar (LDA) culture media while the highest number of spores (2.5104 mL{sup -}1) were recorded on LDA medium. The antagonist Trichoderma harzianum was found to be a good bio-control agent against B. cinerea. Among the seven fungicides Bavistin 50 WP (Carbendazim), CP-Zim 50 WP (Carbendazim), Sunphanate 70 WP (Thiophanate methyl) and Rovral 50 WP (Iprodione) were the most effective to inhibit the mycelial radial growth of B. cinerea at 500 mg L{sup -}1 concentration. (Author) 13 refs.

  10. Further evidence that de novo missense and truncating variants in ZBTB18 cause intellectual disability with variable features.

    Science.gov (United States)

    Cohen, J S; Srivastava, S; Farwell Hagman, K D; Shinde, D N; Huether, R; Darcy, D; Wallerstein, R; Houge, G; Berland, S; Monaghan, K G; Poretti, A; Wilson, A L; Chung, W K; Fatemi, A

    2017-05-01

    Identification of rare genetic variants in patients with intellectual disability (ID) has been greatly accelerated by advances in next generation sequencing technologies. However, due to small numbers of patients, the complete phenotypic spectrum associated with pathogenic variants in single genes is still emerging. Among these genes is ZBTB18 (ZNF238), which is deleted in patients with 1q43q44 microdeletions who typically present with ID, microcephaly, corpus callosum (CC) abnormalities, and seizures. Here we provide additional evidence for haploinsufficiency or dysfunction of the ZBTB18 gene as the cause of ID in five unrelated patients with variable syndromic features who underwent whole exome sequencing revealing separate de novo pathogenic or likely pathogenic variants in ZBTB18 (two missense alterations and three truncating alterations). The neuroimaging findings in our cohort (CC hypoplasia seen in 4/4 of our patients who underwent MRI) lend further support for ZBTB18 as a critical gene for CC abnormalities. A similar phenotype of microcephaly, CC agenesis, and cerebellar vermis hypoplasia has been reported in mice with central nervous system-specific knockout of Zbtb18. Our five patients, in addition to the previously described cases of de novo ZBTB18 variants, add to knowledge about the phenotypic spectrum associated with ZBTB18 haploinsufficiency/dysfunction. © 2016 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Helicobacter pylori: types of diseases, diagnosis, treatment and causes of therapeutic failure

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    Cosmin Vasile Obleaga

    2016-10-01

    Full Text Available Acute upper gastrointestinal lesions have a multifactorial etiology but, regardless of the cause, they are related to mucosal barrier destruction. Since Helicobacter pylori induces a superficial chronic gastritis with the infiltration of neutrophils in the mucosa, it was speculated that Helicobacter pylori infection could also cause bleeding lesions. The diagnosis, the proper treatment and the revaluation of its effectiveness actually represent the prophylaxis of some diseases such as peptic ulcer, gastric lymphoma or mucosa-associated lymphoid tissue (MALT and gastric cancer. These diseases and their severe complications are life-threatening for the patient. Periodic renewal of the treatment and knowing the real causes of Helicobacter pylori resistance to various antibiotics must always be understood by the clinician. Although Helicobacter pylori treatment fails in about 20% of cases, moral support of the patient by the clinician, information about possible evolutional complications of Helicobacter pylori infection, and periodic evaluation of the patient during therapy, are important tools on which the therapeutic success depends.

  12. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study

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    Raaschou-Nielsen Ole

    2012-09-01

    Full Text Available Abstract Background Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. Methods We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993–1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO2 since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs with adjustment for potential confounders. Results Mean levels of NO2 at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06–1.51, per doubling of NO2 concentration and all causes (MRR, 1.13; 95% CI, 1.04–1.23, per doubling of NO2 concentration after adjustment for potential confounders. For participants who ate  Conclusions Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.

  13. Two new mutations in the glucose-6-phosphatase gene cause glycogen storage disease in Hungarian patients.

    Science.gov (United States)

    Parvari, R; Lei, K J; Szonyi, L; Narkis, G; Moses, S; Chou, J Y

    1997-01-01

    Glycogen storage disease type 1a (von Gierke disease, GSD-1A) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the identification of the mutations causing GSD-1a. This, in turn, allows the development of non-invasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. Here we report on two new mutations E110Q and D38V causing GSD-1a in two Hungarian patients. The analyses of these mutations by site-directed mutagenesis followed by transient expression assays demonstrated that E110Q retains 17% of G6Pase enzymatic activity while the D38V abolishes the enzymatic activity. The patient with the E110Q has G222R as his other mutation. G222R was also shown to preserve about 4% of the G6Pase enzymatic activity. Nevertheless, the patient presented with the classical severe symptomatology of the GSD-1a.

  14. Hemolytic disease of the fetus and newborn caused by anti-E

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    Adiyyatu Sa′idu Usman

    2013-01-01

    Full Text Available Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.

  15. Laparoscopy improves clinical outcome of gastrointestinal fistula caused by Crohn's disease.

    Science.gov (United States)

    Ren, Jianan; Liu, Song; Wang, Gefei; Gu, Guosheng; Ren, Huajian; Hong, Zhiwu; Li, Jieshou

    2016-01-01

    Benefits of laparoscopic surgery in the management of gastrointestinal fistula caused by Crohn disease need to be fully elucidated. We conducted this retrospective study to investigate the safety and feasibility and emphasize the advantages of laparoscopy compared with that of laparotomy for patients with gastrointestinal fistula caused by Crohn disease. A total of 1213 patients with gastrointestinal fistula in our center were screened, and 318 qualified patients were enrolled and divided into laparoscopy (n = 122) and laparotomy (n = 196) groups. Postoperative complications, length of hospital stay, systemic stress responses to surgery, postoperative mortality, and economic burden were collected and compared. A total of 125 laparoscopic interventions were performed with a conversion rate of 20.0%. Fifteen versus 84 postoperative complications were obtained in laparoscopy and laparotomy groups, respectively (P = 0.0033). Total hospitalization was 22.7 d and 38.0 d in laparoscopy and laparotomy groups, respectively (P laparoscopy was significantly lower than that to laparotomy. Reduced postoperative mortality (P = 0.0292) and postoperative cost (P = 0.0292) were observed in laparoscopy instead of laparotomy group. Laparoscopic approach is safe and feasible and could improve clinical outcome in gastrointestinal fistula patients with Crohn disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.

    Science.gov (United States)

    Chen, Jonathan L; VanEtten, Damian M; Fountain, Matthew A; Yildirim, Ilyas; Disney, Matthew D

    2017-07-11

    RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.

  17. Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency.

    Science.gov (United States)

    Lemmens, Robin; Maugeri, Alessandra; Niessen, Hans W M; Goris, An; Tousseyn, Thomas; Demaerel, Philippe; Corveleyn, Anniek; Robberecht, Wim; van der Knaap, Marjo S; Thijs, Vincent N; Zwijnenburg, Petra J G

    2013-01-15

    Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused by haploinsufficiency. Two families with various clinical presentations of cerebral microangiopathy and autosomal dominant inheritance were examined. Clinical, neuroradiological and genetic investigations were performed. Electron microscopy of the skin was also performed. In one of the families, sequence analysis revealed a one base deletion, c.2085del, leading to a frameshift and a premature stopcodon, p.(Gly696fs). In the other family, a splice site mutation was identified, c.2194-1G>A, which most likely leads to skipping of an exon with a frameshift and premature termination as a result. In fibroblasts of affected individuals from both the families, nonsense-mediated decay (NMD) of the mutant COL4A1 messenger RNAs (mRNAs) and a clear reduction of COL4A1 protein expression were demonstrated, indicating haploinsufficiency of COL4A1. Moreover, thickening of the capillary basement membrane in the skin was documented, similar to reports in patients with COL4A1 missense mutations. These findings suggest haploinsufficiency, a different mechanism from the commonly assumed dominant-negative effect, for COL4A1 mutations as a cause of (antenatal) intracerebral hemorrhage and white matter disease.

  18. [Causes, diagnostics and course of disease in 194 cats with anemia].

    Science.gov (United States)

    Merten, Nina; Weingart, Christiane; Kohn, Barbara

    2015-01-01

    Anemia is a common hematological alteration in cats. The objective of this study was to evaluate the frequency of different types of anemia and the course of disease in cats with a hematocrit (hct) anemia groups based on history, physical examination and laboratory parameters. Most cats had acute blood loss anemia (BA; 75/194; 38.7%). Frequent causes were trauma (39/75), hematuria (13/75) and hemostatic disorders (9/75). Anemia of inflammatory and neoplastic disease (AID) occurred in 22.2% (43/194) and hemolytic anemia (HA) in 18% (35/194). Half of those were presumptively immune-mediated (IHA). Four cats were diagnosed with hemotropic mycoplasma infection. Rare causes of anemia included anemia of renal disease (ARD; 18/194; 9.3%) and intramedullary non-regenerative anemia (INR; 13/194; 6.7%). The latter either had retroviral infection (6/13) or neoplasia (6/13). In cats with HA and INR anemia was often severe and very severe (Hct anemia was detected for the first time. Cats with HA had the highest survival rate.

  19. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.

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    Yi-Chu Liao

    Full Text Available Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive.Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability.GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.

  20. Gender, Age and Season as Modifiers of the Effects of Diurnal Temperature Range on Emergency Room Admissions for Cause-Specific Cardiovascular Disease among the Elderly in Beijing

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    Shan Zheng

    2016-04-01

    Full Text Available Background: Diurnal temperature range (DTR is an important index of climate change and variability. It is also a risk factor affecting human health. However, limited evidence is available to illustrate the effect of DTR modification on cause-specific cardiovascular disease among the elderly. Methods: A semi-parametric generalized additive model (GAM was used to analyze the exposure-effect relationship between DTR and daily emergency room (ER admissions for cause-specific cardiovascular diseases among the elderly from 2009 to 2011 in Beijing. We examined the effects of DTR for stratified groups by gender and age, and examined the effects of DTR in the warm season and cold season for cause-specific cardiovascular diseases. Results: Significant associations were found between DTR and ER admissions for all cardiovascular and cerebrovascular disease among elderly males, while DTR was significantly associated with ER admissions for all cardiovascular disease, ischemic heart disease and cerebrovascular disease among elderly females. People aged 75 years and older were more vulnerable to DTR. DTR caused greater adverse effects on both genders in the warm season, whereas the effect estimates on females were higher in cold season than in warm season. Conclusions: A short-term increase of DTR was significantly associated with ER admissions for cause-specific cardiovascular disease among the elderly in Beijing. Gender, age and season may modify the acute health effect of DTR. Some prevention programs that target the high risk subgroups in the elderly for impending large temperature changes may reduce the impact of DTR on people’s health.

  1. Blood pressure variability and cardiovascular autonomic control during hemodialysis in peripheral vascular disease patients

    International Nuclear Information System (INIS)

    Titapiccolo, Jasmine Ion; Cerutti, Sergio; Signorini, Maria Gabriella; Ferrario, Manuela; Garzotto, Francesco; Cruz, Dinna; Ronco, Claudio; Moissl, Ulrich; Tetta, Ciro

    2012-01-01

    Hemodialysis (HD) patients with peripheral vascular disease (PVD) are at higher risk of mortality. The main objectives of this work were to investigate the hypothesis of an association between the PVD and an altered control system on peripheral resistance in response to volume depletion induced by HD treatment; and to investigate whether HD induced increase of pulse pressure (PP) is associated with PVD. Continuous blood pressure (BP) was recorded during HD treatment at the beginning and at the end of HD. The overhydration condition was evaluated by means of whole body bioimpedance spectroscopy, measured before each HD treatment. BP variability, heart rate variability and baroreflex sensitivity were then analyzed. Patients affected by PVD reported a prevalence of peripheral local control as shown by higher values of very low frequency in diastolic blood pressure (DBP) variability and a reduced cardiac baroreflex with respect to patients not affected by this pathology. HD treatment induced a significant increase of PP and LF% in DBP series in PVD patients only. Our results suggested that differences in BP variability and PP changes could be related not only to an underlying vascular disease, but also to an alteration in autonomic control. (paper)

  2. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options.

    NARCIS (Netherlands)

    Nouws, J.; Nijtmans, L.G.J.; Smeitink, J.A.M.; Vogel, R.O.

    2012-01-01

    Complex I deficiency is the most frequent cause of oxidative phosphorylation disorders. The disease features a large diversity of clinical symptoms often leading to progressive encephalomyopathies with a fatal outcome. There is currently no cure, and although disease-causing mutations have been

  3. Two novel MYH7 proline substitutions cause Laing Distal Myopathy-like phenotypes with variable expressivity and neck extensor contracture.

    Science.gov (United States)

    Feinstein-Linial, Miora; Buvoli, Massimo; Buvoli, Ada; Sadeh, Menachem; Dabby, Ron; Straussberg, Rachel; Shelef, Ilan; Dayan, Daniel; Leinwand, Leslie Anne; Birk, Ohad S

    2016-08-12

    Human skeletal muscles express three major myosin heavy chain (MyHC) isoforms: MyHCIIx (MYH1) in fast type 2B muscle fibers, MyHCIIa (MYH2) in fast type 2A fibers and MyHCI/β-cardiac MyHC (MYH7) in slow type I skeletal fibers and cardiac ventricles. In line with its expression pattern, MYH7 mutations have been reported in association with hypertrophic or dilated cardiomyopathy, skeletal myopathies or a combination of both. We analyzed the clinical and molecular phenotype of two unrelated families of Jewish Moroccan ancestry that presented with apparently autosomal dominant inheritance of progressive Laing-like distal myopathy with non-specific myopathic changes, but uncommon marked contractures and wasting of the neck extensors. Clinical phenotyping, whole exome sequencing and restriction analysis, generation of mutants followed by cell culture transfection and imaging. Using whole exome sequencing we identified in both families two novel heterozygous proline substitutions located in exon 31 of MYH7 within its rod domain: c.4309G>C (p.Ala1437Pro) and c.4301G>C (p.Arg1434Pro). Here we show that the phenotype caused by these mutations includes marked cervical muscle contracture, and report that the severity of the phenotype varies significantly, to the extent of non-penetrance in one of the families. Finally, we provide evidence that both proline substitutions impair myosin self-assembly in non-muscle cells transfected with β-myosin constructs carrying the mutations, but do not prevent incorporation of the mutant molecules into the sarcomere. This study expands our clinical and molecular knowledge of MYH7 rod mutations causing skeletal myopathies, and underscores the importance of discussing disease penetrance during genetic counseling.

  4. Tight Bra in a 34-Year-Old Woman: An Unusual Cause of Mondor’s Disease

    Science.gov (United States)

    2014-01-01

    Mondor’s disease is characterized by thrombophlebitis of the superficial veins of the breast and the chest wall. The list of causes is long. Various types of clothing, mainly tight bras and girdles, have been postulated as causes. We report a case of a 34-year-old woman who referred typical symptoms and signs of Mondor’s disease, without other possible risk factors, and showed the cutaneous findings of the tight bra. Therefore, after distinguishing benign causes of Mondor’s disease from hidden malignant causes, the clinicians should consider this clinical entity. PMID:24995060

  5. Opinions in Denmark on the causes of peptic ulcer disease. A survey among Danish physicians and patients

    DEFF Research Database (Denmark)

    Christensen, A H; Gjørup, T; Andersen, I B

    1994-01-01

    of medicine, and working conditions played a causal role. Around 95% of the physicians indicated that medical drugs and smoking were contributory causes of peptic ulcer disease, and around 80% that alcohol and psychologic factors were so. Only 30-40% of the physicians believed that coffee/tea, food habits...... stated more causes than did their male colleagues (p smoking, side effects......, infection, and working conditions could play a causal role in ulcer disease. It is concluded that the opinion on causal agents in peptic ulcer disease differ considerably among both patients and physicians. Opinions on causes of diseases may influence the way we treat and advise our patients, and attempts...

  6. Neuropsychological Testing and Machine Learning Distinguish Alzheimer's Disease from Other Causes for Cognitive Impairment.

    Science.gov (United States)

    Gurevich, Pavel; Stuke, Hannes; Kastrup, Andreas; Stuke, Heiner; Hildebrandt, Helmut

    2017-01-01

    With promising results in recent treatment trials for Alzheimer's disease (AD), it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET) or inaccurate Magnetic Resonance Imaging (MRI). This study investigates the potential of neuropsychological testing (NPT) to specifically identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI) or dementia for various causes. Patients were divided into an early stage and a late stage group according to their Mini Mental State Examination (MMSE) score and labeled as AD or non-AD patients based on a post-mortem validated threshold of the ratio between total tau and beta amyloid in the cerebrospinal fluid (CSF; Total tau/Aβ(1-42) ratio, TB ratio). All patients completed the established Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB) test battery and two additional newly-developed neuropsychological tests (recollection and verbal comprehension) that aimed at carving out specific Alzheimer-typical deficits. Based on these test results, an underlying AD (pathologically increased TB ratio) was predicted with a machine learning algorithm. To this end, the algorithm was trained in each case on all patients except the one to predict (leave-one-out validation). In the total group, 82% of the patients could be correctly identified as AD or non-AD. In the early group with small general cognitive impairment, classification accuracy was increased to 89%. NPT thus seems to be capable of discriminating between AD patients and patients with cognitive impairment due to other neurodegenerative or vascular causes with a high accuracy, and may be used for screening in clinical routine and drug studies, especially in the early course of this disease.

  7. Mutations in MME cause an autosomal‐recessive Charcot–Marie–Tooth disease type 2

    Science.gov (United States)

    Higuchi, Yujiro; Hashiguchi, Akihiro; Yuan, Junhui; Yoshimura, Akiko; Mitsui, Jun; Ishiura, Hiroyuki; Tanaka, Masaki; Ishihara, Satoshi; Tanabe, Hajime; Nozuma, Satoshi; Okamoto, Yuji; Matsuura, Eiji; Ohkubo, Ryuichi; Inamizu, Saeko; Shiraishi, Wataru; Yamasaki, Ryo; Ohyagi, Yasumasa; Kira, Jun‐ichi; Oya, Yasushi; Yabe, Hayato; Nishikawa, Noriko; Tobisawa, Shinsuke; Matsuda, Nozomu; Masuda, Masayuki; Kugimoto, Chiharu; Fukushima, Kazuhiro; Yano, Satoshi; Yoshimura, Jun; Doi, Koichiro; Nakagawa, Masanori; Morishita, Shinichi; Tsuji, Shoji

    2016-01-01

    Objective The objective of this study was to identify new causes of Charcot–Marie–Tooth (CMT) disease in patients with autosomal‐recessive (AR) CMT. Methods To efficiently identify novel causative genes for AR‐CMT, we analyzed 303 unrelated Japanese patients with CMT using whole‐exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation. Results We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta‐amyloid (Aβ)‐degrading enzymes. All patients had a similar phenotype consistent with late‐onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss‐of‐function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aβ in Pittsburgh compound‐B positron emission tomography imaging. Interpretation Our results indicate that loss‐of‐function MME mutations are the most frequent cause of adult‐onset AR‐CMT2 in Japan, and we propose that this new disease should be termed AR‐CMT2T. A loss‐of‐function MME mutation did not cause early‐onset Alzheimer's disease. Identifying the MME mutation responsible for AR‐CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT. Ann Neurol 2016;79:659–672 PMID:26991897

  8. [Causes of lymphocytic meningitis in people with HIV admitted to the Infectious Disease department of Conakry].

    Science.gov (United States)

    Traoré, F A; Cissoko, Y; Tounkara, T M; Sako, F B; Mouelle, A D; Kpami, D O; Traoré, M; Doumbouya, M

    2015-01-01

    The advent of HIV infection has significantly changed the distribution of the causes of lymphocytic meningitis. The objective of this study was to identify these causes among persons with HIV hospitalized in the infectious disease department of the CHU of Conakry. This retrospective study examined hospital records of patients with HIV infection admitted for lymphocytic meningitis over a 10-year period. Of the 8649 hospitalizations in the department during the study period, 3167 patients had HIV infection, and 85 of the latter were diagnosed with lymphocytic meningitis. Slightly more than half were male (sex ratio M/F = 1.1). Their mean age was 32 years. Of these 85 patients, 73 were positive for HIV-1 only and 12 for HIV1+2. A CD4 count was performed only in 13/85 patients and averaged 140 cells/mm3. The main causes associated with lymphocytic meningitis were cryptococcosis (58%), toxoplasmosis (5%), and tuberculosis (2%). Streptococcus pneumoniae, Neisseria meningitidis, and Hæmophilus influenzae were also identified in 16% of cases. In 18% of cases no microbe was identified. The overall lethality rate was 68%; it reached 100% for tuberculous meningitis and for the cases without any identified cause and was 75%-76% for the patients with toxoplasmosis and cryptococcosis. The survival rate was 100% for all bacterial causes. A cause for lymphocytic meningitis was identified in more than 81% of the patients in our series, and the most common microbe was Cryptococcus neoformans. A better microbiological technical platform and improved accessibility to treatment would enable us to provide more relevant results and treatment.

  9. Anti-Mur as the most likely cause of mild hemolytic disease of the newborn.

    Science.gov (United States)

    Bakhtary, Sara; Gikas, Anastasia; Glader, Bertil; Andrews, Jennifer

    2016-05-01

    Although rare in the United States, anti-Mur is relatively common in Southeast Asia and has been reported to have clinical significance in Chinese and Taiwanese populations. The infant was full term and the second child of a Chinese mother and Vietnamese father, presenting with jaundice. He was clinically diagnosed with immune-mediated hemolytic anemia. The direct antiglobulin test indicated that the infant's red blood cells were coated only with anti-IgG. Anti-Mur was identified in the maternal serum and the neonate's plasma. The father was found to be positive for the Mur antigen. The cause of the infant's hemolytic anemia was determined to be most likely anti-Mur. Since anti-Mur is implicated in causing hemolytic disease of the newborn, it is important to recognize this antibody more commonly found in Asian patients in the United States as the Mur+ phenotype has a higher prevalence in this population. © 2016 AABB.

  10. A new F-box protein 7 gene mutation causing typical Parkinson's disease.

    Science.gov (United States)

    Lohmann, Ebba; Coquel, Anne-Sophie; Honoré, Aurélie; Gurvit, Hakan; Hanagasi, Hasmet; Emre, Murat; Leutenegger, Anne L; Drouet, Valérie; Sahbatou, Mourad; Guven, Gamze; Erginel-Unaltuna, Nihan; Deleuze, Jean-Francois; Lesage, Suzanne; Brice, Alexis

    2015-07-01

    Recessive mutations in the F-box protein 7 gene (FBXO7; PARK15) have been identified as a cause of the parkinsonian-pyramidal syndrome. Here, we report clinical and genetic findings in a Turkish family with novel FBXO7 mutations. Whole exome and targeted Sanger sequencing were performed for genetic analysis in a family with two members affected by Parkinson's disease (PD). All family members underwent detailed clinical, mental, and neurological examination. The new p.L34R (c.101 T>G) FBXO7 mutation was detected in a homozygous state in two Turkish sibs with typical levodopa-responsive PD. This is the first time a FBXO7 mutation has been identified that causes a phenotype compatible with typical idiopathic PD and presents with some of its common nonmotor features, such as rapid eye movement sleep behavior disorder, depression, and anxiety. © 2015 International Parkinson and Movement Disorder Society.

  11. Effect of gamma radiation treatment on some fungi causing storage diseases of banana fruits

    International Nuclear Information System (INIS)

    EL-Ashmawi, A.M.M.

    1982-01-01

    Banana is one of the most popular fruits in many tropical and sub-tropical countries. in recent years, the quality of egyptian banana markedly declined. A major factor contributing to this decline is the development of fruit rot, which is the most widely occurring disease either in the field or in storage. Different fungi attack banana fruits causing considerable losses. Most of the fungi responsible for post harvest rots of banana are usually carried from the field, on the surface of the fruit itself or in injured and rotting fruits causing severe rats during storage. These rots make the fruits difficult to handle and undesirable to the consumers. Botryodiplodia theobromae is known to be the most important pathogen responsible for the infection in storage

  12. COMPOSITE PEPTIDE COMPOUNDS FOR DIAGNOSIS AND TREATMENT OF DISEASES CAUSED BY PRION PROTEINS

    DEFF Research Database (Denmark)

    2004-01-01

    The present invention relates to diseases caused by prion proteins, Novel composite peptide compounds are disclosed which comprise two or more peptides or peptide fragments optionally linked to a backbone and the peptides or peptide fragments are spatially positioned relative to each other so...... that they together form a non-linear sequence which mimics the tertiary structure of one or more PrPSc-specific epitopes as evidenced by the test described herein. The use of such conjugates as immunogens for the production of antibodies that specifically bind to the pathogenic form of a prion protein is revealed....... Other uses of the composite peptide compounds are also disclosed, such as use in diagnostic assays, production of antibodies and uses as vaccine immunogens for the prophylactic protection and therapeutic treatment of subjects against transmissible prion disease....

  13. Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls

    DEFF Research Database (Denmark)

    Frandsen, Rune; Baandrup, Lone; Kjellberg, Jakob

    2014-01-01

    AIM: Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD...... of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04-1.36; Control HR = 1.77, 95% CI = 1.64-1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0.......20-1.76; Control HR = 2.00, 95% CI 1.66-2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups. CONCLUSIONS: The use of psychotropic medication in the elderly is associated with increased...

  14. Early Stage of Chronic Kidney Disease with Renal Injury Caused by Hypertension in a Dog

    Directory of Open Access Journals (Sweden)

    Akira Yabuki

    2011-01-01

    Full Text Available A 10-year-old spayed female Papillon weighing 4.0 kg presented with a history of persistent hematuria and pollakiuria. Concurrent bladder calculi, a mammary gland tumor, and nonazotemic early stage of chronic kidney disease with contracted kidneys were noted in this dog. The dog underwent cystectomy, unilateral mastectomy, and intraoperative renal biopsy. On the basis of histopathological analysis of renal biopsy results, it was suspected that renal injury of the dog was caused by persistent hypertension, and a follow-up examination revealed severe hypertension. The dog was treated with a combination of an angiotensin-converting enzyme inhibitor and calcium channel blocker. The treatment produced a good outcome in the dog, and there has been no progression of the chronic kidney disease for over 2 years.

  15. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  16. Occupational heavy lifting and risk of ischemic heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Petersen, Christina Bjørk; Eriksen, Louise; Tolstrup, Janne S

    2012-01-01

    ABSTRACT: BACKGROUND: Occupational heavy lifting is known to impose a high cardiovascular strain, but the risk of ischemic heart disease (IHD) from occupational heavy lifting is unknown. The objective was to investigate the association between occupational heavy lifting and risk of IHD and all...... risk was associated with occupational (HR: 0.50, 95 % CI: 0.37, 0.68) and leisure time (HR: 0.73, 95 % CI: 0.56, 0.95) physical activity. Referencing men with high occupational physical activity and no heavy lifting, men with high occupational physical activity and heavy lifting did not have...... cardiovascular disease at baseline. Conventional risk factors for the outcomes IHD and all-cause mortality were controlled for in Cox analyses. RESULTS: Among men, heavy lifting was associated with increased risk for IHD (hazard ratio (HR): 1.52, 95 % Confidence interval (95 % CI): 1.15, 2.02), while a decreased...

  17. Cryptococcus gattii: An Emerging Cause of Fungal Disease in North America

    Directory of Open Access Journals (Sweden)

    Ashwin Dixit

    2009-01-01

    Full Text Available During the latter half of the twentieth century, fungal pathogens such as Cryptococcus neoformans were increasingly recognized as a significant threat to the health of immune compromised populations throughout the world. Until recently, the closely related species C. gattii was considered to be a low-level endemic pathogen that was confined to tropical regions such as Australia. Since 1999, C. gattii has emerged in the Pacific Northwest region of North America and has been responsible for a large disease epidemic among generally healthy individuals. The changing epidemiology of C. gattii infection is likely to be a consequence of alterations in fungal ecology and biology and illustrates its potential to cause serious human disease. This review summarizes selected biological and clinical aspects of C. gattii that are particularly relevant to the recent North American outbreak and compares these to the Australian and South American experience.

  18. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Aune, Dagfinn; Keum, NaNa; Giovannucci, Edward; Fadnes, Lars T; Boffetta, Paolo; Greenwood, Darren C; Tonstad, Serena; Vatten, Lars J; Riboli, Elio; Norat, Teresa

    2016-06-14

     To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality.  PubMed and Embase searched up to 3 April 2016.  Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality.  Summary relative risks and 95% confidence intervals calculated with a random effects model.  45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings-for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I(2)=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I(2)=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I(2)=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I(2)=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I(2)=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I(2)=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I(2)=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I(2)=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I(2)=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I(2)=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular

  19. Body adiposity index and all-cause and cardiovascular disease mortality in men

    Science.gov (United States)

    Moliner-Urdiales, Diego; Artero, Enrique G; Lee, Duck-chul; España-Romero, Vanesa; Sui, Xuemei; Blair, Steven N

    2013-01-01

    Objective To evaluate the association of body adiposity index (BAI) with all-cause and cardiovascular disease (CVD) mortality risk. Design and Methods The current analysis comprised 19 756 adult men who enrolled in the Aerobics Centre Longitudinal Study and completed a baseline examination during 1988-2002. All-cause and CVD mortality was registered till December 31, 2003. Results During an average follow-up of 8.3 years (163 844 man-years), 353 deaths occurred (101 CVD deaths). Age- and examination year-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality risk were higher for men with high values of BMI (HR = 1.63, 95% CI = 1.19–2.23), waist circumference (1.55, 1.22-1.96) and percentage of body fat (%BF) (1.36, 1.04-1.31), but not for men with high values of BAI (1.28, 0.98-1.66). The HRs for CVD mortality risks were higher for men with high values in all adiposity measures (HRs ranged from 1.73 to 2.06). Most of these associations, however, became nonsignificant after adjusting for multiple confounders including cardiorespiratory fitness. Conclusion BAI is not a better predictor of all-cause and CVD mortality risk than BMI, waist circumference or %BF. PMID:23512375

  20. Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

    Science.gov (United States)

    Stanley, Molly; Macauley, Shannon L.

    2016-01-01

    Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942

  1. Phylogenetic and chronological analysis of proteins causing Alzheimer's, Parkinson's and Huntington's diseases

    Directory of Open Access Journals (Sweden)

    Bilal Hussain

    2012-09-01

    Full Text Available It is evident that Neurodegenerative diseases (Alzheimer's, Parkinson's and Huntington's have many similarities at cellular and molecular level as they carry parallel mechanisms including protein aggregation and inclusion body formation caused by protein mis-folding. The main objective of this study was to have detailed insight on variation and resemblance among these proteins. One hundred and four protein sequences, both directly and indirectly involved in disease mechanism to perform phylogenetic analysis revealing insight on evolutionary relationship among these proteins, were selected. The percentage of replicate trees, in which the associated taxa clustered together in the bootstrap test, was 1000 replicates. Various statistical tests were performed for the confirmation of results e.g., Tajma's Neutrality Test showed D gt 6, nucleotide diversity π gt 0.6 and ps value as greater than 1. Phylogenetic analysis showed that the protein sequences of neurodegenerative diseases had high sequence similarity and identity to each other as depicted by the evolutionary tree. It showed the similar mechanism of evolving from each other and had similar mechanism of generating mis-folding leading towards symptoms of disease.

  2. Heterogeneity of mitochondrial diseases caused by defects in mitochondrial respiratory chain complex I

    Directory of Open Access Journals (Sweden)

    E. A. Nikolaeva

    2015-01-01

    Full Text Available The common cause of mitochondrial diseases is hereditary defects in mitochondrial respiratory chain complex I, which account for about 30% of the cases of mitochondrial diseases in children. Complex I is the largest and most complicated enzyme complex of the respiratory electron chain. The function of Complex I is controlled by both nuclear and mitochondrial genomes and it seems to be determined by at least 300 genes. Complex I is comprised of 45 subunits: 7 of them are encoded by mitochondrial DNA, the others are by nuclear DNA. Besides, there are additional factors that are located outside Complex I, but determine its stability and activity. The paper analyzes the clinical forms of Complex I deficiency-induced diseases; the most common of them is Leigh syndrome. The diseases are generally characterized by an early onset, severe involvement of the nervous, muscular, and cardiovascular systems. If the treatment is ineffective, it is particularly important to identify a gene mutation to verify the diagnosis, as well as antenatal diagnosis. 

  3. Recent Trends in Control Methods for Bacterial Wilt Diseases Caused by Ralstonia solanacearum

    Science.gov (United States)

    Yuliar; Nion, Yanetri Asi; Toyota, Koki

    2015-01-01

    Previous studies have described the development of control methods against bacterial wilt diseases caused by Ralstonia solanacearum. This review focused on recent advances in control measures, such as biological, physical, chemical, cultural, and integral measures, as well as biocontrol efficacy and suppression mechanisms. Biological control agents (BCAs) have been dominated by bacteria (90%) and fungi (10%). Avirulent strains of R. solanacearum, Pseudomonas spp., Bacillus spp., and Streptomyces spp. are well-known BCAs. New or uncommon BCAs have also been identified such as Acinetobacter sp., Burkholderia sp., and Paenibacillus sp. Inoculation methods for BCAs affect biocontrol efficacy, such as pouring or drenching soil, dipping of roots, and seed coatings. The amendment of different organic matter, such as plant residue, animal waste, and simple organic compounds, have frequently been reported to suppress bacterial wilt diseases. The combined application of BCAs and their substrates was shown to more effectively suppress bacterial wilt in the tomato. Suppression mechanisms are typically attributed to the antibacterial metabolites produced by BCAs or those present in natural products; however, the number of studies related to host resistance to the pathogen is increasing. Enhanced/modified soil microbial communities are also indirectly involved in disease suppression. New promising types of control measures include biological soil disinfection using substrates that release volatile compounds. This review described recent advances in different control measures. We focused on the importance of integrated pest management (IPM) for bacterial wilt diseases. PMID:25762345

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

    Science.gov (United States)

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

    2017-08-01

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

  5. Recent trends in control methods for bacterial wilt diseases caused by Ralstonia solanacearum.

    Science.gov (United States)

    Yuliar; Nion, Yanetri Asi; Toyota, Koki

    2015-01-01

    Previous studies have described the development of control methods against bacterial wilt diseases caused by Ralstonia solanacearum. This review focused on recent advances in control measures, such as biological, physical, chemical, cultural, and integral measures, as well as biocontrol efficacy and suppression mechanisms. Biological control agents (BCAs) have been dominated by bacteria (90%) and fungi (10%). Avirulent strains of R. solanacearum, Pseudomonas spp., Bacillus spp., and Streptomyces spp. are well-known BCAs. New or uncommon BCAs have also been identified such as Acinetobacter sp., Burkholderia sp., and Paenibacillus sp. Inoculation methods for BCAs affect biocontrol efficacy, such as pouring or drenching soil, dipping of roots, and seed coatings. The amendment of different organic matter, such as plant residue, animal waste, and simple organic compounds, have frequently been reported to suppress bacterial wilt diseases. The combined application of BCAs and their substrates was shown to more effectively suppress bacterial wilt in the tomato. Suppression mechanisms are typically attributed to the antibacterial metabolites produced by BCAs or those present in natural products; however, the number of studies related to host resistance to the pathogen is increasing. Enhanced/modified soil microbial communities are also indirectly involved in disease suppression. New promising types of control measures include biological soil disinfection using substrates that release volatile compounds. This review described recent advances in different control measures. We focused on the importance of integrated pest management (IPM) for bacterial wilt diseases.

  6. Outbreak of upper respiratory disease in horses caused by Streptococcus equi subsp. zooepidemicus ST-24.

    Science.gov (United States)

    Lindahl, Susanne B; Aspán, Anna; Båverud, Viveca; Paillot, Romain; Pringle, John; Rash, Nicola L; Söderlund, Robert; Waller, Andrew S

    2013-09-27

    Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is generally considered a commensal and an opportunistic pathogen of the upper airways in horses. Establishing whether certain strains of S. zooepidemicus can cause upper respiratory disease as a host-specific pathogen of horses, and if there are certain genogroups of S. zooepidemicus that are more virulent than others is of major clinical importance. In this study, we describe an outbreak of upper respiratory disease in horses that was associated with S. zooepidemicus. Upper respiratory samples were cultured, analyzed by real-time PCR for S. zooepidemicus and S. equi, and genetically differentiated by sequencing of the SzP protein gene and multi-locus sequence typing (MLST). Serum samples were analyzed for antibodies against S. equi and common viral respiratory pathogens. The ST-24 strain of S. zooepidemicus was isolated from all horses with clinical signs of disease, while the healthy horses carried other strains of S. zooepidemicus. Bacteriological, molecular and serological analyses strongly suggest that a single strain (ST-24) was responsible for the disease outbreak, and that certain strains of this presumed commensal may be more virulent than others. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. [Occupational diseases caused by ionizing radiation in Poland, 1971-2006].

    Science.gov (United States)

    Wilczyńska, Urszula; Szeszenia-Dabrowska, Neonila

    2008-01-01

    The whole spectrum of disorders of the hematopoietic tissue, eye and skin induced by ionizing radiation covers complex pathologies termed as a postirradiation syndrome, as well as various malignancies. The aim of this work is to present the data on incidence of occupational diseases with ionizing radiation as a causative agent. The work is based on the data compiled from "Occupational Diseases Reporting Forms" for the years 1971-2006 collected in the Central Register of Occupational Diseases. The incidence of certified occupational diseases with ionizing radiation as a causative agent is expressed in absolute numbers and the rate per 100 000 employees. The data comprise information on disease entities, gender, age, exposure duration and the branch of national economy. In total, 599 diseases (0.2% of all occupational diseases) were diagnosed as those induced by ionizong radiation. Annual incidence rates per 100,000 employees fell within the range of 0.0-0.7. Miners formed the major (51.9%) occupational group affected by ionizing radiation. They were followed by health care (34.3%) and construction (6.4%) workers. Cancers made over 50% of pathologies located at 28 sites. These included cancers of lung (59.2%), skin (10.0%) and hematopoietic tissue (8.7%). Almost all (99.35) diseases recorded in the mining industry were cancers. Non-cancer diseases were more frequent in health care workers, among them postradiation cataract occupied the first place. A great deal of reported cancer sites give rise to controversy in terms of the cause-effect association with ionizing radiation exposure and also due to incomplete data on exposure level. Postradiation cancers among health care workers have not been registered over recent years, which means that occupational exposure surveillance carried out for many years proves to be effective. Distant effects of exposure to ionizing radiation, revealed in workers of no longer existing uranium mine, appeared to be a particular problem

  8. Occupational Diseases Caused by Ionizing Radiation in Poland, 1971-2006

    International Nuclear Information System (INIS)

    Wilczynska, U.; Szeszenia-Dabrowska, N.

    2008-01-01

    The whole spectrum of disorders of the hematopoietic tissue, eye and skin induced by ionizing radiation covers complex pathologies termed as a postirradiation syndrome, as well as various malignancies. The aim of this work is to present the data on incidence of occupational diseases with ionizing radiation as a causative agent. The work is based on the data compiled from 'Occupational Diseases Reporting Forms' for the years 1971-2006 collected in the Central Register of Occupational Diseases. The incidence of certified occupational diseases with ionizing radiation as a causative agent is expressed in absolute numbers and the rate per 100 000 employees. The data comprise information on disease entities, gender, age, exposure duration and the branch of national economy. In total, 599 diseases (0.2% of all occupational diseases) were diagnosed as those induced by ionizing radiation. Annual incidence rates per 100 000 employees fell within the range of 0.0-0.7. Miners formed the major (51.9%) occupational group affected by ionizing radiation. They were followed by health care (34.3%) and construction (6.4%) workers. Cancers made over 50% of pathologies located at 28 sites. These included cancers of lung (59.2%), skin (10.0%) and hematopoietic tissue (8.7%). Almost all (99.35) diseases recorded in the mining industry were cancers. Non-cancer diseases were more frequent in health care workers, among them postradiation cataract occupied the first place. A great deal of reported cancer sites give rise to controversy in terms of the cause-effect association with ionizing radiation exposure and also due to incomplete data on exposure duration. Postradiation cancers among health care workers have not been registered over recent years, which means that occupational exposure surveillance carried out for many years proves to be effective. Distant effects of exposure to ionizing radiation, revealed in workers of no longer existing uranium mine, appeared to be a particular problem

  9. Xanthomonas euvesicatoria Causes Bacterial Spot Disease on Pepper Plant in Korea

    Directory of Open Access Journals (Sweden)

    Min-Seong Kyeon

    2016-10-01

    Full Text Available In 2004, bacterial spot-causing xanthomonads (BSX were reclassified into 4 species—Xanthomonas euvesicatoria, X. vesicatoria, X. perforans, and X. gardneri. Bacterial spot disease on pepper plant in Korea is known to be caused by both X. axonopodis pv. vesicatoria and X. vesicatoria. Here, we reidentified the pathogen causing bacterial spots on pepper plant based on the new classification. Accordingly, 72 pathogenic isolates were obtained from the lesions on pepper plants at 42 different locations. All isolates were negative for pectolytic activity. Five isolates were positive for amylolytic activity. All of the Korean pepper isolates had a 32 kDa-protein unique to X. euvesicatoria and had the same band pattern of the rpoB gene as that of X. euvesicatoria and X. perforans as indicated by PCR-restriction fragment length polymorphism analysis. A phylogenetic tree of 16S rDNA sequences showed that all of the Korean pepper plant isolates fit into the same group as did all the reference strains of X. euvesicatoria and X. perforans. A phylogenetic tree of the nucleotide sequences of 3 housekeeping genes—gapA, gyrB, and lepA showed that all of the Korean pepper plant isolates fit into the same group as did all of the references strains of X. euvesicatoria. Based on the phenotypic and genotypic characteristics, we identified the pathogen as X. euvesicatoria. Neither X. vesicatoria, the known pathogen of pepper bacterial spot, nor X. perforans, the known pathogen of tomato plant, was isolated. Thus, we suggest that the pathogen causing bacterial spot disease of pepper plants in Korea is X. euvesicatoria.

  10. Epidemiology of Foodborne Disease Outbreaks Caused by Clostridium perfringens, United States, 1998–2010

    Science.gov (United States)

    Grass, Julian E.; Gould, L. Hannah; Mahon, Barbara E.

    2015-01-01

    Clostridium perfringens is estimated to be the second most common bacterial cause of foodborne illness in the United States, causing one million illnesses each year. Local, state, and territorial health departments voluntarily report C. perfringens outbreaks to the U.S. Centers for Disease Control and Prevention through the Foodborne Disease Outbreak Surveillance System. Our analysis included outbreaks confirmed by laboratory evidence during 1998–2010. A food item was implicated if C. perfringens was isolated from food or based on epidemiologic evidence. Implicated foods were classified into one of 17 standard food commodities when possible. From 1998 to 2010, 289 confirmed outbreaks of C. perfringens illness were reported with 15,208 illnesses, 83 hospitalizations, and eight deaths. The number of outbreaks reported each year ranged from 16 to 31 with no apparent trend over time. The annual number of outbreak-associated illnesses ranged from 359 to 2,173, and the median outbreak size was 24 illnesses. Outbreaks occurred year round, with the largest number in November and December. Restaurants (43%) were the most common setting of food preparation. Other settings included catering facility (19%), private home (16%), prison or jail (11%), and other (10%). Among the 144 (50%) outbreaks attributed to a single food commodity, beef was the most common commodity (66 outbreaks, 46%), followed by poultry (43 outbreaks, 30%), and pork (23 outbreaks, 16%). Meat and poultry outbreaks accounted for 92% of outbreaks with an identified single food commodity. Outbreaks caused by C. perfringens occur regularly, are often large, and can cause substantial morbidity yet are preventable if contamination of raw meat and poultry products is prevented at the farm or slaughterhouse or, after contamination, if these products are properly handled and prepared, particularly in restaurants and catering facilities. PMID:23379281

  11. Epidemiology of foodborne disease outbreaks caused by Clostridium perfringens, United States, 1998-2010.

    Science.gov (United States)

    Grass, Julian E; Gould, L Hannah; Mahon, Barbara E

    2013-02-01

    Clostridium perfringens is estimated to be the second most common bacterial cause of foodborne illness in the United States, causing one million illnesses each year. Local, state, and territorial health departments voluntarily report C. perfringens outbreaks to the U.S. Centers for Disease Control and Prevention through the Foodborne Disease Outbreak Surveillance System. Our analysis included outbreaks confirmed by laboratory evidence during 1998-2010. A food item was implicated if C. perfringens was isolated from food or based on epidemiologic evidence. Implicated foods were classified into one of 17 standard food commodities when possible. From 1998 to 2010, 289 confirmed outbreaks of C. perfringens illness were reported with 15,208 illnesses, 83 hospitalizations, and eight deaths. The number of outbreaks reported each year ranged from 16 to 31 with no apparent trend over time. The annual number of outbreak-associated illnesses ranged from 359 to 2,173, and the median outbreak size was 24 illnesses. Outbreaks occurred year round, with the largest number in November and December. Restaurants (43%) were the most common setting of food preparation. Other settings included catering facility (19%), private home (16%), prison or jail (11%), and other (10%). Among the 144 (50%) outbreaks attributed to a single food commodity, beef was the most common commodity (66 outbreaks, 46%), followed by poultry (43 outbreaks, 30%), and pork (23 outbreaks, 16%). Meat and poultry outbreaks accounted for 92% of outbreaks with an identified single food commodity. Outbreaks caused by C. perfringens occur regularly, are often large, and can cause substantial morbidity yet are preventable if contamination of raw meat and poultry products is prevented at the farm or slaughterhouse or, after contamination, if these products are properly handled and prepared, particularly in restaurants and catering facilities.

  12. Bronchopulmonary Disease Caused by Flagellated Protozoa Infection in 15 Chinese Children.

    Science.gov (United States)

    Liu, Jinrong; Li, Shaogang; Li, Huimin; Fan, Yimu; Yang, Haiming; Xu, Hui; Shen, Yuelin; Zhao, Shunying

    2017-04-01

    Bronchopulmonary disease caused by flagellated protozoa infection (BPFP) is thought to be rare in children but may be an emerging or underestimated disease, especially in developing countries. In this study, we retrospectively reviewed records of 15 patients who were presented with a cough, wheezing or bronchopulmonary disease of unknown causes during admission, and patients who were finally diagnosed with BPFP from January 2014 to January 2015 were enrolled. Protozoa were observed in bronchoalveolar lavage fluid by light microscopy. A total of 15 pediatric cases (11 male and 4 female individuals, from 1 year 8 months to 12 years 1 month of age) with flagellated protozoa infection diagnosed by light microscopy were recruited. The course of the disease at the time of diagnosis was from 10 days to 11 months. Patients presented with a fever (N = 9), cough (N = 11), wheezing (N = 5) and chest pain (N = 5). Laboratory data showed elevated peripheral blood leucocytes (N = 6), eosinophilic granulocytes (N = 3), C-reactive protein (N = 5) and immunoglobulin E (N = 3). Bronchoscopy revealed a mucus plug (N = 3) and bronchiectasis (N = 1). Lung computed tomography results indicated ground-glass opacification (N = 2), atelectasis (N = 3), bronchiectasis (N = 1), bronchial wall thickening (N = 3) or nodular opacity (N = 6, including 1 case of pulmonary embolism). All children responded to metronidazole for a 2- to 5-week treatment period. Patients with BPFP often have a chronic or recurrent course and present with recurrent fever, cough, wheezing and chest pain. Chest imaging may reveal ground-glass opacification, atelectasis, bronchiectasis or nodular opacity (including pulmonary embolism). BPFP responds favorably to metronidazole treatment.

  13. Granulomatous-lymphocytic interstitial lung disease as the first manifestation of common variable immunodeficiency.

    Science.gov (United States)

    Tashtoush, Basheer; Memarpour, Roya; Ramirez, Jose; Bejarano, Pablo; Mehta, Jinesh

    2018-01-01

    Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies, which is characterized by reduced serum immunoglobulin levels and B-lymphocyte dysfunction. There are many clinical manifestations of this disease, the most common of which are recurrent respiratory tract infections. Among the most recently recognized autoimmune manifestation of CVID is a disease described as granulomatous-lymphocytic interstitial lung disease (GLILD), where CVID coexists with a small airway lymphoproliferative disorder, mimicking follicular bronchiolitis, or lymphocytic interstitial pneumonitis (LIP) on histology specimens. We herein describe the clinical and radiological features of GLILD in a 55-year-old woman where the diagnosis of CVID was actively pursued and eventually confirmed after her lung biopsy showed characteristic features of GLILD. The patient had dramatic response to treatment with IVIG and corticosteroids for 3 months followed by Mycophenolate mofetil for maintenance therapy. © 2016 John Wiley & Sons Ltd.

  14. Variability in results from negative binomial models for Lyme disease measured at different spatial scales.

    Science.gov (United States)

    Tran, Phoebe; Waller, Lance

    2015-01-01

    Lyme disease has been the subject of many studies due to increasing incidence rates year after year and the severe complications that can arise in later stages of the disease. Negative binomial models have been used to model Lyme disease in the past with some success. However, there has been little focus on the reliability and consistency of these models when they are used to study Lyme disease at multiple spatial scales. This study seeks to explore how sensitive/consistent negative binomial models are when they are used to study Lyme disease at different spatial scales (at the regional and sub-regional levels). The study area includes the thirteen states in the Northeastern United States with the highest Lyme disease incidence during the 2002-2006 period. Lyme disease incidence at county level for the period of 2002-2006 was linked with several previously identified key landscape and climatic variables in a negative binomial regression model for the Northeastern region and two smaller sub-regions (the New England sub-region and the Mid-Atlantic sub-region). This study found that negative binomial models, indeed, were sensitive/inconsistent when used at different spatial scales. We discuss various plausible explanations for such behavior of negative binomial models. Further investigation of the inconsistency and sensitivity of negative binomial models when used at different spatial scales is important for not only future Lyme disease studies and Lyme disease risk assessment/management but any study that requires use of this model type in a spatial context. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.E.S. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Beal, I. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Dilworth, J.P. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Tormey, V. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Haddock, J. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom)]. E-mail: jamandahaddock@royalfree.nhs.uk

    2005-06-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly.

  16. Estimating the global burden of thalassogenic diseases: human infectious diseases caused by wastewater pollution of the marine environment.

    Science.gov (United States)

    Shuval, Hillel

    2003-06-01

    This paper presents a preliminary attempt at obtaining an order-of-magnitude estimate of the global burden of disease (GBD) of human infectious diseases associated with swimming/bathing in coastal waters polluted by wastewater, and eating raw or lightly steamed filter-feeding shellfish harvested from such waters. Such diseases will be termed thalassogenic--caused by the sea. Until recently these human health effects have been viewed primarily as local phenomena, not generally included in the world agenda of marine scientists dealing with global marine pollution problems. The massive global scale of the problem can be visualized when one considers that the wastewater and human body wastes of a significant portion of the world's population who reside along the coastline or in the vicinity of the sea are discharged daily, directly or indirectly, into the marine coastal waters, much of it with little or no treatment. Every cubic metre of raw domestic wastewater discharged into the sea can carry millions of infectious doses of pathogenic microorganisms. It is estimated that globally, foreign and local tourists together spend some 2 billion man-days annually at coastal recreational resorts and many are often exposed there to coastal waters polluted by wastewater. Annually some 800 million meals of potentially contaminated filter-feeding shellfish/bivalves and other sea foods, harvested in polluted waters are consumed, much of it raw or lightly steamed. A number of scientific studies have shown that swimmers swallow significant amounts of polluted seawater and can become ill with gastrointestinal and respiratory diseases from the pathogens they ingest. Based on risk assessments from the World Health Organization (WHO) and academic research sources the present study has made an estimate that globally, each year, there are in excess of 120 million cases of gastrointestinal disease and in excess of 50 million cases of more severe respiratory diseases caused by swimming and

  17. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013

    NARCIS (Netherlands)

    Naghavi, Mohsen; Wang, Haidong; Lozano, Rafael; Davis, Adrian; Liang, Xiaofeng; Zhou, Maigeng; Vollset, Stein Emil; Ozgoren, Ayse Abbasoglu; Abdalla, Safa; Abd-Allah, Foad; Aziz, Muna I. Abdel; Abera, Semaw Ferede; Aboyans, Victor; Abraham, Biju; Abraham, Jerry P.; Abuabara, Katrina E.; Abubakar, Ibrahim; Abu-Raddad, Laith J.; Abu-Rmeileh, Niveen M. E.; Achoki, Tom; Adelekan, Ademola; Ademi, Zanfi Na; Adofo, Koranteng; Adou, Arsene Kouablan; Adsuar, Jose C.; Aernlov, Johan; Agardh, Emilie Elisabet; Akena, Dickens; Al Khabouri, Mazin J.; Alasfoor, Deena; Albittar, Mohammed; Alegretti, Miguel Angel; Aleman, Alicia V.; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Mohammed K.; Ali, Raghib; Alla, Francois; Al Lami, Faris; Allebeck, Peter; AlMazroa, Mohammad A.; Salman, Rustam Al-Shahi; Alsharif, Ubai; Alvarez, Elena; Alviz-Guzman, Nelson; Amankwaa, Adansi A.; Amare, Azmeraw T.; Ameli, Omid; Hoek, Hans W.

    2015-01-01

    Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries

  18. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, R.M.; Bhutta, Zulfiqar; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coates, M.; Geleijnse, J.M.

    2016-01-01

    Background
    Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249

  19. Managing scab diseases of potato and radish caused by Streptomyces spp. using Bacillus amyloliquefaciens BAC03 and other biomaterials

    Science.gov (United States)

    Streptomyces spp. cause scab disease in plants like potato and radish. To seek effective control methods of this disease, biologically based materials were examined on their efficacies for disease control. In greenhouse or growth chamber tests, potting soil was infested with Streptomyces scabies (10...

  20. Clinical characteristics of chronic kidney disease of nontraditional causes in Salvadoran farming communities.

    Science.gov (United States)

    Herrera, Raúl; Orantes, Carlos M; Almaguer, Miguel; Alfonso, Pedro; Bayarre, Héctor D; Leiva, Irma M; Smith, Magaly J; Cubias, Ricardo A; Torres, Carlos G; Almendárez, Walter O; Cubias, Francisco R; Morales, Fabrizio E; Magaña, Salvador; Amaya, Juan C; Perdomo, Edgard; Ventura, Mercedes C; Villatoro, Juan F; Vela, Xavier F; Zelaya, Susana M; Granados, Delmy V; Vela, Eduardo; Orellana, Patricia; Hevia, Reynaldo; Fuentes, E Jackeline; Mañalich, Reinaldo; Bacallao, Raymed; Ugarte, Mario; Arias, María I; Chávez, Jackelin; Flores, Nelson E; Aparicio, Claudia E

    2014-04-01

    Chronic kidney disease is a serious health problem in El Salvador. Since the 1990s, there has been an increase in cases unassociated with traditional risk factors. It is the second leading cause of death in men aged >18 years. In 2009, it was the first cause of in-hospital death for men and the fifth for women. The disease has not been thoroughly studied. Characterize clinical manifestations (including extrarenal) and pathophysiology of chronic kidney disease of nontraditional causes in Salvadoran farming communities. A descriptive clinical study was carried out in 46 participants (36 men, 10 women), identified through chronic kidney disease population screening of 5018 persons. Inclusion criteria were age 18-59 years; chronic kidney disease at stages 2, 3a and 3b, or at 3a and 3b with diabetes or hypertension and without proteinuria; normal fundoscopic exam; no structural abnormalities on renal ultrasound; and HIV-negative. Examinations included social determinants; psychological assessment; clinical exam of organs and systems; hematological and biochemical parameters in blood and urine; urine sediment analysis; markers of renal damage; glomerular and tubular function; and liver, pancreas and lung functions. Renal, prostate and gynecological ultrasound; and Doppler echocardiography and peripheral vascular and renal Doppler ultrasound were performed. Patient distribution by chronic kidney disease stages: 2 (32.6%), 3a (23.9%), 3b (43.5%). Poverty was the leading social determinant observed. Risk factor prevalence: agrochemical exposure (95.7%), agricultural work (78.3%), male sex (78.3%), profuse sweating during work (76.3%), malaria (43.5%), NSAID use (41.3%), hypertension (36.9%), diabetes (4.3%). General symptoms: arthralgia (54.3%), asthenia (52.2%), cramps (45.7%), fainting (30.4). Renal symptoms: nycturia (65.2%), dysuria (39.1%), foamy urine (63%). Markers of renal damage: macroalbuminuria (80.4%), ß2 microglobulin (78.2%), NGAL (26.1%). Renal function

  1. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

    Science.gov (United States)

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. Copyright© Ferrata Storti

  2. First results of investigations into causes of diseases of cultivated chamomile (Matricaria recutita L. in Germany

    Directory of Open Access Journals (Sweden)

    Gärber, Ute

    2016-07-01

    Full Text Available Diseases on cultivated chamomile have occurred in Germany since 2007, which have severely been affecting the crop yields. The causes of damage are very complex and have not been identified yet. Additionally to the damage in the stems caused by larvae, fungal pathogens are of relevance. Tests of the Julius Kühn-Institute first revealed that a new, not yet identified fungus is pathogenic to chamomile. Symptoms observed in infection tests like chlorosis, browning and black coloration of stems and leaflets were identical to those in the field. The fungus sporulated on diseased plant parts under the conditions of climatic chamber (20 °C to 22 °C and 12 hours of light, 122 μmol from 17 days after inoculation (dai and could be reisolated on agar plates. The identification, biology and epidemiology of the fungus as well as the specific harmful effect and interaction with other harmful factors, especially animal pests, are being studied presently in a project funded by the Agency for Renewable Resources (Fachagentur Nachwachsende Rohstoffe, FNR. The goal is to develop sustainable plant protection concepts based on the knowledge about the pathogens to enable a stable cultivation of chamomile in Germany.

  3. The Nature and Causes of Chronic Obstructive Pulmonary Disease: A Historical Perspective

    Directory of Open Access Journals (Sweden)

    C Peter W Warren

    2009-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is the currently favoured name for the diseases formerly known as emphysema and bronchitis. COPD has been recognized for more than 200 years. Its cardinal symptoms are cough, phlegm and dyspnea, and its pathology is characterized by enlarged airspaces and obstructed airways. In the 19th century, the diagnosis of COPD depended on its symptoms and signs of a hyperinflated chest, and reduced expiratory breath sounds. The airflow obstruction evident on spirometry was identified in that century, but did not enter into clinical practice. Bronchitis, and the mechanical forces required to overcome its obstruction, was believed to be responsible for emphysema, although the inflammation present was recognized. The causes of bronchitis, and hence emphysema, included atmospheric and domestic air pollution, as well as dusty occupations. Cigarette smoking only became recognized as the dominant cause in the 20th century. The lessons learned of the risks for COPD in 19th-century Britain are very pertinent to the world today.

  4. Waldmann's disease: a rare cause of protein losing enteropathy in an adult patient

    Directory of Open Access Journals (Sweden)

    Cláudio Martins

    Full Text Available Primary intestinal lymphangiectasia or Waldmann's disease is an uncommon cause of protein losing enteropathy with an unknown etiology and is usually diagnosed during childhood. It is characterized by dilation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia. Differential diagnosis should include erosive and non-erosive gastrointestinal disorders, conditions involving mesenteric lymphatic obstruction and cardiovascular disorders that increase central venous pressure. Since there are no accurate serological or radiological available tests, enteroscopy with histopathological examination based on intestinal biopsy specimens is currently the gold standard diagnostic modality of intestinal lymphangiectasia. We report a rare case of a primary intestinal lymphangiectasia in a 60-year-old Caucasian female who presented with asymptomatic hypoalbuminemia and hypogammaglobulinemia. After the diagnosis of a protein losing enteropathy, the patient underwent an enteroscopy and biopsies were taken, whose histological examination confirmed dilated intestinal lymphatics with broadened villi of the small bowel. Secondary causes of intestinal lymphangiectasia were excluded and the diagnosis of Waldmann's disease was recorded. The patient was put on a high-protein and low-fat diet with medium-chain triglyceride supplementation with improvement.

  5. Clinical application of multifocal visual evoked potentials in children with epilepsy caused by intracranial disease

    International Nuclear Information System (INIS)

    Yukawa, Eiichi; Kim, Yeong-Jin; Kawasaki, Kensuke; Yoshii, Toshiaki; Hara, Yoshiaki

    2006-01-01

    We investigated whether visual field defects could be objectively evaluated using multifocal visual evoked potential (m-VEP) in two children with epilepsy caused by intracranial disease in whom it was difficult to measure the visual field. To determine normal waves in m-VEP, recording was performed using a visual evoked response imaging system (VERIS) Junior Science program (Mayo, Aichi, Japan) in 20 healthy children (20 eyes) peak latency and amplitude were used for assessment. In the two children with epilepsy, m-VEPs were recorded, and compared with the results of static perimetry or the lesions observed by Magnetic Resonance Imaging (MRI). In the 20 healthy children, there was no significant difference in the peak latency or amplitude among 4 quadrants by one-way analysis of variance. m-VEP in the children with epilepsy showed abnormal waves, corresponding to the visual field defects in the static perimetry or the lesions observed by MRI. Objective evaluation of visual field defects using m-VEP may be useful in children with epilepsy caused by intracranial disease in whom kinetic/static perimetry as a subjective examination is difficult. (author)

  6. Bromodomain Inhibitors Correct Bioenergetic Deficiency Caused by Mitochondrial Disease Complex I Mutations.

    Science.gov (United States)

    Barrow, Joeva J; Balsa, Eduardo; Verdeguer, Francisco; Tavares, Clint D J; Soustek, Meghan S; Hollingsworth, Louis R; Jedrychowski, Mark; Vogel, Rutger; Paulo, Joao A; Smeitink, Jan; Gygi, Steve P; Doench, John; Root, David E; Puigserver, Pere

    2016-10-06

    Mitochondrial diseases comprise a heterogeneous group of genetically inherited disorders that cause failures in energetic and metabolic function. Boosting residual oxidative phosphorylation (OXPHOS) activity can partially correct these failures. Herein, using a high-throughput chemical screen, we identified the bromodomain inhibitor I-BET 525762A as one of the top hits that increases COX5a protein levels in complex I (CI) mutant cybrid cells. In parallel, bromodomain-containing protein 4 (BRD4), a target of I-BET 525762A, was identified using a genome-wide CRISPR screen to search for genes whose loss of function rescues death of CI-impaired cybrids grown under conditions requiring OXPHOS activity for survival. We show that I-BET525762A or loss of BRD4 remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by mutations or chemical inhibition of CI. These studies show that BRD4 inhibition may have therapeutic implications for the treatment of mitochondrial diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Junjie Shao

    2015-05-01

    Full Text Available Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV to highly virulent hemorrhagic fever (HF causing viruses such as Lassa (LASV, Junin (JUNV, Machupo (MACV, Lujo (LUJV, Sabia (SABV, Guanarito (GTOV, and Chapare (CHPV, for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

  8. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Science.gov (United States)

    Sutherland, Kathryn Patterson; Shaban, Sameera; Joyner, Jessica L; Porter, James W; Lipp, Erin K

    2011-01-01

    Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  9. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Directory of Open Access Journals (Sweden)

    Kathryn Patterson Sutherland

    Full Text Available Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS, a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens to a marine invertebrate (A. palmata. These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  10. Two parvoviruses that cause different diseases in mink have different transcription patterns: Transcription analysis of mink enteritis virus and Aleutian mink disease parvovirus the same cell line

    DEFF Research Database (Denmark)

    Storgaard, T.; Oleksiewicz, M.; Bloom, M.E.

    1997-01-01

    The two parvoviruses of mink cause very different diseases, Mink enteritis virus (MEV) is associated with rapid, high-level viral replication and acute disease, In contrast, infection with Aleutian mink disease parvovirus (ADV) is associated with persistent, low-level viral replication and chronic...

  11. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  12. ALS5/SPG11/ KIAA1840 mutations cause autosomal recessive axonal Charcot–Marie–Tooth disease

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L.; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H.; Barsottini, Orlando G. P.; Kawarai, Toshitaka

    2016-01-01

    Abstract Charcot–Marie–Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/ KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot–Marie–Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot–Marie–Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/ KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot–Marie–Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot–Marie–Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot–Marie-Tooth disease (CMT2A2/HMSN2A2/ MFN2 , CMT2B1/ LMNA , CMT2B2/ MED25 , CMT2B5/ NEFL , ARCMT2F/dHMN2B/ HSPB1 , CMT2K/ GDAP1 , CMT2P/ LRSAM1 , CMT2R/ TRIM2 , CMT2S/ IGHMBP2 , CMT2T/ HSJ1 , CMTRID/ COX6A1 , ARAN-NM/ HINT and GAN/ GAN ), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/ PGN , SPG15/ ZFYVE26, SPG21/ ACP33 , SPG35/ FA2H , SPG46/ GBA2 , SPG55/ C12orf65 and SPG56/ CYP2U1 ), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum ( SLC12A6 ) . Mitochondrial disorders related to Charcot–Marie–Tooth disease type 2 were also excluded by sequencing POLG and

  13. Proportion of Pelvic Inflammatory Disease Cases Caused by Chlamydia trachomatis: Consistent Picture From Different Methods.

    Science.gov (United States)

    Price, Malcolm J; Ades, A E; Welton, Nicky J; Simms, Ian; Macleod, John; Horner, Paddy J

    2016-08-15

    Pelvic inflammatory disease (PID) is a leading cause of both tubal factor infertility and ectopic pregnancy. Chlamydia trachomatis is an important risk factor for PID, but the proportion of PID cases caused by C. trachomatis is unclear. Estimates of this are required to evaluate control measures. We consider 5 separate methods of estimating age-group-specific population excess fractions (PEFs) of PID due to C. trachomatis, using routine data, surveys, case-control studies, and randomized controlled trials, and apply these to data from the United Kingdom before introduction of the National Chlamydia Screening Programme. As they are informed by randomized comparisons and national exposure and outcome estimates, our preferred estimates of the proportion of PID cases caused by C. trachomatis are 35% (95% credible interval [CrI], 11%-69%) in women aged 16-24 years and 20% (95% CrI, 6%-38%) in women aged 16-44 years in the United Kingdom. There is a fair degree of consistency between adjusted estimates of PEF, but all have wide 95% CrIs. The PEF decreases from 53.5% (95% CrI, 15.6%-100%) in women aged 16-19 years to 11.5% (95% CrI, 3.0%-25.7%) in women aged 35-44 years. The PEFs of PID due to C. trachomatis decline steeply with age by a factor of around 5-fold between younger and older women. Further studies of the etiology of PID in different age groups are required. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Low physical activity and obesity: causes of chronic disease or simply predictors?

    Science.gov (United States)

    Telford, Richard D

    2007-08-01

    Many studies have shown associations between risk of morbidity and mortality with both obesity and low physical activity (PA), but association does not imply causality. Moreover, there is an inverse relationship between PA and obesity; therefore, controlling for one of these factors when investigating the risk associated with the other is essential. The purpose of this review is to determine whether low PA and obesity actually cause metabolic dysfunction and chronic disease, especially type 2 diabetes (T2D), rather than simply operating as predictors or markers. The case for causality is strengthened if the following two conditions are satisfied: first, that significant associations between obesity or low PA and risk persist after controlling appropriately; and second, that the physiological mechanisms by which obesity or low PA may exert a causal effect are clearly established. The studies examined include those that have used cardiorespiratory (CR) fitness as a surrogate measure for PA, thus also providing evidence for low CR fitness as an independent risk factor in its own right. Low PA and poor CR fitness are independent predictors of mortality related to type 2 diabetes and chronic disease in general. Together with well-demonstrated mechanisms, there is strong evidence that low PA and low CR fitness are direct, independent causes of metabolic dysfunction and type 2 diabetes. Despite some reports to the contrary, there is evidence that both general and visceral obesity are predictors of mortality and morbidity after controlling for PA. However, in the absence of established mechanisms, evidence is insufficient to conclude that either general or visceral obesity is a direct, independent cause of metabolic dysfunction or type 2 diabetes.

  15. Synergistic interaction and mode of action of Citrus hystrix essential oil against bacteria causing periodontal diseases.

    Science.gov (United States)

    Wongsariya, Karn; Phanthong, Phanida; Bunyapraphatsara, Nuntavan; Srisukh, Vimol; Chomnawang, Mullika Traidej

    2014-03-01

    Citrus hystrix de Candolle (Rutaceae), an edible plant regularly used as a food ingredient, possesses antibacterial activity, but there is no current data on the activity against bacteria causing periodontal diseases. C. hystrix essential oil from leaves and peel were investigated for antibiofilm formation and mode of action against bacteria causing periodontal diseases. In vitro antibacterial and antibiofilm formation activities were determined by broth microdilution and time kill assay. Mode of action of essential oil was observed by SEM and the active component was identified by bioautography and GC/MS. C. hystrix leaves oil exhibited antibacterial activity at the MICs of 1.06 mg/mL for P. gingivalis and S. mutans and 2.12 mg/mL for S. sanguinis. Leaf oil at 4.25 mg/mL showed antibiofilm formation activity with 99% inhibition. The lethal effects on P. gingivalis were observed within 2 and 4 h after treated with 4 × MIC and 2 × MIC, respectively. S. sanguinis and S. mutans were completely killed within 4 and 8 h after exposed to 4 × MIC and 2 × MIC of oil. MICs of tested strains showed 4 times reduction suggesting synergistic interaction of oil and chlorhexidine. Bacterial outer membrane was disrupted after treatment with leaves oil. Additionally, citronellal was identified as the major active compound of C. hystrix oil. C. hystrix leaf oil could be used as a natural active compound or in combination with chlorhexidine in mouthwash preparations to prevent the growth of bacteria associated with periodontal diseases and biofilm formation.

  16. Susceptibilities of Chlamydia trachomatis isolates causing uncomplicated female genital tract infections and pelvic inflammatory disease.

    Science.gov (United States)

    Rice, R J; Bhullar, V; Mitchell, S H; Bullard, J; Knapp, J S

    1995-03-01

    The in vitro susceptibilities of 45 recent clinical isolates of Chlamydia trachomatis obtained from women with asymptomatic genital tract infection, mucopurulent cervicitis, or pelvic inflammatory disease to doxycycline, azithromycin, ofloxacin, and clindamycin were determined. In addition, susceptibilities of 12 isolates to amoxicillin and trimethoprim-sulfamethoxazole were also determined. Isolates also were serotyped with a panel of monoclonal antibodies specific for chlamydial major outer membrane protein; 24 of 45 (53%) belonged to serovars Ia and E. For all isolates, the MIC range of doxycycline was 0.008 to 0.06 micrograms/ml, for trimethoprim-sulfamethoxazole it was 0.03 to 0.25 micrograms/ml, for azithromycin it was 0.125 to 2.0 micrograms/ml, for ofloxacin it was 0.5 to 1.0 micrograms/ml, for clindamycin it was 0.25 to 2.0 micrograms/ml, and for amoxicillin it was 0.25 to 4.0 microgram/ml. The ranges of minimum chlamydiacidal concentrations were generally 1 to 4 dilutions above the MICs of most agents, with a rank order similar to those of the MICs. Comparing the minimum chlamydiacidal concentrations for 90% of isolates tested, isolates causing asymptomatic infection belonged to a greater variety of serovars and were relatively more susceptible to doxycycline and azithromycin than isolates causing mucopurulent cervicitis or pelvic inflammatory disease; these differences in susceptibility were not detected among the other study agents. These data indicate that additional studies are needed to better define the apparent association of certain chlamydial serovars with the clinical severity of disease and the in vitro susceptibilities to certain antimicrobial agents.

  17. Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes.

    Science.gov (United States)

    Beres, Stephen B; Kachroo, Priyanka; Nasser, Waleed; Olsen, Randall J; Zhu, Luchang; Flores, Anthony R; de la Riva, Ivan; Paez-Mayorga, Jesus; Jimenez, Francisco E; Cantu, Concepcion; Vuopio, Jaana; Jalava, Jari; Kristinsson, Karl G; Gottfredsson, Magnus; Corander, Jukka; Fittipaldi, Nahuel; Di Luca, Maria Chiara; Petrelli, Dezemona; Vitali, Luca A; Raiford, Annessa; Jenkins, Leslie; Musser, James M

    2016-05-31

    For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that

  18. Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Shao, H.; Chen, H. Z., E-mail: chenhz@enzemed.com; Zhu, J. S. [Department of Infectious Diseases, Taizhou Hospital Affiliated to Wenzhou Medical College, Linhai (China); Ruan, B. [State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou (China); Zhang, Z. Q. [Department of Infectious Disease, Xianju Hospital of Traditional Chinese Medicine, Xianju (China); Lin, X.; Gan, M. F. [Department of Infectious Diseases, Taizhou Hospital Affiliated to Wenzhou Medical College, Linhai (China)

    2015-11-23

    This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

  19. IS RHEUMATIC HEART DISEASE STILL THE MOST COMMON CAUSE OF ATRIAL FIBRILLATION IN INDIA?

    Directory of Open Access Journals (Sweden)

    Lokanath S

    2017-12-01

    Full Text Available BACKGROUND The past decade has witnessed an extraordinary growth in the knowledge regarding atrial fibrillation. It is a heterogeneous rhythm that appears with several conditions and crosses the path of almost all clinicians. It is the most common sustained cardiac arrhythmia and the third leading cause of death due to cardiovascular diseases. The incidence of atrial fibrillation approximately doubles with each decade of adult life and ranges from 2 or 3 new cases per 1000 population per year between the ages of 55 and 64 years to 35 new cases per 1000 population per year between the ages of 85 and 94 years. Although, the vast majority of patients with atrial fibrillation are relatively asymptomatic, patients can have profoundly limiting symptoms. The initial presentation of atrial fibrillation maybe an embolic complication or exacerbation of heart failure, but most patients complain of palpitations, chest pain, dyspnoea, fatigue, lightheadedness or syncope. For patients with symptomatic atrial fibrillation lasting many weeks, initial therapy maybe anticoagulation and rate control while the long-term goal is to restore sinus rhythm. When cardioversion is contemplated and the duration of atrial fibrillation is unknown or exceeds 48 hours, patients who do not require long-term anticoagulation may benefit from short-term anticoagulation. If rate control offers inadequate symptomatic relief, restoration of sinus rhythm becomes a clear long-term goal. Early cardioversion may be necessary, if atrial fibrillation causes hypotension or worsening heart failure. Experimental studies have explored the mechanisms of the onset and maintenance of the arrhythmia; drugs have been tailored to specific cardiac ion channels; non-pharmacologic therapies have been introduced that are designed to control or prevent atrial fibrillation; and data have emerged that demonstrate a genetic predisposition in some patients. MATERIALS AND METHODS It is a prospective

  20. Snake fungal disease caused by Ophidiomyces ophiodiicola in a free-ranging mud snake (Farancia abacura).

    Science.gov (United States)

    Last, Lisa A; Fenton, Heather; Gonyor-McGuire, Jessica; Moore, Matthew; Yabsley, Michael J

    2016-11-01

    Snake fungal disease is an emerging infectious disease caused by the fungus Ophidiomyces ophiodiicola leading to severe dermatitis and facial disfiguration in numerous free-ranging and captive snakes. A free-ranging mud snake (Farancia abacura) from Bulloch County, Georgia, was presented for autopsy because of facial swelling and emaciation. Extensive ulceration of the skin, which was especially severe on the head, and retained shed were noted on external examination. Microscopic examination revealed severe heterophilic dermatitis with intralesional fungal hyphae and arthroconidia consistent with O. ophiodiicola A skin sample incubated on Sabouraud dextrose agar yielded a white-to-tan powdery fungal culture that was confirmed to be O. ophiodiicola by polymerase chain reaction and sequence analysis. Heavy infestation with adult tapeworms (Ophiotaenia faranciae) was present within the intestine. Various bacterial and fungal species, interpreted to either be secondary invaders or postmortem contaminants, were associated with oral lesions. Although the role of these other organisms in the overall health of this individual is not known, factors such as concurrent infections or immunosuppression should be considered in order to better understand the overall manifestation of snake fungal disease, which remains poorly characterized in its host range and geographic distribution. © 2016 The Author(s).

  1. Cacao Phylloplane: The First Battlefield against Moniliophthora perniciosa, Which Causes Witches' Broom Disease.

    Science.gov (United States)

    Almeida, D S M; Gramacho, K P; Cardoso, T H S; Micheli, F; Alvim, F C; Pirovani, C P

    2017-07-01

    The phylloplane is the first contact surface between Theobroma cacao and the fungus Moniliophthora perniciosa, which causes witches' broom disease (WBD). We evaluated the index of short glandular trichomes (SGT) in the cacao phylloplane and the effect of irrigation on the disease index of cacao genotypes with or without resistance to WBD, and identified proteins present in the phylloplane. The resistant genotype CCN51 and susceptible Catongo presented a mean index of 1,600 and 700 SGT cm -2 , respectively. The disease index in plants under drip irrigation was reduced by approximately 30% compared with plants under sprinkler irrigation prior to inoculation. Leaf water wash (LWW) of the cacao inhibited the germination of spores by up to 98%. Proteins from the LWW of CCN51 were analyzed by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by tandem mass spectrometry. The gel showed 71 spots and identified a total of 42 proteins (28 from the plant and 14 from bacteria). Proteins related to defense and synthesis of defense metabolites and involved in nucleic acid metabolism were identified. The results support the hypothesis that the proteins and water-soluble compounds secreted to the cacao phylloplane participate in the defense against pathogens. They also suggest that SGT can contribute to the resistance of cacao.

  2. Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by Coxsackie virus A6.

    Science.gov (United States)

    Feder, Henry M; Bennett, Nicholas; Modlin, John F

    2014-01-01

    A previously well infant aged 9 months presented with an acute, self-limiting illness characterised by high fever and a papular eruption that started on the face. Although fever subsided within 3 days, the rash worsened and extended over the whole body, with some papules evolving into vesiculobullous lesions. The infant had been exposed to children with a similar illness 1 week before onset. PCR of vesicular swabs and stool samples taken on day 6 of illness showed Coxsackie virus A6. The illness resolved within 10 days of onset, although onychomadesis was seen on both big toes at follow-up 5 weeks later. Our case exemplifies the severe, atypical cases of hand, foot, and mouth disease that have been reported worldwide since 2008, and in the USA since the 2011. Atypical hand, foot, and mouth disease is caused by a new lineage of Coxsackie virus A6 and is characterised by high fever and vesiculobullous eruptions on the calves and backs of the hands. Infants with eczema might be predisposed to severe disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias

    Directory of Open Access Journals (Sweden)

    Matute-Cruz Petra

    2009-04-01

    Full Text Available Abstract Background Mortality from invasive meningococcal disease (IMD has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods A retrospective analysis was made of clinical reports of all patients (n = 848 diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and pre-hospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results Data were recorded on 848 patients, 49 (5.72% of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93. Conclusion Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

  4. Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias.

    Science.gov (United States)

    Perea-Milla, Emilio; Olalla, Julián; Sánchez-Cantalejo, Emilio; Martos, Francisco; Matute-Cruz, Petra; Carmona-López, Guadalupe; Fornieles, Yolanda; Cayuela, Aurelio; García-Alegría, Javier

    2009-04-03

    Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and pre-hospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15-0.93). Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

  5. End-of-life care for people with chronic kidney disease: cause of death, place of death and hospital costs.

    Science.gov (United States)

    Kerr, Marion; Matthews, Beverley; Medcalf, James F; O'Donoghue, Donal

    2017-09-01

    End-of-life care for people with chronic kidney disease (CKD) has been identified as an area of great clinical need internationally. We estimate causes and place of death and cost of hospital care for people with CKD in England in the final 3 years of life. Hospital Episode Statistics data were linked to Office for National Statistics mortality data to identify all patients in England aged ≥18 years who died 1 April 2006-31 March 2010, and had a record of hospital care after 1 April 2003 (the study group). The underlying cause and place of death were examined in Office for National Statistics data, for patients without and with CKD (identified by International Classification of Diseases version 10 codes N18, I12 and I13). Costs of hospital admissions and outpatient attendances were estimated using National Health Service Reference Cost data. Associations between CKD and hospital costs, and between place of death and hospital costs in those with CKD, were examined using multivariate regressions. There were 1 602 105 people in the study group. Of these, 13.2% were recorded as having CKD. The proportion of deaths at home was 10.7% in people with CKD and 17.2% in the age- and gender-matched non-CKD group. Regression analysis suggests that CKD was associated with an increase in hospital costs of £3380 in the last 12 months of life, holding constant place of death, comorbidities and other variables. For the CKD group, home death was associated with a reduction in hospital costs of £2811 in the 12 months before death. The most commonly recorded cause of death in people with CKD was heart disease. CKD was not mentioned on the death certificate in two-thirds of deaths in people with the condition. People with CKD are less likely to die at home than those without CKD. The condition is associated with increased hospital costs at the end of life regardless of place of death. Home death in CKD is associated with a substantial reduction in hospital costs at the end of life

  6. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

    Directory of Open Access Journals (Sweden)

    Patricia Blanchet

    2017-08-01

    Full Text Available Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense. The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  7. Needs for Flexibility Caused by the Variability and Uncertainty in Wind and Solar Generation in 2020, 2030 and 2050 Scenarios

    DEFF Research Database (Denmark)

    Koivisto, Matti Juhani; Sørensen, Poul Ejnar; Maule, Petr

    The growing share of variable renewable energy sources (VRE) in Nordic and Baltic countries is expected to increase the need for flexibility in the energy systems. VRE generation is highly variable because it is determined by weather conditions, and it is uncertain due to forecasting errors. Both...

  8. Social Support: a Key Variable for Health Promotion and Chronic Disease Management in Hispanic Patients with Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    Alyssa T. Brooks

    2014-01-01

    Full Text Available Chronic diseases, including rheumatic diseases, can cause immense physical and psychosocial burden for patients. Many Hispanics suffering with arthritis face activity limitations. Social support, or the functional content of relationships, may be important to consider when examining treatment and outcomes for Hispanic individuals. Participants were recruited from an urban community health center (CHC as part of a larger health behavior study. A cross-sectional, descriptive, mixed methods analysis was conducted to explore the role of social support in the sample. Only Hispanic/Latino patients (n = 46 were included in this analysis. Interviews were conducted in both English and Spanish. The majority of the sample (87% perceived some presence of social support in their lives. The two most commonly cited types of social support were emotional and instrumental. The two most common sources of social support were family members other than spouses (52.2% and spouses (32.6%. Body mass index (BMI was significantly correlated with the number of perceived sources of support. The presence or absence and the role of social support in supporting optimal health outcomes should be considered for Hispanics with chronic rheumatic diseases. Involving family members and spouses in the plan of care for this population could facilitate health promotion and chronic disease management.

  9. Accounting for Pharmacokinetic Variability of Certolizumab Pegol in Patients with Crohn's Disease.

    Science.gov (United States)

    Vande Casteele, Niels; Mould, Diane R; Coarse, Jason; Hasan, Iram; Gils, Ann; Feagan, Brian; Sandborn, William J

    2017-12-01

    Certolizumab pegol is an effective biologic for patients with Crohn's disease (CD). Individual differences in certolizumab pegol apparent clearance (CL/F) affect exposure and possibly efficacy. A previously developed population pharmacokinetic (PK) model did not account for dynamic changes in clinical parameters during therapy. The aim of this study was to refine the existing PK model to capture the time-varying influence of covariates. Data collected from 2157 Crohn's disease patients in nine studies were analyzed using nonlinear mixed-effects modeling software (NONMEM). Certolizumab pegol concentration-time data were described by a one-compartment PK model with first-order absorption, and one-compartment disposition with linear, time-dependent elimination using antidrug antibody (ADAb) concentration as a continuous variable. The final dataset consisted of 12,926 analyzable records. Parameter estimates were absorption rate constant 1.83/day, CL/F 0.527 L/day, and apparent volume of distribution (V/F) 8.33 L. ADAb concentration (2.5-214 units/mL) increased the median CL/F by 142-174%. For a typical patient, body weight (46.8-100.5 kg) increased the median CL/F and V/F from 82 to 120%. Albumin (32-48 g/L) decreased and C-reactive protein (0.5-54.0 mg/L) increased the median CL/F from 123 to 85% and from 83 to 113%, respectively. Between-patient variability of CL/F was 19.6%. By incorporating time-varying covariates, this population PK model reduces between-patient variability on CL/F estimates, and the relative influence of ADAb can now be assessed. As Crohn's disease patient covariates are often time-dependent, this model is more reflective of patient drug exposure with sustained treatment.

  10. Association of blood pressure variability and neurocognition in children with chronic kidney disease.

    Science.gov (United States)

    Lande, Marc B; Mendley, Susan R; Matheson, Matthew B; Shinnar, Shlomo; Gerson, Arlene C; Samuels, Joshua A; Warady, Bradley A; Furth, Susan L; Hooper, Stephen R

    2016-11-01

    Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV), which has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine whether children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV. This was a cross-sectional and longitudinal analysis of the relation between BPV and neurocognitive test performance in children ≥6 years enrolled in the Chronic Kidney Disease in Children (CKiD) study. Visit-to-visit BPV was assessed by the standard deviation of visit BPs (BPV-SD) and average real variability (ARV). Ambulatory BPV was assessed by SD of wake and sleep periods on 24-h ambulatory BP monitoring. We assessed 650 children with a mean follow-up period of 4.0 years. Children with systolic visit-to-visit BPV in the upper tertile had lower scores on Delis-Kaplan Executive Function System (D-KEFS) Verbal Category Switching than those with BPV in the lower tertile (BPV-SD, 8.3 vs. 9.5, p = 0.006; ARV, 8.5 vs. 9.6, p = 0.02). On multivariate analysis, the association between lower Category Switching score and increased BPV remained significant after controlling for mean BP, demographic characteristics, and disease-related variables [BPV-SD, β = -0.7, 95 % confidence interval (CI) -1.28 to -0.12; ARV, β = -0.54, CI -1.05 to -0.02). Ambulatory BPV was not independently associated with any cognitive measure. Higher systolic visit-to-visit BPV was independently associated with decreased D-KEFS Category Switching scores in children with mild-to-moderate CKD.

  11. Renal transplantation in systemic lupus erythematosus: Comparison of graft survival with other causes of end-stage renal disease.

    Science.gov (United States)

    Horta-Baas, Gabriel; Camargo-Coronel, Adolfo; Miranda-Hernández, Dafhne Guadalupe; Gónzalez-Parra, Leslie Gabriela; Romero-Figueroa, María Del Socorro; Pérez-Cristóbal, Mario

    2017-08-14

    End-stage renal disease (ESRD) due to lupus nephritis (LN) occurs in 10%-30% of patients. Initially systemic lupus erythematosus (SLE) was a contraindication for kidney transplantation (KT). Today, long-term graft survival remains controversial. Our objective was to compare the survival after KT in patients with SLE or other causes of ESRD. All SLE patients who had undergone KT in a retrospective cohort were included. Renal graft survival was compared with that of 50 controls, matched for age, sex, and year of transplantation. Survival was evaluated by the Kaplan-Meier test and the Cox proportional hazards model. Twenty-five subjects with SLE were included. The estimated 1-year, 2- and 5-year survival rates for patients with SLE were 92%, 66% and 66%. Renal graft survival did not differ between patients with SLE and other causes of ESRD (P=.39). The multivariate analysis showed no significant difference in graft survival between the two groups (hazard ratio, HR=1.95, 95% confidence interval [CI] 0.57-6.61, P=.28). The recurrence rate of LN was 8% and was not associated with graft loss. Acute rejection was the only variable associated with graft loss in patients with SLE (HR=16.5, 95% CI 1.94-140.1, P=.01). Renal graft survival in SLE patients did not differ from that reported for other causes of ESRD. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  12. Influenza A (H10N7 Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

    Directory of Open Access Journals (Sweden)

    Judith M A van den Brand

    Full Text Available Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7 in harbor seals (Phoca vitulina. This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals

  13. Association of body mass index with all-cause and cardiovascular disease mortality in the elderly.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Wu

    Full Text Available OBJECTIVES: To evaluate the associations of body mass index (BMI with all-cause, cardiovascular disease (CVD, and expanded CVD mortality in the elderly. DESIGN: Observational cohort study. SETTING: Annual physical examination program for the elderly from 2006 to 2010. PARTICIPANTS: We included 77,541 Taipei residents aged ≥ 65 years (39,365 men and 38,176 women. MEASUREMENTS: BMI was categorized as underweight (BMI<18.5, normal weight (18.5 ≤ BMI<25, overweight (25 ≤ BMI<30, grade 1 obesity (30 ≤ BMI<35, or grade 2-3 obesity (BMI ≥ 35. Mortality was ascertained by national death files. RESULTS: Underweight (hazard ratios [HRs] of all-cause, CVD, and expanded CVD mortality: 1.92, 1.74, and 1.77, respectively, grade 2-3 obesity (HRs: 1.59, 2.36, and 2.22, respectively, older age, male sex, smoking, and high fasting blood sugar were significant predictors of mortality. Meanwhile, being married/cohabitating, higher education, alcohol consumption, more regular exercise, and high total cholesterol were inversely associated with mortality. Multivariate stratified subgroup analyses verified smokers (HRs of all-cause, CVD, and expanded CVD mortality: 3.25, 10.71, and 7.86, respectively, for grade 2-3 obesity, the high triglyceride group (HRs: 5.82, 10.99, and 14.22, respectively for underweight, and patients with 3-4 factors related to metabolic syndrome (HRs: 4.86, 12.72, and 11.42, respectively, for underweight were associated with mortality. CONCLUSION: The associations of BMI with all-cause, CVD, expanded CVD mortality in the elderly are represented by U-shaped curves, suggesting unilateral promotions or interventions in weight reduction in the elderly may be inappropriate. Heterogeneous effects of grades 1 and 2-3 obesity on mortality were observed and should be treated as different levels of obesity.

  14. Localized Cystic Disease of the Kidney: A Rare Cause of Hypertension in a Young Adult

    Directory of Open Access Journals (Sweden)

    Aynur Solak

    2013-01-01

    Full Text Available Localized cystic disease of kidney (LCDK is a rare, non-familial, non-progressive renal disorder that is not associated with cysts or disorders in other organs. Only a few cases have been reported in the literature. While this condition is morphologically identical to the autosomal dominant form of polycystic kidney disease, it is not inherited and is not associated with significant deterioration of renal function. We present a case of a 16-year-old male patient who suffered from hypertension for over two years. On imaging we found several, variable-sized cysts in the upper half of the right kidney. The left kidney and lower segment of the right kidney were normal. Selective renal vein catheterization and sampling showed markedly elevated renin level in the right upper segmental vein (92 pg/ml, normal value: 11-33 pg/ml. The patient underwent a right upper heminephrectomy and histopathology was suggestive of LCDK. After surgery, the patient′s blood pressure returned to normal levels without any need of antihypertensive medication and he is under follow-up on outpatient basis for the past two years.

  15. Sulfhydryl variable-5 extended spectrum β-lactamase in nosocomial enteric bacteria causing sepsis in mexican children

    Directory of Open Access Journals (Sweden)

    Angélica Flores-Pérez

    2015-10-01

    Full Text Available Introduction: Enteric bacteria causing nosocomial infections are often resistant to third-generation cephalosporins due to the production of extended-spectrum β-lactamases (ESBLs. Objective: To describe and characterize the ESBLs pattern present in Klebsiella pneumoniae and Serratia marcescens strains, isolated as causative of nosocomial sepsis in pediatric patients at Instituto Nacional de Pediatría (National Institute of Pediatrics. Material and methods: We analyzed 94 strains of K. pneumoniae and 7 of S. marcescens isolated from clinical specimens from 2002-2005, causative of sepsis in a children’s hospital. We evaluated antibiotic susceptibility and detection of ESBL phenotypes by disk diffusion methods; ceftazidime-resistant isolates were further characterized by pulsed field gel electrophoresis (PFGE; and ESBLs were phenotypically and genotypically characterized by isoelectric focusing, polymerase chain reaction (PCR and sequencing. We also assed for presence of conjugative plasmids bearing the ESBL gene. Results: 51/94 (54% of K. pneumoniae isolates, and 5/7 (71% of S. marcescens isolates were resistant to ceftazidime; all carried a blaSHV-5 gene. All K. pneumoniae isolates had a distinct PFGE profile, yet all carried a ~48-Kb plasmid, that was conjugatively transferable to an Escherichia coli receptor, which expressed the resistance phenotype. On the other hand, all S. marcescens isolates had a similar PFGE profile, were unable to transfer the ceftazidime-resistance phenotype, and were isolated from the same ward in a short time-span suggesting an outbreak. Conclusions: The overall prevalence of ESBL-producing enteric bacteria in this hospital is high but similar to other Latin American reports. The sulfhydryl variable-5 (SHV-5 ESBL gene appears to reside in a highly mobile plasmid, capable of spreading among different K. pneumoniae clones and perhaps even to S. marcescens.

  16. Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution?

    Directory of Open Access Journals (Sweden)

    María Carmen Cenit

    2015-08-01

    Full Text Available It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD patients, untreated and treated with a gluten-free diet (GFD, compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant’s gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc. could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis.

  17. Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution?

    Science.gov (United States)

    Cenit, María Carmen; Olivares, Marta; Codoñer-Franch, Pilar; Sanz, Yolanda

    2015-08-17

    It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant's gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis.

  18. Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution?

    Science.gov (United States)

    Cenit, María Carmen; Olivares, Marta; Codoñer-Franch, Pilar; Sanz, Yolanda

    2015-01-01

    It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant’s gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis. PMID:26287240

  19. Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim-Chester disease.

    Science.gov (United States)

    Chiapparini, Luisa; Cavalli, Giulio; Langella, Tiziana; Venerando, Anna; De Luca, Giacomo; Raspante, Sergio; Marotta, Giorgio; Pollo, Bianca; Lauria, Giuseppe; Cangi, Maria Giulia; Gerevini, Simonetta; Botturi, Andrea; Pareyson, Davide; Dagna, Lorenzo; Salsano, Ettore

    2018-02-01

    Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL. We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD. There were seven males and three females; mean age at clinical onset was 49.6 years (range 38-59); cerebellar ataxia with or without other neurological symptoms was the only or the main clinical manifestation; diabetes insipidus was present in three individuals. Eight patients had white matter focal supratentorial abnormalities, in addition to the infratentorial white matter changes. Six out of eight patients had spinal cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients, whole-body FDG-PET revealed increased glucose uptake in the long bones of the legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism in one patient. In eight patients, ECD was confirmed by bone scintigraphy, pathological data, or both. Two ECD patients treated with vemurafenib showed a marked improvement of neurological symptoms and brain MRI abnormalities at 1 year follow-up. Symptoms of PIL can be the only clinical manifestation of ECD. Adult patients with PIL of unknown origin should undergo investigations aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The early diagnosis allows starting disease-modifying therapies of an otherwise life-threatening disease.

  20. [Sickle cell anemia causes varied symptoms and high morbidity. Serious prognosis in the most common genetic disease in the world].

    Science.gov (United States)

    Kjellander, Christian; Sennström, Maria K B; Stiller, Viveka; Ågren, Anna

    2015-03-03

    Sickle cell anemia is a life-threatening disease, and the most common genetic disease in the world. The prevalence of sickle cell anemia in Sweden is unknown. Sickle cell anemia is an important disease, because of its variable complications, in many medical and surgical specialties. The overview highlights common medical problems encountered in sickle cell anemia presented through a case report of a pregnant woman.

  1. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

    Science.gov (United States)

    Oláhová, Monika; Hardy, Steven A; Hall, Julie; Yarham, John W; Haack, Tobias B; Wilson, William C; Alston, Charlotte L; He, Langping; Aznauryan, Erik; Brown, Ruth M; Brown, Garry K; Morris, Andrew A M; Mundy, Helen; Broomfield, Alex; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Moeslinger, Dorothea; Koch, Johannes; Stettner, Georg M; Bonnen, Penelope E; Prokisch, Holger; Lightowlers, Robert N; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Taylor, Robert W

    2015-12-01

    Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients' fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels

  2. Dairy Food Intake and All-Cause, Cardiovascular Disease, and Cancer Mortality: The Golestan Cohort Study.

    Science.gov (United States)

    Farvid, Maryam S; Malekshah, Akbar F; Pourshams, Akram; Poustchi, Hossein; Sepanlou, Sadaf G; Sharafkhah, Maryam; Khoshnia, Masoud; Farvid, Mojtaba; Abnet, Christian C; Kamangar, Farin; Dawsey, Sanford M; Brennan, Paul; Pharoah, Paul D; Boffetta, Paolo; Willett, Walter C; Malekzadeh, Reza

    2017-04-15

    We investigated the association between dairy product consumption and all-cause, cardiovascular disease (CVD), and cancer mortality in the Golestan Cohort Study, a prospective cohort study launched in January 2004 in Golestan Province, northeastern Iran. A total of 42,403 men and women participated in the study and completed a diet questionnaire at enrollment. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. We documented 3,291 deaths (1,467 from CVD and 859 from cancer) during 11 years of follow-up (2004-2015). The highest quintile of total dairy product consumption (versus the lowest) was associated with 19% lower all-cause mortality risk (hazard ratio (HR) = 0.81, 95% confidence interval (CI): 0.72, 0.91; Ptrend = 0.006) and 28% lower CVD mortality risk (HR = 0.72, 95% CI: 0.60, 0.86; Ptrend = 0.005). High consumption of low-fat dairy food was associated with lower risk of all-cause (HR = 0.83, 95% CI: 0.73, 0.94; Ptrend = 0.002) and CVD (HR = 0.74, 95% CI: 0.61, 0.89; Ptrend = 0.001) mortality. We noted 11% lower all-cause mortality and 16% lower CVD mortality risk with high yogurt intake. Cheese intake was associated with 16% lower all-cause mortality and 26% lower CVD mortality risk. Higher intake of high-fat dairy food and milk was not associated with all-cause or CVD mortality. Neither intake of individual dairy products nor intake of total dairy products was significantly associated with overall cancer mortality. High consumption of dairy products, especially yogurt and cheese, may reduce the risk of overall and CVD mortality. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Disaggregation of Cause-Specific Cardiovascular Disease Mortality Among Hispanic Subgroups.

    Science.gov (United States)

    Rodriguez, Fatima; Hastings, Katherine G; Boothroyd, Derek B; Echeverria, Sandra; Lopez, Lenny; Cullen, Mark; Harrington, Robert A; Palaniappan, Latha P

    2017-03-01

    Hispanics are the largest minority group in the United States and face a disproportionate burden of risk factors for cardiovascular disease (CVD) and low socioeconomic position. However, Hispanics paradoxically experience lower all-cause mortality rates compared with their non-Hispanic white (NHW) counterparts. This phenomenon has been largely observed in Mexicans, and whether this holds true for other Hispanic subgroups or whether these favorable trends persist over time remains unknown. To disaggregate a decade of national CVD mortality data for the 3 largest US Hispanic subgroups. Deaths from CVD for the 3 largest US Hispanic subgroups-Mexicans, Puerto Ricans, and Cubans-compared with NHWs were extracted from the US National Center for Health Statistics mortality records using the underlying cause of death based on coding from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (I00-II69). Mortality data were evaluated from January 1, 2003, to December 31, 2012. Population estimates were calculated using linear interpolation from the 2000 and 2010 US Census reports. Data were analyzed from November 2015 to July 2016. Mortality due to CVD. Participants included 688 074 Mexican, 163 335 Puerto Rican, 130 397 Cuban, and 19 357 160 NHW individuals (49.0% men and 51.0% women; mean [SD] age, 75 [15] years). At the time of CVD death, Mexicans (age, 67 [18] years) and Puerto Ricans (age, 68 [17] years) were younger compared with NHWs (age, 76 [15] years). Mortality rates due to CVD decreased from a mean of 414.2 per 100 000 in 2003 to 303.3 per 100 000 in 2012. Estimated decreases in mortality rate for CVD from 2003 to 2012 ranged from 85 per 100 000 for all Hispanic women to 144 per 100 000 for Cuban men, but rate differences between groups vary substantially, with Puerto Ricans exhibiting similar mortality patterns to NHWs, and Mexicans experiencing lower mortality. Puerto Ricans experienced higher

  4. Disaggregation of Cause-Specific Cardiovascular Disease Mortality Among Hispanic Subgroups

    Science.gov (United States)

    Rodriguez, Fatima; Hastings, Katherine G.; Boothroyd, Derek B.; Echeverria, Sandra; Lopez, Lenny; Cullen, Mark; Harrington, Robert A.; Palaniappan, Latha P.

    2017-01-01

    IMPORTANCE Hispanics are the largest minority group in the United States and face a disproportionate burden of risk factors for cardiovascular disease (CVD) and low socioeconomic position. However, Hispanics paradoxically experience lower all-cause mortality rates compared with their non-Hispanic white (NHW) counterparts. This phenomenon has been largely observed in Mexicans, and whether this holds true for other Hispanic subgroups or whether these favorable trends persist over time remains unknown. OBJECTIVE To disaggregate a decade of national CVD mortality data for the 3 largest US Hispanic subgroups. DESIGN, SETTING, AND PARTICIPANTS Deaths from CVD for the 3 largest US Hispanic subgroups—Mexicans, Puerto Ricans, and Cubans—compared with NHWs were extracted from the US National Center for Health Statistics mortality records using the underlying cause of death based on coding from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (I00-II69). Mortality data were evaluated from January 1, 2003, to December 31, 2012. Population estimates were calculated using linear interpolation from the 2000 and 2010 US Census reports. Data were analyzed from November 2015 to July 2016. MAIN OUTCOMES AND MEASURES Mortality due to CVD. RESULTS Participants included 688 074 Mexican, 163 335 Puerto Rican, 130 397 Cuban, and 19 357 160 NHW individuals (49.0 % men and 51.0% women; mean [SD] age, 75 [15] years). At the time of CVD death, Mexicans (age, 67 [18] years) and Puerto Ricans (age, 68 [17] years) were younger compared with NHWs (age, 76 [15] years). Mortality rates due to CVD decreased from a mean of 414.2 per 100 000 in 2003 to 303.3 per 100 000 in 2012. Estimated decreases in mortality rate for CVD from 2003 to 2012 ranged from 85 per 100 000 for all Hispanic women to 144 per 100 000 for Cuban men, but rate differences between groups vary substantially, with Puerto Ricans exhibiting similar mortality patterns to NHWs

  5. Cardiovascular disease, risk factors and heart rate variability in the elderly general population: Design and objectives of the CARdiovascular disease, Living and Ageing in Halle (CARLA Study

    Directory of Open Access Journals (Sweden)

    Kuss Oliver

    2005-11-01

    Full Text Available Abstract Background The increasing burden of cardiovascular diseases (CVD in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic. In order to improve prevention, detection, therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany, it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality, potential causal mechanisms and prognostic factors in the elderly. Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient. A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age. Nevertheless, there is a lack of population-based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population. There also is a paucity of epidemiological data describing the health situation in Eastern Germany. Therefore, we conduct a population-based study to examine the distribution of CVD, heart rate variability and CVD risk factors and their associations in an elderly East German population. This paper describes the design and objectives of the CARLA Study. Methods/design For this study, a random sample of 45–80 year-old inhabitants of the city of Halle (Saale in Eastern Germany was drawn from the population registry. By the end of the baseline examination (2002–2005, 1750 study participants will have been examined. A multi-step recruitment strategy aims at achieving a 70 % response rate. Detailed information is collected on own and family medical history, socioeconomic, psychosocial, behavioural and biomedical factors. Medical examinations include anthropometric measures, blood pressure of arm and ankle, a 10-second and a 20

  6. Factors associated with the variability in caregiver assessments of the capacities of patients with Alzheimer disease.

    Science.gov (United States)

    Conde-Sala, Josep L; Reñé-Ramírez, Ramón; Turró-Garriga, Oriol; Gascón-Bayarri, Jordi; Juncadella-Puig, Montserrat; Moreno-Cordón, Laura; Viñas-Diez, Vanesa; Vilalta-Franch, Joan; Garre-Olmo, Josep

    2013-06-01

    Several studies have identified certain caregiver factors that can produce variability in their assessments of the capacities of patients with Alzheimer disease (AD). To identify the caregiver variables associated with variability in their ratings of patients' capacities. Consecutive sample of 221 outpatients with AD and their family caregivers. The capacities evaluated by caregivers were the degree of functional disability, using the Disability Assessment for Dementia (DAD); psychological and behavioral symptoms, via the Neuropsychiatric Inventory (NPI); anosognosia, with the Anosognosia Questionnaire-Dementia (AQ-D); and quality of life, using the Quality of Life in AD (QOL-AD). The relationship between these measures and caregiver's gender, burden, depression, and health was analyzed by means of a bivariate analysis, calculating the effect size (Cohen d) and subsequently by a regression analysis, calculating the contribution coefficient (CC). The greatest variability in caregiver assessments was observed in relation to patients with early-stage dementia, where caregiver's burden was the main factor associated with a more negative evaluation (d = 1.02-1.25). Depression in the caregiver was associated with less variability and only in the assessments of patients with moderate dementia (d = 0.38-0.69). In the regression analysis, caregiver factors were associated with greater variance in scores on the NPI (CC = 37.4%) and QOL-AD (CC = 27.2%), and lower variance in AQ-D (CC = 21.6%) and DAD (CC = 10.3%) scores. Caregiver's burden and depression were associated with more negative assessments of patients' psychological and behavioral symptoms and quality of life.

  7. A Validated Smartphone-Based Assessment of Gait and Gait Variability in Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Robert J Ellis

    Full Text Available A well-established connection exists between increased gait variability and greater fall likelihood in Parkinson's disease (PD; however, a portable, validated means of quantifying gait variability (and testing the efficacy of any intervention remains lacking. Furthermore, although rhythmic auditory cueing continues to receive attention as a promising gait therapy for PD, its widespread delivery remains bottlenecked. The present paper describes a smartphone-based mobile application ("SmartMOVE" to address both needs.The accuracy of smartphone-based gait analysis (utilizing the smartphone's built-in tri-axial accelerometer and gyroscope to calculate successive step times and step lengths was validated against two heel contact-based measurement devices: heel-mounted footswitch sensors (to capture step times and an instrumented pressure sensor mat (to capture step lengths. 12 PD patients and 12 age-matched healthy controls walked along a 26-m path during self-paced and metronome-cued conditions, with all three devices recording simultaneously.Four outcome measures of gait and gait variability were calculated. Mixed-factorial analysis of variance revealed several instances in which between-group differences (e.g., increased gait variability in PD patients relative to healthy controls yielded medium-to-large effect sizes (eta-squared values, and cueing-mediated changes (e.g., decreased gait variability when PD patients walked with auditory cues yielded small-to-medium effect sizes-while at the same time, device-related measurement error yielded small-to-negligible effect sizes.These findings highlight specific opportunities for smartphone-based gait analysis to serve as an alternative to conventional gait analysis methods (e.g., footswitch systems or sensor-embedded walkways, particularly when those methods are cost-prohibitive, cumbersome, or inconvenient.

  8. Myeloproliferative Disease: An Unusual Cause of Raynaud's Phenomenon and Digital Ischaemia.

    Science.gov (United States)

    Beynon, Celia; Huws, Gwenan; Lawson, Tom

    2016-01-01

    We describe a 59-year-old female who presented with ischaemic digits, preceded by a 6-month history of Raynaud's phenomenon affecting her fingers and toes. There were no clinical or laboratory features of primary vasculitis or connective tissue disease, Doppler imaging was normal, and bloods were unremarkable aside from a platelet count of 786 × 109/L (150-400) and white cells of 16 × 109/L (4-11). In view of the thrombocytosis a JAK2 mutation assay was requested which confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET) as the cause. She received treatment with hydroxycarbamide which normalised her platelet count and led to a complete resolution of her Raynaud's symptoms. Raynaud's phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET should be considered in the differential diagnosis of Raynaud's phenomenon and vasculitis.

  9. Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia

    Science.gov (United States)

    NikNadia, NMN; Sam, I-Ching; Rampal, Sanjay; WanNorAmalina, WMZ; NurAtifah, Ghazali; Verasahib, Khebir; Ong, Chia Ching; MohdAdib, MohdAidinniza; Chan, Yoke Fun

    2016-01-01

    Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2–3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs. PMID:27010319

  10. Cause, care, cure: research priorities for Alzheimer's disease and related dementias.

    Science.gov (United States)

    Stolee, Paul; Hillier, Loretta M; Cook, Sheila; Rockwood, Kenneth

    2011-12-01

    Part of Ontario's strategy on Alzheimer's disease and related dementias (ADRD) was to develop research priorities and recommend strategies for building research capacity. The process to achieve these objectives included an environmental scan, key informant interviews, surveys, and a consensus workshop; this process involved over 100 researchers, clinicians, persons with early dementia, and family caregivers. This article describes the process undertaken, key issues identified, and recommendations for research priorities and for building research capacity; and provides a strategic direction for dementia research in Ontario that is relevant for other jurisdictions. ADRD research in all aspects is required to advance knowledge of ADRD cause, care, and cure; gaps currently exist in understanding effective approaches to care and knowledge transfer. Capacity for high-calibre research hinges on maintaining attractive career paths for researchers, solid infrastructures, and strong partnerships. For research to inform policy and practice, better mechanisms are needed for knowledge exchange.

  11. Review of epidemiology, clinical presentation, diagnosis, and treatment of common primary psychiatric causes of cutaneous disease.

    Science.gov (United States)

    Krooks, J A; Weatherall, A G; Holland, P J

    2017-11-05

    Approximately half of all patients presenting to dermatologists exhibit signs and symptoms of psychiatric conditions that are either primary or secondary to cutaneous disease. Because patients typically resist psychiatric consult, dermatologists often are on the front line in evaluating and treating these patients. Accordingly, distinguishing the specific underlying or resulting psychiatric condition is essential for effective treatment. The etiology, epidemiology, clinical presentation, diagnosis, and first-line treatment of specific primary psychiatric causes of dermatologic conditions, including delusional infestation, Morgellons syndrome, olfactory reference syndrome, body dysmorphic disorder, excoriation disorder, trichotillomania, and dermatitis artefacta are discussed here, followed by a discussion of the recommended treatment approach with an overview of the different first-line therapies discussed in this review, specifically cognitive behavioral therapy, atypical antipsychotics, selective serotonin reuptake inhibitors, and tricyclic antidepressants. Included is a guide for dermatologists to use while prescribing these medications.

  12. S-phase-dependent cell cycle disturbances caused by Aleutian mink disease parvovirus

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Alexandersen, Søren

    1997-01-01

    arrest occurred exclusively in cells containing de novo-synthesized viral nonstructural (NS) proteins. Production of ADV NS proteins, indicative of ADV replication, was triggered during S-phase traverse. The NS+ cells that were generated during later parts of S phase did not undergo cytokinesis...... with subthreshold levels of ADV products through the late S/G(2) block and, consequently, that the binary pattern of ADV-induced cell cycle arrest may be governed merely by viral replication levels within a single S phase. Flow cytometric analysis of propidium iodide fluorescence and bromodeoxyuridine uptake showed......We examined replication of the autonomous parovirus Aleutian mink disease parovirus (ADV) in relation to cell cycle progression of permissive Crandell feline kidney (CRFK) cells. Flow cytometric analysis showed that ADV caused a composite, binary pattern of cell cycle arrest. ADV-induced cell cycle...

  13. New Rust Disease of Korean Willow (Salix koreensis) Caused by Melampsora yezoensis, Unrecorded Pathogen in Korea.

    Science.gov (United States)

    Yun, Yeo Hong; Ahn, Geum Ran; Yoon, Seong Kwon; Kim, Hoo Hyun; Son, Seung Yeol; Kim, Seong Hwan

    2016-12-01

    During the growing season of 2015, leaf specimens with yellow rust spots were collected from Salix koreensis Andersson, known as Korean willow, in riverine areas in Cheonan, Korea. The fungus on S. koreensis was identified as the rust species, Melampsora yezoensis , based on the morphology of urediniospores observed by light and scanning electron microscopy, and the molecular properties of the internal transcribed spacer rDNA region. Pathogenicity tests confirmed that the urediniospores are the causal agent of the rust symptoms on the leaves and young stems of S. koreensis . Here, we report a new rust disease of S. koreensis caused by the rust fungus, M. yezoensis , a previously unrecorded rust pathogen in Korea.

  14. Recurrent spontaneous subserosal hematoma of ileum causing intestinal obstruction in a patient with menkes disease

    Science.gov (United States)

    Weng, Shu-Chao; Hsu, Chyong-Hsin; Wang, Nien-Lu; Lin, Shuan-Pei; Jiang, Chuen-Bin

    2016-01-01

    Abstract Background: Menkes disease (MD) is a disorder of copper metabolism due to ATP7A gene mutation that leads to severe copper deficiency. Deformed blood vessels can be found in many parts of the body, and intracranial hematoma is generally reported. Methods: We report a Taiwanese boy with MD who had recurrent spontaneous subserosal hematoma of ileum presenting as intestinal obstruction, with the 2 episodes 23 months apart. The patient returned to the usual physical status after surgical removal of the hematoma. Results: The defective copper metabolism causes dysfunction of a plenty of copper-dependent enzymes, giving rise to unique kinky hair appearance, progressive neurodegeneration, and connective tissue abnormalities. To our knowledge, this is the first report on recurrent subserosal hemorrhage of intestine in MD. Conclusion: Owing to the fragile structure of blood vessels, subserosal hematoma should be considered when patients with MD having intestinal obstruction. PMID:27631241

  15. Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

    Directory of Open Access Journals (Sweden)

    Julie Harvengt

    2014-01-01

    Full Text Available A 1-year-old girl born to consanguineous parents presented with unexplained liver failure, leading to transplantation at 19 months. Subsequent partial splenectomy for persistent cytopenia showed the presence of foamy cells, and Gaucher disease was confirmed by homozygosity for the p.Leu483Pro mutation in the GBA gene. She was treated by enzyme replacement therapy (ERT. Clinical follow-up showed mild developmental delay, strabismus, nystagmus and oculomotor apraxia. Biochemical studies revealed multiple respiratory chain deficiencies and a mosaic pattern of deficient complex IV immunostaining in liver and fibroblast. Molecular analysis identified a mtDNA depletion syndrome due to the homozygous p.Pro98Leu mutation in MPV17. A younger sister unaffected by mtDNA depletion, presented with pancytopenia and hepatosplenomegaly. ERT for Gaucher disease resulted in visceral normalization without any neurological symptom. A third sister, affected by both conditions, had marked developmental delay, strabismus and ophthalmoplegia but no liver cirrhosis. In conclusion, intrafamilal variability occurs in MPV17-related disease. The combined pathological effect of Gaucher and mitochondrial diseases can negatively impact neurological and liver functions and influence the outcome in consanguineous families. The immunocytochemical staining of OXPHOS protein in tissues and cultured cells is a powerful tool revealing mosaic pattern of deficiency pointing to mtDNA-related mitochondrial disorders.

  16. Disorders in melanopsin effect of pupil constriction as a risk factor causing eye diseases

    Directory of Open Access Journals (Sweden)

    V.A. Kaptsov

    2017-03-01

    Full Text Available Risks of eye damage and eyesight deterioration to a great extent depend on how efficient a biomechanical eye system is under energy-saving lighting conditions. The system's efficiency is determined by its adequacy in managing pupils and ciliary muscle. We analyzed mathematical models describing changes in pupil's diameter which were determined by light-technical parameters of illumination environment (luminance level and brightness. We highlighted the importance of ganglionic cells and the role they play in managing pupil's diameter (miosis when they are exposed to blue light within 480 nm spectrum. Basing on the assessment of a pupil's constriction under exposure to various light stimuli (blue, red, and green ones we worked out a melanopsin effect concept of a pupil's retention at miosis and showed that it could be a diagnostic sign of some diseases (age-related direct retinopathy, pancreatic diabetes under exposure to a blue light impulse with a certain wave length. Under exposure to blue light within 480 nm spectrum ganglionic cells form a managing signal for a sphincter muscle of a pupil and ciliary muscle which provides accommodation (as per Helmholtz and regulates aqueous humor flow in ciliary channel. All modern energy-saving light sources have a low energy level at wave length equal to 480 nm due to gap in their spectrum in comparison with sunlight spectrum with the same light temperature and luminance level. Inadequate management of pupil's diameter under artificial lighting conditions leads to melanopsin effect disorders and causes disharmony in managing aqueous humor outflow. All the above-stated factors under long-term visual load cause eye diseases risks in modern illumination environment. We detected that contemporary mathematic models describing pupil's diameter fluctuations needed to be refined allowing for new knowledge on functional peculiarities of retina cells and energy-saving light sources spectrum.

  17. Infection dynamics in frog populations with different histories of decline caused by a deadly disease.

    Science.gov (United States)

    Sapsford, Sarah J; Voordouw, Maarten J; Alford, Ross A; Schwarzkopf, Lin

    2015-12-01

    Pathogens can drive host population dynamics. Chytridiomycosis is a fungal disease of amphibians that is caused by the fungus Batrachochytrium dendrobatidis (Bd). This pathogen has caused declines and extinctions in some host species whereas other host species coexist with Bd without suffering declines. In the early 1990s, Bd extirpated populations of the endangered common mistfrog, Litoria rheocola, at high-elevation sites, while populations of the species persisted at low-elevation sites. Today, populations have reappeared at many high-elevation sites where they presently co-exist with the fungus. We conducted a capture-mark-recapture (CMR) study of six populations of L. rheocola over 1 year, at high and low elevations. We used multistate CMR models to determine which factors (Bd infection status, site type, and season) influenced rates of frog survival, recapture, infection, and recovery from infection. We observed Bd-induced mortality of individual frogs, but did not find any significant effect of Bd infection on the survival rate of L. rheocola at the population level. Survival and recapture rates depended on site type and season. Infection rate was highest in winter when temperatures were favourable for pathogen growth, and differed among site types. The recovery rate was high (75.7-85.8%) across seasons, and did not differ among site types. The coexistence of L. rheocola with Bd suggests that (1) frog populations are becoming resistant to the fungus, (2) Bd may have evolved lower virulence, or (3) current environmental conditions may be inhibiting outbreaks of the fatal disease.

  18. Genotypes of the Enterovirus Causing Hand Foot and Mouth Disease in Shanghai, China, 2012-2013.

    Directory of Open Access Journals (Sweden)

    Menghua Xu

    Full Text Available Sporadic HFMD (hand foot and mouth disease, HFMD cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic analyses were performed using MEGA 5.0. The ages of the HFMD cases ranged from 3 to 96 months, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of patients had neurologic system complications such as encephalitis, meningoencephalitis or meningitis. Of the 480 samples, 417 were positive for enterovirus (86.9% with RT-PCR. A total of 13 enterovirus genotypes were identified. The most frequent genotypes were CA6 (31.9%, EV71 (30.6%, CA16 (8.8% and CA10 (7.5%. Infections with CA6, EV71, CA16 and CA10 were prevalent throughout the years of study, while the proportion of CA6 notably increased from Sep. 2012 to Dec. 2013. Phylogenetic analyses showed that EV71 strains belonged to the C4a subgenogroup and CA16 was identified as B1b subgenogroup. The CA6 strains were assigned to genogroup F, whereas the CA10 strains were assigned to genogroup D. Patients infected with CA6 were typically younger, had a shorter hospital stay and had a lower incidence of neurologic system complications when compared to patients infected with EV71. Our study demonstrates that the enterovirus genotypes causing HFMD were diversified, and there was an increasing prevalence of the non-EV71 and non-CA16 enteroviruses from 2012 to 2013. CA6 was the most predominant pathogen causing HFMD from Sep. 2012 to Dec. 2013, and it often caused relatively mild HFMD symptoms. Most severe HFMD cases were associated with EV71 infection.

  19. Genotypes of the Enterovirus Causing Hand Foot and Mouth Disease in Shanghai, China, 2012-2013.

    Science.gov (United States)

    Xu, Menghua; Su, Liyun; Cao, Lingfeng; Zhong, Huaqing; Dong, Niuniu; Dong, Zuoquan; Xu, Jin

    2015-01-01

    Sporadic HFMD (hand foot and mouth disease, HFMD) cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic analyses were performed using MEGA 5.0. The ages of the HFMD cases ranged from 3 to 96 months, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of patients had neurologic system complications such as encephalitis, meningoencephalitis or meningitis. Of the 480 samples, 417 were positive for enterovirus (86.9%) with RT-PCR. A total of 13 enterovirus genotypes were identified. The most frequent genotypes were CA6 (31.9%), EV71 (30.6%), CA16 (8.8%) and CA10 (7.5%). Infections with CA6, EV71, CA16 and CA10 were prevalent throughout the years of study, while the proportion of CA6 notably increased from Sep. 2012 to Dec. 2013. Phylogenetic analyses showed that EV71 strains belonged to the C4a subgenogroup and CA16 was identified as B1b subgenogroup. The CA6 strains were assigned to genogroup F, whereas the CA10 strains were assigned to genogroup D. Patients infected with CA6 were typically younger, had a shorter hospital stay and had a lower incidence of neurologic system complications when compared to patients infected with EV71. Our study demonstrates that the enterovirus genotypes causing HFMD were diversified, and there was an increasing prevalence of the non-EV71 and non-CA16 enteroviruses from 2012 to 2013. CA6 was the most predominant pathogen causing HFMD from Sep. 2012 to Dec. 2013, and it often caused relatively mild HFMD symptoms. Most severe HFMD cases were associated with EV71 infection.

  20. Is Chronic Obstructive Pulmonary Disease Caused by Wood Smoke a Different Phenotype or a Different Entity?

    Science.gov (United States)

    Torres-Duque, Carlos A; García-Rodriguez, María Carmen; González-García, Mauricio

    2016-08-01

    Around 40% of the world's population continue using solid fuel, including wood, for cooking or heating their homes. Chronic exposure to wood smoke is a risk factor for developing chronic obstructive pulmonary disease (COPD). In some regions of the world, this can be a more important cause of COPD than exposure to tobacco smoke from cigarettes. Significant differences between COPD associated with wood smoke (W-COPD) and that caused by smoking (S-COPD) have led some authors to suggest that W-COPD should be considered a new COPD phenotype. We present a review of the differences between W-COPD and S-COPD. On the premise that wood smoke and tobacco smoke are not the same and the physiopathological mechanisms they induce may differ, we have analyzed whether W-COPD can be considered as another COPD phenotype or a distinct nosological entity. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford Hill's causality criteria.

    Science.gov (United States)

    Walton, J R

    2014-01-01

    Industrialized societies produce many convenience foods with aluminum additives that enhance various food properties and use alum (aluminum sulfate or aluminum potassium sulfate) in water treatment to enable delivery of large volumes of drinking water to millions of urban consumers. The present causality analysis evaluates the extent to which the routine, life-long intake, and metabolism of aluminum compounds can account for Alzheimer's disease (AD), using Austin Bradford Hill's nine epidemiological and experimental causality criteria, including strength of the relationship, consistency, specificity, temporality, dose-dependent response, biological rationale, coherence with existing knowledge, experimental evidence, and analogy. Mechanisms that underlie the risk of low concentrations of aluminum relate to (1) aluminum's absorption rates, allowing the impression that aluminum is safe to ingest and as an additive in food and drinking water treatment, (2) aluminum's slow progressive uptake into the brain over a long prodromal phase, and (3) aluminum's similarity to iron, in terms of ionic size, allows aluminum to use iron-evolved mechanisms to enter the highly-active, iron-dependent cells responsible for memory processing. Aluminum particularly accumulates in these iron-dependent cells to toxic levels, dysregulating iron homeostasis and causing microtubule depletion, eventually producing changes that result in disconnection of neuronal afferents and efferents, loss of function and regional atrophy consistent with MRI findings in AD brains. AD is a human form of chronic aluminum neurotoxicity. The causality analysis demonstrates that chronic aluminum intake causes AD.

  2. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children.

    Science.gov (United States)

    Brown, Laurie M; Corrado, Michelle M; van der Ende, Rixt M; Derks, Terry G J; Chen, Margaret A; Siegel, Sara; Hoyt, Kate; Correia, Catherine E; Lumpkin, Christopher; Flanagan, Theresa B; Carreras, Caroline T; Weinstein, David A

    2015-05-01

    Ketone formation is a normal response when hypoglycemia occurs. Since the majority of children with recurrent hypoglycemia cannot be diagnosed with a known endocrine or metabolic disorder on a critical sample, ketotic hypoglycemia has been described as the most common cause of low blood glucose concentrations in children. Critical samples, however, will miss the ketotic forms of glycogen storage disease (GSD), which present with elevated ketones, hypoglycemia, and normal hormonal concentrations. A total of 164 children (96 boys, 68 girls) were enrolled in the study. Prediction of pathogenicity of DNA changes using computer modeling confirmed pathology in 20 individuals [four GSD 0, two GSD VI, 12 GSD IX alpha, one GSD IX beta, one GSD IX gamma] (12%). Boys were most likely to have changes in the PHKA2 gene, consistent with GSD IX alpha, an X-linked disorder. Mutations in genes involved in glycogen synthesis and degradation were commonly found in children with idiopathic ketotic hypoglycemia. GSD IX is likely an unappreciated cause of ketotic hypoglycemia in children, while GSD 0 and VI are relatively uncommon. GSD IX alpha should particularly be considered in boys with unexplained hypoglycemia.

  3. Health risk factors in lead polluted environment causing isthemic health disease

    International Nuclear Information System (INIS)

    Khnwal, S.; Rahman, K.U.

    2008-01-01

    Faisalabad is third most populous and industrial city, known as Manchester of Pakistan. Most of the people working in the industries of this city are exposed to highly polluted and toxic environment. Lead is a natural metal found in the environment and its contamination exceeds the range of normal limits by human activities causing a lot of health hazardous. An effort is made to assess the association of anemia and cholesterol with the development IHD among industrial workers who are exposed to the lead polluted environment. For this purpose the study was conducted during a period of one year (2006-7) and the respondents were the patients from industrial area coming to the hospitals visiting at DHQ Hospital Faisalabad. Only those patients were selected for this study who were diagnosed with clinical symptoms of lead toxicity. The demographic features of the respondents regarding their age, gender, marital status, family size, education, income, duration on job, working place and nature of work were considered. The data of this study was categorical nature and this measures the association among exposure to the environment with lead toxicity and causative risk factors i.e., cholesterol level, Hb level (anemia) causing ischemic heart disease (IHD) were studied. (author)

  4. Acute pancreatitis in hand, foot and mouth disease caused by Coxsackievirus A16: case report.

    Science.gov (United States)

    Park, Byungsung; Kwon, Hyuckjin; Lee, Kwanseop; Kang, Minjae

    2017-10-01

    Coxsackievirus A16 (CA16), which primarily causes hand, foot, and mouth disease (HFMD), is associated with complications, such as encephalitis, acute flaccid paralysis, myocarditis, pericarditis, and shock. However, no case of pancreatitis associated with CA16 has been reported in children. We report a case of CA16-associated acute pancreatitis in a 3-year-old girl with HFMD. She was admitted because of poor oral intake and high fever for 1 day. Maculopapular rashes on both hands and feet and multiple vesicles on the soft palate were observed on physical examination. She was treated conservatively with intravenous fluids. On the fourth hospital day, she had severe abdominal pain and vomiting. The serum levels of amylase and lipase were remarkably elevated (amylase, 1,902 IU/L; reference range, 28-100 IU/L; lipase, >1,500 IU/L; reference range, 13-60 IU/L), and ultrasonography showed diffuse swelling of the pancreas with a small amount of ascites. The real-time reverse transcription polymerase chain reaction result from a stool sample was positive for CA16. CA16 can cause acute pancreatitis, and should be considered in the differential diagnosis of abdominal pain in children with HFMD.

  5. Performance-based regulation: enterprise responsibility for reducing death, injury, and disease caused by consumer products.

    Science.gov (United States)

    Sugarman, Stephen D

    2009-12-01

    This article offers a bold new idea for confronting the staggering level of death, injury, and disease caused by five consumer products: cigarettes, alcohol, guns, junk food, and motor vehicles. Business leaders try to frame these negative outcomes as "collateral damage" that is someone else's problem. That framing not only is morally objectionable but also overlooks the possibility that, with proper prodding, industry could substantially lessen these public health disasters. I seek to reframe the public perception of who is responsible and propose to deploy a promising approach called "performance-based regulation" to combat the problem. Performance-based regulation would impose on manufacturers a legal obligation to reduce the negative social costs of their products. Rather than involving them in litigation or forcing them to operate differently (as "command-and-control" regimes do), performance-based regulation allows the firms to determine how best to decrease bad public health consequences. Like other public health strategies, performance-based regulation focuses on those who are far more likely than individual consumers to achieve real gains. Analogous to a tax on causing harm that exceeds a threshold level, performance-based regulation seeks to harness private initiative in pursuit of the public good.

  6. Gastroesophageal Reflux Disease and overall and Cause-specific Mortality: A Prospective Study of 50000 Individuals

    Science.gov (United States)

    Islami, Farhad; Pourshams, Akram; Nasseri-Moghaddam, Siavosh; Khademi, Hooman; Poutschi, Hossein; Khoshnia, Masoud; Norouzi, Alireza; Amiriani, Taghi; Sohrabpour, Amir Ali; Aliasgari, Ali; Jafari, Elham; Semnani, Shahryar; Abnet, Christian C.; Pharaoh, Paul D.; Brennan, Paul; Kamangar, Farin; Dawsey, Sanford M.; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    BACKGROUND Only a few studies in Western countries have investigated the association between gastroesophageal reflux disease (GERD) and mortality at the general population level and they have shown mixed results. This study investigated the association between GERD symptoms and overall and cause-specific mortality in a large prospective population-based study in Golestan Province, Iran. METHODS Baseline data on frequency, onset time, and patient-perceived severity of GERD symptoms were available for 50001 participants in the Golestan Cohort Study (GCS). We identified 3107 deaths (including 1146 circulatory and 470 cancer-related) with an average follow-up of 6.4 years and calculated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for multiple potential confounders. RESULTS Severe daily symptoms (defined as symptoms interfering with daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of participants) were associated with cancer mortality (HR 1.48, 95% CI: 1.04-2.05). This increase was too small to noticeably affect overall mortality. Mortality was not associated with onset time or frequency of GERD and was not increased with mild to moderate symptoms. CONCLUSION We have observed an association with GERD and increased cancer mortality in a small group of individuals that had severe symptoms. Most patients with mild to moderate GERD can be re-assured that their symptoms are not associated with increased mortality. PMID:24872865

  7. How do Mutations in GJB1 Cause X-linked Charcot-Marie-Tooth Disease?

    Science.gov (United States)

    Kleopa, Kleopas A.; Abrams, Charles K.; Scherer, Steven S.

    2012-01-01

    The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most common form of hereditary motor and sensory neuropathy. The clinical phenotype is characterized by progressive weakness, atrophy, and sensory abnormalities that are most pronounced in the distal extremities. Some patients have CNS manifestations. Affected males have moderate to severe symptoms, whereas heterozygous females are usually less affected. Neurophysiology shows intermediate slowing of conduction and length-dependent axonal loss. Nerve biopsies show more prominent axonal degeneration than de/remyelination. Mutations in GJB1, the gene that encodes the gap junction (GJ) protein connexin32 (Cx32) cause CMT1X; more than 400 different mutations have been described. Many Cx32 mutants fail to form functional GJs, or form GJs with abnormal biophysical properties. Schwann cells and oligodendrocytes express Cx32, and the GJs formed by Cx32 play an important role in the homeostasis of myelinated axons. Animal models of CMT1X demonstrate that loss of Cx32 in myelinating Schwann cells causes a demyelinating neuropathy. Effective therapies remain to be developed. PMID:22771394

  8. Trehalose reverses cell malfunction in fibroblasts from normal and Huntington's disease patients caused by proteosome inhibition.

    Directory of Open Access Journals (Sweden)

    Maria Angeles Fernandez-Estevez

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder characterized by progressive motor, cognitive and psychiatric deficits, associated with predominant loss of striatal neurons and is caused by polyglutamine expansion in the huntingtin protein. Mutant huntingtin protein and its fragments are resistant to protein degradation and produce a blockade of the ubiquitin proteasome system (UPS. In HD models, the proteasome inhibitor epoxomicin aggravates protein accumulation and the inductor of autophagy, trehalose, diminishes it. We have investigated the effects of epoxomicin and trehalose in skin fibroblasts of control and HD patients. Untreated HD fibroblasts have increased the levels of ubiquitinized proteins and higher levels of reactive oxygen species (ROS, huntingtin and the autophagy marker LAMP2A. Baseline replication rates were higher in HD than in controls fibroblasts but that was reverted after 12 passages. Epoxomicin increases the activated caspase-3, HSP70, huntingtin, ubiquitinated proteins and ROS levels in both HD and controls. Treatment with trehalose counteracts the increase in ROS, ubiquitinated proteins, huntingtin and activated caspase-3 levels induced by epoxomicin, and also increases the LC3 levels more in HD fibroblast than controls. These results suggest that trehalose could revert protein processing abnormalities in patients with Huntington's Disease.

  9. Biomass Losses Caused by Teratosphaeria Leaf Disease in Eucalyptus globulus Short Rotation Forestry

    Directory of Open Access Journals (Sweden)

    Severiano Pérez

    2017-11-01

    Full Text Available This article presents the results of a study that examines the loss of biomass and energy, per hectare, caused by Teratosphaeria leaf disease (TLD in Eucalyptus globulus short rotation forestry. The 95 Eucalyptus globulus taxa analyzed are from seeds of open pollinated families of both Spanish and Australian origin. Tree height and diameter were measured and the crown damage index (CDI assessed at 27 months of age. Taxa that have a certain tolerance to the disease have been identified. The taxon identified as code 283 is the one that shows lower CDI (42% and with an average volume that exceeded 0.017 m3 at 27 months of age. Biomass losses were determined for each fraction of dry biomass of the tree (leaves, branches, twigs and bark based on CDI. These losses were translated into terms of energy lost per hectare, depending on the CDI. A comparison was then carried out between the productivity of Eucalyptus globulus exhibiting various levels of TLD severity and poplar and willow clones used for bioenergy in Europe. In our region, the results show that despite the losses of biomass associated with TLD, Eucalyptus globulus remains competitive as long as CDI values are lower than 56%.

  10. Coxiella burnetii as a possible cause of autoimmune liver disease: a case report

    Directory of Open Access Journals (Sweden)

    Kaech Chloe

    2009-08-01

    Full Text Available Abstract Introduction Q fever is a zoonotic infection that may cause severe hepatitis. Q-fever hepatitis has not yet been associated with autoimmune hepatitis and/or primary biliary cirrhosis. Case presentation We describe a 39-year-old man of Sri Lankan origin with chronic Q-fever hepatitis who developed autoantibodies compatible with autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Ursodeoxycholic acid in addition to antibiotic therapy markedly improved hepatic enzyme levels suggesting that autoimmunity, potentially triggered by the underlying infection, was involved in the pathogenesis of liver damage. Conclusion We suggest that Coxiella burnetii might trigger autoimmune liver disease. Patients with Q-fever hepatitis who respond poorly to antibiotics should be investigated for serological evidence of autoimmune hepatitis, primary biliary cirrhosis or overlap syndrome, as these patients could benefit from adjunctive therapy with ursodeoxycholic acid. Conversely, C. burnetii serology might be necessary in patients with autoimmune liver disease in order to exclude underlying Coxiella infection.

  11. Characterization of a novel Canine distemper virus causing disease in wildlife.

    Science.gov (United States)

    Pope, Jenny P; Miller, Debra L; Riley, Matthew C; Anis, Eman; Wilkes, Rebecca P

    2016-09-01

    Canine distemper virus (CDV) is a common cause of a multisystemic disease in both domestic dogs and wildlife species, including raccoons and foxes. Outbreaks of CDV in domestic dogs in eastern Tennessee have occurred since 2012, and it was determined that these outbreaks resulted from a novel genotype of CDV. We hypothesized that this virus is also infecting area wildlife and may be a source of the virus for these outbreaks in dogs. From 2013 to 2014, autopsies were performed and tissues collected from raccoons (Procyon lotor; n = 50) and gray foxes (Urocyon cinereoargenteus; n = 8) for CDV testing. A real-time reverse transcription PCR was used to document the presence of CDV in tissue samples, and a portion of the virus was subsequently sequenced for phylogenetic analysis. A high percentage of wildlife, both with (86%) and without (55%) clinical signs, tested positive for CDV, with the majority (77%) testing positive for the novel genotype. Microscopic findings, including syncytia in the lungs and viral inclusion bodies in urothelium, astrocytes, neurons, and bronchiolar epithelium, were also consistent with canine distemper. Minimal inflammation in the central nervous system of affected animals was indicative of the acute neurologic form of the disease. Pneumonia and parasitism were also commonly found in CDV-infected animals. Based on these results, CDV appears to be prevalent in eastern Tennessee wildlife. Subclinical or clinically recovered shedders are a potential source of this novel genotype for domestic dogs, and this genotype is genetically distinct from vaccine strains. © 2016 The Author(s).

  12. Schizophrenia: a pathogenetic autoimmune disease caused by viruses and pathogens and dependent on genes.

    Science.gov (United States)

    Carter, C J

    2011-01-01

    Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a "pathogenetic" autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

  13. Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2011-01-01

    Full Text Available Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

  14. Bleeding points in cerebral hemorrhage caused by Moyamoya disease in adults

    International Nuclear Information System (INIS)

    Sasaki, Tatsuya; Sakurai, Yoshiharu; Shimizu, Yukihiko; Ogawa, Akira; Komatsu, Shinro.

    1983-01-01

    Even before the introduction of CT we reported that the intracranial hemorrhage in Moyamoya disease was not subarachnoid hemorrhage but intraventricular hemorrhage and that the bleeding point was the paraventricular subependymal region of lateral ventricles; these findings were based on our experience with three Moyamoya cases in which ventricular hemorrhage occurred and pseudoaneurysms were revealed in the territory of the posterior choroidal artery. Twelve cases with intracranial hemorrhage caused by Moyamoya disease have now been studied by CT in order to determine (1) whether the hemorrhage is subarachnoid or intraventricular, and (2) where the bleeding point is. In the results for the eight cases for which the CT scan was performed within one day after the onset, intraventricular hemorrhage was shown in all cases. The bleeding point was examined in twelve cases; in four cases it was recognized by initial CT only, but if five cases in which ventricular hemorrhage only appeared in the initial CT,follow-up plain and contrast-enhanced CT were necessary. In a total of nine cases, then, bleeding points were recognized. In one case putaminal hemorrhage penetrated into the lateral ventricle, while in eight cases the intracerebral hematoma was located in the paraventricular region of the lateral ventricle, such as at the head of the caudate nucleus or the thalamus. In some cases, small subependymal hematoma projected into the lateral ventricle. In cases with symptoms of intracranial hemorrhage at the onset, the bleeding points were at the paraventricular parenchyma of the lateral ventricle in almost all cases. (author)

  15. Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease.

    Science.gov (United States)

    Jiang, Hua; Huang, Lv-Yin; Zhen, Li; Jiang, Fan; Li, Dong-Zhi

    Hb H disease is generally a moderate form of α-thalassemia (α-thal) that rarely requires regular blood transfusions. In this study, two Chinese families with members carrying transfusion-dependent Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2). In one family, Hb Zürich-Albisrieden [α59(E8)Gly→Arg; HBA1: c.178G>C] in combination with the Southeast Asian (- - SEA ) deletion was the defect responsible for the severe phenotype. In another family, a novel hemoglobin (Hb) variant named Hb Sichuan (HBA1: c.393_394insT), causes α-thal and a severe phenotype when associated with the - - SEA deletion. As these two HBA1 mutations can present as continuous blood transfusion-dependent α-thal, it is important to take this point into account for detecting the carriers, especially in couples in which one partner is already a known α 0 -thal carrier.

  16. Serotype distribution of Streptococcus pneumoniae causing invasive disease in the Republic of Ireland.

    LENUS (Irish Health Repository)

    Vickers, I

    2011-05-01

    The 7-valent pneumococcal conjugate vaccine (PCV7) was included in the routine infant immunization schedule in Ireland in September 2008. We determined the serotype of 977 S. pneumoniae isolates causing invasive disease between 2000-2002 and 2007-2008, assessed for the presence of the recently described serotype 6C and determined the susceptibility of isolates during 2007-2008 to penicillin and cefotaxime. Serotype 14 was the most common serotype during both periods and 7·7% of isolates previously typed as serotype 6A were serotype 6C. During 2000-2002 and 2007-2008, PCV7 could potentially have prevented 85% and 74% of invasive pneumococcal disease in the target population (i.e. children aged <2 years), respectively. The level of penicillin non-susceptibility was 17% in 2007-2008. Ongoing surveillance of serotypes is required to determine the impact of PCV7 in the Irish population and to assess the potential of new vaccines with expanded valency.

  17. Is Urinary KIM-1 a Predictor of EGFR Decline, Incident Cardiovascular Disease, and All Cause Mortality?

    DEFF Research Database (Denmark)

    Eickhoff, Mie Klessen; von Scholten, Bernt Johan; Reinhard, Henrik

    Background Urinary levels of kidney injury molecule 1 (KIM-1) has shown to reflect tubular pathophysiology. We evaluated KIM-1 as a predictor of decline in estimated glomerular filtration rate (eGFR), incident cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2......D) and microalbuminuria without clinical coronary artery disease. Methods We performed a prospective study including 200 patients, all receiving multifactorial treatment. Urinary KIM-1 was measured at baseline and was available in 191 patients. Adjusted Cox models included sex, age, LDL cholesterol...... the predefined CKD progression endpoint after 4.9 years (median). Higher urinary KIM-1 was a predictor of eGFR decline, unadjusted HR (95% CI): 1.9 (1.2-2.8); p=0.003, and in the adjusted model HR 1.7 (1.0-2.7); p=0.034. For CVD events urinary KIM-1 was a determinant in the unadjusted model (HR 1.4 (1.0-2.1); p...

  18. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings

    Science.gov (United States)

    Pascual, Sergi; Casadevall, Carme; Orozco-Levi, Mauricio; Barreiro, Esther

    2015-01-01

    Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future. PMID:26623119

  19. Development of a sensitive molecular detection assay for mango malformation disease caused by Fusarium mangiferae.

    Science.gov (United States)

    Wu, Jingbo; Liu, Feng; Zhan, Rulin; Li, Guoping; Zhao, Yanlong; Jinmei, Chang; He, Yanbiao

    2016-05-01

    To develop a sensitive and specific molecular assay for detection of mango malformation disease (MMD), which is caused primarily by Fusarium mangiferae. We screened 100 ISSR primers and identified one (UBC888) that directed the stable amplification of a specific gene fragment of 479 bp (GenBank accession number KJ526382). Based on the DNA sequence of this fragment, a pair of SCAR primers (W342 and W1772) were designed to amplify another gene fragment of 1376 bp (GenBank accession number KJ526383), demonstrating the successful conversion of an ISSR marker to a SCAR marker. An effective and simple detection assay for MMD was established based on this pair of PCR primers, with a high level of specificity and sensitivity to the DNA of F. mangiferae and other species of Fusarium both in vitro and in vivo. It can detect as little as 10 pg fungal DNA from the DNA of mango's tissues. Our assay provides a practical method for the early diagnosis so that proper prevention of the mango malformation disease can be developed.

  20. The serum anion gap is associated with disease severity and all-cause mortality in coronary artery disease.

    Science.gov (United States)

    Yang, Shi-Wei; Zhou, Yu-Jie; Zhao, Ying-Xin; Liu, Yu-Yang; Tian, Xiao-Fang; Wang, Zhi-Jian; Jia, De-An; Han, Hong-Ya; Hu, Bin; Shen, Hua; Gao, Fei; Wang, Lu-Ya; Lin, Jie; Pan, Guo-Zhong; Zhang, Jian; Guo, Zhen-Feng; Du, Jie; Hu, Da-Yi

    2017-06-01

    To evaluate the associations between the serum anion gap (AG) with the severity and prognosis of coronary artery disease (CAD). We measured serum electrolytes in 18,115 CAD patients indicated by coronary angiography. The serum AG was calculated according to the equation: AG = Na + [(mmol/L) + K + (mmol/L)] - [Cl - (mmol/L) + HCO3 - (mmol/L)]. A total of 4510 (24.9%) participants had their AG levels greater than 16 mmol/L. The serum AG was independently associated with measures of CAD severity, including more severe clinical types of CAD ( P < 0.001) and worse cardiac function ( P = 0.004). Patients in the 4th quartile of serum AG (≥ 15.92 mmol/L) had a 5.171-fold increased risk of 30 days all-cause death ( P < 0.001). This association was robust, even after adjustment for age, sex, evaluated glomerular filtration rate [hazard ratio (HR): 4.861, 95% confidence interval (CI): 2.150-10.993, P < 0.001], clinical diagnosis, severity of coronary artery stenosis, cardiac function grades, and other confounders (HR: 3.318, 95% CI: 1.76-2.27, P = 0.009). In this large population-based study, our findings reveal a high percentage of increased serum AG in CAD. Higher AG is associated with more severe clinical types of CAD and worse cardiac function. Furthermore, the increased serum AG is an independent, significant, and strong predictor of all-cause mortality. These findings support a role for the serum AG in the risk-stratification of CAD.

  1. Pathology, toxicology, and latency of irritant gases known to cause bronchiolitis obliterans disease: Does diacetyl fit the pattern?

    OpenAIRE

    Kerger, Brent D.; Fedoruk, M. Joseph

    2015-01-01

    Bronchiolitis obliterans (BO) is a rare disease involving concentric bronchiolar fibrosis that develops rapidly following inhalation of certain irritant gases at sufficiently high acute doses. While there are many potential causes of bronchiolar lesions involved in a variety of chronic lung diseases, failure to clearly define the clinical features and pathological characteristics can lead to ambiguous diagnoses. Irritant gases known to cause BO follow a similar pathologic process and time cou...

  2. Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Hiromasa Sato

    2018-03-01

    Full Text Available Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

  3. Biocontrol potential of Trichoderma harzianum in controlling wilt disease of pistachio caused by Verticillium dahliae

    Directory of Open Access Journals (Sweden)

    Fotoohiyan Zeinab

    2017-06-01

    Full Text Available Verticillium wilt caused by Verticillium dahliae, is one of the most devastating diseases in pistachio orchards in the world including Iran. In search for an effective non-chemical strategy for the management of this disease, we evaluated the biocontrol potential of Trichoderma harzianum isolates obtained from the rhizosphere of healthy pistachio trees in different locations of the Kerman province of Iran against V. dahliae under laboratory and greenhouse conditions. Dual culture tests in the laboratory were conducted in a completely randomized design using 72 T. harzianum isolates. Twenty isolates showed the highest in vitro antagonistic activity. The results indicated that all 20 isolates were capable of inhibiting the mycelial growth of V. dahliae significantly. Among them, isolates Tr8 and Tr19 were the most effective by 88.89% and 85.12% inhibition, respectively. Extracted cell free metabolites of all effective isolates also inhibited the growth of V. dahliae in the culture medium significantly. According to the results, isolates Tr4 and Tr6 inhibited fungal pathogen growth by 94.94% and 88.15% respectively, through production of non-volatile metabolites. In the evaluation of volatile metabolites, isolates Tr5 and Tr4 were the most effective by 26.27% and 24.49% growth inhibition, respectively. Based