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Sample records for affect disease development

  1. Lower temperature during the dark cycle affects disease development on Lygodium microphyllum (Old World climbing fern) by Bipolaris sacchari

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Growth chamber studies were conducted to examine environmental parameters affecting disease development by the indigenous pathogen Bipolaris sacchari isolate LJB-1L on the invasive weed Lygodium microphyllum (Old World climbing fern). Initial studies examined three different temperature regimes (20...

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

    Plants were grown under light-emitting diode (LED) arrays with various spectra to determine the effects of light quality on the development of diseases caused by tomato mosaic virus (ToMV) on pepper (Capsicum annuum L.), powdery mildew [Sphaerotheca fuliginea (Schlectend:Fr.) Pollaci] on cucumber (Cucumis sativus L.), and bacterial wilt (Pseudomonas solanacearum Smith) on tomato (Lycopersicon esculentum Mill.). One LED (660) array supplied 99% red light at 660 nm (25 nm bandwidth at half-peak height) and 1% far-red light between 700 to 800 nm. A second LED (660/735) array supplied 83% red light at 660 nm and 17% far-red light at 735 nm (25 nm bandwidth at half-peak height). A third LED (660/BF) array supplied 98% red light at 660 nm, 1% blue light (BF) between 350 to 550 nm, and 1% far-red light between 700 to 800 nm. Control plants were grown under broad-spectrum metal halide (MH) lamps. Plants were grown at a mean photon flux (300 to 800 nm) of 330 micromoles m-2 s-1 under a 12-h day/night photoperiod. Spectral quality affected each pathosystem differently. In the ToMV/pepper pathosystem, disease symptoms developed slower and were less severe in plants grown under light sources that contained blue and UV-A wavelengths (MH and 660/BF treatments) compared to plants grown under light sources that lacked blue and UV-A wavelengths (660 and 660/735 LED arrays). In contrast, the number of colonies per leaf was highest and the mean colony diameters of S. fuliginea on cucumber plants were largest on leaves grown under the MH lamp (highest amount of blue and UV-A light) and least on leaves grown under the 660 LED array (no blue or UV-A light). The addition of far-red irradiation to the primary light source in the 660/735 LED array increased the colony counts per leaf in the S. fuliginea/cucumber pathosystem compared to the red-only (660) LED array. In the P. solanacearum/tomato pathosystem, disease symptoms were less severe in plants grown under the 660 LED array, but the

  3. 78 FR 58316 - Complex Issues in Developing Medical Devices for Pediatric Patients Affected by Rare Diseases...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... inappropriate for pediatric use due to a variety of factors, including patient size, growth, and development, or... practice trends of medical devices in rare disease pediatric populations. For example, how much off-label... pediatric populations? B. HUD/HDE 1. Is there any confusion about the designation process for HUDs or...

  4. Factors affecting illness in the developing world: chronic disease, mental health and traditional medicine cures.

    PubMed

    Douthit, Nathan T; Astatk, Hailemariam Alemu

    2016-01-01

    This is a case report of a 24-year-old Ethiopian woman with a medical history of hepatosplenic schistosomiasis. She suffers from chronic liver failure and portal hypertension. She has been hospitalised for 'hysteria' in the past but did not receive follow-up, outpatient treatment or psychiatric evaluation. After discontinuing her medications and leaving her family to use holy water, a religious medicine used by many Ethiopians, she was found at a nearby monastery. She was non-communicative and difficult to arouse. The patient was rushed to nearby University of Gondar Hospital where she received treatment for hepatic encephalopathy and spontaneous bacterial peritonitis. Her illness is the result of neglected tropical disease, reliance on traditional medicine as opposed to biomedical services and the poor state of psychiatric care in the developing world. PMID:27485874

  5. Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

    PubMed Central

    Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

    2015-01-01

    Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

  6. Affective cycling in thyroid disease

    SciTech Connect

    Tapp, A.

    1988-05-01

    Depression in an elderly man with primary recurrent unipolar depression responded to radioactive iodine treatment of a thyrotoxic nodule, without the addition of psychotropic medications. Two months later, manic symptoms developed concomitant with the termination of the hyperthyroid state secondary to the radioactive iodine treatment. Clinical implications of these findings in relation to the possible mechanism of action of thyroid hormones on affective cycling are discussed.

  7. Current Research in Affective Development.

    ERIC Educational Resources Information Center

    Strayer, Janet

    1985-01-01

    Current research concerning affective development in infants and children is selectively reviewed. The focus of findings and discussion is on three general and related topics: (1) expression of emotion and affective interaction in infancy; (2) socialization and regulation of emotion; (3) comprehension of emotions and empathy with others by…

  8. [Development of the affect system].

    PubMed

    Moser, U; Von Zeppelin, I

    1996-01-01

    The authors show that the development of the affect system commences with affects of an exclusively communicative nature. These regulate the relationship between subject and object. On a different plane they also provide information on the feeling of self deriving from the interaction. Affect is seen throughout as a special kind of information. One section of the article is given over to intensity regulation and early affect defenses. The development of cognitive processes leads to the integration of affect systems and cognitive structures. In the pre-conceptual concretistic phase, fantasies change the object relation in such a way as to make unpleasant affects disappear. Only at a later stage do fantasies acquire the capacity to deal with affects. Ultimately, the affect system is grounded on an invariant relationship feeling. On a variety of different levels it displays the features typical of situation theory and the theory of the representational world, thus making it possible to entertain complex object relations. In this process the various planes of the affect system are retained and practised. Finally, the authors discuss the consequences of their remarks for the understanding of psychic disturbances and the therapies brought to bear on them. PMID:8584745

  9. Grape Cultivar and Sap Culture Conditions Affect the Development of Xylella fastidiosa Phenotypes Associated with Pierce's Disease.

    PubMed

    Hao, Lingyun; Zaini, Paulo A; Hoch, Harvey C; Burr, Thomas J; Mowery, Patricia

    2016-01-01

    Xylella fastidiosa is a xylem-limited bacterium in plant hosts and causes Pierce's disease (PD) of grapevines, which differ in susceptibility according to the Vitis species (spp.). In this work we compared X. fastidiosa biofilm formation and population dynamics when cultured in xylem saps from PD-susceptible and -resistant Vitis spp. under different conditions. Behaviors in a closed-culture system were compared to those in different sap-renewal cultures that would more closely mimic the physicochemical environment encountered in planta. Significant differences in biofilm formation and growth in saps from PD-susceptible and -resistant spp. were only observed using sap renewal culture. Compared to saps from susceptible V. vinifera, those from PD-resistant V. aestivalis supported lower titers of X. fastidiosa and less biofilm and V. champinii suppressed both growth and biofilm formation, behaviors which are correlated with disease susceptibility. Furthermore, in microfluidic chambers X. fastidiosa formed thick mature biofilm with three-dimensional (3-D) structures, such as pillars and mounds, in saps from all susceptible spp. In contrast, only small aggregates of various shapes were formed in saps from four out of five of the resistant spp.; sap from the resistant spp. V. mustangensis was an exception in that it also supported thick lawns of biofilm but not the above described 3-D structures typically seen in a mature biofilm from the susceptible saps. Our findings provide not only critical technical information for future bioassays, but also suggest further understanding of PD susceptibility. PMID:27508296

  10. Grape Cultivar and Sap Culture Conditions Affect the Development of Xylella fastidiosa Phenotypes Associated with Pierce's Disease

    PubMed Central

    Hoch, Harvey C.; Burr, Thomas J.; Mowery, Patricia

    2016-01-01

    Xylella fastidiosa is a xylem-limited bacterium in plant hosts and causes Pierce’s disease (PD) of grapevines, which differ in susceptibility according to the Vitis species (spp.). In this work we compared X. fastidiosa biofilm formation and population dynamics when cultured in xylem saps from PD-susceptible and -resistant Vitis spp. under different conditions. Behaviors in a closed-culture system were compared to those in different sap-renewal cultures that would more closely mimic the physicochemical environment encountered in planta. Significant differences in biofilm formation and growth in saps from PD-susceptible and -resistant spp. were only observed using sap renewal culture. Compared to saps from susceptible V. vinifera, those from PD-resistant V. aestivalis supported lower titers of X. fastidiosa and less biofilm and V. champinii suppressed both growth and biofilm formation, behaviors which are correlated with disease susceptibility. Furthermore, in microfluidic chambers X. fastidiosa formed thick mature biofilm with three-dimensional (3-D) structures, such as pillars and mounds, in saps from all susceptible spp. In contrast, only small aggregates of various shapes were formed in saps from four out of five of the resistant spp.; sap from the resistant spp. V. mustangensis was an exception in that it also supported thick lawns of biofilm but not the above described 3-D structures typically seen in a mature biofilm from the susceptible saps. Our findings provide not only critical technical information for future bioassays, but also suggest further understanding of PD susceptibility. PMID:27508296

  11. Affective Development in University Education

    ERIC Educational Resources Information Center

    Grootenboer, Peter

    2010-01-01

    There seems to be an increasing requirement for university courses and programs to develop students' affective qualities (beliefs, values, dispositions and attitudes). This study explored the ways academics determined what the desirable qualities were for their particular disciplines and the pedagogical strategies and approaches they used to…

  12. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... percent of smokers begin before age 18. Middle-Aged Women: At menopause, a woman's heart disease risk ... risk of developing high blood pressure for women aged 55 is about 90 percent. Beginning at age ...

  13. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

  14. Developing disease management programs.

    PubMed

    Herman, K

    1999-11-01

    Several market forces are driving interest in disease management and its growth, including the need to control costs; improve quality; attract, satisfy, and retain members; and meet accreditation requirements. People with chronic diseases and disabilities represent the most expensive and fastest-growing group of patients in health care, and agencies that develop successful disease management programs for these populations will reap a variety of benefits. PMID:10661985

  15. Parasitic diseases and urban development.

    PubMed Central

    Mott, K. E.; Desjeux, P.; Moncayo, A.; Ranque, P.; de Raadt, P.

    1990-01-01

    The distribution and epidemiology of parasitic diseases in both urban and periurban areas of endemic countries have been changing as development progresses. The following different scenarios involving Chagas disease, lymphatic filariasis, leishmaniasis and schistosomiasis are discussed: (1) infected persons entering nonendemic urban areas without vectors; (2) infected persons entering nonendemic urban areas with vectors; (3) infected persons entering endemic urban areas; (4) non-infected persons entering endemic urban areas; (5) urbanization or domestication of natural zoonotic foci; and (6) vectors entering nonendemic urban areas. Cultural and social habits from the rural areas, such as type of house construction and domestic water usage, are adopted by migrants to urban areas and increase the risk of disease transmission which adversely affects employment in urban populations. As the urban health services must deal with the rise in parasitic diseases, appropriate control strategies for the urban setting must be developed and implemented. PMID:2127380

  16. Environmental issues affecting CCT development

    SciTech Connect

    Reidy, M.

    1997-12-31

    While no final legislative schedule has been set for the new Congress, two issues with strong environmental ramifications which are likely to affect the coal industry seem to top the list of closely watched debates in Washington -- the Environmental Protection Agency`s proposed new ozone and particulate matter standards and utility restructuring. The paper discusses the background of the proposed standards, public comment, the Congressional review of regulations, other legislative options, and utility restructuring.

  17. Treatment of affective disorders in cardiac disease

    PubMed Central

    Mavrides, Nicole; Nemeroff, Charles B.

    2015-01-01

    Patients with cardiovascular disease (CVD) commonly have syndromal major depression, and depression has been associated with an increased risk of morbidity and mortality. Prevalence of depression is between 17% and 47% in CVD patients. Pharmacologic and psychotherapeutic interventions have long been studied, and in general are safe and somewhat efficacious in decreasing depressive symptoms in patients with CVD. The impact on cardiac outcomes remains unclear. The evidence from randomized controlled clinical trials indicates that antidepressants, especially selective serotonin uptake inhibitors, are overwhelmingly safe, and likely to be effective in the treatment of depression in patients with CVD. This review describes the prevalence of depression in patients with CVD, the physiological links between depression and CVD, the treatment options for affective disorders, and the clinical trials that demonstrate efficacy and safety of antidepressant medications and psychotherapy in this patient population. Great progress has been made in understanding potential mediators between major depressive disorder and CVD—both health behaviors and shared biological risks such as inflammation. PMID:26246788

  18. Reading Enjoyment and Affective Development.

    ERIC Educational Resources Information Center

    Reporting on Reading, 1978

    1978-01-01

    The articles in this publication offer ideas for developing enjoyment of reading in children. Among the topics discussed are the following: the need for teachers and parents to build children's self-esteem through increasing their experiences of success, their expectations of success, and the value they place on reading; methods for increasing…

  19. Information superhighway: Issues affecting development

    NASA Astrophysics Data System (ADS)

    1994-09-01

    Technological advances in the transmission of voice, video, and data are fostering fundamental changes in the telecommunications industry. For example, large local telephone companies plan to offer video services in competition with cable and broadcast television, while cable television companies plan to offer local telephone service over their wires in competition with the local telephone companies. The administration believes that these technological changes provide the opportunity to develop an 'Information Superhighway' that could provide every element of society with ready access to data, voice, and video communications. Concurrently, the Congress is considering sweeping changes to telecommunications regulations to keep pace with this dynamic industry. GAO prepared this report to serve as an overview of three key issues that decisionmakers may face as they deliberate telecommunications legislation; it focuses on three pivotal issues they face in formulating new telecommunications legislation: (1) managing the transition to a more competitive local telecommunications marketplace; (2) ensuring that all consumers have access to affordable telecommunications as competition develops; and (3) ensuring that the Information Superhighway provides adequate security, privacy, reliability, and interoperability.

  20. Environmental Factors Affecting Preschoolers' Motor Development

    ERIC Educational Resources Information Center

    Venetsanou, Fotini; Kambas, Antonis

    2010-01-01

    The process of development occurs according to the pattern established by the genetic potential and also by the influence of environmental factors. The aim of the present study was to focus on the main environmental factors affecting motor development. The review of the literature revealed that family features, such as socioeconomic status,…

  1. Neural activities during affective processing in people with Alzheimer's disease.

    PubMed

    Lee, Tatia M C; Sun, Delin; Leung, Mei-Kei; Chu, Leung-Wing; Keysers, Christian

    2013-03-01

    This study examined brain activities in people with Alzheimer's disease when viewing happy, sad, and fearful facial expressions of others. A functional magnetic resonance imaging and a voxel-based morphometry methodology together with a passive viewing of emotional faces paradigm were employed to compare the affective processing in 12 people with mild Alzheimer's disease and 12 matched controls. The main finding was that the clinical participants showed reduced activations in regions associated with the motor simulation system (the ventral premotor cortex) and in regions associated with emotional simulation-empathy (the anterior insula and adjacent frontal operculum). This regional decline in blood oxygen level-dependent signals appeared to be lateralized in the left hemisphere and was not related to any structural degeneration in the clinical participants. Furthermore, the regions that showed changes in neural activity differed for the 3 emotional facial expressions studied. Findings of our study indicate that neural changes in regions associated with the motor and emotional simulation systems might play an important role in the development of Alzheimer's disease. PMID:22840336

  2. Factors Affecting the Quality of Staff Development.

    ERIC Educational Resources Information Center

    Purcell, Larry O.

    A review of the literature concerning the effectiveness and quality of staff development programs focuses on factors that affect the success of such programs. These factors include: individual concerns, training activities, applications, qualifications of consultants, scheduling, strategies, facilities, feedback, collaboration, and outcomes. It is…

  3. Affective Dimensions of Adult Literacy Development.

    ERIC Educational Resources Information Center

    Durgunoglu, Aydin Y.

    To investigate affective dimensions of adult literacy development more systematically, researchers conducted a qualitative comparative analysis of four women participating in an adult literacy program in Istanbul, Turkey. The contrastive study chose two participants who completed the course; each was matched with a participant who had dropped out.…

  4. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease.

    PubMed

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  5. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

    PubMed Central

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  6. Latin America: native populations affected by early onset periodontal disease.

    PubMed

    Nowzari, Hessam; Botero, Javier Enrique

    2011-06-01

    Millions of individuals are affected by early onset periodontal disease in Latin America, a continent that includes more than 20 countries. The decision-makers claim that the disease is not commonly encountered. In 2009, 280,919 authorized immigrants were registered in the United States versus 5,460,000 unauthorized (2,600,000 in California). The objective of the present article is to raise awareness about the high prevalence of the disease among Latin Americans and the good prognosis of preventive measures associated with minimal financial cost. PMID:21823496

  7. Alveolar Development and Disease

    PubMed Central

    Weaver, Timothy E.

    2015-01-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  8. Alveolar development and disease.

    PubMed

    Whitsett, Jeffrey A; Weaver, Timothy E

    2015-07-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  9. A Review of Factors Affecting Vaccine Preventable Disease in Japan

    PubMed Central

    Ching, Michael SL

    2014-01-01

    Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded “routine” (eg, polio, pertussis) and self-pay “voluntary” groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion. PMID:25628969

  10. Identification of mutations in Colombian patients affected with Fabry disease.

    PubMed

    Uribe, Alfredo; Mateus, Heidi Eliana; Prieto, Juan Carlos; Palacios, Maria Fernanda; Ospina, Sandra Yaneth; Pasqualim, Gabriela; da Silveira Matte, Ursula; Giugliani, Roberto

    2015-12-15

    Fabry Disease (FD) is an X-linked inborn error of glycosphingolipid catabolism, caused by a deficiency of the lisosomal α-galactosidase A (AGAL). The disorder leads to a vascular disease secondary to the involvement of kidney, heart and the central nervous system. The mutation analysis is a valuable tool for diagnosis and genetic counseling. Although more than 600 mutations have been identified, most mutations are private. Our objective was to describe the analysis of nine Colombian patients with Fabry disease by automated sequencing of the seven exons of the GLA gene. Two novel mutations were identified in two patients affected with the classical subtype of FD, in addition to other 6 mutations previously reported. The present study confirms the heterogeneity of mutations in Fabry disease and the importance of molecular analysis for genetic counseling, female heterozygotes detection as well as therapeutic decisions. PMID:26297554

  11. Graft-versus-host disease affecting oral cavity. A review

    PubMed Central

    Margaix-Muñoz, Maria; Bagán, José V.; Jiménez, Yolanda; Sarrión, María-Gracia; Poveda-Roda, Rafael

    2015-01-01

    Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival. PMID:25810826

  12. Graft-versus-host disease affecting oral cavity. A review.

    PubMed

    Margaix-Muñoz, Maria; Bagán, José V; Jiménez, Yolanda; Sarrión, María-Gracia; Poveda-Roda, Rafael

    2015-02-01

    Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival. PMID:25810826

  13. A practical approach to diseases affecting dentate nuclei.

    PubMed

    Khadilkar, S; Jaggi, S; Patel, B; Yadav, R; Hanagandi, P; Faria do Amaral, L L

    2016-01-01

    A wide variety of diseases affect the dentate nuclei. When faced with the radiological demonstration of signal changes in the dentate nuclei, radiologists and clinical neurologists have to sieve through the many possibilities, which they do not encounter on a regular basis. This task can be challenging, and therefore, developing a clinical, radiological, and laboratory approach is important. Information on the topic is scattered and the subject has not yet been reviewed. In this review, a combined clinicoradiological approach is presented. The signal changes in T1, T2, fluid-attenuated inversion recovery (FLAIR), diffusion, susceptibility weighted, and gadolinium-enhanced images can give specific or highly suggestive patterns, which are illustrated. The role of computed tomography (CT) in the diagnostic process is discussed. Specific radiological patterns do not exist in a significant proportion of patients where the clinical and laboratory analysis becomes important. In this review, we group the clinical constellations to narrow down the differential diagnosis and highlight the diagnostic clinical signs, such as tendon xanthomas and Kayser-Fleischer rings. As will be seen, a number of these conditions are potentially reversible, and hence, their early diagnosis is desirable. Finally, key diagnostic tests and available therapies are outlined. The practical approach thus begins with the radiologist and winds its way through the clinician, towards carefully selected diagnostic tests defining the therapy options. PMID:26577296

  14. Demographic, socioeconomic and environmental changes affecting circulation of neglected tropical diseases in Egypt.

    PubMed

    Abou-El-Naga, Iman F

    2015-11-01

    Egypt has been plagued by many neglected tropical diseases since Pharaonic time. These diseases are Schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis, leishmaniasis and fascioliasis beside the epidermal parasitic skin diseases. Indeed, theses diseases still persist as public health problem in the country by the influence of demographic, socioeconomic and environmental obstacles. This study seeks for understanding the contribution of each factor in each obstacle in neglected tropical diseases perpetuation which in turn could help the governorate in planning integrated control strategies. It was found that poverty, unregulated urbanization and inadequate sanitation are important socioeconomic factors that have great effect on the transmission dynamics of the diseases. The environmental factors which affect the epidemiology of these diseases in the country are scarcity of water, construction of dams, land reclamation for agriculture beside the climate factors. Unfortunately, the panic increase in the population growth rate minimizes the efforts done by the governorate to elevate the public health services. These conditions also affect the transmission of epidermal parasitic skin diseases including scabies, head lice and hookworm-related cutaneous larva migrans. The control programs and the recommendations to combat the diseases were discussed. The present study showed that the ecological factors affecting each neglected tropical disease in Egypt are somewhat similar which makes it worthy to develop an integrated control approaches aiming at improving the leading factors of neglected tropical diseases circulation in the country. PMID:26614986

  15. Diffusion tensor imaging in Alzheimer's disease and affective disorders.

    PubMed

    Teipel, Stefan J; Walter, Martin; Likitjaroen, Yuttachai; Schönknecht, Peter; Gruber, Oliver

    2014-09-01

    The functional organization of the brain in segregated neuronal networks has become a leading paradigm in the study of brain diseases. Diffusion tensor imaging (DTI) allows testing the validity and clinical utility of this paradigm on the structural connectivity level. DTI in Alzheimer's disease (AD) suggests a selective impairment of intracortical projecting fiber tracts underlying the functional disorganization of neuronal networks supporting memory and other cognitive functions. These findings have already been tested for their utility as clinical markers of AD in large multicenter studies. Affective disorders, including major depressive disorder (MDD) and bipolar disorder (BP), show a high comorbidity with AD in geriatric populations and may even have a pathogenetic overlap with AD. DTI studies in MDD and BP are still limited to small-scale monocenter studies, revealing subtle abnormalities in cortico-subcortial networks associated with affect regulation and reward/aversion control. The clinical utility of these findings remains to be further explored. The present paper presents the methodological background of diffusion imaging, including DTI and diffusion spectrum imaging, and discusses key findings in AD and affective disorders. The results of our review strongly point toward the necessity of large-scale multicenter multimodal transnosological networks to study the structural and functional basis of neuronal disconnection underlying different neuropsychiatric diseases. PMID:24595744

  16. The reproduction in women affected by cooley disease

    PubMed Central

    Pafumi, Carlo; Leanza, Vito; Coco, Luana; Vizzini, Stefania; Ciotta, Lilliana; Messina, Alessandra; Leanza, Gianluca; Zarbo, Giuseppe; D'Agati, Alfio; Palumbo, Marco Antonio; Iemmola, Alessandra; Gulino, Ferdinando Antonio; Teodoro, Maria Cristina; Attard, Matthew; Plesca, Alina Cristina; Soares, Catarina; Kouloubis, Nina; Chammas, Mayada

    2011-01-01

    The health background management and outcomes of 5 pregnancies in 4 women affected by Cooley Disease, from Paediatric Institute of Catania University, are described, considering the preconceptual guidances and cares for such patients. These patients were selected among a group of 100 thalassemic women divided into three subgroups, according to their first and successive menstruation characteristics: i) patients with primitive amenorrhoea, ii) patients with secondary amenorrhoea and iii) patients with normal menstruation. Only one woman, affected by primitive amenorrhoea, needed the induction of ovulation. A precise and detailed pre-pregnancy assessment was effected before each conception. This was constituted by a series of essays, including checks for diabetes and hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover were evaluated: cardiac function, rubella immunity and transaminases. Other pregnancy monitoring, and cares during labour and delivery were effected according to usual obstetrics practice. All the women were in labour when she were 38 week pregnant, and the outcome were five healthy babies born at term, weighting between 2600 and 3200gs. The only complication was the Caesarean section. The improvements of current treatments, especially in the management of iron deposits, the prolongation of survival rate, will result in a continuous increase of pregnancies in thalassemic women. Pregnancy is now a real possibility for women affected by such disease. We are furthermore studying the possibility to collect the fetus' umbilical cord blood, after the delivery, to attempt eterologus transplantation to his mother trying to get a complete marrow reconstitution. PMID:22184526

  17. Cadmium affects retinogenesis during zebrafish embryonic development

    SciTech Connect

    Hen Chow, Elly Suk; Yu Hui, Michelle Nga; Cheng, Chi Wa; Cheng, Shuk Han

    2009-02-15

    Ocular malformations are commonly observed in embryos of aquatic species after exposure to toxicants. Using zebrafish embryos as the model organism, we showed that cadmium exposure from sphere stage (4 hpf) to end of segmentation stage (24 hpf) induced microphthalmia in cadmium-treated embryos. Embryos with eye defects were then assessed for visual abilities. Cadmium-exposed embryos were behaviorally blind, showing hyperpigmentation and loss of camouflage response to light. We investigated the cellular basis of the formation of the small eyes phenotype and the induction of blindness by studying retina development and retinotectal projections. Retinal progenitors were found in cadmium-treated embryos albeit in smaller numbers. The number of retinal ganglion cells (RGC), the first class of retinal cells to differentiate during retinogenesis, was reduced, while photoreceptor cells, the last batch of retinal neurons to differentiate, were absent. Cadmium also affected the propagation of neurons in neurogenic waves. The neurons remained in the ventronasal area and failed to spread across the retina. Drastically reduced RGC axons and disrupted optic stalk showed that the optic nerves did not extend from the retina beyond the chiasm into the tectum. Our data suggested that impairment in neuronal differentiation of the retina, disruption in RGC axon formation and absence of cone photoreceptors were the causes of microphthalmia and visual impairment in cadmium-treated embryos.

  18. Black leaf streak disease affects starch metabolism in banana fruit.

    PubMed

    Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

    2013-06-12

    Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots. PMID:23692371

  19. Lymphangiogenesis in development and disease.

    PubMed

    Liersch, Ruediger; Detmar, Michael

    2007-08-01

    The lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells. The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease. PMID:17721611

  20. Environmental factors affecting inflammatory bowel disease: have we made progress?

    PubMed

    Lakatos, Peter Laszlo

    2009-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is only partially understood; various environmental and host (e.g. genetic, epithelial, immune, and nonimmune) factors are involved. The critical role for environmental factors is strongly supported by recent worldwide trends in IBD epidemiology. One important environmental factor is smoking. A meta-analysis partially confirms previous findings that smoking was found to be protective against ulcerative colitis and, after the onset of the disease, might improve its course, decreasing the need for colectomy. In contrast, smoking increases the risk of developing Crohn's disease and aggravates its course. The history of IBD is dotted by cyclic reports on the isolation of specific infectious agents responsible for Crohn's disease or ulcerative colitis. The more recently published cold chain hypothesis is providing an even broader platform by linking dietary factors and microbial agents. An additional, recent theory has suggested a breakdown in the balance between putative species of 'protective' versus 'harmful' intestinal bacteria - this concept has been termed dysbiosis resulting in decreased bacterial diversity. Other factors such as oral contraceptive use, appendectomy, dietary factors (e.g. refined sugar, fat, and fast food), perinatal events, and childhood infections have also been associated with both diseases, but their role is more controversial. Nonetheless, there is no doubt that economic development, leading to improved hygiene and other changes in lifestyle ('westernized lifestyle') may play a role in the increase in IBD. This review article focuses on the role of environmental factors in the pathogenesis and progression of IBDs. PMID:19786744

  1. CYSTIC FIBROSIS: AN INHERITED DISEASE AFFECTING MUCIN-PRODUCING ORGANS

    PubMed Central

    Ehre, Camille; Ridley, Caroline; Thornton, David J

    2014-01-01

    Our current understanding of cystic fibrosis (CF) has revealed that the biophysical properties of mucus play a considerable role in the pathogenesis of the disease in view of the fact that most mucus-producing organs are affected in CF patients. In this review, we discuss the potential causal relationship between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the production of mucus with abnormal biophysical properties in the intestine and lungs, highlighting what has been learned from cell cultures and animal models that mimic CF pathogenesis. A similar cascade of events, including mucus obstruction, infection and inflammation, is common to all epithelia affected by impaired surface hydration. Hence, the main structural components of mucus, namely the polymeric, gel-forming mucins, are critical to the onset of the disease. Defective CFTR leads to epithelial surface dehydration, altered pH/electrolyte composition and mucin concentration. Further, it can influence mucin transition from the intracellular to extracellular environment, potentially resulting in aberrant mucus gel formation. While defective HCO3− production has long been identified as a feature of CF, it has only recently been considered as a key player in the transition phase of mucins. We conclude by examining the influence of mucins on the biophysical properties of CF sputum and discuss existing and novel therapies aimed at removing mucus from the lungs. PMID:24685676

  2. How urbanization affects the epidemiology of emerging infectious diseases

    PubMed Central

    Neiderud, Carl-Johan

    2015-01-01

    The world is becoming more urban every day, and the process has been ongoing since the industrial revolution in the 18th century. The United Nations now estimates that 3.9 billion people live in urban centres. The rapid influx of residents is however not universal and the developed countries are already urban, but the big rise in urban population in the next 30 years is expected to be in Asia and Africa. Urbanization leads to many challenges for global health and the epidemiology of infectious diseases. New megacities can be incubators for new epidemics, and zoonotic diseases can spread in a more rapid manner and become worldwide threats. Adequate city planning and surveillance can be powerful tools to improve the global health and decrease the burden of communicable diseases. PMID:26112265

  3. How does the treadmill affect gait in Parkinson's disease?

    PubMed

    Bello, Olalla; Fernandez-Del-Olmo, Miguel

    2012-02-01

    Parkinson's disease (PD) is clinically characterized by symptoms of akinesia, rigidity, and resting tremor, which are related to a dopaminergic deficiency of the nigrostriatal pathway. Disorders of gait are common symptoms of PD that affect the quality of life in these patients. One of the main focuses of physical rehabilitation in PD is to improve the gait deficits in the patients. In the last decade, a small number of studies have investigated the use of the treadmill for the rehabilitation of gait in PD patients. Although, the results of these studies are promising, the mechanisms underlying the therapeutic effect of the treadmill in PD are still largely unknown. This paper reviews 10 years of investigation of treadmill training in PD, focusing on the possible mechanisms involved in the therapeutic effect of the treadmill. Understanding these mechanisms may improve the prescription and design of physical therapy programs for PD patients. PMID:21762092

  4. Variables Affecting Economic Development of Wind Energy

    SciTech Connect

    Lantz, E.; Tegen, S.

    2008-07-01

    NREL's JEDI Wind model performed an analysis of wind-power-related economic development drivers. Economic development benefits for wind and coal were estimated using NREL's JEDI Wind and JEDI Coal models.

  5. Cognition and Affect in Early Literacy Development.

    ERIC Educational Resources Information Center

    McNamee, Gillian D.; And Others

    1985-01-01

    Using Vygotsky's theory of development, explores the significance of storytelling and dramatization activities on the intellectual and emotional development of preschool children. Results indicate that dramatizing of children's stories enhances the storytelling of preschool children and, thus, influences their literacy development. (DST)

  6. Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor

    PubMed Central

    Glocker, Erik-Oliver; Kotlarz, Daniel; Boztug, Kaan; Gertz, E. Michael; Schäffer, Alejandro A.; Noyan, Fatih; Perro, Mario; Diestelhorst, Jana; Allroth, Anna; Murugan, Dhaarini; Hätscher, Nadine; Pfeifer, Dietmar; Sykora, Karl-Walter; Sauer, Martin; Kreipe, Hans; Lacher, Martin; Nustede, Rainer; Woellner, Cristina; Baumann, Ulrich; Salzer, Ulrich; Koletzko, Sibylle; Shah, Neil; Segal, Anthony W.; Sauerbrey, Axel; Buderus, Stephan; Snapper, Scott B.; Grimbacher, Bodo; Klein, Christoph

    2009-01-01

    BACKGROUND The molecular cause of inflammatory bowel disease is largely unknown. METHODS We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients’ peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient. RESULTS In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10–induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor α and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10–dependent “negative feedback” regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful. CONCLUSIONS Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic stem-cell transplantation resulted in disease remission in one patient. PMID:19890111

  7. Genetic Factors That Affect Risk of Alcoholic and Nonalcoholic Fatty Liver Disease.

    PubMed

    Anstee, Quentin M; Seth, Devanshi; Day, Christopher P

    2016-06-01

    Genome-wide association studies and candidate gene studies have informed our understanding of factors contributing to the well-recognized interindividual variation in the progression and outcomes of alcoholic liver disease and nonalcoholic fatty liver disease. We discuss the mounting evidence for shared modifiers and common pathophysiological processes that contribute to development of both diseases. We discuss the functions of proteins encoded by risk variants of genes including patatin-like phospholipase domain-containing 3 and transmembrane 6 superfamily member 2, as well as epigenetic factors that contribute to the pathogenesis of alcoholic liver disease and nonalcoholic fatty liver disease. We also discuss important areas of future genetic research and their potential to affect clinical management of patients. PMID:26873399

  8. Temperature affects Aethina tumida (Coleoptera: Nitidulidae) Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of temperature on several life history parameters of small hive beetles (SHB),Aethina tumida, were investigated under laboratory conditions. Our results showed that the development, body size and weight of SHB were dependent on temperature. Exposure of beetles to a lower (room) temperatu...

  9. [Does childhood obesity affect sexual development?].

    PubMed

    Wagner, I V; Sergeyev, E; Dittrich, K; Gesing, J; Neef, M; Adler, M; Geserick, M; Pfäffle, R W; Körner, A; Kiess, W

    2013-04-01

    The process of pubertal development is only partly understood and is influenced by many different factors. During the twentieth century there was a general trend toward earlier pubertal development. Fat mass is thought to be a major inducer of puberty. Owing to the rising epidemic of childhood obesity, the relationship between body composition in children and the rate and timing of puberty needs to be investigated. Some studies suggest that central obesity is associated with an earlier onset of pubertal development. Rapid weight gain in early life is linked to advanced puberty in both sexes. A clear correlation exists between increasing body mass index (BMI) and earlier pubertal development in girls. In boys the data are controversial: The majority of studies propose that there is an earlier puberty and voice break in obese boys, but some studies show the opposite. There are several factors and mechanisms that seem to link obesity and puberty, for example, leptin, adipocytokines, and gut peptides. Important players include genetic variation and environmental factors (e.g., endocrine-disrupting chemicals). This article presents the latest studies and evidence on this topic, underlining the inconsistencies in the data and, therefore, the need for further research in this area. PMID:23529595

  10. Input and output constraints affecting irrigation development

    NASA Astrophysics Data System (ADS)

    Schramm, G.

    1981-05-01

    In many of the developing countries the expansion of irrigated agriculture is used as a major development tool for bringing about increases in agricultural output, rural economic growth and income distribution. Apart from constraints imposed by water availability, the major limitations considered to any acceleration of such programs are usually thought to be those of costs and financial resources. However, as is shown on the basis of empirical data drawn from Mexico, in reality the feasibility and effectiveness of such development programs is even more constrained by the lack of specialized physical and human factors on the input and market limitations on the output side. On the input side, the limited availability of complementary factors such as, for example, truly functioning credit systems for small-scale farmers or effective agricultural extension services impose long-term constraints on development. On the output side the limited availability, high risk, and relatively slow growth of markets for high-value crops sharply reduce the usually hoped-for and projected profitable crop mix that would warrant the frequently high costs of irrigation investments. Three conclusions are drawn: (1) Factors in limited supply have to be shadow-priced to reflect their high opportunity costs in alternative uses. (2) Re-allocation of financial resources from immediate construction of projects to longer-term increase in the supply of scarce, highly-trained manpower resources are necessary in order to optimize development over time. (3) Inclusion of high-value, high-income producing crops in the benefit-cost analysis of new projects is inappropriate if these crops could potentially be grown in already existing projects.

  11. Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease.

    PubMed

    Serranová, Tereza; Jech, Robert; Dušek, Petr; Sieger, Tomáš; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen

    2011-10-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty-four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS-related sensitivity to food reward stimuli cues might drive DBS-treated patients to higher food intake and subsequent weight gain. PMID:21780183

  12. How does smoking affect olfaction in Parkinson's disease?

    PubMed

    Moccia, Marcello; Picillo, Marina; Erro, Roberto; Vitale, Carmine; Amboni, Marianna; Palladino, Raffaele; Cioffi, Dante Luigi; Barone, Paolo; Pellecchia, Maria Teresa

    2014-05-15

    Smoke-induced upper airway damage and Parkinson's disease (PD) can be considered independent risk factors for smell impairment. Interestingly, cigarette smoking has been strongly associated with reduced risk of PD and, therefore, has been suggested to have neuroprotective effects. Our pilot study aimed to evaluate the relationship between smoking and olfaction in PD patients and matched controls. Sixty-eight PD patients and 61 healthy controls were categorized in relation to PD diagnosis and current smoking status, and evaluated by means of the Italian version of the University of Pennsylvania 40-item Smell Identification Test (UPSIT-40). ANOVA analysis with post-hoc Bonferroni correction showed that non-smoker controls presented a higher UPSIT-40 total score than smoker controls (p<0.001), non-smoker PD patients (p<0.001) and smoker PD patients (p<0.001). In this view, smoking seems to affect olfaction in controls but not in PD patients, and no significant differences were found when comparing smoker controls, smoker PD patients and non-smoker PD patients. Several epidemiological studies showed a negative effect of smoking on olfaction in the general population. Otherwise the sense of smell is similar in smoker and non-smoker PD patients. These results suggest that PD and smoking are not independent risk factors for impairment of sense of smell, but they might variably interact. PMID:24655736

  13. Developing countries and neglected diseases: challenges and perspectives

    PubMed Central

    Boutayeb, Abdesslam

    2007-01-01

    It is now commonly admitted that the so-called (most) neglected tropical diseases have been given little attention. According to World Health Organization, neglected diseases are hidden diseases as they affect almost exclusively extremely poor populations living in remote areas beyond the reach of health service. The European Parliament recognised that, to our shame, Neglected Diseases have not received the attention they deserve from EU actions. In the Millennium Development Goals they were given very little attention and mentioned just as other disease. Investing in drugs for these diseases is thought to be not marketable or profitable. However, despite their low mortality, neglected diseases are causing severe and permanent disabilities and deformities affecting approximately 1 billion people in the world, yielding more than 20 millions of Disability Adjusted Life Years (56.6 million according to Lancet's revised estimates) and important socio-economic losses. Urgent pragmatic and efficient measures are needed both at international and national levels. PMID:18036265

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

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

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

  15. Contamination sensitivity and the development of disease-avoidant behaviour

    PubMed Central

    Siegal, Michael; Fadda, Roberta; Overton, Paul G.

    2011-01-01

    Owing to their developing cognitive abilities and their limited knowledge about the biological basis of illness, children often have less expertise at disease avoidance than adults. However, affective reactions to contaminants through the acquisition of disgust and the social and cultural transmissions of knowledge about contamination and contagion provide impetus for children to learn effective disease-avoidant behaviours early in their development. In this article, we review the ontogenetic development of knowledge about contamination and contagion with particular attention to the role of socialization and culture. Together with their emerging cognitive abilities and affective reactions to contaminants, informal and formal cultural learning shape children's knowledge about disease. Through this process, the perceptual cues of contamination are linked to threats of disease outcomes and can act as determinants of disease-avoidant behaviours. PMID:22042919

  16. Affective Development in Advanced Old Age: Analyses of Terminal Change in Positive and Negative Affect

    ERIC Educational Resources Information Center

    Schilling, Oliver K.; Wahl, Hans-Werner; Wiegering, Sarah

    2013-01-01

    Late-life development of affect may unfold terminal changes that are driven more by end-of-life processes and not so much by time since birth. This study aimed to explore time-to-death-related effects in measures of affect in a sample of the very old. We used longitudinal data (2 measurement occasions: 2002 and 2003) from 140 deceased…

  17. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease.

    PubMed

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L; Brull, Astrid; Andreu, Antoni L; Vissing, John

    2016-05-01

    McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray, variations in fiber size, vacuoles, and some internal nuclei associated with cytosolic glycogen accumulation and ongoing regeneration; structural damage was seen only in a minority of human patients. Neither liver nor brain isoforms of glycogen phosphorylase were upregulated in muscles, thus providing no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus, despite differences, the mouse model of McArdle disease shares fundamental physiological and clinical features with the human disease and could be used for studies of pathogenesis and development of therapies. PMID:27030740

  18. Evaluation of Neurodevelopment and Factors Affecting it in Children With Acyanotic Congenital Cardiac Disease

    PubMed Central

    Ozmen, Ayten; Terlemez, Semiha; Tunaoglu, Fatma Sedef; Soysal, Sebnem; Pektas, Ayhan; Cilsal, Erman; Koca, Ulker; Kula, Serdar; Deniz Oguz, Ayse

    2016-01-01

    Background: The rate of congenital heart disease is 0.8% in all live births. The majority of this, however, is acyanotic congenital heart disease. The survival rate of children with cardiac disease has increased with the developments provided in recent years and their lifetime is extended. Objectives: This study aims to evaluate neurodevelopment of children with uncomplicated acyanotic congenital heart disease in preschool period and determine the factors affecting their neurodevelopmental process. Patients and Methods: 132 children with acyanotic congenital heart disease aged 6 - 72 months were involved in the study. Mental development and intelligence levels of patients under 2 years old were assessed by using Bayley Development Scale-III, and Stanford Binet Intelligence test was employed for patients over 2 years old. Denver Developmental Screening Test II was applied to all patients for their personal-social, fine motor, gross motor and language development. Results: The average age of patients (67 girls, 65 boys) included in the study was 35.2 ± 19.6 months. It was determined that there were subnormal mental level in 13 (10%) patients and at least one specific developmental disorder in 33 (25%) patients. Bayley Mental Development Scale score of patients who had received incubator care in perinatal period was found significantly low (88 ± 4.2) compared to those with no incubator care (93.17 ± 8.5) (P = 0.028). Low educational level of father was established to be linked with low mental development scores at the age of 2 and following that age (P < 0.05). Iron deficiency anemia was discovered to be related to low psychometric test scores at every age (P < 0.05). Conclusions: Neurodevelopmental problems in children with acyanotic congenital heart disease were found higher compared to those in society. Mental development and intelligence levels of patients were determined to be closely associated with receiving incubator care, father’s educational level and

  19. Ongoing neural development of affective theory of mind in adolescence

    PubMed Central

    Weigelt, Sarah; Döhnel, Katrin; Smolka, Michael N.; Kliegel, Matthias

    2014-01-01

    Affective Theory of Mind (ToM), an important aspect of ToM, involves the understanding of affective mental states. This ability is critical in the developmental phase of adolescence, which is often related with socio-emotional problems. Using a developmentally sensitive behavioral task in combination with functional magnetic resonance imaging, the present study investigated the neural development of affective ToM throughout adolescence. Eighteen adolescent (ages 12–14 years) and 18 young adult women (aged 19–25 years) were scanned while evaluating complex affective mental states depicted by actors in video clips. The ventromedial prefrontal cortex (vmPFC) showed significantly stronger activation in adolescents in comparison to adults in the affective ToM condition. Current results indicate that the vmPFC might be involved in the development of affective ToM processing in adolescence. PMID:23716712

  20. Ongoing neural development of affective theory of mind in adolescence.

    PubMed

    Vetter, Nora C; Weigelt, Sarah; Döhnel, Katrin; Smolka, Michael N; Kliegel, Matthias

    2014-07-01

    Affective Theory of Mind (ToM), an important aspect of ToM, involves the understanding of affective mental states. This ability is critical in the developmental phase of adolescence, which is often related with socio-emotional problems. Using a developmentally sensitive behavioral task in combination with functional magnetic resonance imaging, the present study investigated the neural development of affective ToM throughout adolescence. Eighteen adolescent (ages 12-14 years) and 18 young adult women (aged 19-25 years) were scanned while evaluating complex affective mental states depicted by actors in video clips. The ventromedial prefrontal cortex (vmPFC) showed significantly stronger activation in adolescents in comparison to adults in the affective ToM condition. Current results indicate that the vmPFC might be involved in the development of affective ToM processing in adolescence. PMID:23716712

  1. Disease painting or painting disease: how does illness and hospitalisation affect children's artistry?

    PubMed

    Bayrakci, Benan; Forouz, Aria; Sahin, Ahmet B; Abali, Mustafa; Aliyeva, Gyulten Z

    2009-01-01

    There are numerous speculations about famous artists and how their perception was affected by their medical conditions. In this study, we examined how illness and hospitalisation affect children's art. A total of 157 paintings by 122 hospitalised children were interpreted by three reputed artists. Works of ill children were compared with those of a control group from an international art exhibition. We also comment on how diseases influenced the technique of famous artists to further examine the possible impact of illness on the artistry of hospitalised children. Developmental delay in painting was evident in the study group. Use of ready-made schemas was a common practice (55%). 56% of the work from patients older than eight years failed in perspective and site perception. The theme in 89% of the drawings had no human figures. Projection of self sufferings, prominent elementary lines, and reflection of distorted perception could be clearly recognised in various study materials; anxiety about assigned surgery was exhibited by scribbling. There exists a close relationship between medicine and humanities. The interpretation of fine art from a medical perspective may help to increase our appreciation of the suffering of an individual. It is obvious that diseases change the artistic style and inner perspective. The question is how do healthcare specialists view this? PMID:20120269

  2. FACTORS AFFECTING SUSCEPTIBILITY OF THE CORAL MONTASTRAEA FAVEOLATE TO BLACK-BAND DISEASE

    EPA Science Inventory

    Black-band disease affects many species of tropical reef-building corals, but it is unclear what factors contribute to the disease-susceptibility of individual corals or how the disease is transmitted between colonies. Studies have suggested that the ability of black-band disease...

  3. Infectious Diseases Affect Marine Fisheries and Aquaculture Economics

    NASA Astrophysics Data System (ADS)

    Lafferty, Kevin D.; Harvell, C. Drew; Conrad, Jon M.; Friedman, Carolyn S.; Kent, Michael L.; Kuris, Armand M.; Powell, Eric N.; Rondeau, Daniel; Saksida, Sonja M.

    2015-01-01

    Seafood is a growing part of the economy, but its economic value is diminished by marine diseases. Infectious diseases are common in the ocean, and here we tabulate 67 examples that can reduce commercial species' growth and survivorship or decrease seafood quality. These impacts seem most problematic in the stressful and crowded conditions of aquaculture, which increasingly dominates seafood production as wild fishery production plateaus. For instance, marine diseases of farmed oysters, shrimp, abalone, and various fishes, particularly Atlantic salmon, cost billions of dollars each year. In comparison, it is often difficult to accurately estimate disease impacts on wild populations, especially those of pelagic and subtidal species. Farmed species often receive infectious diseases from wild species and can, in turn, export infectious agents to wild species. However, the impact of disease export on wild fisheries is controversial because there are few quantitative data demonstrating that wild species near farms suffer more from infectious diseases than those in other areas. The movement of exotic infectious agents to new areas continues to be the greatest concern.

  4. Infectious diseases affect marine fisheries and aquaculture economics

    USGS Publications Warehouse

    Lafferty, Kevin D.; Harvell, C. Drew; Conrad, Jon M.; Friedman, Carolyn S.; Kent, Michael L.; Kuris, Armand M.; Powell, Eric N.; Rondeau, Daniel; Saksida, Sonja M.

    2015-01-01

    Seafood is a growing part of the economy, but its economic value is diminished by marine diseases. Infectious diseases are common in the ocean, and here we tabulate 67 examples that can reduce commercial species' growth and survivorship or decrease seafood quality. These impacts seem most problematic in the stressful and crowded conditions of aquaculture, which increasingly dominates seafood production as wild fishery production plateaus. For instance, marine diseases of farmed oysters, shrimp, abalone, and various fishes, particularly Atlantic salmon, cost billions of dollars each year. In comparison, it is often difficult to accurately estimate disease impacts on wild populations, especially those of pelagic and subtidal species. Farmed species often receive infectious diseases from wild species and can, in turn, export infectious agents to wild species. However, the impact of disease export on wild fisheries is controversial because there are few quantitative data demonstrating that wild species near farms suffer more from infectious diseases than those in other areas. The movement of exotic infectious agents to new areas continues to be the greatest concern.

  5. The Development of the Meta-Affective Trait Scale

    ERIC Educational Resources Information Center

    Uzuntiryaki-Kondakci, Esen; Kirbulut, Zubeyde Demet

    2016-01-01

    The purpose of this study was to develop a Meta-Affective Trait Scale (MATS) to measure the meta-affective inclinations related to emotions that students have while they are studying for their classes. First, a pilot study was performed with 380 10th-grade students. Results of the exploratory factor analysis supported a two-factor structure of the…

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

    SciTech Connect

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

    1988-01-01

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

  7. Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

    PubMed Central

    Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

    2016-01-01

    Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

  8. Factors Affecting the Efficacy of Recombinant Marek's Disease Vaccine Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many factors have the potential to influence the efficacy of Marek's disease (MD) vaccination. Some of these factors include maternal antibody, vaccine dose, age of birds at vaccination or challenge, challenge virus strain and genetic background of chickens. The objective of this study was to evalua...

  9. Endophytic bacteria in potato tubers affected by zebra chip disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato zebra chip disease (ZCD) could drastically reduce quality and value of all market classes of potato, costing growers and processors millions of dollars in losses in North America. Endophytic bacteria colonize the internal tissue and could have both positive and negative effects on host plants...

  10. Developing disease resistant stone fruits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stone fruit (Prunus spp.) (peach, nectarine, plum, apricot, cherry) and almonds are susceptible to a number of pathogens. These pathogens can cause extensive losses in the field, during transport and storage, and in the market. Breeding for disease resistance requires an extensive knowledge of the...

  11. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. We conducted a retrospective chart review of children with BD (ejecti...

  12. Semantic Trouble Sources and Their Repair in Conversations Affected by Parkinson's Disease

    ERIC Educational Resources Information Center

    Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

    2014-01-01

    Background: It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these…

  13. Six-Digit CPK and Mildly Affected Renal Function in McArdle Disease

    PubMed Central

    Mcinnes, Andrew D.; DeGroote, Richard J.

    2014-01-01

    A previously healthy, white 12-year-old girl presented with diffuse body aches and poor perfusion. She developed severe respiratory failure and marked rhabdomyolysis and was mechanically ventilated. Although her CPK peaked at 500,000 IU/L, her renal function was mildly affected and her creatinine did not exceed the 0.8 mg/dL. The rhabdomyolysis was gradually resolved following aggressive fluid hydration. The patient did not require dialysis and made a complete recovery. Genetic studies revealed the diagnosis of McArdle disease. PMID:25371840

  14. Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

    PubMed Central

    Zheng, Guoping; Ge, Menghua; Qiu, Guanguan; Shu, Qiang; Xu, Jianguo

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-α stimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models. PMID:26257791

  15. Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization.

    PubMed

    Zheng, Guoping; Ge, Menghua; Qiu, Guanguan; Shu, Qiang; Xu, Jianguo

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-α stimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models. PMID:26257791

  16. Recent developments in biomarkers in Parkinson disease

    PubMed Central

    Schapira, Anthony H.V.

    2013-01-01

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

  17. Vector-borne pathogens: New and emerging arboviral diseases affecting public health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dengue and Zika have quickly become two of the most important vector-borne diseases affecting Public health around the world. This presentation will introduce vector-borne diseases and all the vectors implicated. A focus will be made on the most important arboviral diseases (Zika and dengue) describ...

  18. Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility.

    PubMed

    Rezazadeh, Maryam; Khorrami, Aziz; Yeghaneh, Tarlan; Talebi, Mahnaz; Kiani, Seyed Jalal; Heshmati, Yaser; Gharesouran, Jalal

    2016-03-01

    Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF α), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF α, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRα (PvuII) was evident only among subjects without the APOE ε4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE ε4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD. PMID:26553058

  19. [Familial incidence of affective diseases in patients with anorexia nervosa].

    PubMed

    Herpertz-Dahlmann, B

    1988-03-01

    Analysis of family history information about first-, second- and third-degree relatives of 45 anorectic patients and 38 control subjects with different types of neurosis showed significantly more depression and eating disorders in the families of the anorectic group. Our data revealed the same prevalence of psychiatric disorders in general for both groups; the alcoholism rate was higher in the anorectic group without a statistic significance. These findings might provide further evidence of a possible genetic relationship between anorexia nervosa and affective illness. PMID:3388987

  20. Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways.

    PubMed

    Sturgeon, John A; Finan, Patrick H; Zautra, Alex J

    2016-09-01

    In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) have an increased prevalence of some mental health disorders, particularly those involving affective or mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and their psychological responses to the disease, and can also impair responses to treatment through disruption of patient-physician relationships and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed. PMID:27411910

  1. Zebrafish Models of Human Liver Development and Disease

    PubMed Central

    Wilkins, Benjamin J.; Pack, Michael

    2016-01-01

    The liver performs a large number of essential synthetic and regulatory functions that are acquired during fetal development and persist throughout life. Their disruption underlies a diverse group of heritable and acquired diseases that affect both pediatric and adult patients. Although experimental analyses used to study liver development and disease are typically performed in cell culture models or rodents, the zebrafish is increasingly used to complement discoveries made in these systems. Forward and reverse genetic analyses over the past two decades have shown that the molecular program for liver development is largely conserved between zebrafish and mammals, and that the zebrafish can be used to model heritable human liver disorders. Recent work has demonstrated that zebrafish can also be used to study the mechanistic basis of acquired liver diseases. Here, we provide a comprehensive summary of how the zebrafish has contributed to our understanding of human liver development and disease. PMID:23897685

  2. Concentration of carp edema virus (CEV) DNA in koi tissues affected by koi sleepy disease (KSD).

    PubMed

    Adamek, Mikolaj; Jung-Schroers, Verena; Hellmann, John; Teitge, Felix; Bergmann, Sven Michael; Runge, Martin; Kleingeld, Dirk Willem; Way, Keith; Stone, David Michael; Steinhagen, Dieter

    2016-05-26

    Carp edema virus (CEV), the causative agent of 'koi sleepy disease' (KSD), appears to be spreading worldwide and to be responsible for losses in koi, ornamental varieties of the common carp Cyprinus carpio. Clinical signs of KSD include lethargic behaviour, swollen gills, sunken eyes and skin alterations and can easily be mistaken for other diseases, such as infection with cyprinid herpesvirus 3 (CyHV-3). To improve the future diagnosis of CEV infection and to provide a tool to better explore the relationship between viral load and clinical disease, we developed a specific quantitative PCR (qPCR) for strains of the virus known to infect koi carp. In samples from several clinically affected koi, CEV-specific DNA was present in a range from 1 to 2,046,000 copies, with a mean of 129,982 copies and a median of 45 copies per 250 ng of isolated DNA, but virus DNA could not be detected in all clinically affected koi. A comparison of the newly developed qPCR, which is based on a dual-labelled probe, to an existing end-point PCR procedure revealed higher specificity and sensitivity of the qPCR and demonstrated that the new protocol could improve CEV detection in koi. In addition to improved diagnosis, the newly developed qPCR test would be a useful research tool. For example, studies on the pathobiology of CEV could employ controlled infection experiments in which the development of clinical signs could be examined in parallel with a quantitative determination of virus load. PMID:27225208

  3. MBT domain proteins in development and disease

    PubMed Central

    Bonasio, Roberto; Lecona, Emilio; Reinberg, Danny

    2013-01-01

    The Malignant Brain Tumor (MBT) domain is a “chromatin reader”, a protein module that binds to post-translational modifications on histone tails that are thought to affect a variety of chromatin processes, including transcription. More specifically, MBT domains recognize mono- and di-methylated lysines at a number of different positions on histone H3 and H4 tails. Three Drosophila proteins, SCM, L(3)MBT and SFMBT contain multiple adjacent MBT repeats and have critical roles in development, maintenance of cell identity, and tumor suppression. Although they function in different pathways, these proteins all localize to chromatin in vivo and repress transcription by a currently unknown molecular mechanism that requires the MBT domains. The human genome contains several homologues of these MBT proteins, some of which have been linked to important gene regulatory pathways, such as E2F/Rb- and Polycomb-mediated repression, and to the insurgence of certain neurological tumors. Here, we review the genetics, biochemistry, and cell biology of MBT proteins and their role in development and disease. PMID:19778625

  4. Development and psychometric validation of the verbal affective memory test.

    PubMed

    Jensen, Christian G; Hjordt, Liv V; Stenbæk, Dea S; Andersen, Emil; Back, Silja K; Lansner, Jon; Hageman, Ida; Dam, Henrik; Nielsen, Anna P; Knudsen, Gitte M; Frokjaer, Vibe G; Hasselbalch, Steen G

    2016-10-01

    We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults' valence ratings of 210 common and non-taboo words. Second, we studied the test's psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory, rs ≥ .77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory. PMID:26401886

  5. Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence.

    PubMed

    Bilski, Jan; Mazur-Bialy, Agnieszka; Brzozowski, Bartosz; Magierowski, Marcin; Zahradnik-Bilska, Janina; Wójcik, Dagmara; Magierowska, Katarzyna; Kwiecien, Slawomir; Mach, Tomasz; Brzozowski, Tomasz

    2016-08-01

    The inflammatory bowel disease (IBD) consisting of Crohn's disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients' mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models. PMID:27255494

  6. Affect development as a need to preserve homeostasis.

    PubMed

    Dönmez, Aslıhan; Ceylan, Mehmet Emin; Ünsalver, Barış Önen

    2016-03-01

    In this review, we aim to present our hypothesis about the neural development of affect. According to this view, affect develops at a multi-layered process, and as a mediator between drives, emotion and cognition. This development is parallel to the evolution of the brain from reptiles to mammals. There are five steps in this process: (1) Because of the various environmental challenges, changes in the autonomic nervous system occur and homeostasis becomes destabilized; (2) Drives arise from the destabilized homeostasis; (3) Drives trigger the neural basis of the basic emotional systems; (4) These basic emotions evolve into affect to find the particular object to invest the emotional energy; and (5) In the final stage, cognition is added to increase the possibility of identifying a particular object. In this paper, we will summarize the rationale behind this view, which is based on neuroscientific proofs, such as evolution of autonomic nervous system, neural basis the raw affective states, the interaction between affect and cognition, related brain areas, related neurotransmitters, as well as some clinical examples. PMID:26762485

  7. Developing Worksheet Based on Science Process Skills: Factors Affecting Solubility

    ERIC Educational Resources Information Center

    Karsli, Fethiye; Sahin, Cigdem

    2009-01-01

    The purpose of this study is to develop a worksheet about the factors affecting solubility, which could be useful for the prospective science teachers (PST) to remind and regain their science process skills (SPS). The pilot study of the WS was carried out with 32 first grade PST during the 2007-2008 academic year in the education department at…

  8. Development and validation of the Affective Self Rating Scale for manic, depressive, and mixed affective states.

    PubMed

    Adler, Mats; Liberg, Benny; Andersson, Stig; Isacsson, Göran; Hetta, Jerker

    2008-01-01

    Most rating scales for affective disorders measure either depressive or hypomanic/manic symptoms and there are few scales for hypomania/mania in a self-rating format. We wanted to develop and validate a self-rating scale for comprehensive assessment of depressive, manic/hypomanic and mixed affective states. We developed an 18-item self-rating scale starting with the DSM-IV criteria for depression and mania, with subscales for depression and mania. The scale was evaluated on 61 patients with a diagnosis of affective disorder, predominantly bipolar disorder type I, using Montgomery-Asberg Depression Rating Scale (MADRS), Hypomania Interview Guide-Clinical version (HIGH-C) and Clinical Global Impression scale, modified for bipolar patients (CGI-BP) as reference scales. Internal consistency of the scale measured by Cronbach's alpha was 0.89 for the depression subscale and 0.91 for the mania subscale. Spearman's correlation coefficients (two-tailed) between the depression subscale and MADRS was 0.74 (P<0.01) and between mania subscale and HIGH-C 0.80 (P<0.01). A rotated factor analysis of the scale supported the separation of symptoms in the mania and depression subscale. We established that the self-rating scales sensitivity to identify mixed states, with combined cut-offs on the MADRS and HIGH-C as reference, was 0.90 with a specificity of 0.71. The study shows that the Affective Self Rating Scale is highly correlated with ratings of established interview scales for depression and mania and that it may aid the detection of mixed affective states. PMID:18569776

  9. Lower urinary tract development and disease.

    PubMed

    Rasouly, Hila Milo; Lu, Weining

    2013-01-01

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

  10. Lower urinary tract development and disease

    PubMed Central

    Rasouly, Hila Milo; Lu, Weining

    2013-01-01

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

  11. HCV Infection Enhances Th17 Commitment, Which Could Affect the Pathogenesis of Autoimmune Diseases

    PubMed Central

    Kondo, Yasuteru; Ninomiya, Masashi; Kimura, Osamu; Machida, Keigo; Funayama, Ryo; Nagashima, Takeshi; Kobayashi, Koju; Kakazu, Eiji; Kato, Takanobu; Nakayama, Keiko; Lai, Michael M. C.; Shimosegawa, Tooru

    2014-01-01

    Background Various kinds of autoimmune diseases have been reported to have a significant relationship with persistent hepatitis c virus (HCV) infection and Th17 cells. Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation. Methods Therefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro. Results The prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C) was significantly higher than in other types of chronic hepatitis (hepatitis B and NASH). A significantly higher frequency of IL6 and TGF-β double-high patients was detected in CH-C than in other liver diseases. Moreover, these double-high patients had significantly higher positivity of anti-nuclear antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-β, IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1b lymphotropic HCV (Ly-HCV), by deep sequencing analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells with various kinds of cytokine-conditions including IL1β, IL23, IL6 and TGF-β in vitro. Infection by HCV could significantly enhance the development of Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core protein, which could enhance the STAT-3 signaling and up-regulate the expression of RORγt as a Th17 master gene. Conclusion Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases. PMID:24905921

  12. Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

    PubMed

    Cannas, A; Spissu, A; Floris, G L; Congia, S; Saddi, M V; Melis, M; Mascia, M M; Pinna, F; Tuveri, A; Solla, P; Milia, A; Giagheddu, M; Tacconi, P

    2002-09-01

    Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP). PMID:12548347

  13. Glia in mammalian development and disease.

    PubMed

    Zuchero, J Bradley; Barres, Ben A

    2015-11-15

    Glia account for more than half of the cells in the mammalian nervous system, and the past few decades have witnessed a flood of studies that detail novel functions for glia in nervous system development, plasticity and disease. Here, and in the accompanying poster, we review the origins of glia and discuss their diverse roles during development, in the adult nervous system and in the context of disease. PMID:26577203

  14. Epigenetic mechanisms in heart development and disease.

    PubMed

    Martinez, Shannalee R; Gay, Maresha S; Zhang, Lubo

    2015-07-01

    Suboptimal intrauterine development has been linked to predisposition to cardiovascular disease in adulthood, a concept termed 'developmental origins of health and disease'. Although the exact mechanisms underlying this developmental programming are unknown, a growing body of evidence supports the involvement of epigenetic regulation. Epigenetic mechanisms such as DNA methylation, histone modifications and micro-RNA confer added levels of gene regulation without altering DNA sequences. These modifications are relatively stable signals, offering possible insight into the mechanisms underlying developmental origins of health and disease. This review will discuss the role of epigenetic mechanisms in heart development as well as aberrant epigenetic regulation contributing to cardiovascular disease. Additionally, we will address recent advances targeting epigenetic mechanisms as potential therapeutic approaches to cardiovascular disease. PMID:25572405

  15. [Recent developments in genetic kidney diseases].

    PubMed

    Liebau, M C; Benzing, T

    2011-05-01

    The improved understanding of genetic kidney diseases has given rise to a more detailed understanding of kidney function within the last decade. Insights into the pathophysiological principles of frequent kidney diseases - partly inherited, partly acquired - have been obtained by the investigation of rare genetic disorders and can now serve as a starting point for the development of novel therapeutic strategies. In this way various clinical multicenter trials, which are based on the observations made in basic science have been established for the very common autosomal dominant polycystic kidney disease. Furthermore, the influence of genetic aspects on frequent kidney diseases, e. g. diabetic nephropathy, is becoming more obvious. This article aims to give an overview over essential recent development in the field of genetic kidney diseases. PMID:21544793

  16. Genomic architecture of inflammatory bowel disease in five families with multiple affected individuals

    PubMed Central

    Stittrich, Anna B; Ashworth, Justin; Shi, Mude; Robinson, Max; Mauldin, Denise; Brunkow, Mary E; Biswas, Shameek; Kim, Jin-Man; Kwon, Ki-Sun; Jung, Jae U; Galas, David; Serikawa, Kyle; Duerr, Richard H; Guthery, Stephen L; Peschon, Jacques; Hood, Leroy; Roach, Jared C; Glusman, Gustavo

    2016-01-01

    Currently, the best clinical predictor for inflammatory bowel disease (IBD) is family history. Over 163 sequence variants have been associated with IBD in genome-wide association studies, but they have weak effects and explain only a fraction of the observed heritability. It is expected that additional variants contribute to the genomic architecture of IBD, possibly including rare variants with effect sizes larger than the identified common variants. Here we applied a family study design and sequenced 38 individuals from five families, under the hypothesis that families with multiple IBD-affected individuals harbor one or more risk variants that (i) are shared among affected family members, (ii) are rare and (iii) have substantial effect on disease development. Our analysis revealed not only novel candidate risk variants but also high polygenic risk scores for common known risk variants in four out of the five families. Functional analysis of our top novel variant in the remaining family, a rare missense mutation in the ubiquitin ligase TRIM11, suggests that it leads to increased nuclear factor of kappa light chain enhancer in B-cells (NF-κB) signaling. We conclude that an accumulation of common weak-effect variants accounts for the high incidence of IBD in most, but not all families we analyzed and that a family study design can identify novel rare variants conferring risk for IBD with potentially large effect size, such as the TRIM11 p.H414Y mutation. PMID:27081563

  17. Affective disorders as complex dynamic diseases--a perspective from systems biology.

    PubMed

    Tretter, F; Gebicke-Haerter, P J; an der Heiden, U; Rujescu, D; Mewes, H W; Turck, C W

    2011-05-01

    Understanding mental disorders and their neurobiological basis encompasses the conceptual management of "complexity" and "dynamics". For example, affective disorders exhibit several fluctuating state variables on psychological and biological levels and data collected of these systems levels suggest quasi-chaotic periodicity leading to use concepts and tools of the mathematics of nonlinear dynamic systems. Regarding this, we demonstrate that the concept of "Dynamic Diseases" could be a fruitful way for theory and empirical research in neuropsychiatry. In a first step, as an example, we focus on the analysis of dynamic cortisol regulation that is important for understanding depressive disorders. In this case, our message is that extremely complex phenomena of a disease may be explained as resulting from perplexingly simple nonlinear interactions of a very small number of variables. Additionally, we propose that and how widely used complex circuit diagrams representing the macroanatomic structures and connectivities of the brain involved in major depression or other mental disorders may be "animated" by quantification, even by using expert-based estimations (dummy variables). This method of modeling allows to develop exploratory computer-based numerical models that encompass the option to explore the system by computer simulations (in-silico experiments). Also inter- and intracellular molecular networks involved in affective disorders could be modeled by this procedure. We want to stimulate future research in this theoretical context. PMID:21544742

  18. Decision Aids for Multiple-Decision Disease Management as Affected by Weather Input Errors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many disease management decision support systems (DSS) rely, exclusively or in part, on weather inputs to calculate an indicator for disease hazard. Error in the weather inputs, typically due to forecasting, interpolation or estimation from off-site sources, may affect model calculations and manage...

  19. Survey of state water laws affecting coal slurry pipeline development

    SciTech Connect

    Rogozen, M.B.

    1980-11-01

    This report summarizes state water laws likely to affect the development of coal slurry pipelines. It was prepared as part of a project to analyze environmental issues related to energy transportation systems. Coal slurry pipelines have been proposed as a means to expand the existing transportation system to handle the increasing coal shipments that will be required in the future. The availability of water for use in coal slurry systems in the coal-producing states is an issue of major concern.

  20. Discrimination and evocation of affectively intoned speech in patients with right parietal disease.

    PubMed

    Tucker, D M; Watson, R T; Heilman, K M

    1977-10-01

    Patients with right parietal disease have disturbed comprehension of affective speech. Ability to discriminate affective speech (make same/different discriminations) and ability to repeat emotionally bland sentences with affective tones were tested in three groups of subjects--patients with right parietal dysfunction and neglect, conduction aphasics with left hemispheric lesions, and patients without intracranial disease. Patients with right parietal dysfunction performed significantly poorer than did aphasic controls on both a recognition and discrimination task. Patients with right parietal dysfunction also scored poorer on the evocative task than the nonaphasic controls. PMID:561908

  1. Epigenetic mechanisms in heart development and disease

    PubMed Central

    Martinez, Shannalee R.; Gay, Maresha S.; Zhang, Lubo

    2015-01-01

    Suboptimal intrauterine development has been linked to predisposition to cardiovascular disease in adulthood, a concept termed ‘developmental origins of health and disease’. Although the exact mechanisms underlying this developmental programming are unknown, a growing body of evidence supports the involvement of epigenetic regulation. Epigenetic mechanisms such as DNA methylation, histone modifications and micro-RNA confer added levels of gene regulation without altering DNA sequences. These modifications are relatively stable signals, offering possible insight into the mechanisms underlying developmental origins of health and disease. This review will discuss the role of epigenetic mechanisms in heart development as well as aberrant epigenetic regulation contributing to cardiovascular disease. Additionally, we will address recent advances targeting epigenetic mechanisms as potential therapeutic approaches to cardiovascular disease. PMID:25572405

  2. Relationship between hearing threshold at the affected and unaffected ear in unilateral Meniere's disease.

    PubMed

    Albera, Roberto; Canale, Andrea; Cassandro, Claudia; Albera, Andrea; Sammartano, Azia Maria; Dagna, Federico

    2016-01-01

    Hearing loss in Menière's disease has been described to affect above all low frequencies (upward curve) with a tendency to become irreversible and non-fluctuating at the higher frequencies (peaked curve) over time. The aim of the study was to determine the effects of MD on hearing function on the basis of differences existing between the affected and the unaffected ear in a group of patients affected by definite unilateral MD and whose contralateral ear was not affected by any disease other than age-related hearing loss (ARHL). Following this procedure we have also evaluated the possible effects of age and disease duration on hearing loss in MD. The study group consisted of 86 subjects affected by definite unilateral MD. In our sample a peaked audiometric curve characterized the affected ears; however, the result after subtracting the normal ear hearing threshold was an upward sloping curve, which highlighted the greater suffering at the lower frequencies. On the basis of differences existing between affected and unaffected ear, our data suggest that threshold evolution is more related to disease duration rather than to age. PMID:25552243

  3. The Factors that Affect Science Teachers' Participation in Professional Development

    NASA Astrophysics Data System (ADS)

    Roux, Judi Ann

    Scientific literacy for our students and the possibilities for careers available in Science, Technology, Engineering, and Mathematics (STEM) areas are important topics for economic growth as well as global competitiveness. The achievement of students in science learning is dependent upon the science teachers' effectiveness and experienced science teachers depend upon relevant professional development experiences to support their learning. In order to understand how to improve student learning in science, the learning of science teachers must also be understood. Previous research studies on teacher professional development have been conducted in other states, but Minnesota science teachers comprised a new and different population from those previously studied. The purpose of this two-phase mixed methods study was to identify the current types of professional development in which experienced, Minnesota secondary science teachers participated and the factors that affect their participation in professional development activities. The mixed-methods approach s utilized an initial online survey followed by qualitative interviews with five survey respondents. The results of the quantitative survey and the qualitative interviews indicated the quality of professional development experiences and the factors which affected the science teachers' participation in professional development activities. The supporting and inhibiting factors involved the availability of resources such as time and money, external relationships with school administrators, teacher colleagues, and family members, and personal intrinsic attributes such as desires to learn and help students. This study also describes implications for science teachers, school administrators, policymakers, and professional development providers. Recommendations for future research include the following areas: relationships between and among intrinsic and extrinsic factors, science-related professional development activities

  4. Analysis of optical neural stimulation effects on neural networks affected by neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Zverev, M.; Fanjul-Vélez, F.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2016-03-01

    The number of people in risk of developing a neurodegenerative disease increases as the life expectancy grows due to medical advances. Multiple techniques have been developed to improve patient's condition, from pharmacological to invasive electrodes approaches, but no definite cure has yet been discovered. In this work Optical Neural Stimulation (ONS) has been studied. ONS stimulates noninvasively the outer regions of the brain, mainly the neocortex. The relationship between the stimulation parameters and the therapeutic response is not totally clear. In order to find optimal ONS parameters to treat a particular neurodegenerative disease, mathematical modeling is necessary. Neural networks models have been employed to study the neural spiking activity change induced by ONS. Healthy and pathological neocortical networks have been considered to study the required stimulation to restore the normal activity. The network consisted of a group of interconnected neurons, which were assigned 2D spatial coordinates. The optical stimulation spatial profile was assumed to be Gaussian. The stimulation effects were modeled as synaptic current increases in the affected neurons, proportional to the stimulation fluence. Pathological networks were defined as the healthy ones with some neurons being inactivated, which presented no synaptic conductance. Neurons' electrical activity was also studied in the frequency domain, focusing specially on the changes of the spectral bands corresponding to brain waves. The complete model could be used to determine the optimal ONS parameters in order to achieve the specific neural spiking patterns or the required local neural activity increase to treat particular neurodegenerative pathologies.

  5. Training affects the development of postural adjustments in sitting infants.

    PubMed Central

    Hadders-Algra, M; Brogren, E; Forssberg, H

    1996-01-01

    1. The present study addressed the question of whether daily balance training can affect the development of postural adjustments in sitting infants. 2. Postural responses during sitting on a moveable platform were assessed in twenty healthy infants at 5-6, 7-8 and 9-10 months of age. Multiple surface EMGs and kinematics were recorded while the infants were exposed to slow and fast horizontal forward (Fw) and backward (Bw) displacements of the platform. After the first session the parents of nine infants trained their child's sitting balance daily. 3. At the youngest age, when none of the infants could sit independently, the muscle activation patterns were direction specific and showed a large variation. This variation decreased with increasing age, resulting in selection of the most complete responses. Training facilitated response selection both during Fw and Bw translations. This suggests a training effect on the first level of the central pattern generator (CPG) model of postural control. 4. Training also affected the development of response modulation during Fw translations. It accelerated the development of: (1) the ability to modulate EMG amplitude with respect to platform velocity and initial sitting position, (2) antagonist activity and (3) a distal onset of the response. These findings point to a training effect on the second level of the CPG model of postural adjustments. Images Figure 1 Figure 4 PMID:8735713

  6. Functions of noncoding RNAs in neural development and neurological diseases

    PubMed Central

    Bian, Shan; Sun, Tao

    2011-01-01

    The development of the central nervous system (CNS) relies on precisely orchestrated gene expression regulation. Dysregualtion of both genetic and environmental factors can affect proper CNS development and results in neurological diseases. Recent studies have shown that similar to protein coding genes, noncoding RNA molecules have a significant impact on normal CNS development and on causes and progression of human neurological disorders. In this review, we have highlighted discoveries of functions of noncoding RNAs, in particular microRNAs and long noncoding RNAs, in neural development and neurological diseases. Emerging evidence has shown that microRNAs play an essential role in many aspects of neural development, such as proliferation of neural stem cells and progenitors, neuronal differentiation, maturation and synaptogenesis. Misregulation of microRNAs is associated with some mental disorders and neurodegeneration diseases. In addition, long noncoding RNAs are found to play a role in neural development by regulating expression of protein coding genes. Therefore, examining noncoding RNA-mediated gene regulations has revealed novel mechanisms of neural development and provided new insights into the etiology of human neurological diseases. PMID:21969146

  7. Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes

    PubMed Central

    Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A.; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg

    2016-01-01

    Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii. Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii. An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID:26883594

  8. Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes.

    PubMed

    Maaz, Denny; Rausch, Sebastian; Richter, Dania; Krücken, Jürgen; Kühl, Anja A; Demeler, Janina; Blümke, Julia; Matuschka, Franz-Rainer; von Samson-Himmelstjerna, Georg; Hartmann, Susanne

    2016-05-01

    Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID:26883594

  9. Rhizosphere microbiome assemblage is affected by plant development

    PubMed Central

    Chaparro, Jacqueline M; Badri, Dayakar V; Vivanco, Jorge M

    2014-01-01

    There is a concerted understanding of the ability of root exudates to influence the structure of rhizosphere microbial communities. However, our knowledge of the connection between plant development, root exudation and microbiome assemblage is limited. Here, we analyzed the structure of the rhizospheric bacterial community associated with Arabidopsis at four time points corresponding to distinct stages of plant development: seedling, vegetative, bolting and flowering. Overall, there were no significant differences in bacterial community structure, but we observed that the microbial community at the seedling stage was distinct from the other developmental time points. At a closer level, phylum such as Acidobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria and specific genera within those phyla followed distinct patterns associated with plant development and root exudation. These results suggested that the plant can select a subset of microbes at different stages of development, presumably for specific functions. Accordingly, metatranscriptomics analysis of the rhizosphere microbiome revealed that 81 unique transcripts were significantly (P<0.05) expressed at different stages of plant development. For instance, genes involved in streptomycin synthesis were significantly induced at bolting and flowering stages, presumably for disease suppression. We surmise that plants secrete blends of compounds and specific phytochemicals in the root exudates that are differentially produced at distinct stages of development to help orchestrate rhizosphere microbiome assemblage. PMID:24196324

  10. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

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

    PubMed Central

    Chakravarty, Ambar

    2011-01-01

    The case of an 82-year-old female with probable Alzheimer's disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed. PMID:22346020

  12. Drug Development for Alzheimer's Disease: Recent Progress

    PubMed Central

    Ji, Wonjin

    2010-01-01

    Alzheimer's disease, the most common cause of dementia, is characterized by two major pathological hallmarks: amyloid plaques and neurofibrillary tangles. Based on these two indicators, an amyloid cascade hypothesis was proposed, and accordingly, most current therapeutic approaches are now focused on the removal of β-amyloid peptides (Aβ from the brain. Additionally, strategies for blocking tau hyperphosphorylation and aggregation have been suggested, including the development of drugs that can block the formation of tangles. However, there are no true disease-modifying drugs in the current market, though many drugs based on theories other than Aβ and tau pathology are under development. The purpose of this review was to provide information on the current development of AD drugs and to discuss the issues related to drug development. PMID:22110351

  13. Developing disease resistance in CP-Cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disease resistance is an important selection criterion in the Canal Point (CP) Sugarcane Cultivar Development Program. Ratoon stunt (RSD, caused by Leifsonia xyli subsp. Xyli Evtsuhenko et al.), leaf scald (caused by Xanthomonas albilineans Ashby, Dowson), mosaic (caused by Sugarcane mosaic virus st...

  14. Translational neurophysiology in sheep: measuring sleep and neurological dysfunction in CLN5 Batten disease affected sheep

    PubMed Central

    Perentos, Nicholas; Martins, Amadeu Q.; Watson, Thomas C.; Bartsch, Ullrich; Mitchell, Nadia L.; Palmer, David N.; Jones, Matthew W.

    2015-01-01

    Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders. PMID:25724202

  15. Translational neurophysiology in sheep: measuring sleep and neurological dysfunction in CLN5 Batten disease affected sheep.

    PubMed

    Perentos, Nicholas; Martins, Amadeu Q; Watson, Thomas C; Bartsch, Ullrich; Mitchell, Nadia L; Palmer, David N; Jones, Matthew W; Morton, A Jennifer

    2015-04-01

    Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders. PMID:25724202

  16. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  17. Bone development in black ducks as affected by dietary toxaphene

    USGS Publications Warehouse

    Mehrle, P.M.; Finley, M.T.; Ludke, J.L.; Mayer, F.L.; Kaiser, T.E.

    1979-01-01

    Black ducks, Anas rubripes, were exposed to dietary toxaphene concentrations of 0, 10, or 50 μg/g of food for 90 days prior to laying and through the reproductive season. Toxaphene did not affect reproduction or survival, but reduced growth and impaired backbone development in ducklings. Collagen, the organic matrix of bone, was decreased significantly in cervical vertebrae of ducklings fed 50 μg/g, and calcium conentrations increased in vertebrae of ducklings fed 10 or 50 μg/g. The effects of toxaphene were observed only in female ducklings. In contrast to effects on vertebrae, toxaphene exposure did not alter tibia development. Toxaphene residues in carcasses of these ducklings averaged slightly less than the dietary levels.

  18. Beneficial Microbes Affect Endogenous Mechanisms Controlling Root Development.

    PubMed

    Verbon, Eline H; Liberman, Louisa M

    2016-03-01

    Plants have incredible developmental plasticity, enabling them to respond to a wide range of environmental conditions. Among these conditions is the presence of plant growth-promoting rhizobacteria (PGPR) in the soil. Recent studies show that PGPR affect Arabidopsis thaliana root growth and development by modulating cell division and differentiation in the primary root and influencing lateral root development. These effects lead to dramatic changes in root system architecture that significantly impact aboveground plant growth. Thus, PGPR may promote shoot growth via their effect on root developmental programs. This review focuses on contextualizing root developmental changes elicited by PGPR in light of our understanding of plant-microbe interactions and root developmental biology. PMID:26875056

  19. Disease models for the development of therapies for lysosomal storage diseases.

    PubMed

    Xu, Miao; Motabar, Omid; Ferrer, Marc; Marugan, Juan J; Zheng, Wei; Ottinger, Elizabeth A

    2016-05-01

    Lysosomal storage diseases (LSDs) are a group of rare diseases in which the function of the lysosome is disrupted by the accumulation of macromolecules. The complexity underlying the pathogenesis of LSDs and the small, often pediatric, population of patients make the development of therapies for these diseases challenging. Current treatments are only available for a small subset of LSDs and have not been effective at treating neurological symptoms. Disease-relevant cellular and animal models with high clinical predictability are critical for the discovery and development of new treatments for LSDs. In this paper, we review how LSD patient primary cells and induced pluripotent stem cell-derived cellular models are providing novel assay systems in which phenotypes are more similar to those of the human LSD physiology. Furthermore, larger animal disease models are providing additional tools for evaluation of the efficacy of drug candidates. Early predictors of efficacy and better understanding of disease biology can significantly affect the translational process by focusing efforts on those therapies with the higher probability of success, thus decreasing overall time and cost spent in clinical development and increasing the overall positive outcomes in clinical trials. PMID:27144735

  20. Mfn2 Affects Embryo Development via Mitochondrial Dysfunction and Apoptosis

    PubMed Central

    Liu, Qun; Xiang, Wenpei

    2015-01-01

    Background Growth factors, energy sources, and mitochondrial function strongly affect embryo growth and development in vitro. The biological role and prospective significance of the mitofusin gene Mfn2 in the development of preimplantation embryos remain poorly understood. Our goal is to profile the role of Mfn2 in mouse embryos and determine the underlying mechanism of Mfn2 function in embryo development. Methods We transfected Mfn2-siRNA into 2-cell fertilized eggs and then examined the expression of Mfn2, the anti-apoptotic protein Bcl-2, and the apoptosis-promoting protein Bax by Western blot. Additionally, we determined the blastocyst formation rate and measured ATP levels, mtDNA levels, mitochondrial membrane potential (ΔΨm), and apoptosis in all of the embryos. Results The results indicate that the Mfn2 and Bcl-2 levels were markedly decreased, whereas Bax levels were increased in the T group (embryos transfected with Mfn2-siRNA) compared with the C group (embryos transfected with control-siRNA). The blastocyst formation rate was significantly decreased in the T group. The ATP content and the relative amounts of mtDNA and cDNA in the T group were significantly reduced compared with the C group. In the T group, ΔΨm and Ca2+ levels were reduced, and the number of apoptotic cells was increased. Conclusion Low in vitro expression of Mfn2 attenuates the blastocyst formation rate and cleavage speed in mouse zygotes and causes mitochondrial dysfunction, as confirmed by the ATP and mtDNA levels and mitochondrial membrane potential. Mfn2 deficiency induced apoptosis through the Bcl-2/Bax and Ca2+ pathways. These findings indicate that Mfn2 could affect preimplantation embryo development through mitochondrial function and cellular apoptosis. PMID:25978725

  1. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases.

    PubMed

    Ruchat, Stephanie-May; Houde, Andrée-Anne; Voisin, Grégory; St-Pierre, Julie; Perron, Patrice; Baillargeon, Jean-Patrice; Gaudet, Daniel; Hivert, Marie-France; Brisson, Diane; Bouchard, Luigi

    2013-09-01

    Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring's methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. DNA methylation was measured at>485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10(-06); none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10(-13)diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. PMID:23975224

  2. Retinal angiogenesis in development and disease

    NASA Astrophysics Data System (ADS)

    Gariano, Ray F.; Gardner, Thomas W.

    2004-12-01

    The retina has long been regarded as `an approachable part of the brain' for investigating neurosensory processes. Cell biologists are now capitalizing on the accessibility of the retina to investigate important aspects of developmental angiogenesis, including how it relates to neuronal and glial development, morphogenesis, oxygen sensing and progenitor cells. Pathological angiogenesis also occurs in the retina and is a major feature of leading blinding diseases, particularly diabetic retinopathy. The retina and its clinical disorders have a pivotal role in angiogenesis research and provide model systems in which to investigate neurovascular relationships and angiogenic diseases.

  3. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington’s Disease T Lymphocytes

    PubMed Central

    Miller, James R. C.; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J.

    2015-01-01

    Huntington’s disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington’s disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington’s disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington’s disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington’s disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington’s disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington’s disease innate immune system should not be extended to include the adaptive immune system. PMID:26529236

  4. [Development of Disease-modifying Therapy for Alzheimer's Disease].

    PubMed

    Akiyama, Haruhiko

    2016-04-01

    The development of disease-modifying therapy (DMT) that can arrest the pathological processes of Alzheimer's disease (AD) has emerged as one of the highest priorities of medical research. Two pathological hallmarks, amyloid-beta (Abeta) protein deposition and tau accumulation, are the major targets of DMT. Immunotherapy for Abeta removal and secretase inhibitors/modulators that reduce total or accumulation-prone Abeta are candidate DMTs against Abeta. Compounds that prevent tau aggregation are also under development. Clinical trials that test the efficacy of these DMT candidates are in preparation or ongoing. Recent studies of biomarkers of AD brain lesions have indicated that Abeta and tau accumulation appears 10 to 30 years before the occurrence of dementia and gradually propagate to reach the level that causes symptoms. Therefore, efficacy of DMT has to be evaluated in the preclinical stage of AD. The incidence of preclinical AD in the cognitively normal, aged population are estimated to be around 19%. Thus, currently available biomarkers, amyloid/tau PET imaging and cerebrospinal fluid measurements of Abeta and tau, are, perhaps, too invasive and costly. An international collaborative effort is needed to overcome this issue. PMID:27056864

  5. Development of brain mechanisms for processing affective touch

    PubMed Central

    Björnsdotter, Malin; Gordon, Ilanit; Pelphrey, Kevin A.; Olausson, Håkan; Kaiser, Martha D.

    2014-01-01

    Affective tactile stimulation plays a key role in the maturation of neural circuits, but the development of brain mechanisms processing touch is poorly understood. We therefore used functional magnetic resonance imaging (fMRI) to study brain responses to soft brush stroking of both glabrous (palm) and hairy (forearm) skin in healthy children (5–13 years), adolescents (14–17 years), and adults (25–35 years). Adult-defined regions-of-interests in the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), insular cortex and right posterior superior temporal sulcus (pSTS) were significantly and similarly activated in all age groups. Whole-brain analyses revealed that responses in the ipsilateral SII were positively correlated with age in both genders, and that responses in bilateral regions near the pSTS correlated significantly and strongly with age in females but not in males. These results suggest that brain mechanisms associated with both sensory-discriminative and affective-motivational aspects of touch are largely established in school-aged children, and that there is a general continuing maturation of SII and a female-specific increase in pSTS sensitivity with age. Our work establishes a groundwork for future comparative studies of tactile processing in developmental disorders characterized by disrupted social perception such as autism. PMID:24550800

  6. [What useful developments for my inflammatory bowel disease practice have come from Digestive Disease Week 2014?].

    PubMed

    Chaparro, María

    2014-09-01

    The objective of this article is to summarize reports presented at Digestive Disease Week 2014 that relate to fertility and pregnancy, inflammatory bowel disease in elderly patients, the risk of cancer and its relationship to treatment and finally, developments regarding psychological aspects that may affect patients with inflammatory bowel disease. Studies were selected at the discretion of the author, mainly considering those with conclusions that can be applied immediately to clinical practice. Using anti-TNF drugs during pregnancy is safe in the short term. This currently seems to be true for the medium and the long term. To limit fetal exposure, the mother can safely stop taking the anti-TNF drugs in the second trimester of the pregnancy if she is in remission. Elderly patients with inflammatory bowel disease require stricter monitoring than younger patients due to the risk of complications, especially infections associated with the disease and treatments. The effect of inflammatory bowel disease and the drugs for its treatment on the risk of development is still not well established, but the magnitude of the effect seems possibly lower than previously described. The causal link between psychological factors and the occurrence of IBD relapse is by no means established. PMID:25294263

  7. The affect of infectious bursal disease virus on avian influenza virus vaccine efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunosuppressive viruses are known to affect vaccinal immunity, however the impact of virally induced immunosuppression on avian influenza vaccine efficacy has not been quantified. In order to determine the effect of exposure to infectious bursal disease virus (IBDV) on vaccinal immunity to highly ...

  8. Sensory activity affects sensory axon development in C. elegans.

    PubMed

    Peckol, E L; Zallen, J A; Yarrow, J C; Bargmann, C I

    1999-05-01

    The simple nervous system of the nematode C. elegans consists of 302 neurons with highly reproducible morphologies, suggesting a hard-wired program of axon guidance. Surprisingly, we show here that sensory activity shapes sensory axon morphology in C. elegans. A class of mutants with deformed sensory cilia at their dendrite endings have extra axon branches, suggesting that sensory deprivation disrupts axon outgrowth. Mutations that alter calcium channels or membrane potential cause similar defects. Cell-specific perturbations of sensory activity can cause cell-autonomous changes in axon morphology. Although the sensory axons initially reach their targets in the embryo, the mutations that alter sensory activity cause extra axon growth late in development. Thus, perturbations of activity affect the maintenance of sensory axon morphology after an initial pattern of innervation is established. This system provides a genetically tractable model for identifying molecular mechanisms linking neuronal activity to nervous system structure. PMID:10101123

  9. [The White man's burden - a case study caught between bipolar affective disorder and Huntington's disease].

    PubMed

    Nowidi, K; Kunisch, R; Bouna-Pyrrou, P; Meißner, D; Hennig-Fast, K; Weindl, A; Förster, S; Neuhann, T M; Falkai, P; Berger, M; Musil, R

    2013-06-01

    We report upon a case of a 55 year old patient with a bipolar affective disorder, presenting herself with a depressive symptomatology in addition to a severe motor perturbation. The main emphasis upon admittance was perfecting and improving her latest medication. Four weeks prior to her stay at our clinic a thorough neurological examination had taken place in terms of an invalidity pension trial which did not result in any diagnostic findings. Therefore a neurological disease seemed at first highly unlikely. Even though the prior testing was negative, the ensuing neurological examination at our clinic resulted in movement disorders very much indicative of Huntington's Disease. A detailed investigation in regards to the particular family history of the patient was positive for Huntington's Disease. However, whether the patient's mother had also been a genetic carrier of Huntington's Disease was still unknown at the time the patient was admitted to our clinic. It was nevertheless discovered that her mother had also suffered from a bipolar affective disorder. A genetic testing that followed the neurological examination of the patient proved positive for Huntington's Disease. Neuro-imaging resulted in a bicaudate-index of 2.4 (the critical value is 1.8). In a clinical psychological test battery the ensuing results were highly uncommon for patients with solely a bipolar affective disorder people. Under the medical regimen of Quetiapine, Citalopram and Tiaprid the patient's mood could be stabilized and there was some improvement of her motor pertubation. PMID:23612984

  10. DNA methylation in hematopoietic development and disease.

    PubMed

    Gore, Aniket V; Weinstein, Brant M

    2016-09-01

    DNA methylation is an important epigenetic modification that can have profound and widespread effects on gene expression and on cellular fate and function. Recent work has indicated that DNA methylation plays a critical role in hematopoietic development and hematopoietic disease. DNA methyltransferases and Ten-eleven translocation enzymes are required to add and remove methyl "marks" from DNA, respectively, and both sets of genes have been found necessary for proper formation and maintenance of hematopoietic stem cells and for differentiation of downstream hematopoietic lineages during development. DNA methylation and demethylation enzymes have also been implicated in hematopoietic disorders such as acute myeloid leukemia and myelodysplastic syndrome. Here, we review some of the recent literature regarding the role of DNA methylation in hematopoietic health and disease. PMID:27178734

  11. Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50–60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups. PMID:20200503

  12. Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease.

    PubMed

    Fischer, Michael J; Kimmel, Paul L; Greene, Tom; Gassman, Jennifer J; Wang, Xuelei; Brooks, Deborah H; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A; Bruce, Marino A; Kusek, John W; Norris, Keith C; Lash, James P

    2010-06-01

    Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50-60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups. PMID:20200503

  13. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  14. Development of Lymantria dispar affected by manganese in food.

    PubMed

    Kula, Emanuel; Martinek, Petr; Chromcová, Lucie; Hedbávný, Josef

    2014-10-01

    We studied the response of gypsy moth (Lymantria dispar (Linnaeus) (Lepidoptera: Lymantriidae)) to the content of manganese in food in the laboratory breeding of caterpillars. The food of the caterpillars {Betula pendula Roth (Fagales: Betulaceae) leaves} was contaminated by dipping in the solution of MnCl2 · 4H2O with manganese concentrations of 0, 0.5, 5 and 10 mg ml(-1), by which differentiated manganese contents (307; 632; 4,087 and 8,124 mg kg(-1)) were reached. Parameters recorded during the rearing were as follows: effect of manganese on food consumption, mortality and length of the development of caterpillars, pupation and hatching of imagoes. At the same time, manganese concentrations were determined in the offered and unconsumed food, excrements, and exuviae of the caterpillars, pupal cases and imagoes by using the AAS method. As compared with the control, high manganese contents in the food of gypsy moth caterpillars affected the process of development particularly by increased mortality of the first instar caterpillars (8 % mortality for caterpillars with no Mn contamination (T0) and 62 % mortality for subjects with the highest contamination by manganese (T3)), by prolonged development of the first-third instar (18.7 days (T0) and 27.8 days (T3)) and by increased food consumption of the first-third instar {0.185 g of leaf dry matter (T0) and 0.483 g of leaf dry matter (T3)}. The main defence strategy of the caterpillars to prevent contamination by the increased manganese content in food is the translocation of manganese into frass and exuviae castoff in the process of ecdysis. In the process of development, the content of manganese was reduced by excretion in imagoes to 0.5 % of the intake level even at its maximum inputs in food. PMID:25028315

  15. Maternal Photoperiodic History Affects Offspring Development in Syrian Hamsters

    PubMed Central

    Beery, Annaliese K.; Paul, Matthew J.; Routman, David M.; Zucker, Irving

    2009-01-01

    During the first 7 weeks of postnatal life, short day lengths inhibit the onset of puberty in many photoperiodic rodents, but not in Syrian hamsters. In this species, timing of puberty and fecundity are independent of the early postnatal photoperiod. Gestational day length affects postnatal reproductive development in several rodents; its role in Syrian hamsters has not been assessed. We tested the hypothesis that cumulative effects of pre- and postnatal short day lengths would restrain gonadal development in male Syrian hamsters. Males with prenatal short day exposure were generated by dams transferred to short day lengths 6 weeks, 3 weeks, and 0 weeks prior to mating. Additional groups were gestated in long day lengths and transferred to short days at birth, at 4 weeks of age, or not transferred (control hamsters). In pups of dams exposed to short day treatment throughout gestation, decreased testis growth was apparent by 3 weeks and persisted through 9 weeks of age, at which time maximum testis size was attained. A subset of males (14%), whose dams had been in short days for 3 to 6 weeks prior to mating displayed pronounced delays in testicular development, similar to those of other photoperiodic rodents. This treatment also increased the percentage of male offspring that underwent little or no gonadal regression postnatally (39%). By 19 weeks of age, males housed in short days completed spontaneous gonadal development. After prolonged long day treatment to break refractoriness, hamsters that initially were classified as nonregressors underwent testicular regression in response to a 2nd sequence of short day lengths. The combined action of prenatal and early postnatal short day lengths diminishes testicular growth of prepubertal Syrian hamsters no later than the 3rd week of postnatal life, albeit to a lesser extent than in other photoperiodic rodents. PMID:18838610

  16. Spaceflight affects postnatal development of the aortic wall in rats.

    PubMed

    Katsuda, Shin-ichiro; Yamasaki, Masao; Waki, Hidefumi; Miyake, Masao; O-ishi, Hirotaka; Katahira, Kiyoaki; Nagayama, Tadanori; Miyamoto, Yukako; Hasegawa, Masamitsu; Wago, Haruyuki; Okouchi, Toshiyasu; Shimizu, Tsuyoshi

    2014-01-01

    We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta. PMID:25210713

  17. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

    PubMed Central

    Yamasaki, Masao; Waki, Hidefumi; Miyake, Masao; Nagayama, Tadanori; Miyamoto, Yukako; Wago, Haruyuki; Okouchi, Toshiyasu; Shimizu, Tsuyoshi

    2014-01-01

    We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta. PMID:25210713

  18. The melanocyte lineage in development and disease

    PubMed Central

    Mort, Richard L.; Jackson, Ian J.; Patton, E. Elizabeth

    2015-01-01

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. PMID:25670789

  19. How infectious disease outbreaks affect community-based primary care physicians

    PubMed Central

    Jaakkimainen, R. Liisa; Bondy, Susan J.; Parkovnick, Meredith; Barnsley, Jan

    2014-01-01

    Abstract Objective To compare how the infectious disease outbreaks H1N1 and severe acute respiratory syndrome (SARS) affected community-based GPs and FPs. Design A mailed survey sent after the H1N1 outbreak compared with the results of similar survey completed after the SARS outbreak. Setting Greater Toronto area in Ontario. Participants A total of 183 randomly selected GPs and FPs who provided office-based care. Main outcome measures The perceptions of GPs and FPs on how serious infectious disease outbreaks affected their clinical work and personal lives; their preparedness for a serious infectious disease outbreak; and the types of information they want to receive and the sources they wanted to receive information from during a serious infectious disease outbreak. The responses from this survey were compared with the responses of GPs and FPs in the greater Toronto area who completed a similar survey in 2003 after the SARS outbreak. Results After the H1N1 outbreak, GPs and FPs still had substantial concerns about the effects of serious infectious disease outbreaks on the health of their family members. Physicians made changes to various office practices in order to manage and deal with patients with serious infectious diseases. They expressed concerns about the effects of an infectious disease on the provision of health care services. Also, physicians wanted to quickly receive accurate information from the provincial government and their medical associations. Conclusion Serious community-based infectious diseases are a personal concern for GPs and FPs, and have considerable effects on their clinical practice. Further work examining the timely flow of relevant information through different health care sectors and government agencies still needs to be undertaken. PMID:25316747

  20. How do economic crises affect migrants’ risk of infectious disease? A systematic-narrative review

    PubMed Central

    Karanikolos, Marina; Williams, Gemma; Mladovsky, Philipa; King, Lawrence; Pharris, Anastasia; Suk, Jonathan E.; Hatzakis, Angelos; McKee, Martin; Noori, Teymur; Stuckler, David

    2015-01-01

    Background: It is not well understood how economic crises affect infectious disease incidence and prevalence, particularly among vulnerable groups. Using a susceptible-infected-recovered framework, we systematically reviewed literature on the impact of the economic crises on infectious disease risks in migrants in Europe, focusing principally on HIV, TB, hepatitis and other STIs. Methods: We conducted two searches in PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, websites of key organizations and grey literature to identify how economic changes affect migrant populations and infectious disease. We perform a narrative synthesis in order to map critical pathways and identify hypotheses for subsequent research. Results: The systematic review on links between economic crises and migrant health identified 653 studies through database searching; only seven met the inclusion criteria. Fourteen items were identified through further searches. The systematic review on links between economic crises and infectious disease identified 480 studies through database searching; 19 met the inclusion criteria. Eight items were identified through further searches. The reviews show that migrant populations in Europe appear disproportionately at risk of specific infectious diseases, and that economic crises and subsequent responses have tended to exacerbate such risks. Recessions lead to unemployment, impoverishment and other risk factors that can be linked to the transmissibility of disease among migrants. Austerity measures that lead to cuts in prevention and treatment programmes further exacerbate infectious disease risks among migrants. Non-governmental health service providers occasionally stepped in to cater to specific populations that include migrants. Conclusions: There is evidence that migrants are especially vulnerable to infectious disease during economic crises. Ring-fenced funding of prevention programs, including screening and treatment, is important for

  1. Semantic trouble sources and their repair in conversations affected by Parkinson's disease

    PubMed Central

    Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

    2014-01-01

    Background It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these problems become manifest in everyday conversations or how conversation partners handle such problems. Aims To describe the pragmatic problems related to the use of words that occur in everyday conversational interaction in dyads including an individual with Parkinson's disease, and to explore how interactants in conversation handle the problems to re-establish mutual understanding. Methods & Procedures Twelve video-recorded everyday conversations involving three couples where one of the individuals had Parkinson's disease were included in the study. All instances of other-initiated repair following a contribution from the people with Parkinson's disease were analysed. Those instances involving a trouble source relating to the use of words were analysed with a qualitative interaction analysis based on the principles of conversation analysis. Outcomes & Results In 70% of the instances of other-initiated repair the trouble source could be related to the semantic content produced by the individual with Parkinson's disease. The problematic contributions were typically characterized by more or less explicit symptoms of word search or use of atypical wording. The conversation partners completed the repair work collaboratively, but typically the non-impaired individual made a rephrasing or provided a suggestion for what the intended meaning had been. Conclusions & Implications In clinical work with people with Parkinson's disease and their conversation partners it is important to establish what type of trouble sources occur in conversations in a specific dyad. It may often be necessary to look beyond intelligibility and into aspects of pragmatics

  2. New Developments in Extraesophageal Reflux Disease

    PubMed Central

    Saritas Yuksel, Elif

    2012-01-01

    Gastroesophageal reflux disease (GERD) can present with a wide variety of extraesophageal symptoms that are usually difficult to diagnose because of the absence of typical GERD symptoms (ie, regurgitation or heartburn). The diagnostic process is further complicated by the lack of a definitive test for identifying GERD as the cause of extraesophageal reflux symptoms. Due to the low predictive value of upper endoscopy and pH testing—as well as the lack of reliability of the symptom index and symptom association probability—extraesophageal reflux disease is still an area of investigation. This paper discusses recent developments in this field, with special emphasis on new diagnostic modalities and treatment options. PMID:23483833

  3. Exogenous retroelement integration in sperm and embryos affects preimplantation development.

    PubMed

    Kitsou, C; Lazaros, L; Bellou, S; Vartholomatos, G; Sakaloglou, P; Hatzi, E; Markoula, S; Zikopoulos, K; Tzavaras, T; Georgiou, I

    2016-09-01

    Retroelement transcripts are present in male and female gametes, where they are typically regulated by methylation, noncoding RNAs and transcription factors. Such transcripts are required for occurrence of retrotransposition events, while failure of retrotransposition control may exert negative effects on cellular function and proliferation. In order to investigate the occurrence of retrotransposition events in mouse epididymal spermatozoa and to address the impact of uncontrolled retroelement RNA expression in early preimplantation embryos, we performed in vitro fertilization experiments using spermatozoa preincubated with plasmid vectors containing the human retroelements LINE-1, HERVK-10 or the mouse retroelement VL30, tagged with an enhanced green fluorescence (EGFP) gene-based cassette. Retrotransposition events in mouse spermatozoa and embryos were detected using PCR, FACS analysis and confocal microscopy. Our findings show that: (i) sperm cell incorporates exogenous retroelements and favors retrotransposition events, (ii) the inhibition of spermatozoa reverse transcriptase can decrease the retrotransposition frequency in sperm cells, (iii) spermatozoa can transfer exogenous human or mouse retroelements to the oocyte during fertilization and (iv) retroelement RNA overexpression affects embryo morphology and impairs preimplantation development. These findings suggest that the integration of exogenous retroelements in the sperm genome, as well as their transfer into the mouse oocyte, could give rise to new retrotransposition events and genetic alterations in mouse spermatozoa and embryos. PMID:27450800

  4. Large-scale mapping of mutations affecting zebrafish development

    PubMed Central

    Geisler, Robert; Rauch, Gerd-Jörg; Geiger-Rudolph, Silke; Albrecht, Andrea; van Bebber, Frauke; Berger, Andrea; Busch-Nentwich, Elisabeth; Dahm, Ralf; Dekens, Marcus PS; Dooley, Christopher; Elli, Alexandra F; Gehring, Ines; Geiger, Horst; Geisler, Maria; Glaser, Stefanie; Holley, Scott; Huber, Matthias; Kerr, Andy; Kirn, Anette; Knirsch, Martina; Konantz, Martina; Küchler, Axel M; Maderspacher, Florian; Neuhauss, Stephan C; Nicolson, Teresa; Ober, Elke A; Praeg, Elke; Ray, Russell; Rentzsch, Brit; Rick, Jens M; Rief, Eva; Schauerte, Heike E; Schepp, Carsten P; Schönberger, Ulrike; Schonthaler, Helia B; Seiler, Christoph; Sidi, Samuel; Söllner, Christian; Wehner, Anja; Weiler, Christian; Nüsslein-Volhard, Christiane

    2007-01-01

    Background Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. Results We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. Conclusion By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations. PMID:17212827

  5. Factors affecting epilepsy development and epilepsy prognosis in cerebral palsy.

    PubMed

    Mert, Gulen Gul; Incecik, Faruk; Altunbasak, Sakir; Herguner, Ozlem; Mert, Mustafa Kurthan; Kiris, Nurcihan; Unal, Ilker

    2011-08-01

    A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy. PMID:21763948

  6. Whole transcriptome data analysis of zebrafish mutants affecting muscle development.

    PubMed

    Armant, Olivier; Gourain, Victor; Etard, Christelle; Strähle, Uwe

    2016-09-01

    Formation of the contractile myofibril of the skeletal muscle is a complex process which when perturbed leads to muscular dystrophy. Herein, we provide a mRNAseq dataset on three different zebrafish mutants affecting muscle organization during embryogenesis. These comprise the myosin folding chaperone unc45b (unc45b-/-), heat shock protein 90aa1.1 (hsp90aa1.1-/-) and the acetylcholine esterase (ache-/-) gene. The transcriptome analysis was performed in duplicate experiments at 72 h post-fertilization (hpf) for all three mutants, with two additional times of development (24 hpf and 48 hpf) for unc45b-/-. A total of 20 samples were analyzed by hierarchical clustering for differential gene expression. The data from this study support the observation made in Etard et al. (2015) [1] (http://dx.doi.org/10.1186/s13059-015-0825-8) that a failure to fold myosin activates a unique transcriptional program in the skeletal muscles that is different from that induced in stressed muscle cells. PMID:27274534

  7. Oligosaccharides Affect Performance and Gut Development of Broiler Chickens

    PubMed Central

    Ao, Z.; Choct, M.

    2013-01-01

    The effects of oligosaccharide supplementation on the growth performance, flock uniformity and GIT development of broiler chickens were investigated. Four diets, one negative control, one positive control supplemented with zinc-bacitracin, and two test diets supplemented with mannoligosaccharide (MOS) and fructooligosaccharide (FOS), were used for the experiment. Birds given MOS or FOS had improved body weight (BW) and feed efficiency (FCR), compared to those fed the negative control diet during the 35-d trial period. The effect on FCR became less apparent when the birds got older. FOS and MOS supplementation reduced the pancreas weight as a percentage of BW, with an effect similar to that of the antibiotic, at 35 d of age. Birds given MOS tended to have a heavier bursa (p = 0.164) and lower spleen/bursa weight ratio (p = 0.102) at 35 d of age. MOS and Zn-bacitracin showed a clear improvement on flock uniformity, compared to FOS. The mortality rate was not affected by FOS or MOS. PMID:25049713

  8. Effecting Affect: Developing a Positive Attitude to Primary Mathematics Learning

    ERIC Educational Resources Information Center

    Sparrow, Len; Hurst, Chris

    2010-01-01

    Most adults' attitudes to mathematics come from their experiences of mathematics in school when they were children. Children's mathematical worlds are complex places containing both cognitive and affective elements. One cannot ignore the affective domain if one wishes to understand children's mathematical learning. Teacher education students…

  9. Developing Primary Intervention Strategies to Prevent Allergic Disease.

    PubMed

    Rueter, Kristina; Haynes, Aveni; Prescott, Susan L

    2015-07-01

    Allergic diseases are a major cause of morbidity in the developed world, now affecting up to 40 % of the population with no evidence that this is abating. If anything, the prevalence of early onset allergic diseases such as eczema and food allergy appears to be still increasing. This is almost certainly due to the changing modern environment and lifestyle factors, acting to promote immune dysfunction through early perturbations in immune maturation, immune tolerance and regulation. This early propensity to inflammation may also have implications for the rising risk of other inflammatory non-communicable diseases (NCDs) later in life. Identifying risk factors and pathways for preventing early onset immune disease like allergy is likely to have benefits for many aspects of human health, particularly as many NCDs share similar risk factors. This review focuses on recent advances in primary intervention strategies for promoting early immune health and preventing allergic disease, highlighting the current evidence-based guidelines where applicable and areas requiring further investigation. PMID:26143389

  10. Factors affecting poor nutritional status after small bowel resection in patients with Crohn disease.

    PubMed

    Jang, Ki Ung; Yu, Chang Sik; Lim, Seok-Byung; Park, In Ja; Yoon, Yong Sik; Kim, Chan Wook; Lee, Jong Lyul; Yang, Suk-Kyun; Ye, Byong Duk; Kim, Jin Cheon

    2016-07-01

    In Crohn disease, bowel-preserving surgery is necessary to prevent short bowel syndrome due to repeated operations. This study aimed to determine the remnant small bowel length cut-off and to evaluate the clinical factors related to nutritional status after small bowel resection in Crohn disease.We included 394 patients (69.3% male) who underwent small bowel resection for Crohn disease between 1991 and 2012. Patients who were classified as underweight (body mass index < 17.5) or at high risk of nutrition-related problems (modified nutritional risk index < 83.5) were regarded as having a poor nutritional status. Preliminary remnant small bowel length cut-offs were determined using receiver operating characteristic curves. Variables associated with poor nutritional status were assessed retrospectively using Student t tests, chi-squared tests, Fisher exact tests, and logistic regression analyses.The mean follow-up period was 52.9 months and the mean patient ages at the time of the last bowel surgery and last follow-up were 31.2 and 35.7 years, respectively. The mean remnant small bowel length was 331.8 cm. Forty-three patients (10.9%) underwent ileostomy, 309 (78.4%) underwent combined small bowel and colon resection, 111 (28.2%) had currently active disease, and 105 (26.6%) underwent at least 2 operations for recurrent disease. The mean body mass index and modified nutritional risk index were 20.6 and 100.8, respectively. The independent factors affecting underweight status were remnant small bowel length ≤240 cm (odds ratio: 4.84, P < 0.001), ileostomy (odds ratio: 4.70, P < 0.001), and currently active disease (odds ratio: 4.16, P < 0.001). The independent factors affecting high nutritional risk were remnant small bowel length ≤230 cm (odds ratio: 2.84, P = 0.012), presence of ileostomy (odds ratio: 3.36, P = 0.025), and currently active disease (odds ratio: 4.90, P < 0.001).Currently active disease, ileostomy, and remnant small

  11. Synaptic AMPA receptor composition in development, plasticity and disease.

    PubMed

    Henley, Jeremy M; Wilkinson, Kevin A

    2016-06-01

    AMPA receptors (AMPARs) are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs, and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity and in response to neuronal stress in disease. Recently, the subunit dependence of AMPAR trafficking has been questioned, leading to a reappraisal of this field. In this Review, we discuss what is known, uncertain, conjectured and unknown about the roles of the individual subunits, and how they affect AMPAR assembly, trafficking and function under both normal and pathological conditions. PMID:27080385

  12. Metatranscriptomic Analysis of Pycnopodia helianthoides (Asteroidea) Affected by Sea Star Wasting Disease.

    PubMed

    Gudenkauf, Brent M; Hewson, Ian

    2015-01-01

    Sea star wasting disease (SSWD) describes a suite of symptoms reported in asteroids of the North American Pacific Coast. We performed a metatranscriptomic survey of asymptomatic and symptomatic sunflower star (Pycnopodia helianthoides) body wall tissues to understand holobiont gene expression in tissues affected by SSWD. Metatranscriptomes were highly variable between replicate libraries, and most differentially expressed genes represented either transcripts of associated microorganisms (particularly Pseudomonas and Vibrio relatives) or low-level echinoderm transcripts of unknown function. However, the pattern of annotated host functional genes reflects enhanced apoptotic and tissue degradation processes and decreased energy metabolism, while signalling of death-related proteins was greater in asymptomatic and symptomatic tissues. Our results suggest that the body wall tissues of SSWD-affected asteroids may undergo structural changes during disease progression, and that they are stimulated to undergo autocatalytic cell death processes. PMID:26020776

  13. Metatranscriptomic Analysis of Pycnopodia helianthoides (Asteroidea) Affected by Sea Star Wasting Disease

    PubMed Central

    Gudenkauf, Brent M.; Hewson, Ian

    2015-01-01

    Sea star wasting disease (SSWD) describes a suite of symptoms reported in asteroids of the North American Pacific Coast. We performed a metatranscriptomic survey of asymptomatic and symptomatic sunflower star (Pycnopodia helianthoides) body wall tissues to understand holobiont gene expression in tissues affected by SSWD. Metatranscriptomes were highly variable between replicate libraries, and most differentially expressed genes represented either transcripts of associated microorganisms (particularly Pseudomonas and Vibrio relatives) or low-level echinoderm transcripts of unknown function. However, the pattern of annotated host functional genes reflects enhanced apoptotic and tissue degradation processes and decreased energy metabolism, while signalling of death-related proteins was greater in asymptomatic and symptomatic tissues. Our results suggest that the body wall tissues of SSWD-affected asteroids may undergo structural changes during disease progression, and that they are stimulated to undergo autocatalytic cell death processes. PMID:26020776

  14. Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease.

    PubMed

    Uranga, José Antonio; López-Miranda, Visitación; Lombó, Felipe; Abalo, Raquel

    2016-08-01

    Inflammatory bowel diseases (ulcerative colitis; Crohn's disease) are debilitating relapsing inflammatory disorders affecting the gastrointestinal tract, with deleterious effect on quality of life, and increasing incidence and prevalence. Mucosal inflammation, due to altered microbiota, increased intestinal permeability and immune system dysfunction underlies the symptoms and may be caused in susceptible individuals by different factors (or a combination of them), including dietary habits and components. In this review we describe the influence of the Western diet, obesity, and different nutraceuticals/functional foods (bioactive peptides, phytochemicals, omega 3-polyunsaturated fatty acids, vitamin D, probiotics and prebiotics) on the course of IBD, and provide some hints that could be useful for nutritional guidance. Hopefully, research will soon offer enough reliable data to slow down the spread of the disease and to make diet a cornerstone in IBD therapy. PMID:27267792

  15. Autologous Stem Cell Therapy: How Aging and Chronic Diseases Affect Stem and Progenitor Cells

    PubMed Central

    Efimenko, Anastasia Yu.; Kochegura, Tatiana N.; Akopyan, Zhanna A.; Parfyonova, Yelena V.

    2015-01-01

    Abstract During recent years different types of adult stem/progenitor cells have been successfully applied for the treatment of many pathologies, including cardiovascular diseases. The regenerative potential of these cells is considered to be due to their high proliferation and differentiation capacities, paracrine activity, and immunologic privilege. However, therapeutic efficacy of the autologous stem/progenitor cells for most clinical applications remains modest, possibly because of the attenuation of their regenerative potential in aged patients with chronic diseases such as cardiovascular diseases and metabolic disorders. In this review we will discuss the risk factors affecting the therapeutic potential of adult stem/progenitor cells as well as the main approaches to mitigating them using the methods of regenerative medicine. PMID:26309780

  16. [Development of new drugs for Alzheimer's disease].

    PubMed

    Tabira, Takeshi

    2010-07-01

    Currently, only donepezil is available for the treatment of Alzheimer disease (AD) in Japan. Clinical trials of galantamine, rivastigmine, and memantine have been completed in Japan, and patients are awaiting government approval for the use of these drugs. The herbal medicine yokukansan was found to be effective for behavioral and psychological symptoms of dementia (BPSD) in patients, and juzentaihoto was found to reduce AD pathology in a mouse model. In addition, muscarinic and nicotinic acetylcholine receptor agonists, serotonergic agonists, other drugs are being developed. These medicines have little effect on the improvement of cognitive functions. The anti-histamine dimebolin was expected to have a significant effect on the improvement of cognitive functions, but unfortunately, it was rejected during phase III clinical trials. Disease modifying drugs such as alpha-secretase activators, beta- and gamma-secretase inhibitors or modulators, inhibitors of Abeta and tau aggregation, enhancers of Abeta degradation, immunotherapies to remove Abeta oligomers and fibrils, and neurotrophic factors are being developed. Some of these drugs are in phase III clinical trials and are expected to be available for clinical use in the near future. PMID:20675883

  17. A Look at Recent Legal Developments Affecting Residential Living.

    ERIC Educational Resources Information Center

    Miller, Thomas E.; And Others

    1979-01-01

    Reviews court decisions concerning search and seizure, intervisitation between sexes, canvassing and solicitation, and damage assessments. College administrators must rely on fairness, ethics and sound educational philosophies in the design of policies affecting residence halls. (JAC)

  18. Research gaps in understanding how climate change will affect arboviral diseases.

    PubMed

    Baylis, Matthew

    2013-12-01

    Climate change is widely expected to cause the emergence and spread of vector-borne diseases, and predictive models are needed so that we can be prepared. We developed a climate-sensitive, predictive, model that describes the risk of bluetongue, an arboviral disease of ruminants, which has emerged dramatically in Europe. Developing the predictive bluetongue model led to the identification of numerous gaps in both the understanding and the availability of data. These mostly pertain to the vectors and their interaction with hosts. Closing these gaps will allow better models, with more precise predictions, to be produced. These research gaps apply to many other arboviral diseases as well. As a consequence, there needs to be an increase in research on the vectors that transmit arboviral diseases. Priorities are the training of a new generation of taxonomists, studies on the field biology of potential vectors, and increased coordination of vector surveillance and recording between countries facing similar threats. PMID:24152973

  19. Infectious Diseases in a Global Economy - Consequences for Developing Nations

    PubMed Central

    Peter, McDonald AM

    2006-01-01

    Since the end of the cold war the world economy has become dominated by Western [largely US] interests. In this period there have developed several pandemics or epidemics of infectious diseases that have affected most nations. HIV, SARS, Avian Influenza, Hepatitis-C, Bovine Spongiform Encephalopathy, drug-resistant TB, viral zoonoses, are specific examples that will be discussed in terms of their genesis, economic impact and consequences for ways of life in the range of economies – developed, developing and under developed countries. The burden falls most on the underdeveloped countries who are least able to mount the resources to combat the consequences of these global infections. The capability to diagnose, prevent, treat and manage is largely in the hands of commercial interests that are anchored into international trade agreements. This circumstance contrasts with the situation that existed for vaccine development and distribution in the early parts of 20th century. Most countries established “public good” institutions that developed vaccines for public health purposes [diphtheria, tetanus, polio, pneumococcal antisera are examples]. In this 21st century the international capability for developing vaccines is largely in the hands of industry. Thus the developing countries need support of UN or similar global organizations to underwrite product development that suits their needs. The process of product development, safety and efficacy assessment will be presented in a manner that indicates the crucial and essential role of developing nations – and why they should receive fair recognition for their contributions.

  20. Student Cognitive and Affective Development in the Context of Classroom-Level Curriculum Development

    ERIC Educational Resources Information Center

    Shawer, Saad Fathy; Gilmore, Deanna; Banks-Joseph, Susan Rae

    2008-01-01

    This qualitative study examined the impact of teacher curriculum approaches (curriculum-transmitter/curriculum-developer/curriculum-maker) on student cognitive change (reading, writing, speaking, and listening abilities) and their affective change (motivation and interests). This study's conceptual framework was grounded in teacher curriculum…

  1. Psychosocial burden of sickle cell disease on parents with an affected child in Cameroon.

    PubMed

    Wonkam, Ambroise; Mba, Caryl Zameyo; Mbanya, Dora; Ngogang, Jeanne; Ramesar, Raj; Angwafo, Fru F

    2014-04-01

    The chronicity of Sickle Cell Disease (SCD) could impair the quality of life of caregivers. We performed a quantitative study to assess various indices of psychosocial burden on Cameroonian parents (N = 130) with at least one living SCD-affected child. Demographic and medical information were obtained from the participants and the review of the patients' medical records. The survey instrument included a 38-item stress factors scale using Likert-type statements, evaluating general perceptions of stress and five main specific stressors: disease factors (clinical severity), hospital factors, financial factors, family factors (life/dynamic) and SCD-child factors (perceived quality of life). The items pertaining to burden involved four response options with increasing severity: 0, 1, 2 or 3. Descriptive statistics and non-parametric tests were used for analysis. Participants were typically aged 38 years, urban dwellers (89%), female (80%), married (60.2%), employed (61.7%) and had secondary/tertiary education (82%). Median age of SCD-affected children was 9 years. The median age at diagnosis of SCD was 6 months; 47.8% had more than 3 painful crises per year. The majority of participants (88.3%) experienced moderate to severe difficulty coping with SCD. On a 0-3 scale, median score of SCD clinical severity was the major factor to undermine the coping ability of parents (2.2); vaso-occlusive painful events (>3 per year) was the disease-related stressor that most impacted their coping ability. The family life dynamic was the least stressful (0.7). Unemployment affected all the stressors' categories. Stressors scores also increased with female, single, low education level, age of SCD-affected children or more than 3 children in the family. In Cameroon, there is an urgent need to implement practices that ensure affordable access to health-care and activities that would reduce SCD morbidity. PMID:23881472

  2. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

    PubMed Central

    Berretta, Regina; Moscato, Pablo

    2016-01-01

    Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD

  3. Osteoarthritis, a disease bridging development and regeneration

    PubMed Central

    Lories, Rik J U; Luyten, Frank P

    2012-01-01

    The osteoarthritic diseases are common disorders characterized by progressive destruction of the articular cartilage in the joints, and associated with remodeling of the subchondral bone, synovitis and the formation of bone outgrowths at the joint margins, osteophytes. From the clinical perspective, osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the leading cause of progressive disability. New data from genetic, translational and basic research have demonstrated that pathways with essential roles in joint and bone development also contribute to the postnatal homeostasis of the articular cartilage and are involved in osteoarthritis, making these potential therapeutic targets. Other systems of interest are the tissue-destructive enzymes that break down the extracellular matrix of the cartilage as well as mediators of inflammation that contribute to synovitis. However, the perspective of a durable treatment over years to decades highlights the need for a personalized medicine approach encompassing a global view on the disease and its management, thereby including nonpharmaceutical approaches such as physiotherapy and advanced surgical methods. Integration of novel strategies based on their efficacy and safety with the identification of individuals at risk and optimal individual rehabilitation management remains a major challenge for the medical community in particular, as the incidence of osteoarthritis is likely to further increase with the overall aging of the population. PMID:23951516

  4. Affect Regulation Training (ART) for Alcohol Use Disorders: Development of a Novel Intervention for Negative Affect Drinkers

    PubMed Central

    Stasiewicz, Paul R.; Bradizza, Clara M.; Schlauch, Robert C.; Coffey, Scott F.; Gulliver, Suzy B.; Gudleski, Gregory; Bole, Christopher W.

    2013-01-01

    Although negative affect is a common precipitant of alcohol relapse, there are few interventions for alcohol dependence that specifically target negative affect. In this Stage 1a/1b treatment development study, several affect regulation strategies (e.g., mindfulness, prolonged exposure, distress tolerance) were combined to create a new treatment supplement called Affect Regulation Training (ART), which could be added to enhance Cognitive-Behavioral Therapy (CBT) for alcohol dependence. A draft therapy manual was given to therapists and treatment experts before being administered to several patients who also provided input. After two rounds of manual development (Stage 1a), a pilot randomized clinical trial (N = 77) of alcohol-dependent outpatients who reported drinking often in negative affect situations was conducted (Stage 1b). Participants received 12-weekly, 90-minute sessions of either CBT for alcohol dependence plus ART (CBT + ART) or CBT plus a healthy lifestyles control condition (CBT + HLS). Baseline, end-of-treatment, and 3- and 6-month posttreatment interviews were conducted. For both treatment conditions, participant ratings of treatment satisfaction were high, with CBT + ART rated significantly higher. Drinking outcome results indicated greater reductions in alcohol use for CBT + ART when compared to CBT + HLS, with moderate effect sizes for percent days abstinent, drinks per day, drinks per drinking day, and percent heavy drinking days. Overall, findings support further research on affect regulation interventions for negative affect drinkers. PMID:23876455

  5. Maternal Stress and Affect Influence Fetal Neurobehavioral Development.

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; Hilton, Sterling C.; Hawkins, Melissa; Costigan, Kathleen A.; Pressman, Eva K.

    2002-01-01

    Investigated associations between maternal psychological and fetal neurobehavioral functioning with data provided at 24, 30, and 36 weeks gestation. Found that fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more pregnancy-specific hassles were more active across gestation. Fetuses of women…

  6. Child Studies through Fantasy: Cognitive-Affective Patterns in Development.

    ERIC Educational Resources Information Center

    Gould, Rosalind

    This book presents a study of cognitive-affective interdependence as shown in children's fantasy behavior. The systems of Piaget and Freud are the foundation of analysis. The study data consist of approximately one hundred verbatim recordings of the dramatic play of 3-, 4-, and 5-year-olds (in groups or alone) collected by trained teachers in a…

  7. The First Four Months: Development of Affect, Cognition, and Synchrony.

    ERIC Educational Resources Information Center

    Guillory, Andrea; And Others

    The relationship between affective responsiveness, synchrony of mother/infant interaction, and developmental status was examined in 32 normal infants (eight infants each at the ages of 4, 8, 12, and 16 weeks). Data were collected in infants' homes and included (1) naturalistic mother/infant play; (2) presentation of auditory, tactile, visual, and…

  8. The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis.

    PubMed

    Sheng, Xiang-Xiang; Sun, Ying-Jie; Zhan, Yuan; Qu, Yu-Rong; Wang, Hua-Xia; Luo, Miao; Liao, Ying; Qiu, Xu-Sheng; Ding, Chan; Fan, Hong-Jie; Mao, Xiang

    2016-09-01

    Newcastle disease (ND) is a contagious disease that affects most species of birds. Its causative pathogen, Newcastle disease virus (NDV), also exhibits considerable oncolytic activity against mammalian cancers. A better understanding of the pathogenesis of NDV will help us design efficient vaccines and novel anticancer strategies. GW3965, a widely used synthetic ligand of liver X receptor (LXR), induces the expression of LXRs and its downstream genes, including ATP-binding cassette transporter A1 (ABCA1). ABCA1 regulates cellular cholesterol homeostasis. Here, we found that GW3965 inhibited NDV infection in DF-1 cells. It also inhibited NF-κB activation and reduced the upregulation of proinflammatory cytokines induced by the infection. Further studies showed that GW3965 exerted its inhibitory effects on virus entry and replication. NDV infection increased the mRNA levels of several lipogenic genes but decreased the ABCA1 mRNA level. Overexpression of ABCA1 inhibited NDV infection and reduced the cholesterol content in DF-1 cells, but when the cholesterol was replenished, NDV infection was restored. GW3965 treatment prevented cholesterol accumulation in the perinuclear area of the infected cells. In summary, our studies suggest that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis. PMID:27357231

  9. Calf and disease factors affecting growth in female Holstein calves in Florida, USA.

    PubMed

    Donovan, G A; Dohoo, I R; Montgomery, D M; Bennett, F L

    1998-01-01

    A prospective cohort study was undertaken to determine calf-level factors that affect performance (growth) between birth and 14 months of age in a convenience sample of approximately 3300 female Holstein calves born in 1991 on two large Florida dairy farms. Data collected on each calf at birth included farm of origin, birth date, weight, height at the pelvis, and serum total protein (a measure of colostral immunoglobulin absorption). Birth season was dichotomized into summer and winter using meteorological data collected by University of Florida Agricultural Research Stations. Data collected at approximately 6 and 14 months of age included age, weight, height at the pelvis, and height at the withers. Growth in weight and stature (height) was calculated for each growth period; growth period 1 (GP1) = birth to 6 months, and growth period 2 (GP2) = 6 to 14 months. Health data collected included data of initial treatment and number of treatments for the diseases diarrhea, omphalitis, septicemia, pneumonia and keratoconjunctivitis. After adjusting for disease occurrence, passive transfer of colostral immunoglobulins had no significant effect on body weight gain or pelvic height growth. Season of birth and occurrence of diarrhea, septicemia and respiratory disease were significant variables decreasing heifer growth (height and weight) in GP1. These variables plus farm, birth weight and exact age when '6 month' data were collected explained 20% and 31% of the variation in body weight gain and pelvic height growth, respectively, in GP1. The number of days treated for pneumonia before 6 months of age significantly decreased average daily weight gain in GP2 (P < 0.025), but did not affect stature growth. Treatment for pneumonia after 6 months of age did not significantly affect weight or height gain after age 6 months. Neither omphalitis nor keratoconjunctivitis explained variability in growth in either of the growth periods. PMID:9500160

  10. Skewed X-chromosome inactivation in women affected by Alzheimer's disease.

    PubMed

    Bajic, Vladan; Mandusic, Vesna; Stefanova, Elka; Bozovic, Ana; Davidovic, Radoslav; Zivkovic, Lada; Cabarkapa, Andrea; Spremo-Potparevic, Biljana

    2015-01-01

    X-chromosome instability has been a long established feature in Alzheimer's disease (AD). Premature centromere division and aneuploidy of the X-chromosome has been found in peripheral blood lymphocytes and neuronal tissue in female AD patients. Interestingly, only one chromosome of the X pair has been affected. These results raised a question, "Is the X-chromosome inactivation pattern altered in peripheral blood lymphocytes of women affected by AD?" To address this question, we analyzed the methylation status of androgen receptor promoter which may show us any deviation from the 50 : 50% X inactivation status in peripheral blood lymphocytes of women with AD. Our results showed skewed inactivation patterns (>90%). These findings suggest that an epigenetic alteration on the inactivation centers of the X-chromosome (or skewing) relates not only to aging, by might be a novel property that could account for the higher incidence of AD in women. PMID:25159673

  11. Systematic review of telemedicine services for patients affected by chronic obstructive pulmonary disease (COPD).

    PubMed

    Bartoli, Laura; Zanaboni, Paolo; Masella, Cristina; Ursini, Niccoló

    2009-11-01

    The aim of the present study was to conduct a systematic literature review focused on telemedicine services for patients affected by chronic obstructive pulmonary disease (COPD). In particular, it addresses (1) which telemedicine applications and related organizational models have been adopted for patients affected by COPD and (2) the impact of these applications. A computerized literature search was performed utilizing MEDLINE and Cochrane Library databases, selecting articles published between 1996 and 2008 using the following combination of keywords: [COPD] AND [telemedicine OR telehealth OR ehealth OR telecare] and after exclusions, 40 articles were considered. The adoption of telemedicine inevitably resulted in the reconfiguration of the existing practices and sociomaterial relationships. These organizational changes must be understood and addressed. PMID:19919194

  12. Cortical correlates of affective syndrome in dementia due to Alzheimer's disease.

    PubMed

    Hayata, Thaís T; Bergo, Felipe P G; Rezende, Thiago J; Damasceno, Alfredo; Damasceno, Benito P; Cendes, Fernando; Stella, Florindo; Balthazar, Marcio L F

    2015-07-01

    Neuropsychiatric symptoms in Alzheimer's disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy's patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices. PMID:26200048

  13. Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease

    PubMed Central

    Nichols, Tracy A.; Spraker, Terry R.; Gidlewski, Thomas; Cummings, Bruce; Hill, Dana; Kong, Qingzhong; Balachandran, Aru; VerCauteren, Kurt C.; Zabel, Mark D.

    2016-01-01

    ABSTRACT Chronic wasting disease (CWD), the only known wildlife prion disease, affects deer, elk and moose. The disease is an ongoing and expanding problem in both wild and captive North American cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit disease years after initial contamination. The role of exogenous factors in CWD transmission and progression is largely unexplored. In an effort to understand the influence of environmental and dietary constituents on CWD, we collected and analyzed water and soil samples from CWD-negative and positive captive cervid facilities, as well as from wild CWD-endozootic areas. Our analysis revealed that, when compared with CWD-positive sites, CWD-negative sites had a significantly higher concentration of magnesium, and a higher magnesium/copper (Mg/Cu) ratio in the water than that from CWD-positive sites. When cevidized transgenic mice were fed a custom diet devoid of Mg and Cu and drinking water with varied Mg/Cu ratios, we found that higher Mg/Cu ratio resulted in significantly longer survival times after intracerebral CWD inoculation. We also detected reduced levels of inflammatory cytokine gene expression in mice fed a modified diet with a higher Mg/Cu ratio compared to those on a standard rodent diet. These findings indicate a role for dietary Mg and Cu in CWD pathogenesis through modulating inflammation in the brain. PMID:27216881

  14. Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease.

    PubMed

    Nichols, Tracy A; Spraker, Terry R; Gidlewski, Thomas; Cummings, Bruce; Hill, Dana; Kong, Qingzhong; Balachandran, Aru; VerCauteren, Kurt C; Zabel, Mark D

    2016-05-01

    Chronic wasting disease (CWD), the only known wildlife prion disease, affects deer, elk and moose. The disease is an ongoing and expanding problem in both wild and captive North American cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit disease years after initial contamination. The role of exogenous factors in CWD transmission and progression is largely unexplored. In an effort to understand the influence of environmental and dietary constituents on CWD, we collected and analyzed water and soil samples from CWD-negative and positive captive cervid facilities, as well as from wild CWD-endozootic areas. Our analysis revealed that, when compared with CWD-positive sites, CWD-negative sites had a significantly higher concentration of magnesium, and a higher magnesium/copper (Mg/Cu) ratio in the water than that from CWD-positive sites. When cevidized transgenic mice were fed a custom diet devoid of Mg and Cu and drinking water with varied Mg/Cu ratios, we found that higher Mg/Cu ratio resulted in significantly longer survival times after intracerebral CWD inoculation. We also detected reduced levels of inflammatory cytokine gene expression in mice fed a modified diet with a higher Mg/Cu ratio compared to those on a standard rodent diet. These findings indicate a role for dietary Mg and Cu in CWD pathogenesis through modulating inflammation in the brain. PMID:27216881

  15. Parasitic diarrheal disease: drug development and targets

    PubMed Central

    Azam, Amir; Peerzada, Mudasir N.; Ahmad, Kamal

    2015-01-01

    Diarrhea is the manifestation of gastrointestinal infection and is one of the major causes of mortality and morbidity specifically among the children of less than 5 years age worldwide. Moreover, in recent years there has been a rise in the number of reports of intestinal infections continuously in the industrialized world. These are largely related to waterborne and food borne outbreaks. These occur by the pathogenesis of both prokaryotic and eukaryotic organisms like bacteria and parasites. The parasitic intestinal infection has remained mostly unexplored and under assessed in terms of therapeutic development. The lack of new drugs and the risk of resistance have led us to carry out this review on drug development for parasitic diarrheal diseases. The major focus has been depicted on commercially available drugs, currently synthesized active heterocyclic compounds and unique drug targets, that are vital for the existence and growth of the parasites and can be further exploited for the search of therapeutically active anti-parasitic agents. PMID:26617574

  16. L-serine in disease and development.

    PubMed Central

    de Koning, Tom J; Snell, Keith; Duran, Marinus; Berger, Ruud; Poll-The, Bwee-Tien; Surtees, Robert

    2003-01-01

    The amino acid L-serine, one of the so-called non-essential amino acids, plays a central role in cellular proliferation. L-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. It has long been recognized that, in cell cultures, L-serine is a conditional essential amino acid, because it cannot be synthesized in sufficient quantities to meet the cellular demands for its utilization. In recent years, L-serine and the products of its metabolism have been recognized not only to be essential for cell proliferation, but also to be necessary for specific functions in the central nervous system. The findings of altered levels of serine and glycine in patients with psychiatric disorders and the severe neurological abnormalities in patients with defects of L-serine synthesis underscore the importance of L-serine in brain development and function. This paper reviews these recent insights into the role of L-serine and the pathways of L-serine utilization in disease and during development, in particular of the central nervous system. PMID:12534373

  17. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.

    PubMed

    Zhang, Deng-Feng; Li, Jin; Wu, Huan; Cui, Yue; Bi, Rui; Zhou, He-Jiang; Wang, Hui-Zhen; Zhang, Chen; Wang, Dong; Kong, Qing-Peng; Li, Tao; Fang, Yiru; Jiang, Tianzi; Yao, Yong-Gang

    2016-03-01

    The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress. PMID:26243271

  18. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    PubMed

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  19. Lifestyle-Related Diseases Affect Surgical Outcomes after Posterior Lumbar Interbody Fusion.

    PubMed

    Sakaura, Hironobu; Miwa, Toshitada; Yamashita, Tomoya; Kuroda, Yusuke; Ohwada, Tetsuo

    2016-02-01

    Study Design Retrospective study. Objective Hyperlipidemia (HL) and hypertension (HT) lead to systemic atherosclerosis. Not only atherosclerosis but also bone fragility and/or low bone mineral density result from diabetes mellitus (DM) and chronic kidney disease (CKD). The purpose of this study was to examine whether these lifestyle-related diseases affected surgical outcomes after posterior lumbar interbody fusion (PLIF). Methods The subjects comprised 122 consecutive patients who underwent single-level PLIF for degenerative lumbar spinal disorders. The clinical results were assessed using the Japanese Orthopaedic Association (JOA) score before surgery and at 2 years postoperatively. The fusion status was graded as union in situ, collapsed union, or nonunion at 2 years after surgery. The abdominal aorta calcification (AAC) score was assessed using preoperative lateral radiographs of the lumbar spine. Results HL did not significantly affect the JOA score recovery rate. On the other hand, HT and CKD (stage 3 to 4) had a significant adverse effect on the recovery rate. The recovery rate was also lower in the DM group than in the non-DM group, but the difference was not significant. The AAC score was negatively correlated with the JOA score recovery rate. The fusion status was not significantly affected by HL, HT, DM, or CKD; however, the AAC score was significantly higher in the collapsed union and nonunion group than in the union in situ group. Conclusions At 2 years after PLIF, the presence of HT, CKD, and AAC was associated with significantly worse clinical outcomes, and advanced AAC significantly affected fusion status. PMID:26835195

  20. Alterations in lignin content and phenylpropanoids pathway in date palm (Phoenix dactylifera L.) tissues affected by brittle leaf disease.

    PubMed

    Saidi, Mohammed Najib; Bouaziz, Donia; Hammami, Ines; Namsi, Ahmed; Drira, Noureddine; Gargouri-Bouzid, Radhia

    2013-10-01

    Brittle leaf disease or Maladie de la Feuille Cassante (MFC) is a lethal disorder of date palm that has assumed epidemic proportions in the oases of Tunisia and Algeria. No pathogen could ever be associated with the disease, while leaflets of affected palms have been previously shown to be deficient in manganese. The work reported here aims to understand the biochemical basis of the date palm response to this disorder. Since the typical disease symptom is the leaf fragility, we have investigated lignin content in leaves and roots. Strong decrease in total lignin content was observed in affected leaves, while lignin content increased in affected roots. Histochemical analyses showed hyperlignification thicker suberin layer in roots cortical cells. The phenylpropanoids pathway was also disrupted in leaves and roots, cinnamoyl-CoA reductase and cinnamyl-alcohol dehydrogenase gene expression was affected by the disease which severely affects the cell wall integrity. PMID:23987806

  1. What can we learn from inflammatory bowel disease in developing countries?

    PubMed

    Wong, Sunny H; Ng, Siew C

    2013-03-01

    Inflammatory bowel diseases occur due to an aberrant immune response to luminal antigens in genetically predisposed individuals. Although specific genetic loci have been identified underlying the predisposition, they have not fully explained the disease etiology. Striking epidemiological observations implicate the critical role of environmental influences on disease penetrance. The emergence of disease consistently observed as a society becomes modernized or developed may be attributed to westernization of diet, changing antibiotic use, or improved hygiene status. These factors are linked with changes in the gastrointestinal microbiota which, in turn, may affect development of the immune system and influence the risk of disease occurrence. Geographic variations within developing countries suggest that the strength of influence by risk factors in a society varies greatly. Studies of IBD in populations of developing countries where there are opportunities to prospectively collect changing exposure data over time may provide clues to the disease etiology. PMID:23389655

  2. Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease

    PubMed Central

    Sutton, C; Yang, H; Li, Z; Rotter, J; Targan, S; Braun, J

    2000-01-01

    BACKGROUND—Crohn's disease is a familial disorder, and antiglycan antibodies to the cell wall mannan of Saccharomyces cerevisiae (ASCA) are highly correlated with Crohn's disease.
AIMS—To determine whether there is a familial pattern for expression of serum levels of anti-mannan Ig, and whether this trait is expressed in clinically unaffected Crohn's disease family members.
METHODS—349 patients with Crohn's disease, 87 Crohn's disease affected relatives, 333 inflammatory bowel disease (IBD) free relatives, 58 spouses, and 190 healthy control patients were studied. Serum IgG and IgA binding activity to S cerevisiae cell wall mannan was quantitated by ELISA.
RESULTS—A high percentage of patients with Crohn's disease (51.9%) and affected family members (56.3%) were seropositive for anti-mannan Ig, compared with the normal control population (3.7%). Seropositive and seronegative phenotypes of Crohn's disease probands were correlated among all affected relatives, and this association was stronger in affected first degree relatives. Statistical intraclass correlations of quantitative anti-mannan Ig levels revealed significantly less variation within, rather than between families. A significant familial aggregation was observed for affected relatives; this was even stronger for unaffected relatives. While a significant familial aggregation was observed among unaffected siblings pairs, there was no significant correlation among marital pairs.
CONCLUSION—Results show that anti-mannan Ig in family members affected and unaffected with Crohn's disease is a familial trait for both affected and unaffected relatives. The lack of concordance in marital pairs indicates that familiality is due in part to a genetic factor or childhood environmental exposure.


Keywords: Crohn's disease; inflammatory bowel disease; ulcerative colitis; anti-mannan antibodies; intraclass correlation; statistical genetics PMID:10601056

  3. Chagas Heart Disease: Report on Recent Developments

    PubMed Central

    Machado, Fabiana S.; Jelicks, Linda A.; Kirchhoff, Louis V.; Shirani, Jamshid; Nagajyothi, Fnu; Mukherjee, Shankar; Nelson, Randin; Coyle, Christina M.; Spray, David C.; Campos de Carvalho, Antonio C.; Guan, Fangxia; Prado, Cibele M.; Lisanti, Michael P.; Weiss, Louis M.; Montgomery, Susan P.; Tanowitz, Herbert B.

    2011-01-01

    Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. It is now being diagnosed in non-endemic areas due to immigration. Typical cardiac manifestations of Chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism and stroke. Clinical and laboratory-based research to define the pathology resulting from T. cruzi infection has shed light on many of the cellular and molecular mechanisms leading to these manifestations. Antiparasitic treatment may not be appropriate for patients with advanced cardiac disease. Clinical management of Chagas heart disease is similar to that used for cardiomyopathies due to other processes. Cardiac transplantation has been successfully performed in a small number of patients with Chagas heart disease. PMID:22293860

  4. Oral impacts affecting daily performance in a low dental disease Thai population.

    PubMed

    Adulyanon, S; Vourapukjaru, J; Sheiham, A

    1996-12-01

    The aim of the study was to measure incidence of oral impacts on daily performances and their related features in a low dental disease population. 501 people aged 35-44 years in 16 rural villages in Ban Phang district, Khon Kaen, Thailand, were interviewed about oral impacts on nine physical, psychological and social aspects of performance during the past 6 months, and then had an oral examination. The clinical and behavioural data showed that the sample had low caries (DMFT = 2.7) and a low utilization of dental services. 73.6% of all subjects had at least one daily performance affected by an oral impact. The highest incidence of performances affected were Eating (49.7%), Emotional stability (46.5%) and Smiling (26.1%). Eating, Emotional stability and Cleaning teeth performances had a high frequency or long duration of impacts, but a low severity. The low frequency performances; Physical activities, Major role activity and Sleeping were rated as high severity. Pain and discomfort were mainly perceived as the causes of impacts (40.1%) for almost every performance except Smiling. Toothache was the major causal oral condition (32.7%) of almost all aspects of performance. It was concluded that this low caries people have as high an incidence of oral impacts as industrialized, high dental disease populations. Frequency and severity presented the paradoxical effect on different performances and should both be taken into account for overall estimation of impacts. PMID:9007354

  5. The early course of affective and cognitive symptoms in de novo patients with Parkinson's disease.

    PubMed

    Spalletta, Gianfranco; Robinson, Robert G; Cravello, Luca; Pontieri, Francesco E; Pierantozzi, Mariangela; Stefani, Alessandro; Long, Jeffrey D; Caltagirone, Carlo; Assogna, Francesca

    2014-06-01

    Neuropsychiatric and cognitive symptoms are common in patients with Parkinson's disease (PD) from the early stage of the disease but their course is still unclear. In this study we investigated prospectively the progression of affective and cognitive symptoms and disorders in de novo idiopathic PD patients. Twenty-four de novo drug naïve PD patients underwent a comprehensive neurological, psychopathological and neuropsychological evaluation at the first diagnostic visit (OFF), after 4-6 months when the antiparkinsonian therapy regimen was stabilized (ON-1), and at one year following the ON-1 follow-up visit (ON-2). Generalized least squares analysis revealed a significant improvement over time in the depressive mood, short and long term episodic verbal memory, visual memory, and the motor symptoms. Pairwise comparisons showed a significant change from OFF to ON-1 for all the aforementioned variables, except for short term episodic verbal memory which approached significance. A significant improvement from ON-1 to ON-2, however, was shown for short term episodic verbal memory. An ancillary analysis indicated that overall level and change in a number of cognitive variables, but not depression, was conditional upon age of onset, education, and sometime gender. In conclusion, early stage PD is not associated with affective and cognitive deterioration. On the contrary, very specific neuropsychiatric and cognitive symptoms may improve. This study provides Class III evidence that antiparkinsonian treatment commonly used in the clinical practice improves memory performance and depression severity in de novo patients with PD. PMID:24695996

  6. Collaborative Development: A New Culture Affects an Old Organization

    ERIC Educational Resources Information Center

    Phelps, Jim; Ruzicka, Terry

    2008-01-01

    At the University of Wisconsin (UW)-Madison, the Registrar's Office and the Division of Information Technology (DoIT) apply a collaborative development process to joint projects. This model differs from a "waterfall" model in that technical and functional staff work closely to develop requirements, prototypes, and the product throughout its life…

  7. Development of a Behavioral Affective Relationship Scale for Encounter Research.

    ERIC Educational Resources Information Center

    Shadish, William R., Jr.; Zarle, Thomas

    The paper outlines several studies over a two-year period to develop a self-report and observer-rating measure of sensitivity/encounter group outcome. The initial form of the scale was taken from McMillan (1971) who developed a measure of 16 categories of group outcome; McMillan's work indicated the scale had high reliability. Subsequent study…

  8. Chronic kidney disease hotspots in developing countries in South Asia.

    PubMed

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

    2016-02-01

    In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan. PMID:26798474

  9. Chronic kidney disease hotspots in developing countries in South Asia

    PubMed Central

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

    2016-01-01

    In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan. PMID:26798474

  10. Translation of rare disease research into orphan drug development: disease matters.

    PubMed

    Heemstra, Harald E; van Weely, Sonja; Büller, Hans A; Leufkens, Hubert G M; de Vrueh, Remco L A

    2009-12-01

    More than 25 years of orphan drug regulations have yielded several new treatments for patients with rare diseases. Here, we show that successful translation of rare disease research into an orphan drug discovery and development programme is dependent on the disease class, its prevalence and the disease-specific scientific output. Our findings indicate that current orphan drug legislation alone is not sufficient to stimulate orphan drug development for diseases with a very low prevalence. Consequently, additional incentives should focus on stimulating the specific needs of rare disease research at disease class level. PMID:19818412

  11. SOCS proteins in development and disease

    PubMed Central

    Trengove, Monique C; Ward, Alister C

    2013-01-01

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

  12. Epigenetic mechanisms in cardiac development and disease.

    PubMed

    Vallaster, Marcus; Vallaster, Caroline Dacwag; Wu, Sean M

    2012-01-01

    During mammalian development, cardiac specification and ultimately lineage commitment to a specific cardiac cell type is accomplished by the action of specific transcription factors (TFs) and their meticulous control on an epigenetic level. In this review, we detail how cardiac-specific TFs function in concert with nucleosome remodeling and histone-modifying enzymes to regulate a diverse network of genes required for processes such as cell growth and proliferation, or epithelial to mesenchymal transition (EMT), for instance. We provide examples of how several cardiac TFs, such as Nkx2.5, WHSC1, Tbx5, and Tbx1, which are associated with developmental and congenital heart defects, are required for the recruitment of histone modifiers, such as Jarid2, p300, and Ash2l, and components of ATP-dependent remodeling enzymes like Brg1, Baf60c, and Baf180. Binding of these TFs to their respective sites at cardiac genes coincides with a distinct pattern of histone marks, indicating that the precise regulation of cardiac gene networks is orchestrated by interactions between TFs and epigenetic modifiers. Furthermore, we speculate that an epigenetic signature, comprised of TF occupancy, histone modifications, and overall chromatin organization, is an underlying mechanism that governs cardiac morphogenesis and disease. PMID:22194017

  13. The ATM signaling network in development and disease

    PubMed Central

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

    2013-01-01

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

  14. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

    PubMed

    Eyring, Kenneth R; Pedersen, Brent S; Yang, Ivana V; Schwartz, David A

    2015-01-01

    Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. PMID:26642056

  15. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome

    PubMed Central

    Eyring, Kenneth R.; Pedersen, Brent S.; Yang, Ivana V.; Schwartz, David A.

    2015-01-01

    Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. PMID:26642056

  16. Spatiotemporal and species-specific patterns of diseases affecting crustose coralline algae in Curaçao

    NASA Astrophysics Data System (ADS)

    Quéré, G.; Steneck, R. S.; Nugues, M. M.

    2015-03-01

    Distribution and abundance of coral diseases have been well documented, but only a few studies considered diseases affecting crustose coralline algae (CCA), particularly at the species level. We investigated the spatiotemporal dynamics of diseases affecting CCA along the south coast of Curaçao, southern Caribbean. Two syndromes were detected: the Coralline White Band Syndrome (CWBS) previously described and the Coralline White Patch Disease (CWPD) reported here for the first time. Diseases were present at all six study sites, and our results did not reveal a relationship between disease occurrence and human influence. Both diseases were more prevalent on the shallower reef flat than on the deeper reef slope, and during the warm/rainy season than during the cold/dry season. The patterns observed were consistent with a positive link between temperature and disease occurrence. Reef flat communities were dominated by Neogoniolithon mamillare and Paragoniolithon solubile, whereas deeper habitats were dominated by Hydrolithon boergesenii. Diseases affected all the species encountered, and no preferable host was detected. There was a significant relationship between both disease occurrences and CCA cover. Monitoring of affected patches revealed that 90 % of lesions in CWBS increased in size, whereas 88 % of CWPD lesions regenerated over time. CWBS linear progression rate did not vary between seasons or species and ranged from 0.15 to 0.36 cm month-1, which is in the same order of magnitude as rates previously documented. We conclude that diseases have the potential to cause major loss in CCA cover, particularly in shallow waters. As CCA play a key role in reef ecosystems, our study suggests that the emergence of diseases affecting these algae may pose a real threat to coral reef ecosystems. The levels of disease reported here will provide a much-needed local baseline allowing future comparisons.

  17. The workshop on energy development issues affecting Appalachia. Final report

    SciTech Connect

    Blaney, B.L.; Jelen, V.F.; Waldman, M.; Evans, J.; Bovee, R.

    1981-08-01

    This report describes the results of a workshop involving representatives of private industries, government agencies and public interest groups that was held in January of 1979 to raise and discuss issues related to Appalachian energy development.

  18. THE WORKSHOP ON ENERGY DEVELOPMENT ISSUES AFFECTING APPALACHIA

    EPA Science Inventory

    This report describes the results of a workshop involving representatives of private industries, government agencies and public interest groups that was held in January of 1979 to raise and discuss issues related to Appalachian energy development.

  19. Factors affecting adherence to a gluten-free diet in children with celiac disease

    PubMed Central

    MacCulloch, Katherine; Rashid, Mohsin

    2014-01-01

    BACKGROUND: The treatment of celiac disease is a strict, life-long gluten-free (GF) diet. This diet is complex and can be challenging. Factors affecting adherence to the GF diet are important to identify for improving adherence. OBJECTIVE: To identify factors that inhibit or improve adherence to a GF diet in children with celiac disease. METHODS: Patients (<18 years of age) with biopsy-confirmed celiac disease followed by the gastroenterology service at a tertiary care paediatric institution were surveyed using a mailed questionnaire. Factors influencing adherence to a GF diet were scored from 1 to 10 based on how often they were problematic (1 = never, 10 = always). Parents of patients <13 years of age were instructed to complete the survey with their child. Adolescents ≥13 years of age were asked to complete the survey themselves. RESULTS: Of 253 subjects, 126 completed the survey; the median age was 12 years (range two to 18 years). Forty percent were adolescents. Overall, participants reported good adherence at home and school, but lower adherence at social events. Adolescents reported lower adherence compared with parents. Availability of GF foods and cost were the most significant barriers. Other factors identified to help with a GF diet included education for schools/restaurants and improved government support. CONCLUSIONS: Availability, cost and product labelling are major barriers to adherence to a GF diet. Better awareness, improved labelling and income support are needed to help patients. PMID:25332660

  20. The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease

    PubMed Central

    Eitam, Harel; Yishay, Moran; Schiavini, Fausta; Soller, Morris; Bagnato, Alessandro; Shabtay, Ariel

    2016-01-01

    Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity. PMID:27077383

  1. The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease.

    PubMed

    Lipkin, Ehud; Strillacci, Maria Giuseppina; Eitam, Harel; Yishay, Moran; Schiavini, Fausta; Soller, Morris; Bagnato, Alessandro; Shabtay, Ariel

    2016-01-01

    Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity. PMID:27077383

  2. Surface wind observations affected by agricultural development over Northwest China

    NASA Astrophysics Data System (ADS)

    Han, Songjun; Tang, Qiuhong; Zhang, Xuezhen; Xu, Di; Kou, Lihang

    2016-05-01

    Meteorological stations in Northwest China are surrounded by large proportions of cultivated land. The relations between the change of surface wind speed and the cultivated land fractions (CF) within a 4 km radius at 135 meteorological stations over arid Northwest China are investigated. Stations with larger CF experienced larger declines in surface wind speed from 1960 to 2007. Compared with the wind speed variation in the Tibetan Plateau where agricultural development is negligible, stations with low CF show similar variation, whereas the wind speed at stations with large CF illustrates a sharp decrease in the 1970s–1980s, during which irrigated agriculture developed rapidly. The observed wind speed at the station surrounded by irrigated fields in the Jingtai Irrigation District, shows a rapid wind speed decrease during the same period when the irrigated area expanded. By contrast, rapid wind decrease is not observed at a nearby station with minimal influence of agricultural development.

  3. A novel family of small proteins that affect plant development

    SciTech Connect

    John Charles Walker

    2011-04-29

    The DVL genes represent a new group of plant proteins that influence plant growth and development. Overexpression of DVL1, and other members of the DVL family, causes striking phenotypic changes. The DVL proteins share sequence homology in their C-terminal half. Point mutations in the C-terminal domain show it is necessary and deletion studies demonstrate the C-terminal domain is sufficient to confer the overexpression phenotypes. The phenotypes observed, and the conservation of the protein sequence in the plant kingdom, does suggest the DVL proteins have a role in modulating plant growth and development. Our working hypothesis is the DVL proteins function as regulators of cellular signaling pathways that control growth and development.

  4. Professional Development: Designing for the Cognitive and Affective Domains

    ERIC Educational Resources Information Center

    Doherty, Iain

    2014-01-01

    This paper critically reflects on the pedagogical approach underlying a professional development course in eLearning. The aim of the course was to teach faculty based eLearning officers the necessary practical and theoretical skills to fulfil their roles in supporting Faculties with eLearning initiatives. Whilst the course was successful--judged…

  5. Factors Affecting Teachers' Participation in Professional Development Activities in Turkey

    ERIC Educational Resources Information Center

    Bayar, Adem

    2013-01-01

    The purpose of this study was to examine the relationship between factors (internal [personal] and external [environmental]) and teachers' participation in professional development (PD) programs in Turkey. The researcher employed a survey design, using a multiple-stage sampling method, selecting 30 out of 66 elementary schools in the Center…

  6. Early Social Experience Affects the Development of Eye Gaze Processing.

    PubMed

    Senju, Atsushi; Vernetti, Angélina; Ganea, Natasa; Hudry, Kristelle; Tucker, Leslie; Charman, Tony; Johnson, Mark H

    2015-12-01

    Eye gaze is a key channel of non-verbal communication in humans. Eye contact with others is present from birth, and eye gaze processing is crucial for social learning and adult-infant communication. However, little is known about the effect of selectively different experience of eye contact and gaze communication on early social and communicative development. To directly address this question, we assessed 14 sighted infants of blind parents (SIBPs) longitudinally at 6-10 and 12-16 months. Face scanning and gaze following were assessed using eye tracking. In addition, naturalistic observations were made when the infants were interacting with their blind parent and with an unfamiliar sighted adult. Established measures of emergent autistic-like behaviors and standardized tests of cognitive, motor, and linguistic development were also collected. These data were then compared with those obtained from a group of infants of sighted parents. Despite showing typical social skills development overall, infants of blind parents allocated less attention to adult eye movements and gaze direction, an effect that increased between 6-10 and 12-16 months of age. The results suggest that infants adjust their use of adults' eye gaze depending on gaze communication experience from early in life. The results highlight that human functional brain development shows selective experience-dependent plasticity adaptive to the individual's specific social environment. PMID:26752077

  7. Factors affecting early seedling development in whole pine tree substrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wood-based materials derived from pine trees, such as processed whole pine tree (WPT), can be a viable option for producers looking to offset pine bark or peatmoss usage in container substrates. Reduced root development of stem cuttings rooted in WPT compared with pine bark (PB) has been observed, b...

  8. The maize rachis affects Aspergillus flavus movement during ear development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus expressing green fluorescent protein (GFP) was used to follow infection in ears of maize hybrids resistant and susceptible to the fungus. Developing ears were needle-inoculated with GFP-transformed A. flavus 20 days after silk emergence, and GFP fluorescence in the pith was evalu...

  9. Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

    ERIC Educational Resources Information Center

    Hawley, Theresa

    Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

  10. Does prenatal stress affect the motoric development of rat pups?

    PubMed

    Patin, V; Vincent, A; Lordi, B; Caston, J

    2004-04-19

    Pregnant rats were exposed to an acute or a repeated stress (presence of a cat) either at the 10th or the 14th gestational day, and the development of their offspring was studied during the first 2 weeks of life. Motor development was measured by different tests: rooting reflex, vibrissae placing response, righting reflex, negative geotaxis. Other landmarks such as eye opening and spontaneous locomotor activity were also recorded. The results showed that, except for the rooting reflex which was most often enhanced (while not significantly) in prenatally stressed rats, the development of the vibrissae placing response, the righting reflex and the negative geotaxis behavior was delayed in the offspring of dams stressed at the 10th gestational day and not (or almost not) in the offspring of dams stressed at the 14th gestational day, the delay being more severe when the prenatal stress was repeated than when it was acutely administered. The spontaneous motor activity was also altered in repeatedly prenatally stressed rats, whatever the day of pregnancy when it was administered, while it was unaffected in acutely prenatally stressed animals. The delay in motor reflexes development was interpreted as alterations in maturation of nervous structures sustaining motor skills, while permanent decrease of spontaneous motor activity was explained by emotional and motivational alterations due to prenatal stress. PMID:15063088

  11. Traumatic Experience in Infancy: How Responses to Stress Affect Development

    ERIC Educational Resources Information Center

    Witten, Molly Romer

    2010-01-01

    Responses to traumatic stress during the earliest years of life can change quickly and can be difficult to identify because of the young child's rapid rate of development. The symptoms of traumatic stress will depend on the child's developmental level and individual coping styles, as well as the quality and nature of the child's most important…

  12. Early Social Experience Affects the Development of Eye Gaze Processing

    PubMed Central

    Senju, Atsushi; Vernetti, Angélina; Ganea, Natasa; Hudry, Kristelle; Tucker, Leslie; Charman, Tony; Johnson, Mark H.

    2015-01-01

    Summary Eye gaze is a key channel of non-verbal communication in humans [1, 2, 3]. Eye contact with others is present from birth [4], and eye gaze processing is crucial for social learning and adult-infant communication [5, 6, 7]. However, little is known about the effect of selectively different experience of eye contact and gaze communication on early social and communicative development. To directly address this question, we assessed 14 sighted infants of blind parents (SIBPs) longitudinally at 6–10 and 12–16 months. Face scanning [8] and gaze following [7, 9] were assessed using eye tracking. In addition, naturalistic observations were made when the infants were interacting with their blind parent and with an unfamiliar sighted adult. Established measures of emergent autistic-like behaviors [10] and standardized tests of cognitive, motor, and linguistic development [11] were also collected. These data were then compared with those obtained from a group of infants of sighted parents. Despite showing typical social skills development overall, infants of blind parents allocated less attention to adult eye movements and gaze direction, an effect that increased between 6–10 and 12–16 months of age. The results suggest that infants adjust their use of adults’ eye gaze depending on gaze communication experience from early in life. The results highlight that human functional brain development shows selective experience-dependent plasticity adaptive to the individual’s specific social environment. PMID:26752077

  13. Inferring rare disease risk variants based on exact probabilities of sharing by multiple affected relatives

    PubMed Central

    Bureau, Alexandre; Younkin, Samuel G.; Parker, Margaret M.; Bailey-Wilson, Joan E.; Marazita, Mary L.; Murray, Jeffrey C.; Mangold, Elisabeth; Albacha-Hejazi, Hasan; Beaty, Terri H.; Ruczinski, Ingo

    2014-01-01

    Motivation: Family-based designs are regaining popularity for genomic sequencing studies because they provide a way to test cosegregation with disease of variants that are too rare in the population to be tested individually in a conventional case–control study. Results: Where only a few affected subjects per family are sequenced, the probability that any variant would be shared by all affected relatives—given it occurred in any one family member—provides evidence against the null hypothesis of a complete absence of linkage and association. A P-value can be obtained as the sum of the probabilities of sharing events as (or more) extreme in one or more families. We generalize an existing closed-form expression for exact sharing probabilities to more than two relatives per family. When pedigree founders are related, we show that an approximation of sharing probabilities based on empirical estimates of kinship among founders obtained from genome-wide marker data is accurate for low levels of kinship. We also propose a more generally applicable approach based on Monte Carlo simulations. We applied this method to a study of 55 multiplex families with apparent non-syndromic forms of oral clefts from four distinct populations, with whole exome sequences available for two or three affected members per family. The rare single nucleotide variant rs149253049 in ADAMTS9 shared by affected relatives in three Indian families achieved significance after correcting for multiple comparisons (p=2×10−6). Availability and implementation: Source code and binaries of the R package RVsharing are freely available for download at http://cran.r-project.org/web/packages/RVsharing/index.html. Contact: alexandre.bureau@msp.ulaval.ca or ingo@jhu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24740360

  14. Maternal seizures can affect the brain developing of offspring.

    PubMed

    Cossa, Ana Carolina; Lima, Daiana Correia; do Vale, Tiago Gurgel; de Alencar Rocha, Anna Karynna Alves; da Graça Naffah-Mazzacoratti, Maria; da Silva Fernandes, Maria José; Amado, Debora

    2016-08-01

    To elucidate the impact of maternal seizures in the developing rat brain, pregnant Wistar rats were subjected to the pilocarpine-induced seizures and pups from different litters were studied at different ages. In the first 24 h of life, blood glucose and blood gases were analyzed. (14)C-leucine [(14)C-Leu] incorporation was used to analyze protein synthesis at PN1, and Western Blot method was used to analyze protein levels of Bax, Bcl-2 and Poly(ADP-ribose) polymerase-1 (PARP-1) in the hippocampus (PN3-PN21). During the first 22 days of postnatal life, body weight gain, length, skull measures, tooth eruption, eye opening and righting reflex have been assessed. Pups from naive mothers were used as controls. Experimental pups showed a compensated metabolic acidosis and hyperglycemia. At PN1, the [(14)C-Leu] incorporation into different studied areas of experimental pups was lower than in the control pups. During development, the protein levels of Bax, Bcl-2 and PARP-1 in the hippocampus of experimental pups were altered when compared with control pups. A decreased level of pro- and anti-apoptotic proteins was verified in the early postnatal age (PN3), and an increased level of pro-apoptotic proteins concomitant with a reduced level of anti-apoptotic protein was observed at the later stages of the development (PN21). Experimental pups had a delay in postnatal growth and development beyond disturb in protein synthesis and some protein expression during development. These changes can be result from hormonal alterations linked to stress and/or hypoxic events caused by maternal epileptic seizures during pregnancy. PMID:27085526

  15. Remodelling the extracellular matrix in development and disease

    PubMed Central

    Bonnans, Caroline; Chou, Jonathan; Werb, Zena

    2015-01-01

    The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics. PMID:25415508

  16. Echocardiography in pericardial diseases: new developments.

    PubMed

    Veress, Gabriella; Feng, Dali; Oh, Jae K

    2013-05-01

    Echocardiography is one of the most important clinical tools in the diagnosis and management of various pericardial diseases, including constrictive pericarditis, effusive constrictive pericarditis, pericardial effusion, tamponade, absence of the pericardium and cysts or tumors. During recent years, remarkable progress has been made in echocardiography: cardiac tissue Doppler analysis (TDI), strain and strain rate imaging by speckle tracking imaging (STE) and three-dimensional (3D) echocardiography. The assessment of early diastolic annulus velocity and annulus reversus by TDI improves the differentiation of constriction from restrictive myocardial disease, which can be further facilitated by STE as a complementary tool. 3D echocardiography may be useful for the more precise assessment of pericardial diseases, such as pericardial effusion or pericardial masses as it provides incremental value to 2D echocardiography by detecting anatomic structures with higher accuracy. Applications of these newer echocardiographic techniques in the assessment of pericardial diseases are discussed in this chapter. PMID:22752511

  17. Reading Instruction Affects the Cognitive Skills Supporting Early Reading Development

    ERIC Educational Resources Information Center

    McGeown, Sarah P.; Johnston, Rhona S.; Medford, Emma

    2012-01-01

    This study examined the cognitive skills associated with early reading development when children were taught by different types of instruction. Seventy-nine children (mean age at pre-test 4;10 (0.22 S.D.) and post-test 5;03 (0.21 S.D.)) were taught to read either by an eclectic approach which included sight-word learning, guessing from context and…

  18. Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review

    PubMed Central

    Severson, Tyler J; Besur, Siddesh; Bonkovsky, Herbert L

    2016-01-01

    AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review. METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur. RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine. CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management. PMID:27547017

  19. Antenatal Glucocorticoid Treatment Affects Hippocampal Development in Mice

    PubMed Central

    Noorlander, Cornelle W.; Tijsseling, Deodata; Hessel, Ellen V. S.; de Vries, Willem B.; Derks, Jan B.

    2014-01-01

    Synthetic glucocorticoids are administered to pregnant women at risk for preterm delivery, to enhance fetal lung maturation. The benefit of this treatment is well established, however caution is necessary because of possible unwanted side effects on development of different organ systems, including the brain. Actions of glucocorticoids are mediated by corticosteroid receptors, which are highly expressed in the hippocampus, a brain structure involved in cognitive functions. Therefore, we analyzed the effects of a single antenatal dexamethasone treatment on the development of the mouse hippocampus. A clinically relevant dose of dexamethasone (0.4 mg/kg) was administered to pregnant mice at embryonic day 15.5 and the hippocampus was analyzed from embryonic day 16 until adulthood. We investigated the effects of dexamethasone treatment on anatomical changes, apoptosis and proliferation in the hippocampus, hippocampal volume and on total body weight. Our results show that dexamethasone treatment reduced body weight and hippocampal volume transiently during development, but these effects were no longer detected at adulthood. Dexamethasone treatment increased the number of apoptotic cells in the hippocampus until birth, but postnatally no effects of dexamethasone treatment on apoptosis were found. During the phase with increased apoptosis, dexamethasone treatment reduced the number of proliferating cells in the subgranular zone of the dentate gyrus. The number of proliferative cells was increased at postnatal day 5 and 10, but was decreased again at the adult stage. This latter long-term and negative effect of antenatal dexamethasone treatment on the number of proliferative cells in the hippocampus may have important implications for hippocampal network function. PMID:24465645

  20. Early development of Xenopus embryos is affected by simulated gravity

    NASA Technical Reports Server (NTRS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-01-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  1. Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients.

    PubMed

    Shapiro, Barbara E; Logigian, Eric L; Kolodny, Edwin H; Pastores, Gregory M

    2008-08-01

    Late-onset Tay-Sachs (LOTS) disease is a chronic, progressive, lysosomal storage disorder caused by a partial deficiency of beta-hexosaminidase A (HEXA) activity. Deficient levels of HEXA result in the intracellular accumulation of GM2-ganglioside, resulting in toxicity to nerve cells. Clinical manifestations primarily involve the central nervous system (CNS) and lower motor neurons, and include ataxia, weakness, spasticity, dysarthria, dysphagia, dystonia, seizures, psychosis, mania, depression, and cognitive decline. The prevalence of peripheral nervous system (PNS) involvement in LOTS has not been well documented, but it has traditionally been thought to be very low. We examined a cohort of 30 patients with LOTS who underwent clinical and electrophysiologic examination, and found evidence of a predominantly axon loss polyneuropathy affecting distal nerve segments in the lower and upper extremities in eight patients (27%). PMID:18642377

  2. Effect of blending Huanglongbing (HLB) disease affected orange juice with juice from healthy oranges on flavor quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Huanglongbing, or citrus greening disease, has been a concern for the citrus industry as it progressively damages and ultimately kills citrus trees. While this disease does not affect human health, it is associated with bitter off-flavor for orange juice. The objective of this study was to determine...

  3. Community history affects the predictability of microbial ecosystem development

    PubMed Central

    Pagaling, Eulyn; Strathdee, Fiona; Spears, Bryan M; Cates, Michael E; Allen, Rosalind J; Free, Andrew

    2014-01-01

    Microbial communities mediate crucial biogeochemical, biomedical and biotechnological processes, yet our understanding of their assembly, and our ability to control its outcome, remain poor. Existing evidence presents conflicting views on whether microbial ecosystem assembly is predictable, or inherently unpredictable. We address this issue using a well-controlled laboratory model system, in which source microbial communities colonize a pristine environment to form complex, nutrient-cycling ecosystems. When the source communities colonize a novel environment, final community composition and function (as measured by redox potential) are unpredictable, although a signature of the community's previous history is maintained. However, when the source communities are pre-conditioned to their new habitat, community development is more reproducible. This situation contrasts with some studies of communities of macro-organisms, where strong selection under novel environmental conditions leads to reproducible community structure, whereas communities under weaker selection show more variability. Our results suggest that the microbial rare biosphere may have an important role in the predictability of microbial community development, and that pre-conditioning may help to reduce unpredictability in the design of microbial communities for biotechnological applications. PMID:23985743

  4. Does bilingual experience affect early visual perceptual development?

    PubMed Central

    Schonberg, Christina; Sandhofer, Catherine M.; Tsang, Tawny; Johnson, Scott P.

    2014-01-01

    Visual attention and perception develop rapidly during the first few months after birth, and these behaviors are critical components in the development of language and cognitive abilities. Here we ask how early bilingual experiences might lead to differences in visual attention and perception. Experiments 1–3 investigated the looking behavior of monolingual and bilingual infants when presented with social (Experiment 1), mixed (Experiment 2), or non-social (Experiment 3) stimuli. In each of these experiments, infants' dwell times (DT) and number of fixations to areas of interest (AOIs) were analyzed, giving a sense of where the infants looked. To examine how the infants looked at the stimuli in a more global sense, Experiment 4 combined and analyzed the saccade data collected in Experiments 1–3. There were no significant differences between monolingual and bilingual infants' DTs, AOI fixations, or saccade characteristics (specifically, frequency, and amplitude) in any of the experiments. These results suggest that monolingual and bilingual infants process their visual environments similarly, supporting the idea that the substantial cognitive differences between monolinguals and bilinguals in early childhood are more related to active vocabulary production than perception of the environment. PMID:25566116

  5. Does Vitamin C Deficiency Affect Cognitive Development and Function?

    PubMed Central

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(−/−) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies. PMID:25244370

  6. Nuclear positioning in muscle development and disease

    PubMed Central

    Folker, Eric S.; Baylies, Mary K.

    2013-01-01

    Muscle disease as a group is characterized by muscle weakness, muscle loss, and impaired muscle function. Although the phenotype is the same, the underlying cellular pathologies, and the molecular causes of these pathologies, are diverse. One common feature of many muscle disorders is the mispositioning of myonuclei. In unaffected individuals, myonuclei are spaced throughout the periphery of the muscle fiber such that the distance between nuclei is maximized. However, in diseased muscles, the nuclei are often clustered within the center of the muscle cell. Although this phenotype has been acknowledged for several decades, it is often ignored as a contributor to muscle weakness. Rather, these nuclei are taken only as a sign of muscle repair. Here we review the evidence that mispositioned myonuclei are not merely a symptom of muscle disease but also a cause. Additionally, we review the working models for how myonuclei move from two different perspectives: from that of the nuclei and from that of the cytoskeleton. We further compare and contrast these mechanisms with the mechanisms of nuclear movement in other cell types both to draw general themes for nuclear movement and to identify muscle-specific considerations. Finally, we focus on factors that can be linked to muscle disease and find that genes that regulate myonuclear movement and positioning have been linked to muscular dystrophy. Although the cause-effect relationship is largely speculative, recent data indicate that the position of nuclei should no longer be considered only a means to diagnose muscle disease. PMID:24376424

  7. Epigenetics of osteoarticular diseases: recent developments.

    PubMed

    Roberts, S B; Wootton, E; De Ferrari, L; Albagha, O M; Salter, D M

    2015-08-01

    A variety of osteoarticular conditions possess an underlying genetic aetiology. Large-scale genome-wide association studies have identified several genetic loci associated with osteoarticular conditions, but were unable to fully account for their estimated heritability. Epigenetic modifications including DNA methylation, histone modification, nucleosome positioning, and microRNA expression may help account for this incomplete heritability. This articles reviews insights from epigenetic studies in osteoarticular diseases, focusing on osteoarthritis, but also examines recent advances in rheumatoid arthritis, osteoporosis, systemic lupus erythematosus (SLE), ankylosing spondylitis, and sarcoma. Genome-wide methylation studies are permitting identification of novel candidate genes and molecular pathways, and the pathogenic mechanisms with altered methylation status are beginning to be elucidated. These findings are gradually translating into improved understanding of disease pathogenesis and clinical applications. Functional studies in osteoarthritis, rheumatoid arthritis, and SLE are now identifying downstream molecular alterations that may confer disease susceptibility. Epigenetic markers are being validated as prognostic and therapeutic disease biomarkers in sarcoma, and clinical trials of hypomethylating agents as treatments for sarcoma are being conducted. In concert with advances in throughput and cost-efficiency of available technologies, future epigenetic research will enable greater characterisation and treatment for both common and rare osteoarticular diseases. PMID:25812537

  8. 48 CFR 335.071 - Special determinations and findings affecting research and development contracting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... findings affecting research and development contracting. 335.071 Section 335.071 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 335.071 Special determinations and findings affecting research and development contracting....

  9. Recombination affects accumulation of damaging and disease-associated mutations in human populations.

    PubMed

    Hussin, Julie G; Hodgkinson, Alan; Idaghdour, Youssef; Grenier, Jean-Christophe; Goulet, Jean-Philippe; Gbeha, Elias; Hip-Ki, Elodie; Awadalla, Philip

    2015-04-01

    Many decades of theory have demonstrated that, in non-recombining systems, slightly deleterious mutations accumulate non-reversibly, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion; however, it is not clear the extent to which damaging mutations accumulate along chromosomes with highly variable rates of crossing over. Using high-coverage sequencing data from over 1,400 individuals in the 1000 Genomes and CARTaGENE projects, we show that recombination rate modulates the distribution of putatively deleterious variants across the entire human genome. Exons in regions of low recombination are significantly enriched for deleterious and disease-associated variants, a signature varying in strength across worldwide human populations with different demographic histories. Regions with low recombination rates are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effects on health, a phenomenon likely affecting disease susceptibility in humans. PMID:25685891

  10. Surgical infrainguinal revascularization for peripheral arterial disease: factors affecting patency rate

    PubMed Central

    Jafarian, Ali; Elyasinia, Fezzeh; Keramati, Mohammad Reza; Ahmadi, Farham; Parsaei, Reza

    2015-01-01

    Background: Peripheral arterial disease is a source of morbidity and mortality. Surgical vascular reconstruction is a treatment option but probability of failure and complications are important concerns. In this study, we evaluated outcome of surgical infrainguinal reconstruction and factors affecting graft patency for a period of one year. Methods: In this cohort study, 85 consecutive patients with chronic ischemia who underwent lower extremity surgical vascular reconstruction (including 52 femoropopliteal and 25 femorofemoral bypass) from March 2007 to Feb 2009 were recruited. Graft patency was evaluated before discharge from hospital and one year after the surgical operation using duplex ultrasonography. Association between possible risk factors and graft patency were evaluated. Results: In general, 71% (37 patients) of femoropopliteal and 52% (13 patients) of femorofemoral reconstructions were patent during the follow up period. Diabetes mellitus, hypertension, smoking, opium use and ischemic heart disease were significantly associated with decreased rate of patency (p<0.05). Conclusion: Assessing risk factors that predict perioperative mortality and graft patency is essential for selecting patients that would benefit from surgery. Omitting surgical reconstruction and endovascular intervention may be preferable especially when multiple risk factors are present or in the absence of critical limb ischemia. PMID:26793669

  11. Development of a Comprehensive Heart Disease Knowledge Questionnaire

    ERIC Educational Resources Information Center

    Bergman, Hannah E.; Reeve, Bryce B.; Moser, Richard P.; Scholl, Sarah; Klein, William M. P.

    2011-01-01

    Background: Heart disease is the number one killer of both men and women in the United States, yet a comprehensive and evidence-based heart disease knowledge assessment is currently not available. Purpose: This paper describes the two-phase development of a novel heart disease knowledge questionnaire. Methods: After review and critique of the…

  12. Psychological Perspectives on the Development of Coronary Heart Disease

    ERIC Educational Resources Information Center

    Matthews, Karen A.

    2005-01-01

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

  13. Development of the Motor Neuron Disease Carer Questionnaire.

    PubMed

    Mockford, Carole; Jenkinson, Crispin; Fitzpatrick, Raymond

    2009-01-01

    Our objective was to develop a validated questionnaire that can measure the extent to which dimensions of caring affect the health of carers of patients with motor neuron disease. An initial 190-item questionnaire was developed from in-depth interviews, focus groups and two pilot studies with carers. Factor analysis was applied to the data obtained from a large survey in the UK that identified the underlying dimensions of caring. The newly formed scales were tested for reliability using Cronbach's alpha, and for construct validity. The SF36-v2 was the benchmark instrument on which correlations were made to ascertain the relationship with carers' health. A 34-item instrument was developed which has demonstrated promising evidence of internal reliability and validity for six scales: emotional well-being, physical well-being, self care, disturbed sleep, carers' support needs and statutory services. High correlations were found with the Mental Component Score summary scale of the SF-36v2 (0.40-0.66). The development and testing of the MNDCQ indicates that as the carers' score on the MNDCQ increases, suggesting a higher level of burden, they are more likely to report poor health. Further longitudinal studies are needed to further test the instruments' ability to detect change over time. PMID:19922141

  14. The retromer complex in development and disease

    PubMed Central

    Wang, Shiuan; Bellen, Hugo J.

    2015-01-01

    The retromer complex is a multimeric protein complex involved in recycling proteins from endosomes to the trans-Golgi network or plasma membrane. It thus regulates the abundance and subcellular distribution of its cargo within cells. Studies using model organisms show that the retromer complex is involved in specific developmental processes. Moreover, a number of recent studies implicate aberrant retromer function in photoreceptor degeneration, Alzheimer's disease and Parkinson's disease. Here, and in the accompanying poster, we provide an overview of the molecular and cellular mechanisms of retromer-mediated protein trafficking, highlighting key examples of retromer function in vivo. PMID:26199408

  15. Induced Autoimmunity against Gonadal Proteins Affects Gonadal Development in Juvenile Zebrafish

    PubMed Central

    Presslauer, Christopher; Nagasawa, Kazue; Dahle, Dalia; Babiak, Joanna; Fernandes, Jorge M. O.; Babiak, Igor

    2014-01-01

    A method to mitigate or possibly eliminate reproduction in farmed fish is highly demanded. The existing approaches have certain applicative limitations. So far, no immunization strategies affecting gonadal development in juvenile animals have been developed. We hypothesized that autoimmune mechanisms, occurring spontaneously in a number of diseases, could be induced by targeted immunization. We have asked whether the immunization against specific targets in a juvenile zebrafish gonad will produce an autoimmune response, and, consequently, disturbance in gonadal development. Gonadal soma-derived factor (Gsdf), growth differentiation factor (Gdf9), and lymphocyte antigen 75 (Cd205/Ly75), all essential for early gonad development, were targeted with 5 immunization tests. Zebrafish (n = 329) were injected at 6 weeks post fertilization, a booster injection was applied 15 days later, and fish were sampled at 30 days. We localized transcripts encoding targeted proteins by in situ hybridization, quantified expression of immune-, apoptosis-, and gonad-related genes with quantitative real-time PCR, and performed gonadal histology and whole-mount immunohistochemistry for Bcl2-interacting-killer (Bik) pro-apoptotic protein. The treatments resulted in an autoimmune reaction, gonad developmental retardation, intensive apoptosis, cell atresia, and disturbed transcript production. Testes were remarkably underdeveloped after anti-Gsdf treatments. Anti-Gdf9 treatments promoted apoptosis in testes and abnormal development of ovaries. Anti-Cd205 treatment stimulated a strong immune response in both sexes, resulting in oocyte atresia and strong apoptosis in supporting somatic cells. The effect of immunization was FSH-independent. Furthermore, immunization against germ cell proteins disturbed somatic supporting cell development. This is the first report to demonstrate that targeted autoimmunity can disturb gonadal development in a juvenile fish. It shows a straightforward potential

  16. How human practices have affected vector-borne diseases in the past: a study of malaria transmission in Alpine valleys

    PubMed Central

    Sérandour, Julien; Girel, Jacky; Boyer, Sebastien; Ravanel, Patrick; Lemperière, Guy; Raveton, Muriel

    2007-01-01

    Background Malaria was endemic in the Rhône-Alpes area of eastern France in the 19th century and life expectancy was particularly shortened in Alpine valleys. This study was designed to determine how the disease affected people in the area and to identify the factors influencing malaria transmission. Methods Demographic data of the 19th century were collected from death registers of eight villages of the flood-plain of the river Isère. Correlations were performed between these demographic data and reconstructed meteorological data. Archive documents from medical practitioners gave information on symptoms of ill people. Engineer reports provided information on the hydraulic project developments in the Isère valley. Results Description of fevers was highly suggestive of endemic malaria transmission in the parishes neighbouring the river Isère. The current status of anopheline mosquitoes in the area supports this hypothesis. Mean temperature and precipitation were poorly correlated with demographic data, whereas the chronology of hydrological events correlated with fluctuations in death rates in the parishes. Conclusion Nowadays, most of the river development projects involve the creation of wet areas, enabling controlled flooding events. Flood-flow risk and the re-emergence of vector-borne diseases would probably be influenced by the climate change. The message is not to forget that human disturbance of any functioning hydrosystem has often been linked to malaria transmission in the past. PMID:17727700

  17. Foot-and-mouth disease in the Americas: epidemiology and ecologic changes affecting distribution.

    PubMed

    Saraiva, Victor

    2004-10-01

    Foot-and-mouth disease(FMD) was first recorded in South America (SA) circa 1870, in Buenos Aires, Argentina, in Uruguay, and in southern Brazil as a result of the introduction of cattle from Europe during the early days of colonization. Livestock production to trade with neighboring countries was established in the La Plata Region, and the trade of livestock and products with Chile, northeastern and central western states of Brazil, to Peru, Bolivia, and Paraguay spread FMD, which reached Venezuela and Colombia in the 1950s and finally Ecuador in 1961. The traditional forms of livestock husbandry influence the diffusion and maintenance of the FMD virus (FMDV) in different areas. Cattle production in SA depends mainly on a strong relation between cattle-calf operations and fattening operations in a complementary cycle, revealing the vulnerability and susceptibility of these areas to FMDV. Understanding the relationship between time-space behavior of the disease and the forms of production defines the FMD ecosystems, a key concept to elaborating the control/eradication strategies of national FMD eradication programs, which must be modified when trade opportunities between zones of differing sanitary status change. The role of other susceptible species besides bovines, including wildlife, in maintaining and spreading FMDV has been the subject of several studies, but in SA, bovines are so far considered to determine disease presentation. Buffalo (Bubalus bubalis) have been implicated in the spread of the disease between farms in at least one case in Brazil. Sheep are almost on a par with bovine in terms of number, especially in the Southern Cone, but their role in the maintenance of infection is not considered important, possibly owing to rearing practices. Camelid populations in the Andean region do not play an important role in the maintenance of FMD, because of short persistence of infection and low population densities in these species. The importance of wildlife

  18. Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome.

    PubMed

    Braga-Neto, Pedro; Pedroso, José Luiz; Gadelha, Ary; Laureano, Maura Regina; de Souza Noto, Cristiano; Garrido, Griselda Jara; Barsottini, Orlando Graziani Povoas

    2016-08-01

    Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale-Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p < 0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical-cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome. PMID:26298474

  19. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice.

    PubMed

    Hu, Youjia; Jin, Ping; Peng, Jian; Zhang, Xiaojun; Wong, F Susan; Wen, Li

    2016-08-01

    Environmental factors clearly influence the pathogenesis of Type 1 diabetes, an autoimmune disease. We have studied gut microbiota as important environmental agents that could affect the initiation or progression of type 1 diabetes especially in the prenatal period. We used neomycin, targeting mainly Gram negative or vancomycin, targeting mainly Gram positive bacteria, to treat pregnant NOD mothers and to study autoimmune diabetes development in their offspring. Neomycin-treated offspring were protected from diabetes, while vancomycin-treated offspring had accelerated diabetes development, and both antibiotics caused distinctly different shifts in gut microbiota composition compared with the offspring from untreated control mice. Our study demonstrated that neomycin treatment of pregnant mothers leads to generation of immune-tolerogenic antigen-presenting cells (APCs) in the offspring and these APCs had reduced specific autoantigen-presenting function both in vitro and in vivo. Moreover, the protection from diabetes mediated by tolerogenic APCs was vertically transmissible to the second generation. In contrast, more diabetogenic inflammatory T cells were found in the lymphoid organs of the offspring from the vancomycin-treated pregnant mothers. This change however was not transmitted to the second generation. Our results suggested that prenatal exposure to antibiotic influenced gut bacterial composition at the earliest time point in life and is critical for consequent education of the immune system. As different bacteria can induce different immune responses, understanding these differences and how to generate self-tolerogenic APCs could be important for developing new therapy for type 1 diabetes. PMID:27178773

  20. Current Status of Celiac Disease Drug Development.

    PubMed

    Wungjiranirun, Manida; Kelly, Ciaran P; Leffler, Daniel A

    2016-06-01

    Celiac disease (CeD) is one of the most common immune-mediated diseases. Symptoms and disease activity are incompletely controlled by the gluten-free diet, which is currently the only available therapy. Although no therapies are yet approved, there is a growing field of candidates and an improving understanding of the regulatory pathway. In this review, we briefly discuss the epidemiology, pathophysiology, and current treatment paradigm for CeD. We also review the major classes of therapies being considered for CeD and discuss extensively what is known and can be surmised regarding the regulatory pathway for approval of a CeD therapeutic. The coming years will see an increasing number and diversity of potential therapies entering clinical trials and hopefully the first approved agents targeting this significant unmet medical need. Although biomarkers including histology and serology will always be important in therapeutic clinical trials, they currently lack the necessary evidence linking them to improved patient outcomes required for use as primary outcomes for drug approval. For this reason, patient-reported outcomes will likely be primary end points in Phase III CeD trials for the foreseeable future. PMID:27021196

  1. [Factors influencing development and progression of alcoholic liver disease].

    PubMed

    Abdelrahman, K; Marot, A; Deltenre, P

    2015-09-01

    Only a minority ot excessive drinkers develop cirrhosis. The main cofactors implicated in the pathophysiology of alcoholic liver disease are obesity, diabetes or the metabolic syndrome. Several genetic polymorphisms have been associated with a higher risk of alcoholic cirrhosis. Recent data indicate that gut microbiota could play a role in the pathogenesis of alcoholic liver disease. The aim of this review is to summarize the factors that influence development and progression of alcoholic liver disease. PMID:26502621

  2. Development and Validation of Children's Environmental Affect (Attitude, Sensitivity and Willingness to Take Action) Scale

    ERIC Educational Resources Information Center

    Erdogan, Mehmet; Marcinkowski, Thomas

    2015-01-01

    This study focuses on the design, development, validation, and psychometric properties of the Children's Environmental Affect Scale (CEAS). The following steps were taken in developing the CEAS. A substantial review of literature on environmental affect and EL helped the researchers identify several scales and questionnaires that, in turn, help…

  3. Cell position during larval development affects postdiapause development in Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Yocum, George D; Rinehart, Joseph P; Kemp, William P

    2014-08-01

    Megachile rotundata (F.) (Hymenoptera: Megachilidae) is the primary pollinator of alfalfa in the northwestern United States and western Canada and provides pollination services for onion, carrot, hybrid canola, various legumes, and other specialty crops. M. rotundata females are gregarious, nest in cavities either naturally occurring or in artificial nesting blocks, where they construct a linear series of brood cells. Because of the physical layout of the nest, the age of the larvae within the nest and the microenvironment the individual larvae experience will vary. These interacting factors along with other maternal inputs affect the resulting phenotypes of the nest mates. To further our understanding of in-nest physiology, gender and developmental rates were examined in relationship to cell position within the nest. Eighty-two percent of the females were located within the first three cells, those furthest from the nest entrance. For those individuals developing in cells located in the deepest half of the nest, the sex of the previous bee had a significant effect on the female decision of the gender of the following nest mate. Removing the prepupae from the nest and rearing them under identical conditions demonstrated that position within the nest during larval development had a significant effect on the postdiapause developmental rates, with males whose larval development occurred deeper in the nest developing more slowly than those toward the entrance. No positional effect on postdiapause developmental rates was noted for the females. The cell position effect on male postdiapause developmental rate demonstrates that postdiapause development is not a rigid physiological mechanism uniform in all individuals, but is a dynamic plastic process shaped by past environmental conditions. PMID:24914676

  4. Factors Affecting Hemodialysis Adequacy in Cohort of Iranian Patient with End Stage Renal Disease

    PubMed Central

    Shahdadi, Hosein; Balouchi, Abbas; Sepehri, Zahra; Rafiemanesh, Hosein; Magbri, Awad; Keikhaie, Fereshteh; Shahakzehi, Ahmad; Sarjou, Azizullah Arbabi

    2016-01-01

    Background: There are many factors that can affect dialysis adequacy; such as the type of vascular access, filter type, device used, and the dose, and rout of erythropoietin stimulation agents (ESA) used. The aim of this study was investigating factors affecting Hemodialysis adequacy in cohort of Iranian patient with end stage renal disease (ESRD). Methods: This is a cross-sectional study conducted on 133 Hemodialysis patients referred to two dialysis units in Sistan-Baluchistan province in the cities of Zabol and Iranshahr, Iran. We have looked at, (the effects of the type of vascular access, the filter type, the device used, and the dose, route of delivery, and the type of ESA used) on Hemodialysis adequacy. Dialysis adequacy was calculated using kt/v formula, two-part information questionnaire including demographic data which also including access type, filter type, device used for hemodialysis (HD), type of Eprex injection, route of administration, blood groups and hemoglobin response to ESA were utilized. The data was analyzed using the SPSS v16 statistical software. Descriptive statistical methods, Mann-Whitney statistical test, and multiple regressions were used when applicable. Results: The range of calculated dialysis adequacy is 0.28 to 2.39 (units of adequacy of dialysis). 76.7% of patients are being dialyzed via AVF and 23.3% of patients used central venous catheters (CVC). There was no statistical significant difference between dialysis adequacy, vascular access type, device used for HD (Fresenius and B. Braun), and the filter used for HD (p> 0.05). However, a significant difference was observed between the adequacy of dialysis and Eprex injection and patients’ time of dialysis (p <0.05). Conclusion: Subcutaneous ESA (Eprex) injection and dialysis shift (being dialyzed in the morning) can have positive impact on dialysis adequacy. Patients should be educated on the facts that the type of device used for HD and the vascular access used has no

  5. The Equine Neonatal Central Nervous System: Development and Diseases.

    PubMed

    Tennent-Brown, Brett S; Morrice, Ashleigh V; Reed, Stephen

    2015-12-01

    Neonatal encephalopathy is the most common neurologic condition affecting newborn foals and shares similarities with perinatal asphyxia syndrome of human infants. In many cases of neonatal encephalopathy there is no obvious episode of acute or chronic hypoxia and other mechanisms likely play a role in the pathogenesis. Increased concentrations of neuroactive progestagens are found in affected foals; whether these molecules are protective, as has been suggested, or play a role in the pathogenesis is unknown. Neurologic diseases other than neonatal encephalopathy affect foals occasionally and should be considered when evaluating sick foals with clinical signs of neurologic dysfunction. PMID:26612749

  6. MST kinases in development and disease

    PubMed Central

    2015-01-01

    The mammalian MST kinase family, which is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1). MST kinases are emerging as key signaling molecules that influence cell proliferation, organ size, cell migration, and cell polarity. Here we review the regulation and function of these kinases in normal physiology and pathologies, including cancer, endothelial malformations, and autoimmune disease. PMID:26370497

  7. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.

    PubMed

    Kishnani, Priya S; Goldenberg, Paula C; DeArmey, Stephanie L; Heller, James; Benjamin, Danny; Young, Sarah; Bali, Deeksha; Smith, Sue Ann; Li, Jennifer S; Mandel, Hanna; Koeberl, Dwight; Rosenberg, Amy; Chen, Y-T

    2010-01-01

    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients. We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA. Patients were from the clinical setting and from clinical trials of rhGAA, were 6 months of age, were not invasively ventilated, and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks. Outcome measures included survival, invasive ventilator-free survival, cardiac status, gross motor development, development of antibodies to rhGAA, and levels of urinary Glc(4). Following 52 weeks of treatment, 6/11 (54.5%) CRIM-negative and 1/21 (4.8%) CRIM-positive patients were deceased or invasively ventilated (p<0.0001). By age 27.1 months, all CRIM-negative patients and 4/21 (19.0%) CRIM-positive patients were deceased or invasively ventilated. Cardiac function and gross motor development improved significantly more in the CRIM-positive group. IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group. CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA. The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein. PMID:19775921

  8. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants

    PubMed Central

    Kishnani, Priya S.; Goldenberg, Paula C.; DeArmey, Stephanie L.; Heller, James; Benjamin, Danny; Young, Sarah; Bali, Deeksha; Smith, Sue Ann; Li, Jennifer S.; Mandel, Hanna; Koeberl, Dwight; Rosenberg, Amy; Chen, Y-T

    2013-01-01

    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients. We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA. Patients were from the clinical setting and from clinical trials of rhGAA, were ≤6 months of age, were not invasively ventilated, and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks. Outcome measures included survival, invasive ventilator-free survival, cardiac status, gross motor development, development of antibodies to rhGAA, and levels of urinary Glc4. Following 52 weeks of treatment, 6/11 (54.5%) CRIM-negative and 1/21 (4.8%) CRIM-positive patients were deceased or invasively ventilated (p < 0.0001). By age 27.1 months, all CRIM-negative patients and 4/21 (19.0%) CRIM-positive patients were deceased or invasively ventilated. Cardiac function and gross motor development improved significantly more in the CRIM-positive group. IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group. CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA. The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein. PMID:19775921

  9. Disease Management: What Is It? Why Is It Necessary? How Will It Affect Me?

    ERIC Educational Resources Information Center

    Seifer, Frederic D.

    2008-01-01

    How does one "manage" a disease? For most patients, it feels like the disease manages them. It effects how a person feels, their energy level, healthcare expenditures, doctor appointments, longevity and, ultimately, the individual's quality of life. However, disease management turns the tables on disease and puts patients and their physicians in…

  10. Factors affecting regional pulmonary blood flow in chronic ischemic heart disease

    SciTech Connect

    Pistolesi, M.; Miniati, M.; Bonsignore, M.; Andreotti, F.; Di Ricco, G.; Marini, C.; Rindi, M.; Biagini, A.; Milne, E.N.; Giuntini, C.

    1988-07-01

    To assess the effect of left heart disease on pulmonary blood flow distribution, we measured mean pulmonary arterial and wedge pressures, cardiac output, pulmonary vascular resistance, pulmonary blood volume, and arterial oxygen tension before and after treatment in 13 patients with longstanding ischemic heart failure and pulmonary edema. Pulmonary edema was evaluated by a radiographic score, and regional lung perfusion was quantified on a lung scan by the upper to lower third ratio (U:L ratio) of pulmonary blood flow per unit of lung volume. In all cases, redistribution of lung perfusion toward the apical regions was observed; this pattern was not affected by treatment. After treatment, pulmonary vascular pressures, resistance, and edema were reduced, while pulmonary blood volume did not change. At this time, pulmonary vascular resistance showed a positive correlation with the U:L ratio (r = 0.78; P less than 0.01), whereas no correlation was observed between U:L ratio and wedge pressure, pulmonary edema, or arterial oxygen tension. Hence, redistribution of pulmonary blood flow, in these patients, reflects chronic structural vascular changes prevailing in the dependent lung regions.

  11. Gait kinematics and kinetics are affected more by peripheral arterial disease than age

    PubMed Central

    Myers, Sara A.; Applequist, Bryon C.; Huisinga, Jessie M.; Pipinos, Iraklis I.; Johanning, Jason M.

    2016-01-01

    Peripheral arterial disease (PAD) produces abnormal gait and disproportionately affects older individuals. The current study investigated PAD gait biomechanics in young and older subjects. Sixty-one (31 < 65 years, age: 57.4 ± 5.3 years and 30 ≥ 65 years; age: 72.2 ± 5.4 years) patients with PAD and 52 healthy age matched controls were included. Patients with PAD were tested during pain free walking and compared to matched healthy controls. Joint kinematics and kinetics (torques) were compared using a 2 × 2 ANOVA (Groups: PAD vs. Control, Age: Younger vs. Older). Patients with PAD had significantly increased ankle and decreased hip range of motion during the stance phase as well as decreased ankle dorsiflexor torque compared to controls. Gait changes in older individuals are largely constrained to time-distance parameters. Joint kinematics and kinetics are significantly altered in patients with PAD during pain free ambulation. Symptomatic PAD produces a consistent ambulatory deficit across ages definable by advanced biomechanical analysis. The most important finding of the current study is that gait, in the absence of PAD and other ambulatory comorbidities, does not decline significantly with age based on advanced biomechanical analysis. Therefore, previous studies must be examined in the context of potential PAD patients being present in the population and future ambulatory studies must include PAD as a confounding factor when assessing the gait function of elderly individuals. PMID:27149635

  12. von Willebrand Factor Propeptide: A Potential Disease Biomarker Not Affected by ABO Blood Groups

    PubMed Central

    Marianor, Mahat; Zaidah, Abdullah Wan; Maraina, CH Che

    2015-01-01

    Epidemiological studies have shown that vascular-related disorders are associated with high von Willebrand factor antigen (VWF:Ag) and VWF propeptide (VWFpp). VWFpp is secreted together with VWF:Ag upon endothelial cell activation, hence it could be a potential biomarker. This study was conducted to compare between VWF:Ag and VWFpp levels among 30 healthy individuals and 42 patients with high levels of VWF:Ag in different medical conditions and ABO blood groups. VWFpp levels were strongly correlated with VWF:Ag. VWF:Ag and VWFpp levels were significantly increased in patients compared to healthy individuals. VWFpp is not affected by ABO blood group in both healthy individual and patient groups unlike VWF:Ag. As expected, this study showed that VWFpp levels increased in parallel with VWF:Ag levels in patients with diseases associated with endothelial activation. VWFpp though nonspecific is a potential biomarker reflecting underlying pathophysiological changes in various medical conditions with an additional advantage of not being influenced by ABO blood groups. PMID:26339184

  13. Developmental diseases and the hypothetical Master Development Program.

    PubMed

    Parris, George E

    2010-03-01

    Small deletions and duplications frequently occur in the pericentromeric region of chromosomes and many of these are associated with developmental abnormalities. These developmental syndromes are conventionally attributed to abnormal expression of protein-coding genes in the affected region. A hypothesis has recently been published concerning a Master Development Program based on noncoding transcripts from these regions (Parris GE. A hypothetical Master Development Program for multi-cellular organisms: Ontogeny and phylogeny. Biosci Hypotheses 2009;2:3-12.). This paper summarizes and expands the recently published hypothesis to include it application to developmental diseases. The author proposes that development of multi-cellular organisms is guided by a Master Development Program (MDP) located primarily in the pericentromeric heterochromatin. The MDP is believed to consist of a series of Generation-Specific Control Keys (GSCK) transcribed in sequence by Ikaros family transcription factors unless the GSCKs are suppressed by Sall1-family or Dnmt3b-family proteins. The MDP is proposed to increment with each cell cycle to the next GSCK resulting in development of the clone. A clone may be programmed to split into two clones as necessary through a two-cycle mitosis processes. The transcripts of the GSCKs presumably yield noncoding nuclear messenger RNAs (nmRNAs, 8-30 nt units) that act directly (e.g., as primers for RNA polymerase II) and indirectly to regulate HOX and other high-level transcription factor and developmental genes. As envisioned, the MDP would evolve by terminal addition of new GSCKs. The new GSCKs are produced by evolutionary consolidation of retro-transcripts into pyknons that collect and evolve at the end of the pericentromeric heterochromatin and are eventually incorporated into the MDP. The retro-transcripts are though to be produced during episodic retrovirus epidemics and account for punctuated equilibrium in species evolution. PMID:19833446

  14. Development and Application of Chronic Disease Risk Prediction Models

    PubMed Central

    Oh, Sun Min; Stefani, Katherine M.

    2014-01-01

    Currently, non-communicable chronic diseases are a major cause of morbidity and mortality worldwide, and a large proportion of chronic diseases are preventable through risk factor management. However, the prevention efficacy at the individual level is not yet satisfactory. Chronic disease prediction models have been developed to assist physicians and individuals in clinical decision-making. A chronic disease prediction model assesses multiple risk factors together and estimates an absolute disease risk for the individual. Accurate prediction of an individual's future risk for a certain disease enables the comparison of benefits and risks of treatment, the costs of alternative prevention strategies, and selection of the most efficient strategy for the individual. A large number of chronic disease prediction models, especially targeting cardiovascular diseases and cancers, have been suggested, and some of them have been adopted in the clinical practice guidelines and recommendations of many countries. Although few chronic disease prediction tools have been suggested in the Korean population, their clinical utility is not as high as expected. This article reviews methodologies that are commonly used for developing and evaluating a chronic disease prediction model and discusses the current status of chronic disease prediction in Korea. PMID:24954311

  15. Chemicals and environmentally caused diseases in developing countries

    SciTech Connect

    Jamall, I.S.; Davis, B. )

    1991-06-01

    This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of developing countries, the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries. 52 references.

  16. [Views for research development of control of parasitic diseases].

    PubMed

    Zhao, Qin-Ping; Dong, Hui-Fen; Jiang, Ming-Sen

    2013-12-01

    With the social and technological development, new understandings have been emerged for the research development of the control of parasitic diseases. The present review argues that: the traditional point of view for the control of parasitic diseases, eliminating parasites/media, should be updated. For the long-term interests of science and human perspective, biological diversity, including the parasite biodiversity, and ecological environment should be paid much more attention during the control of parasitic diseases. The leading role of society, economy and culture should be fully developed in the control of parasitic diseases with the progress of scientific and technology, to find a final way of sustainable development in the control of parasitic diseases. PMID:24490386

  17. Somatic development disorders of children with non specific inflammatory bowel diseases.

    PubMed

    Pawłowska, Katarzyna; Iwańczak, Barbara

    2014-01-01

    Frequency of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) tends to increase in developing countries. Nearly 25% of cases affects pediatric patients. Inflammatory bowel diseases are often associated with weight loss and stunting in children. Moreover, weight and height deficiencies are often early symptoms. Initially, nonspecific or latent course of disease delays the diagnostic process. Malnutrition in inflammatory bowel diseases can be caused by disorders of digestion and nutrients' absorption, intestinal loss, increased energy expenditure and appetite impairment. Nutritional deficiencies and inflammatory agents lead to disturbance of tissue metabolism - muscle and bone - and retardation of somatic development of affected children. Thus, deficiencies of muscle mass, bone mineral density and body height are observed. Insufficient normalization of somatic features may be the consequence of recurrent nature of disease and specificity of pharmacological treatment. Present work deals with the current state of knowledge concerning the somatic development disorders of children with inflammatory bowel diseases. Abnormal nutritional status, bone mineral density deficits and growth failure of patients have been discussed in the context of their relations and dependencies on inflammatory, nutritional and therapeutic factors. PMID:25182396

  18. Primary Cilia in Pancreatic Development and Disease

    PubMed Central

    Lodh, Sukanya; O’Hare, Elizabeth A.; Zaghloul, Norann A.

    2014-01-01

    Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with these structures results in perturbation of the development and function of a spectrum of tissue and cell types. Here, we review the role of cilia in mediating the development and function of the pancreas. We focus on ciliary regulation of major pathways involved in pancreatic development, including Shh, Wnt, TGF-β, Notch, and fibroblast growth factor. We also discuss pancreatic phenotypes associated with ciliary dysfunction, including pancreatic cysts and defects in glucose homeostasis, and explore the potential role of cilia in such defects. PMID:24864023

  19. A Drug-Centric View of Drug Development: How Drugs Spread from Disease to Disease

    PubMed Central

    Rodriguez-Esteban, Raul

    2016-01-01

    Drugs are often seen as ancillary to the purpose of fighting diseases. Here an alternative view is proposed in which they occupy a spearheading role. In this view, drugs are technologies with an inherent therapeutic potential. Once created, they can spread from disease to disease independently of the drug creator’s original intentions. Through the analysis of extensive literature and clinical trial records, it can be observed that successful drugs follow a life cycle in which they are studied at an increasing rate, and for the treatment of an increasing number of diseases, leading to clinical advancement. Such initial growth, following a power law on average, has a degree of momentum, but eventually decelerates, leading to stagnation and decay. A network model can describe the propagation of drugs from disease to disease in which diseases communicate with each other by receiving and sending drugs. Within this model, some diseases appear more prone to influence other diseases than be influenced, and vice versa. Diseases can also be organized into a drug-centric disease taxonomy based on the drugs that each adopts. This taxonomy reflects not only biological similarities across diseases, but also the level of differentiation of existing therapies. In sum, this study shows that drugs can become contagious technologies playing a driving role in the fight against disease. By better understanding such dynamics, pharmaceutical developers may be able to manage drug projects more effectively. PMID:27124390

  20. Peritoneal inclusion cysts in patients affected by Crohn's disease: magnetic resonance enterography findings in a case series.

    PubMed

    Mazziotti, Silvio; D'Angelo, Tommaso; Racchiusa, Sergio; Salamone, Ignazio; Blandino, Alfredo; Ascenti, Giorgio

    2016-01-01

    Peritoneal inclusion cystarises when fluid produced by ovary is trapped within peritoneal adhesions. In this article, we describe a case series of patients affected by Crohn's disease, undergoing to magnetic resonance enterography, in whom it was possible not only to monitor the pathological findings of small bowel but also to primarily diagnose the presence of peritoneal inclusion cysts. The current knowledge of peritoneal inclusion cyst concomitant to Crohn's disease is still limited, often leading radiologists to misdiagnose it. PMID:26456117

  1. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging.

    PubMed

    Sawiak, Stephen J; Perumal, Sunthara Rajan; Rudiger, Skye R; Matthews, Loren; Mitchell, Nadia L; McLaughlan, Clive J; Bawden, C Simon; Palmer, David N; Kuchel, Timothy; Morton, A Jennifer

    2015-01-01

    Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy. PMID:26161747

  2. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging

    PubMed Central

    Sawiak, Stephen J.; Perumal, Sunthara Rajan; Rudiger, Skye R.; Matthews, Loren; Mitchell, Nadia L.; McLaughlan, Clive J.; Bawden, C. Simon; Palmer, David N.; Kuchel, Timothy; Morton, A. Jennifer

    2015-01-01

    Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy. PMID:26161747

  3. El Portal Latino Alzheimer's Project: model program for Latino caregivers of Alzheimer's disease-affected people.

    PubMed

    Aranda, Maria P; Villa, Valentine M; Trejo, Laura; Ramírez, Rosa; Ranney, Martha

    2003-04-01

    The article describes the El Portal Latino Alzheimer's Project--a dementia-specific outreach and services program targeting Latino caregivers in the Los Angeles County area. The project is an example of an interorganizational community-based collaborative developed to provide an array of coordinated, ethnic-sensitive services to Latino dementia-affected adults and their family caregivers, using culturally specific outreach and services delivery strategies. Results of an evaluation of service utilization indicate a reduction in barriers to care and an increase in services utilization. Los Angeles County provides a natural urban laboratory to study the special needs and circumstances of older Latinos dealing with chronic and debilitating illnesses. Implications for social work practice are discussed. PMID:12718421

  4. Expression in cultured human neuroblastoma cells of epitopes associated with affected neurons in Alzheimer's disease.

    PubMed Central

    Ko, L. W.; Sheu, K. F.; Young, O.; Thaler, H.; Blass, J. P.

    1990-01-01

    Of three human neuroblastoma lines tested, IMR32K (and IMR32 parental line) was the only cell line that, after its exposure to a differentiation medium, consistently developed materials recognized immunocytochemically by a panel of antibodies against paired helical filaments (PHF). Ultrastructurally, these cells accumulated, at their perikarya and neuritic extensions, spatially discrete arrays of fibrils, which occasionally occurred in twisted pairs. When these fibrillar structures appeared as paired helices, they exhibited dimensions and configurations reminiscent of PHF found in affected Alzheimer neurons, although less compact. Immunoelectron microscope examinations of the fibrillar structures in these neuroblastoma cells with one of these anti-PHF immunoprobes revealed that only subsets of fibrillar structures that appeared thickened or aggregated to form bundles were selectively immunolabeled. Cultures of these immortal neuroblastoma lines may provide a convenient model for studying aspects of PHF formation that are hard to examine in Alzheimer brain obtained at autopsy. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1691594

  5. Systemic and renal lipids in kidney disease development and progression.

    PubMed

    Wahl, Patricia; Ducasa, Gloria Michelle; Fornoni, Alessia

    2016-03-15

    Altered lipid metabolism characterizes proteinuria and chronic kidney diseases. While it is thought that dyslipidemia is a consequence of kidney disease, a large body of clinical and experimental studies support that altered lipid metabolism may contribute to the pathogenesis and progression of kidney disease. In fact, accumulation of renal lipids has been observed in several conditions of genetic and nongenetic origins, linking local fat to the pathogenesis of kidney disease. Statins, which target cholesterol synthesis, have not been proven beneficial to slow the progression of chronic kidney disease. Therefore, other therapeutic strategies to reduce cholesterol accumulation in peripheral organs, such as the kidney, warrant further investigation. Recent advances in the understanding of the biology of high-density lipoprotein (HDL) have revealed that functional HDL, rather than total HDL per se, may protect from both cardiovascular and kidney diseases, strongly supporting a role for altered cholesterol efflux in the pathogenesis of kidney disease. Although the underlying pathophysiological mechanisms responsible for lipid-induced renal damage have yet to be uncovered, several studies suggest novel mechanisms by which cholesterol, free fatty acids, and sphingolipids may affect glomerular and tubular cell function. This review will focus on the clinical and experimental evidence supporting a causative role of lipids in the pathogenesis of proteinuria and kidney disease, with a primary focus on podocytes. PMID:26697982

  6. Effects of the therapist's nonverbal behavior on participation and affect of individuals with Alzheimer's disease during group music therapy sessions.

    PubMed

    Cevasco, Andrea M

    2010-01-01

    In healthcare settings, medical professionals' nonverbal behavior impacts patients' satisfaction and long-term physical, cognitive, and emotional well-being. The purpose of this research was to determine the effects of a music therapist's nonverbal behavior, affect and proximity, on participation and affect of 38 individuals with Alzheimer's disease and other related dementia (ADRD) during movement-to-music, singing, and instrument playing. Data indicated 62% of the individuals evinced positive affect when the therapist utilized affect and proximity combined, followed by the affect only condition (53%), proximity only condition (30%), and no affect or proximity condition (28%). A Friedman analysis indicated a significant difference in individuals' affect according to treatment conditions, chi(r)2 (3, 4) = 34.05, p = .001. Nonverbal behavior also impacted individuals' accuracy of participation, with participation at 79% for both affect and proximity combined, 75% for affect only, 71% for no affect or proximity, and 70% for proximity only. A significant difference occurred for participation by treatment conditions, F (3, 111) = 4.05, p = .009, eta2 = .10. Clinical implications are discussed. PMID:21275336

  7. Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

    PubMed Central

    Ferguson, Lynnette R; Huebner, Claudia; Petermann, Ivonne; Gearry, Richard B; Barclay, Murray L; Demmers, Pieter; McCulloch, Alan; Han, Dug Yeo

    2008-01-01

    AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn’s disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes. PMID:18698679

  8. Connexins in skeletal muscle development and disease.

    PubMed

    Merrifield, Peter A; Laird, Dale W

    2016-02-01

    Gap junctions consist of clusters of intercellular channels composed of connexins that connect adjacent cells and allow the exchange of small molecules. While the 21 member multi-gene family of connexins are ubiquitously found in humans, only Cx39, Cx40, Cx43 and Cx45 have been documented in developing myoblasts and injured adult skeletal muscle while healthy adult skeletal muscle is devoid of connexins. The use of gap junctional blockers and cultured myoblast cell lines have suggested that these connexins play a critical role in myotube formation and muscle regeneration. More recent genetically-modified mouse models where Cx43 function is greatly compromized or ablated have further supported a role for Cx43 in regulating skeletal muscle development. In the last decade, we have become aware of a cohort of patients that have a development disorder known as oculodentodigital dysplasia (ODDD). These patients harbor either gain or loss of Cx43 function gene mutations that result in many organ anomalies raising questions as to whether they suffer from defects in skeletal muscle formation or regeneration upon injury. Interesting, some ODDD patients report muscle weakness and loss of limb control but it is not clear if this is neurogenic or myogenic in origin. This review will focus on the role connexins play in muscle development and repair and discuss the impact of Cx43 mutants on muscle function. PMID:26688333

  9. Identification of viral and phytoplasmal agents responsible for diseases affecting plants of Gaillardia Foug. in Lithuania

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gaillardia plants exhibiting symptoms characteristic of viral and phytoplasmal diseases were collected at botanical gardens and floriculture farms in Lithuania. Cucumber mosaic virus was isolated from diseased plants exhibiting symptoms characterized stunting, color breaking and malformation of flo...

  10. Novel approaches to foot-and-mouth disease vaccine development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The need for better Foot-and-mouth disease (FMD) vaccines is not new, a report from the Research Commission on FMD, authored by F. Loeffler and P. Frosch in 1897, highlighted the need for developing a vaccine against FMD and qualified this as a devastating disease causing “severe economic damage to ...

  11. New developments in the pharmacotherapy of inflammatory bowel disease.

    PubMed

    Harting, J W

    1992-08-21

    In this article the clinical features and aetiology of inflammatory bowel diseases are described and current pharmacotherapeutic possibilities are explored. Also reviewed are recent developments and future prospects for the pharmacotherapy of inflammatory bowel diseases, including aminosalicylates, corticosteroids, immunosuppressants, lipoxygenase inhibitors, fish oil, sucralfate, bismuth compounds, free radical scavengers, (hydroxy)chloroquine, sodium cromoglycate and methotrexate. PMID:1437510

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  13. Does swimming exercise affect experimental chronic kidney disease in rats treated with gum acacia?

    PubMed

    Ali, Badreldin H; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A; Ramkumar, Aishwarya; Waly, Mostafa I; Yasin, Javid; Adham, Sirin A; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine-induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  14. Characterization of vascular lesions in pigs affected by porcine circovirus type 2-systemic disease.

    PubMed

    Resendes, A R; Segalés, J

    2015-05-01

    Vascular lesions and their association with porcine circovirus type 2 (PCV2) were evaluated in multiple organs from 10 pigs affected with PCV2-systemic disease (PCV2-SD). Animals had vascular lesions in multiple organs, consisting of lymphohistiocytic lymphangitis and/or phlebitis, mild to severe necrotizing arteritis, and thrombosis within splenic arterioles and choroid plexus capillaries. Variable amounts of PCV2 nucleic acid detected by in situ hybridization were present within endothelial cells, tunica media myocytes, and perivascular and/or intralesional inflammatory cell infiltrates. PCV2 nucleic acid was detected within endothelial cells of both lymphatic and blood vessels without lesions in the associated tissues. Necrotizing arteritis was principally present in lymph nodes and kidney and consisted of degeneration, necrosis, and pyknosis of myocytes, often with intracytoplasmic, brightly eosinophilic inclusion bodies that were strongly positive for PCV2 nucleic acid. Segmental or circumferential fibrinoid necrosis was mainly present in vessels of the lymph node, spleen, and choroid plexus and was variably associated with PCV2 nucleic acid. Severe lymphangitis associated with strong intralesional PCV2 labeling was frequently detected within the mesenteric and mediastinal lymph nodes and the lamina propria of the ileum. In most tissues, medium and large lymphatics and/or veins often had disruption of the intima and mild mononuclear inflammatory cell infiltration that was variably associated with PCV2 nucleic acid. The present study indicates that vasculitis is a frequent finding in natural cases of PCV2-SD and that PCV2 may have a direct cytopathic effect on tunica media myocytes of small- and medium-sized arteries as well as endothelium. PMID:24963088

  15. Prostate stem cell antigen interacts with nicotinic acetylcholine receptors and is affected in Alzheimer's disease.

    PubMed

    Jensen, Majbrit M; Arvaniti, Maria; Mikkelsen, Jens D; Michalski, Dominik; Pinborg, Lars H; Härtig, Wolfgang; Thomsen, Morten S

    2015-04-01

    Alzheimer's disease (AD) is a neurodegenerative disorder involving impaired cholinergic neurotransmission and dysregulation of nicotinic acetylcholine receptors (nAChRs). Ly-6/neurotoxin (Lynx) proteins have been shown to modulate cognition and neural plasticity by binding to nAChR subtypes and modulating their function. Hence, changes in nAChR regulatory proteins such as Lynx proteins could underlie the dysregulation of nAChRs in AD. Using Western blotting, we detected bands corresponding to the Lynx proteins prostate stem cell antigen (PSCA) and Lypd6 in human cortex indicating that both proteins are present in the human brain. We further showed that PSCA forms stable complexes with the α4 nAChR subunit and decreases nicotine-induced extracellular-signal regulated kinase phosphorylation in PC12 cells. In addition, we analyzed protein levels of PSCA and Lypd6 in postmortem tissue of medial frontal gyrus from AD patients and found significantly increased PSCA levels (approximately 70%). In contrast, no changes in Lypd6 levels were detected. In concordance with our findings in AD patients, PSCA levels were increased in the frontal cortex of triple transgenic mice with an AD-like pathology harboring human transgenes that cause both age-dependent β-amyloidosis and tauopathy, whereas Tg2576 mice, which display β-amyloidosis only, had unchanged PSCA levels compared to wild-type animals. These findings identify PSCA as a nAChR-binding protein in the human brain that is affected in AD, suggesting that PSCA-nAChR interactions may be involved in the cognitive dysfunction observed in AD. PMID:25680266

  16. Monoclonal antibody identification of subpopulations of cerebral cortical neurons affected in Alzheimer disease.

    PubMed Central

    Miller, C A; Rudnicka, M; Hinton, D R; Blanks, J C; Kozlowski, M

    1987-01-01

    Neuronal degeneration is one of the hallmarks of Alzheimer disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, we have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mABs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAB 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1, to the best of our knowledge, do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands on immunoblots of homogenates of normal and AD cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible. Images PMID:3120196

  17. Does Swimming Exercise Affect Experimental Chronic Kidney Disease in Rats Treated with Gum Acacia?

    PubMed Central

    Ali, Badreldin H.; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A.; Ramkumar, Aishwarya; Waly, Mostafa I.; Yasin, Javid; Adham, Sirin A.; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  18. The Development and Application of Affective Assessment in an Upper-Level Cell Biology Course

    ERIC Educational Resources Information Center

    Kitchen, Elizabeth; Reeve, Suzanne; Bell, John D.; Sudweeks, Richard R.; Bradshaw, William S.

    2007-01-01

    This study exemplifies how faculty members can develop instruments to assess affective responses of students to the specific features of the courses they teach. Means for assessing three types of affective responses are demonstrated: (a) student attitudes towards courses with differing instructional objectives and methodologies, (b) student…

  19. Affections in Learning Situations: A Study of an Entrepreneurship Skills Development Course

    ERIC Educational Resources Information Center

    Gondim, Sonia Maria Guedes; Mutti, Clara

    2011-01-01

    Purpose: This paper aims to present the results of a study whose general objective is to characterize the affective states experienced in response to different teaching activities used in a workshop for developing entrepreneurial skills. It seeks to answer the following question: how affections and experiential learning strategies interrelate in…

  20. Guava diseases in Hawaii and the characterization of Pestalotiopsis spp. affecting guava

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Guava (Psidium guajava L.), one of the most widely grown plants in the tropics, is very susceptible to disease which can decrease its marketability. Leaf and fruit spot diseases commonly occur on guava grown in Hawaii. A disease survey was conducted on more than 50 accessions grown at the USDA/ARS T...

  1. Pre-treating channel catfish with copper sulfate affects susceptibility to columnaris disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Columnaris disease is one of the most important bacterial diseases of channel catfish, Ictalurus punctatus, commercially grown in the US. This disease can greatly diminish the profitability of aquaculture operations by large-scale mortality events, particularly in the fingerling production phase. ...

  2. Genetics and Vaccine Efficacy: Host Genetic Variation Affecting Marek's Disease Vaccine Efficacy in White Leghorn Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a T cell lymphoma disease of domestic chickens induced by Marek’s disease viruses (MDV), a naturally oncogenic and highly contagious cell-associated alpha-herpesvirus. Earlier reports have shown that the major histocompatibility complex (MHC) haplotype as well as non-MHC gene...

  3. Non-MHC genomic variation affecting Marek’s disease resistance and vaccine protective efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of the domestic chicken caused by a highly infectious, oncogenic herpesvirus commonly referred to as Marek’s disease virus (MDV). MD has been controlled by vaccination with non-oncogenic turkey herpesvirus (HVT), non-oncogenic chicken herpesvirus...

  4. Is rumen development in newborn calves affected by different liquid feeds and small intestine development?

    PubMed

    Górka, P; Kowalski, Z M; Pietrzak, P; Kotunia, A; Jagusiak, W; Zabielski, R

    2011-06-01

    fed MR. Significant positive Pearson correlations were found between small intestine and reticulorumen weights as well as between activity of brush border lactase, maltase, aminopeptidase A, and aminopeptidase N and reticulorumen weight. Different liquid feeds affect small intestine development, animal growth, solid feed intake and metabolic status of calves and this effect can indirectly influence the development of forestomachs. PMID:21605770

  5. Modeling Development and Disease with Organoids.

    PubMed

    Clevers, Hans

    2016-06-16

    Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina. Organoid technology can therefore be used to model human organ development and various human pathologies 'in a dish." Additionally, patient-derived organoids hold promise to predict drug response in a personalized fashion. Organoids open up new avenues for regenerative medicine and, in combination with editing technology, for gene therapy. The many potential applications of this technology are only beginning to be explored. PMID:27315476

  6. Use of Multicriteria Risk Ranking of Zoonotic Diseases in a Developing Country: Case Study of Mongolia.

    PubMed

    McFadden, A M J; Muellner, P; Baljinnyam, Z; Vink, D; Wilson, N

    2016-03-01

    Many developing countries face significant health burdens associated with a high incidence of endemic zoonoses and difficulties in integrated control measures for both the human and animal populations. The objective of this study was to develop and apply a multicriteria ranking model for zoonoses in Mongolia, a country highly affected by zoonotic disease, to inform optimal resource allocation at the national level. Diseases were evaluated based on their impact on human health, livestock sector health and the wider society through affects on the economic value of livestock, as well as the feasibility of control in both the human and livestock population. Data on disease in Mongolia were collected from various government departments including the Mongolian State Central Laboratory, the Mongolian Department of Veterinary and Animal Breeding, the Mongolian Ministry of Health, Mongolian National Center for Communicable Diseases, the National Center for Zoonotic Disease and expert opinion from a workshop with a number of Mongolian Government officials and researchers. A combined score for both impact of the disease and feasibility of its control was calculated. Five zoonotic diseases were determined to be of high priority from this assessment (i.e. ovine brucellosis, echinococcosis (hydatids), rabies, anthrax and bovine brucellosis). The results supported some of the findings for high-priority diseases (namely brucellosis, rabies and anthrax) from a previous priority setting exercise carried out in Mongolia in 2011, but also identified and ranked additional animal diseases of public health importance. While the process of model development was largely Mongolian specific, the experience of developing and parameterizing this multicriteria ranking model could be replicated by other countries where zoonoses have substantive impacts on both animal and human health. PMID:26177028

  7. Epitranscriptional regulation of cardiovascular development and disease

    PubMed Central

    Dorn, Gerald W; Matkovich, Scot J

    2015-01-01

    Development, homeostasis and responses to stress in the heart all depend on appropriate control of mRNA expression programmes, which may be enacted at the level of DNA sequence, DNA accessibility and RNA-mediated control of mRNA output. Diverse mechanisms underlie promoter-driven transcription of coding mRNAs and their translation into protein, and the ways in which sequence alteration of DNA can make an impact on these processes have been studied for some time. The field of epigenetics explores changes in DNA structure that influence its accessibility by transcriptional machinery, and we are continuing to develop our understanding of how these processes modify cardiac RNA production. In this topical review, we do not focus on how DNA sequence and methylation, and histone interactions, may alter its accessibility, but rather on newly described mechanisms by which some transcribed RNAs may alter initial transcription or downstream processing of other RNAs, involving both short non-coding RNAs (microRNAs) and long non-coding RNAs (lncRNAs). Here we present examples of how these two classes of non-coding RNAs mediate widespread effects on cardiac transcription and protein output in processes for which we use the broad term ‘epitranscriptional regulation’ and that are complementary to the DNA methylation and histone modification events studied by classical epigenetics. PMID:25433070

  8. Use of sample pooling in a genome-wide association study identifies chromosomal regions affecting incidence of bovine respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We hypothesize that genome-wide association (GWA) based on high-density SNP arrays can be used to identify chromosomal regions affecting disease incidence using a case/control type approach. However, the large sample size required to map a lowly heritable trait like susceptibility to bovine respirat...

  9. 9 CFR 309.2 - Livestock suspected of being diseased or affected with certain conditions; identifying suspects...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Livestock suspected of being diseased or affected with certain conditions; identifying suspects; disposition on post-mortem inspection or otherwise. 309.2 Section 309.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION...

  10. Soil pH, soil type and replant disease affect growth and nutrient absorption in apple rootstocks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rootstocks are the foundation of a healthy and productive orchard. They are the interface between the scion and the soil, providing anchorage, water, nutrients, and disease protection that ultimately affect the productivity and sustainability of the orchard. Recent advances in the science of genet...

  11. Evaluation of Factors Affecting Vaccine Efficacy of Recombinant Marek's Disease Virus Lacking the Meq Oncogene in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously reported that deletion of Meq gene from oncogenic rMd5 virus rendered it apathogenic for chickens. Here we examined multiple factors affecting Marek’s disease (MD) vaccine efficacy of this non-pathogenic recombinant Meq null rMd5 virus (rMd5deltaMeq). These factors included host g...

  12. Previous infection with a mesogenic strain of Newcastle disease virus affects infection with highly pathogenic avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide, but little is known on the interactions between these two viruses when infecting birds. In a previous study we found that infection of chickens with a mesogenic strain of...

  13. Anger, Anxiety, and Depression as Risk Factors for Cardiovascular Disease: The Problems and Implications of Overlapping Affective Dispositions

    ERIC Educational Resources Information Center

    Sul, Jerry; Bunde, James

    2005-01-01

    Several recent reviews (e.g., L. C. Gallo & K. Matthews, 2003; A. Rozanski, J. A. Blumenthal, & J. Kaplan, 1999; R. Rugulies, 2002) have identified 3 affective dispositions--depression, anxiety, and anger-hostility--as putative risk factors for coronary heart disease. There are, however, mixed and negative results. Following a critical summary of…

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

    PubMed

    Reddy, Marpadga A; Natarajan, Rama

    2015-08-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  15. Recent Developments in Epigenetics of Acute and Chronic Kidney Diseases

    PubMed Central

    Reddy, Marpadga A.; Natarajan, Rama

    2015-01-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post translational modifications of histones in chromatin are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNA me and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  16. Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases.

    PubMed

    Recke, Andreas; Vidarsson, Gestur; Ludwig, Ralf J; Freitag, Miriam; Möller, Steffen; Vonthein, Reinhard; Schellenberger, Julia; Haase, Ozan; Görg, Siegfried; Nebel, Almut; Flachsbart, Friederike; Schreiber, Stefan; Lieb, Wolfgang; Gläser, Regine; Benoit, Sandrine; Sárdy, Miklós; Eming, Rüdiger; Hertl, Michael; Zillikens, Detlef; König, Inke R; Schmidt, Enno; Ibrahim, Saleh

    2015-07-01

    Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies. PMID:26032265

  17. Shifts in bacterial communities of two caribbean reef-building coral species affected by white plague disease

    PubMed Central

    Cárdenas, Anny; Rodriguez-R, Luis M; Pizarro, Valeria; Cadavid, Luis F; Arévalo-Ferro, Catalina

    2012-01-01

    Coral reefs are deteriorating at an alarming rate mainly as a consequence of the emergence of coral diseases. The white plague disease (WPD) is the most prevalent coral disease in the southwestern Caribbean, affecting dozens of coral species. However, the identification of a single causal agent has proved problematic. This suggests more complex etiological scenarios involving alterations in the dynamic interaction between environmental factors, the coral immune system and the symbiotic microbial communities. Here we compare the microbiome of healthy and WPD-affected corals from the two reef-building species Diploria strigosa and Siderastrea siderea collected at the Tayrona National Park in the Caribbean of Colombia. Microbiomes were analyzed by combining culture-dependent methods and pyrosequencing of 16S ribosomal DNA (rDNA) V5-V6 hypervariable regions. A total of 20 410 classifiable 16S rDNA sequences reads were obtained including all samples. No significant differences in operational taxonomic unit diversity were found between healthy and affected tissues; however, a significant increase of Alphaproteobacteria and a concomitant decrease in the Beta- and Gammaproteobacteria was observed in WPD-affected corals of both species. Significant shifts were also observed in the orders Rhizobiales, Caulobacteriales, Burkholderiales, Rhodobacterales, Aleteromonadales and Xanthomonadales, although they were not consistent between the two coral species. These shifts in the microbiome structure of WPD-affected corals suggest a loss of community-mediated growth control mechanisms on bacterial populations specific for each holobiont system. PMID:21955993

  18. The development of new therapeutics for Alzheimer's disease.

    PubMed

    Carter, M D; Simms, G A; Weaver, D F

    2010-10-01

    Existing treatments for Alzheimer's disease (AD) fail to address the underlying pathology of the disease; they merely provide short-lived symptomatic relief. Consequently, the progression of AD is unrelenting, leading to a continual decrease in cognitive abilities. Recent advances in understanding the genetic factors that predispose to AD, as well as in biomarker development, have brought with them the promise of earlier and more reliable diagnosis of this disease. As improvements continue to be made in these areas, the shortcomings of current AD treatments appear all the more acute because opportunities for early intervention are hindered by a lack of "curative" or even disease-modifying drugs. This State of the Art report reviews existing AD therapeutics and highlights recent progress made in the design and development of drugs that are aimed at disrupting AD disease progression by inhibition of the protein misfolding of β-amyloid (Aβ) into neurotoxic oligomeric aggregates. PMID:20811351

  19. Development of a Measure of Attitude toward Pulmonary Disease Prevention.

    ERIC Educational Resources Information Center

    McGaghie, William C.; And Others

    1993-01-01

    Systematic scale-development procedures, reliability analyses on 2,852 medical students (3 samples), and factor analysis were used to develop and refine a scale reflecting attitudes about pulmonary disease prevention. Development and verification samples included 110 and 2,691 students, respectively. The scale is promising for health education and…

  20. Genetic risk factors for the development of allergic disease identified by genome-wide association

    PubMed Central

    Portelli, M A; Hodge, E; Sayers, I

    2015-01-01

    An increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Allergic diseases are complex and development involves both environmental and genetic factors. Although the existence of a genetic component for allergy was first described almost 100 years ago, progress in gene identification has been hindered by lack of high throughput technologies to investigate genetic variation in large numbers of subjects. The development of Genome-Wide Association Studies (GWAS), a hypothesis-free method of interrogating large numbers of common variants spanning the entire genome in disease and non-disease subjects has revolutionised our understanding of the genetics of allergic disease. Susceptibility genes for asthma, AR and AD have now been identified with confidence, suggesting there are common and distinct genetic loci associated with these diseases, providing novel insights into potential disease pathways and mechanisms. Genes involved in both adaptive and innate immune mechanisms have been identified, notably including multiple genes involved in epithelial function/secretion, suggesting that the airway epithelium may be particularly important in asthma. Interestingly, concordance/discordance between the genetic factors driving allergic traits such as IgE levels and disease states such as asthma have further supported the accumulating evidence for heterogeneity in these diseases. While GWAS have been useful and continue to identify novel genes for allergic diseases through increased sample sizes and phenotype refinement, future approaches will integrate analyses of rare variants, epigenetic mechanisms and eQTL approaches, leading to greater insight into the genetic basis of these diseases. Gene identification will improve our understanding of disease mechanisms and generate potential

  1. Acute myeloid leukemia developing in patients with autoimmune diseases

    PubMed Central

    Ramadan, Safaa M.; Fouad, Tamer M; Summa, Valentina; Hasan, Syed KH; Lo-Coco, Francesco

    2012-01-01

    Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for patients with highly curable primary malignancies and favorable life expectancy. The risk of developing therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with autoimmune diseases compared to the general population, with a further increase in risk after exposure to cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia development and exposure to individual agents used for the treatment of autoimmune diseases. Given the dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune diseases who are exposed to cytotoxic agents as ‘therapy-related leukemias’. A better understanding of the molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better understanding of the association between these two diseases entities. PMID:22180424

  2. Histopathology of crustose coralline algae affected by white band and white patch diseases

    PubMed Central

    Meistertzheim, Anne-Leila; Steneck, Robert S.; Nugues, Maggy M.

    2015-01-01

    Crustose coralline algae (CCA) are major benthic calcifiers that play crucial roles in marine ecosystems, particularly coral reefs. Over the past two decades, epizootics have been reported for several CCA species on coral reefs worldwide. However, their causes remain often unknown in part because few studies have investigated CCA pathologies at a microscopic scale. We studied the cellular changes associated with two syndromes: Coralline White Band Syndrome (CWBS) and Coralline White Patch Disease (CWPD) from samples collected in Curaçao, southern Caribbean. Healthy-looking tissue of diseased CCA did not differ from healthy tissue of healthy CCA. In diseased tissues of both pathologies, the three characteristic cell layers of CCA revealed cells completely depleted of protoplasmic content, but presenting an intact cell wall. In addition, CWBS showed a transition area between healthy and diseased tissues consisting of cells partially deprived of protoplasmic material, most likely corresponding to the white band characterizing the disease at the macroscopic level. This transition area was absent in CWPD. Regrowth at the lesion boundary were sometimes observed in both syndromes. Tissues of both healthy and diseased CCA were colonised by diverse boring organisms. Fungal infections associated with the diseased cells were not seen. However, other bioeroders were more abundant in diseased vs healthy CCA and in diseased vs healthy-looking tissues of diseased CCA. Although their role in the pathogenesis is unclear, this suggests that disease increases CCA susceptibility to bioerosion. Further investigations using an integrated approach are needed to carry out the complete diagnosis of these diseases. PMID:26157617

  3. Drug discovery and development for neglected diseases: the DNDi model.

    PubMed

    Chatelain, Eric; Ioset, Jean-Robert

    2011-01-01

    New models of drug discovery have been developed to overcome the lack of modern and effective drugs for neglected diseases such as human African trypanosomiasis (HAT; sleeping sickness), leishmaniasis, and Chagas disease, which have no financial viability for the pharmaceutical industry. With the purpose of combining the skills and research capacity in academia, pharmaceutical industry, and contract researchers, public-private partnerships or product development partnerships aim to create focused research consortia that address all aspects of drug discovery and development. These consortia not only emulate the projects within pharmaceutical and biotechnology industries, eg, identification and screening of libraries, medicinal chemistry, pharmacology and pharmacodynamics, formulation development, and manufacturing, but also use and strengthen existing capacity in disease-endemic countries, particularly for the conduct of clinical trials. The Drugs for Neglected Diseases initiative (DNDi) has adopted a model closely related to that of a virtual biotechnology company for the identification and optimization of drug leads. The application of this model to the development of drug candidates for the kinetoplastid infections of HAT, Chagas disease, and leishmaniasis has already led to the identification of new candidates issued from DNDi's own discovery pipeline. This demonstrates that the model DNDi has been implementing is working but its DNDi, neglected diseases sustainability remains to be proven. PMID:21552487

  4. Altered lysosomal positioning affects lysosomal functions in a cellular model of Huntington's disease.

    PubMed

    Erie, Christine; Sacino, Matthew; Houle, Lauren; Lu, Michael L; Wei, Jianning

    2015-08-01

    Huntington's disease (HD) is a hereditary and devastating neurodegenerative disorder caused by a mutation in the huntingtin protein. Understanding the functions of normal and mutant huntingtin protein is the key to revealing the pathogenesis of HD and developing therapeutic targets. Huntingtin plays an important role in vesicular and organelle trafficking. Lysosomes are dynamic organelles that integrate several degradative pathways and regulate the activity of mammalian target of rapamycin complex 1 (mTORC1). In the present study, we found that the perinuclear accumulation of lysosomes was increased in a cellular model of HD derived from HD knock-in mice and primary fibroblasts from an HD patient. This perinuclear lysosomal accumulation could be reversed when normal huntingtin was overexpressed in HD cells. When we further investigated the functional significance of the increased perinuclear lysosomal accumulation in HD cells, we demonstrated that basal mTORC1 activity was increased in HD cells. In addition, autophagic influx was also increased in HD cells in response to serum deprivation, which leads to premature fusion of lysosomes with autophagosomes. Taken together, our data suggest that the increased perinuclear accumulation of lysosomes may play an important role in HD pathogenesis by altering lysosomal-dependent functions. PMID:25997742

  5. Premolis semirufa (Walker, 1856) Envenomation, Disease Affecting Rubber Tappers of the Amazon: Searching for Caterpillar-Bristles Toxic Components

    PubMed Central

    Villas-Boas, Isadora Maria; Gonçalves-de-Andrade, Rute Maria; Pidde-Queiroz, Giselle; Assaf, Suely Lucia Muro Rais; Portaro, Fernanda C. V.; Sant'Anna, Osvaldo A.; van den Berg, Carmen W.; Tambourgi, Denise V.

    2012-01-01

    Background The caterpillar of the moth Premolis semirufa (Lepidoptera: Arctiidae), commonly named Pararama, is endemic of the Amazon basin. Accidental contact with these caterpillar bristles causes local symptoms such as intense heat, pain, edema and itching which last for three to seven days; however, after multiples contacts, it may induce joint-space narrowing and bone alteration, as well as degeneration of the articular cartilage and immobilization of the affected joints. Specific treatment for this disease does not exist, but corticosteroids are frequently administered. Despite of the public health hazard of Premolis semirufa caterpillar poisoning, little is known about the nature of the toxic components involved in the induction of the pathology. Methodology/Principal Findings Here we have investigated the biological and immunochemical characteristics of the caterpillar's bristles components. Analysis of the bristles extract in in vitro assays revealed the presence of proteolytic and hyaluronidase activities but no phospholipase A2 activity. In vivo, it was observed that the bristles extract is not lethal but can induce an intense inflammatory process, characterized by the presence of neutrophils in the paw tissues of injected mice. Furthermore, the bristles components stimulated an intense and specific antibody response but autoantibodies such as anti-DNA or anti-collagen type II were not detected. Conclusion The results suggest that Premolis semirufa caterpillar bristles secretion contains a mixture of different enzymes that may act together in the generation and development of the clinical manifestations of the Pararama envenomation. Moreover, the high immunogenicity of the caterpillar bristles components, as shown by the generation of high antibody titers, may also contribute to the induction and establishment of the inflammatory disease. PMID:22389740

  6. Rift Valley Fever and a New Paradigm of Research and Development for Zoonotic Disease Control

    PubMed Central

    McIntyre, Sabrina; Hogarth, Sue; Heymann, David

    2013-01-01

    Although Rift Valley fever is a disease that, through its wider societal effects, disproportionately affects vulnerable communities with poor resilience to economic and environmental challenge, Rift Valley fever virus has since its discovery in 1931 been neglected by major global donors and disease control programs. We describe recent outbreaks affecting humans and animals and discuss the serious socioeconomic effects on the communities affected and the slow pace of development of new vaccines. We also discuss the mixed global response, which has largely been fueled by the classification of the virus as a potential bioterrorism agent and its potential to migrate beyond its traditional eastern African boundaries. We argue for a refocus of strategy with increased global collaboration and a greater sense of urgency and investment that focuses on an equity-based approach in which funding and research are prioritized by need, inspired by principles of equity and social justice. PMID:23347653

  7. A Common Polymorphism in EC-SOD Affects Cardiopulmonary Disease Risk by Altering Protein Distribution

    PubMed Central

    Hartney, John M.; Stidham, Timothy; Goldstrohm, David A.; Oberley-Deegan, Rebecca E.; Weaver, Michael R.; Valnickova-Hansen, Zuzana; Scavenius, Carsten; Benninger, Richard K.P.; Leahy, Katelyn F.; Johnson, Richard; Gally, Fabienne; Kosmider, Beata; Zimmermann, Angela K.; Enghild, Jan J.; Nozik-Grayck, Eva; Bowler, Russell P.

    2014-01-01

    Background The enzyme extracellular superoxide dismutase (EC-SOD; SOD3) is a major antioxidant defense in lung and vasculature. A nonsynonomous single nucleotide polymorphism (SNP) in EC-SOD (rs1799895) leads to an arginine to glycine (Arg->Gly) amino acid substitution at position 213 (R213G) in the heparin-binding domain (HBD). In recent human genetic association studies, this SNP attenuates the risk of lung disease, yet paradoxically increases the risk of cardiovascular disease. Methods and Results Capitalizing on the complete sequence homology between human and mouse in the HBD, we created an analogous R213G SNP knockin mouse. The R213G SNP did not change enzyme activity, but shifted the distribution of EC-SOD from lung and vascular tissue to extracellular fluid (e.g. bronchoalveolar lavage fluid (BALF) and plasma). This shift reduces susceptibility to lung disease (lipopolysaccharide-induced lung injury) and increases susceptibility to cardiopulmonary disease (chronic hypoxic pulmonary hypertension). Conclusions We conclude that EC-SOD provides optimal protection when localized to the compartment subjected to extracellular oxidative stress: thus, the redistribution of EC-SOD from the lung and pulmonary circulation to the extracellular fluids is beneficial in alveolar lung disease but detrimental in pulmonary vascular disease. These findings account for the discrepant risk associated with R213G in humans with lung diseases compared with cardiovascular diseases. PMID:25085920

  8. Brown muscle disease (BMD), an emergent pathology affecting Manila clam Ruditapes philippinarum in Arcachon Bay (SW France).

    PubMed

    Dang, Cécile; de Montaudouin, Xavier; Gonzalez, Patrice; Mesmer-Dudons, Nathalie; Caill-Milly, Nathalie

    2008-08-01

    We describe an emerging pathology, brown muscle disease (BMD), which specifically affects the Manila clam Ruditapes philippinarum in Arcachon Bay (France). BMD induces a transformation of the posterior adductor muscle, which becomes infused by conchiolin and calcified, reducing the ability of clams to bury. The disease affects both types of muscular tissue, with striated muscle becoming affected to a higher degree than smooth muscle. Two indices were created to quantify the symptoms: the Muscle Print Index, used for empty and live shells, and the Final Disease Index, utilized for live clams only. Histological sections were made and observed under light microscopy to examine the muscular damage and to investigate a causal agent. Sections revealed an important inflammatory response with a large invasion of hemocytes into tissues and a heavy necrosis of muscular fibers. Additionally, molecular biology analyses were carried out to search for bacteria and protozoan agents using generic primers. In both histological and molecular assays, bacteria and protozoans were discounted. We monitored 4 sites scattered around the bay over 2 yr. The mean prevalence was <12% without seasonal variation in 3 sites against 30% and a winter peak in 1 site. The latter site was accurately surveyed and revealed that clams at the sediment surface (abnormal position) were affected 3 times more frequently than buried clams (normal position). PMID:18814547

  9. Emerging viral diseases of livestock in the developing world.

    PubMed

    Bayry, Jagadeesh

    2013-12-01

    Emerging and reemerging viral diseases of livestock and human beings are in sharp rise in recent years. Importantly, many of these viruses, including influenza, Hendra, Nipah and corona are of zoonotic importance. Several viral diseases of livestock such as bluetongue, peste des petits ruminants, camel pox, equine infectious anaemia, chicken anaemia and sheep-associated malignant catarrhal fever are crossing their traditional boundaries. Emergence of new serotypes and variant forms of viruses as in the case of blue tongue virus, avian infectious bronchitis virus, Newcastle disease virus adds additional level of complexity. The increased incidence of emerging and reemerging viral diseases could be attributed to several factors including deforestation and surge in direct contact of livestock and humans with wild animals and birds. This special issue of "Indian Journal of Virology" is focused on diverse aspects of above diseases: isolation and characterization of viruses, epidemiology, pathogenesis, diagnosis, prevention measures and vaccine development. PMID:24426290

  10. In vitro growth inhibition by Hypericum extracts and isolated pure compounds of Paenibacillus larvae, a lethal disease affecting honeybees worldwide.

    PubMed

    Hernández-López, Javier; Crockett, Sara; Kunert, Olaf; Hammer, Elfe; Schuehly, Wolfgang; Bauer, Rudolf; Crailsheim, Karl; Riessberger-Gallé, Ulrike

    2014-05-01

    The in vitro inhibitory potential of 50 extracts from various species of the flowering plant genus Hypericum was investigated using the Kirby-Bauer disk diffusion susceptibility test against Paenibacillus larvae, a spore-forming, Gram-positive bacterial pathogen that causes American foulbrood (AFB), a lethal disease affecting honeybee brood worldwide. Of the tested extracts, 14 were identified as highly active against P. larvae as compared to the activity of the positive control, indicating the presence of highly potent antibacterial compounds in the extracts. Examination of these extracts using TLC and HPLC/MS analyses revealed the presence of acylphloroglucinol and filicinic-acid derivatives. Six pure compounds isolated from these extracts, viz., hyperforin (1), uliginosin B (2), uliginosin A (3), 7-epiclusianone (4), albaspidin AA (5), and drummondin E (6), displayed strong antibacterial activity against the vegetative form of P. larvae (MIC ranging from 0.168-220 μM). Incubation of P. larvae spores with the lipophilic extract of Hypericum perforatum and its main acylphloroglucinol constituent 1 led to the observation of significantly fewer colony forming units as compared to the negative control, indicating that the acylphloroglucinol scaffold represents an interesting lead structure for the development of new AFB control agents. PMID:24827680

  11. Roles of EphA2 in Development and Disease

    PubMed Central

    Park, Jeong Eun; Son, Alexander I.; Zhou, Renping

    2013-01-01

    The Eph family of receptor tyrosine kinases (RTKs) has been implicated in the regulation of many aspects of mammalian development. Recent analyses have revealed that the EphA2 receptor is a key modulator for a wide variety of cellular functions. This review focuses on the roles of EphA2 in both development and disease. PMID:24705208

  12. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development

    PubMed Central

    Matsuki, Takahiro; Yahagi, Kana; Mori, Hiroshi; Matsumoto, Hoshitaka; Hara, Taeko; Tajima, Saya; Ogawa, Eishin; Kodama, Hiroko; Yamamoto, Kazuya; Yamada, Takuji; Matsumoto, Satoshi; Kurokawa, Ken

    2016-01-01

    Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications. PMID:27340092

  13. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development.

    PubMed

    Matsuki, Takahiro; Yahagi, Kana; Mori, Hiroshi; Matsumoto, Hoshitaka; Hara, Taeko; Tajima, Saya; Ogawa, Eishin; Kodama, Hiroko; Yamamoto, Kazuya; Yamada, Takuji; Matsumoto, Satoshi; Kurokawa, Ken

    2016-01-01

    Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications. PMID:27340092

  14. Kawasaki Disease

    MedlinePlus

    ... As a result, some children who have Kawasaki disease may develop serious heart problems. Overview The cause of Kawasaki disease ... Early treatment helps reduce the risk of Kawasaki disease affecting the coronary arteries and causing serious problems. Outlook Kawasaki disease can't be prevented. ...

  15. Dysautonomia Differentially Influences the Effect of Affective Pain Perception on Quality of Life in Parkinson's Disease Patients

    PubMed Central

    Rada, D.; Seco, J.; Tijero, B.; Abecia, L. C.; Gómez-Esteban, J. C.

    2016-01-01

    Background. Our aim was to evaluate the real effect of dysautonomic symptoms on the influence of affective pain perception on quality of life in PD patients. Methods. An observational cross-sectional study was carried out using 105 Parkinson's disease (PD) patients of the Movement Disorders Unit, Hospital de Cruces (Bilbao, Spain) [men 59 (56.2%), women 46 (43.85%)]. Statistical analysis was made in order to evaluate the possible association of pain with life quality. Results. Quality of life measured by PDQ-39 (Parkinson's Disease Questionnaire for quality of life) was statistically associated with affective dimension of pain (PRIA, affective pain rating index). However, the influence of this dimension on PDQ-39 was different in the specific case of PD patients that experimented a high score (>12) in SCOPA-AUT (Scale for Outcomes in PD-Autonomic scale). Conclusions. These results confirm the effect of affective perception of pain in life quality of PD patients, indicating the critical role of autonomic symptoms in the modulation of the influence of pain on quality of life and showing the possible utility of dysautonomia as clinical prognostic indicator of quality of life in PD patients affected by pain. PMID:27239367

  16. Dysautonomia Differentially Influences the Effect of Affective Pain Perception on Quality of Life in Parkinson's Disease Patients.

    PubMed

    Rada, D; Seco, J; Echevarría, E; Tijero, B; Abecia, L C; Gómez-Esteban, J C

    2016-01-01

    Background. Our aim was to evaluate the real effect of dysautonomic symptoms on the influence of affective pain perception on quality of life in PD patients. Methods. An observational cross-sectional study was carried out using 105 Parkinson's disease (PD) patients of the Movement Disorders Unit, Hospital de Cruces (Bilbao, Spain) [men 59 (56.2%), women 46 (43.85%)]. Statistical analysis was made in order to evaluate the possible association of pain with life quality. Results. Quality of life measured by PDQ-39 (Parkinson's Disease Questionnaire for quality of life) was statistically associated with affective dimension of pain (PRIA, affective pain rating index). However, the influence of this dimension on PDQ-39 was different in the specific case of PD patients that experimented a high score (>12) in SCOPA-AUT (Scale for Outcomes in PD-Autonomic scale). Conclusions. These results confirm the effect of affective perception of pain in life quality of PD patients, indicating the critical role of autonomic symptoms in the modulation of the influence of pain on quality of life and showing the possible utility of dysautonomia as clinical prognostic indicator of quality of life in PD patients affected by pain. PMID:27239367

  17. Dispelling myths about rare disease registry system development

    PubMed Central

    2013-01-01

    Rare disease registries (RDRs) are an essential tool to improve knowledge and monitor interventions for rare diseases. If designed appropriately, patient and disease related information captured within them can become the cornerstone for effective diagnosis and new therapies. Surprisingly however, registries possess a diverse range of functionality, operate in different, often-times incompatible, software environments and serve various, and sometimes incongruous, purposes. Given the ambitious goals of the International Rare Diseases Research Consortium (IRDiRC) by 2020 and beyond, RDRs must be designed with the agility to evolve and efficiently interoperate in an ever changing rare disease landscape, as well as to cater for rapid changes in Information Communication Technologies. In this paper, we contend that RDR requirements will also evolve in response to a number of factors such as changing disease definitions and diagnostic criteria, the requirement to integrate patient/disease information from advances in either biotechnology and/or phenotypying approaches, as well as the need to adapt dynamically to security and privacy concerns. We dispel a number of myths in RDR development, outline key criteria for robust and sustainable RDR implementation and introduce the concept of a RDR Checklist to guide future RDR development. PMID:24131574

  18. [Current Trend of Drug Development for Neglected Tropical Diseases (NTDs)].

    PubMed

    Kita, Kiyoshi

    2016-01-01

    EBOLA hemorrhagic fever, a typical emerging infectious disease, began in December 2013 in the southern part of Guinea, and killed more than 11000 people by the end of June, 2015. In addition to emerging/re-emerging diseases and the 3 major infectious diseases i.e. HIV/AIDS, tuberculosis and malaria, neglected tropical diseases (NTDs) have recently become important tropical diseases of the poor. It is remarkable that Japan succeeded in the eradication of malaria and other tropical diseases, which include lymphatic filariasis and schistosomiasis. However, despite these achievements, it is important to sustain our efforts when we consider global health. This review highlights the significance of elimination and/or control of NTDs, and then introduces the current situation of drug development activities in Japan, which are aimed towards combating tropical infectious diseases. They include studies on a novel drug target, the "mitochondrial NADH-fumarate reductase system (Fumarate respiration)" composed of complex I, rhodoquinone and complex II, which plays an important role in the anaerobic energy metabolism of many helminths such as Ascaris suum. An additional interesting finding highlighted herein is that ascofuranone, a recently developed anti-African trypanosome drug, shows specific inhibition of fumarate respiration in Echinococcus multilocularis mitochondria. PMID:26831795

  19. The Relationship Between Affective and Cognitive Development in Down's Syndrome Infants.

    ERIC Educational Resources Information Center

    Cicchetti, Dante; Sroufe, L. Alan

    Examined was the association between affective and cognitive development in 14 Down's Syndrome infants (4- to 8-months-old). Mothers administered a series of 30 laughter items each month, and experimenters gave the Uzgiris-Hunt scales of cognitive development at 13 and 16 months, and the Bayley scales and Infant Behavior Record at 16 months.…

  20. The Development of an Emotional Response to Writing Measure: The Affective Cognition Writing Survey

    ERIC Educational Resources Information Center

    Fischer, Ronald G.; Fischer, Jerome M.; Jain, Sachin

    2010-01-01

    This study was designed to develop and initiate the validation of the Affective Cognition Writing Survey (ACWS), a psychological instrument used to measure emotional expression through writing. Procedures for development and validation of the instrument are reported. Subsequently, factor analysis extracted six factors: Positive Processing,…

  1. Developing Connections for Affective Regulation: Age-Related Changes in Emotional Brain Connectivity

    ERIC Educational Resources Information Center

    Perlman, Susan B.; Pelphrey, Kevin A.

    2011-01-01

    The regulation of affective arousal is a critical aspect of children's social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of "hot" executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional…

  2. Recent developments in the management of idiopathic cholestatic liver disease

    PubMed Central

    Imam, Mohamad H.; Weeding, Emma; Lindor, Keith D.

    2012-01-01

    In recent years, the clinical management of patients with idiopathic cholestatic liver disease has shown significant progress. Advancement of diagnostic and therapeutic approaches and better understanding of the pathophysiology underlying these diseases have all contributed considerably to this progress. In this review, we aim to touch briefly on several developments that have occurred in this regard and to discuss novel findings and interventions valuable to clinical practice. PMID:24714257

  3. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients

    PubMed Central

    Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-01-01

    Background Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown. Principal Findings Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels. Conclusions/Significance Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine. PMID:27348302

  4. Low and moderate concentrations of lysobisphosphatidic acid in brain and liver of patients affected by some storage diseases.

    PubMed

    Kahma, K; Brotherus, J; Haltia, M; Renkonen, O

    1976-07-01

    The relative amount of lysobisphosphatidic acid (LBPA), known also as bis(monoacylglycerly)phosphate, among the total phospholipids was analyzed in post mortem samples of brain and liver of patients affected by four storage diseases. In spite of the extensive accumulation of storage lysosomes, none of the samples revealed a highly evelated LBPA content comparable to that found in the liver in Niemann-Pick disease and in the liver in lipidosis induced by 4,4'-diethylaminoethoxyhexestrol. We conclude that, although LBPA is often present in high concentration in lysosomes of many types of cells, it is not always a major component of these organelles. PMID:948249

  5. Development of and Access to Products for Neglected Diseases

    PubMed Central

    Cohen, Joshua; Dibner, Maria Staroselsky; Wilson, Andrew

    2010-01-01

    Introduction Prior research on neglected disease drug development suggested inadequate funding was responsible for relatively few new approvals. In response, significantly more resources have been allocated towards development of drugs targeting neglected diseases. Our objective was to reassess drug development between1975 and 1999, evaluate progress in neglected disease drug development since 2000, and explain how increased numbers of approvals are a necessary but insufficient condition to improving access. Methods To assess numbers of approvals targeting neglected diseases, we employed two distinct methodologies: First, to revisit numbers published in Trouiller et al. (2002) we used their method to count marketed new chemical entities (NCEs) between 1975 and 1999. Second, using the G-Finder report as a benchmark, we identified which diseases are currently considered “neglected” to tally approvals in the 1975–1999 and 2000–2009 periods. Searching PharmaProjects and IMS R&D Focus databases as well as websites from numerous drug regulatory agencies, we identified new drug approvals and indications. Also, we examined the World Health Organization's (WHO) Essential Drug List (EDL) to see which drugs and indications were on the list. Findings Upon recount, using Trouiller et al. methodology, we found that between 1975 and 1999 more NCEs (n = 32) targeting tropical diseases and tuberculosis were approved than reported in Trouiller et al. (n = 16). Using the G-Finder method of defining neglected diseases, we found 46 new drug approvals between 1975 and 1999. WHO included 85% of these drugs on the EDL. In the period 2000 to May 2009, despite much greater funding, only 26 new drugs and vaccines for neglected diseases were marketed. Of these, WHO placed 50% on the EDL. Conclusions Product approvals for neglected diseases have increased, though progress has been uneven, with malaria appearing to benefit most in the short run from increased funding, while less

  6. Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases

    PubMed Central

    Hudson, Gavin; Gomez-Duran, Aurora; Wilson, Ian J.; Chinnery, Patrick F.

    2014-01-01

    Mitochondrial DNA (mtDNA) is highly polymorphic at the population level, and specific mtDNA variants affect mitochondrial function. With emerging evidence that mitochondrial mechanisms are central to common human diseases, it is plausible that mtDNA variants contribute to the “missing heritability” of several complex traits. Given the central role of mtDNA genes in oxidative phosphorylation, the same genetic variants would be expected to alter the risk of developing several different disorders, but this has not been shown to date. Here we studied 38,638 individuals with 11 major diseases, and 17,483 healthy controls. Imputing missing variants from 7,729 complete mitochondrial genomes, we captured 40.41% of European mtDNA variation. We show that mtDNA variants modifying the risk of developing one disease also modify the risk of developing other diseases, thus providing independent replication of a disease association in different case and control cohorts. High-risk alleles were more common than protective alleles, indicating that mtDNA is not at equilibrium in the human population, and that recent mutations interact with nuclear loci to modify the risk of developing multiple common diseases. PMID:24852434

  7. Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

    PubMed Central

    Ochoa-Cortes, Fernando; Liñán-Rico, Andromeda; Jacobson, Kenneth A.; Christofi, Fievos L.

    2014-01-01

    Treatments for IBD, IBS, FD or motility disorders are not adequate, and purinergic drugs offer exciting new possibilities. GI symptoms that could be targeted for therapy include visceral pain, inflammatory pain, dysmotility, constipation and diarrhea. The focus of this review is on potential for developing purinergic drugs for clinical trials to treat GI symptoms. Purinergic receptors are divided into adenosine P1 (A1,A2A,A2B,A3), ionotropic ATP-gated P2X ion channel (P2X1–7) or metabotropic P2Y1,2,4,6,11–14 receptors. There is good experimental evidence for targeting A2A, A2B, A3, P2X7, P2X3 receptors or increasing endogenous adenosine levels to treat IBD, inflammatory pain, IBS/visceral pain, inflammatory-diarrhea and motility disorders. Purine genes are also potential biomarkers of disease. Advances in medicinal-chemistry have an accelerated pace toward clinical trials: Methotrexate and sulfasalazine, used to treat IBD, act by stimulating CD73-dependent adenosine production. ATP protects against NSAID-induced enteropathy and has pain-relieving properties in humans. A P2X7R antagonist AZD9056 is in clinical trials for CD. A3 AR drugs target inflammatory diseases (e.g. CF101; CF102). Dipyridamole, a nucleoside uptake-inhibitor, is in trials for endotoxemia. Drugs for pain in clinical-trials include P2X3/P2X2/3(AF-219) and P2X7(GSK1482160) antagonists and A1(GW493838) or A2A(BVT.115959) agonists. IberogastR is a phytopharmacon targeting purine-mechanisms with efficacy in IBS and FD. Purinergic drugs have excellent safety/efficacy profile for prospective clinical trials in IBD, IBS, FD and inflammatory-diarrhea. Genetic polymorphisms and caffeine consumption may affect susceptibility to treatment. Further studies in animals can clarify mechanisms and test new-generation drugs. Finally, there is still a huge gap in our knowledge of human pathophysiology of purinergic signaling. PMID:24859298

  8. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    PubMed

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. PMID:24691863

  9. Identification of Genetic Loci Affecting the Severity of Symptoms of Hirschsprung Disease in Rats Carrying Ednrbsl Mutations by Quantitative Trait Locus Analysis

    PubMed Central

    Torigoe, Daisuke; Lei, Chuzhao; Lan, Xianyong; Chen, Hong; Sasaki, Nobuya; Wang, Jinxi; Agui, Takashi

    2015-01-01

    Hirschsprung’s disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrbsl/sl, resistant F344-Ednrbsl/sl, and LEH-Ednrbsl/sl) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis. PMID:25790447

  10. Risk and protective haplotypes of the alpha-synuclein gene associated with Parkinson's disease differentially affect cognitive sequence learning.

    PubMed

    Kéri, S; Nagy, H; Myers, C E; Benedek, G; Shohamy, D; Gluck, M A

    2008-02-01

    Alpha-synuclein (SNCA) is a key factor in the regulation of dopaminergic transmission and is related to Parkinson's disease. In this study, we investigated the effects of risk and protective SNCA haplotypes associated with Parkinson's disease on cognitive sequence learning in 204 healthy volunteers. We found that the 3'-block risk SNCA haplotypes are associated with less effective stimulus-reward learning of sequences and with superior context representation of sequences. In contrast, participants with protective haplotypes exhibit better stimulus-reward learning and worse context representation, which suggest that these functions are inversely affected by risk and protective haplotypes. The Rep1 promoter polymorphism does not influence cognitive sequence learning. Because stimulus-reward learning may be mediated by the basal ganglia and context learning may be related to the medial temporal lobe, our data raise the possibility that dopaminergic signals regulated by SNCA inversely affect these memory systems. PMID:17451452

  11. Regulated Noise in the Epigenetic Landscape of Development and Disease

    PubMed Central

    Pujadas, Elisabet; Feinberg, Andrew

    2012-01-01

    In this Perspective, we synthesize past and present observations in the field of epigenetics to propose a model in which the epigenome can modulate cellular plasticity in development and disease by regulating the effects of noise. In this model, the epigenome facilitates phase transitions in development and mediates robustness during cell fate commitment. After grounding our argument in a discussion of stochastic noise and non-genetic heterogeneity, we explore the hypothesis that distinct chromatin domains, which are known to be dysregulated in disease and remodeled during development, might underlie cellular plasticity more generally. We then present a modern portrayal of Waddington's epigenetic landscape through a mathematical formalism. We speculate that this new framework might impact how we approach the unraveling of disease mechanisms. In particular, it may help to explain the observation that the variability of DNA methylation and gene expression are increased in cancer, which leads to tumor cell heterogeneity. PMID:22424224

  12. Surveillance for Occupational Respiratory Diseases in Developing Countries

    PubMed Central

    Antao, Vinicius C.; Pinheiro, Germania A.

    2015-01-01

    The burden of chronic diseases, including occupational respiratory diseases (ORDs), is increasing worldwide. Nevertheless, epidemiological data on these conditions are scarce in most countries. Therefore, it is important to conduct surveillance to monitor ORDs, particularly in developing countries, where the working population is especially vulnerable and the health system infrastructure is usually weak. This article provides a general framework for the implementation of ORD surveillance in developing countries. The main objectives of surveillance are to describe incidence and prevalence of ORDs, as well as to identify sentinel events and new associations between occupational exposures and health outcomes. Diseases with high morbidity and mortality and those in which early diagnosis with standardized tests are available are especially suitable for surveillance activities. Simple strategies, preferably using existing resources and technology, are the best option for surveillance in developing countries. This article offers examples of specific surveillance systems that are in place in Brazil, China, Cuba, India, and South Africa. PMID:26024351

  13. Tracking Official Development Assistance for Reproductive Health in Conflict-Affected Countries

    PubMed Central

    Patel, Preeti; Roberts, Bayard; Guy, Samantha; Lee-Jones, Louise; Conteh, Lesong

    2009-01-01

    Background Reproductive health needs are particularly acute in countries affected by armed conflict. Reliable information on aid investment for reproductive health in these countries is essential for improving the efficiency and effectiveness of aid. The purpose of this study was to analyse official development assistance (ODA) for reproductive health activities in conflict-affected countries from 2003 to 2006. Methods and Findings The Creditor Reporting System and the Financial Tracking System databases were the chosen data sources for the study. ODA disbursement for reproductive health activities to 18 conflict-affected countries was analysed for 2003, 2004, 2005, and 2006. An average of US$20.8 billion in total ODA was disbursed annually to the 18 conflict-affected countries between 2003 and 2006, of which US$509.3 million (2.4%) was allocated to reproductive health. This represents an annual average of US$1.30 disbursed per capita in the 18 sampled countries for reproductive health activities. Non-conflict-affected least-developed countries received 53.3% more ODA for reproductive health activities than conflict-affected least-developed countries, despite the latter generally having greater reproductive health needs. ODA disbursed for HIV/AIDS prevention and treatment increased by 119.4% from 2003 to 2006. The ODA disbursed for other direct reproductive health activities declined by 35.9% over the same period. Conclusions This study provides evidence of inequity in disbursement of reproductive health ODA between conflict-affected countries and non-conflict-affected countries, and between different reproductive health activities. These findings and the study's recommendations seek to support initiatives to make aid financing more responsive to need in the context of armed conflict. PMID:19513098

  14. Vitamin A-retinoid signaling in pulmonary development and disease.

    PubMed

    Marquez, Hector A; Cardoso, Wellington V

    2016-12-01

    Retinoic acid (RA), the active form of vitamin A, regulates key developmental processes in multiple organs. In the developing lung, RA is crucial for normal growth and differentiation of airways. Disruption in RA signaling or vitamin A deficiency (VAD) has been linked to aberrant development of the lung including alterations in the airway smooth muscle (SM) differentiation, development, and function. These alterations have been linked to disease states including asthma in both human and animal models. PMID:27480876

  15. 76 FR 52958 - Draft Guidance for Industry on Neglected Tropical Diseases of the Developing World: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... sponsors in the clinical development of drugs for the treatment or prevention of neglected diseases of the... development program for the treatment or prevention of neglected tropical diseases (NTDs), including clinical trial designs and internal review standards to support approval of drugs. DATES: Although you...

  16. Hit and lead criteria in drug discovery for infectious diseases of the developing world.

    PubMed

    Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

    2015-11-01

    Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale. PMID:26435527

  17. Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

    PubMed Central

    Swan, E J; Salem, R M; Sandholm, N; Tarnow, L; Rossing, P; Lajer, M; Groop, P H; Maxwell, A P; McKnight, A J

    2015-01-01

    polymorphisms (SNPs) in nuclear genes affecting mitochondrial function were found to be associated with diabetic kidney disease. The highlighted SNPs were within the genes implicated in regulation of epigenetic processes. Further research to explore the interactions between hyperglycaemia, uraemia and epigenetic modifications of the genome could shed new light on how these nuclear genome SNPs are associated with kidney disease. PMID:25819010

  18. Identification of seven loci affecting mean telomere length and their association with disease.

    PubMed

    Codd, Veryan; Nelson, Christopher P; Albrecht, Eva; Mangino, Massimo; Deelen, Joris; Buxton, Jessica L; Hottenga, Jouke Jan; Fischer, Krista; Esko, Tõnu; Surakka, Ida; Broer, Linda; Nyholt, Dale R; Mateo Leach, Irene; Salo, Perttu; Hägg, Sara; Matthews, Mary K; Palmen, Jutta; Norata, Giuseppe D; O'Reilly, Paul F; Saleheen, Danish; Amin, Najaf; Balmforth, Anthony J; Beekman, Marian; de Boer, Rudolf A; Böhringer, Stefan; Braund, Peter S; Burton, Paul R; de Craen, Anton J M; Denniff, Matthew; Dong, Yanbin; Douroudis, Konstantinos; Dubinina, Elena; Eriksson, Johan G; Garlaschelli, Katia; Guo, Dehuang; Hartikainen, Anna-Liisa; Henders, Anjali K; Houwing-Duistermaat, Jeanine J; Kananen, Laura; Karssen, Lennart C; Kettunen, Johannes; Klopp, Norman; Lagou, Vasiliki; van Leeuwen, Elisabeth M; Madden, Pamela A; Mägi, Reedik; Magnusson, Patrik K E; Männistö, Satu; McCarthy, Mark I; Medland, Sarah E; Mihailov, Evelin; Montgomery, Grant W; Oostra, Ben A; Palotie, Aarno; Peters, Annette; Pollard, Helen; Pouta, Anneli; Prokopenko, Inga; Ripatti, Samuli; Salomaa, Veikko; Suchiman, H Eka D; Valdes, Ana M; Verweij, Niek; Viñuela, Ana; Wang, Xiaoling; Wichmann, H-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wright, Margaret J; Xia, Kai; Xiao, Xiangjun; van Veldhuisen, Dirk J; Catapano, Alberico L; Tobin, Martin D; Hall, Alistair S; Blakemore, Alexandra I F; van Gilst, Wiek H; Zhu, Haidong; Erdmann, Jeanette; Reilly, Muredach P; Kathiresan, Sekar; Schunkert, Heribert; Talmud, Philippa J; Pedersen, Nancy L; Perola, Markus; Ouwehand, Willem; Kaprio, Jaakko; Martin, Nicholas G; van Duijn, Cornelia M; Hovatta, Iiris; Gieger, Christian; Metspalu, Andres; Boomsma, Dorret I; Jarvelin, Marjo-Riitta; Slagboom, P Eline; Thompson, John R; Spector, Tim D; van der Harst, Pim; Samani, Nilesh J

    2013-04-01

    Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases. PMID:23535734

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

    PubMed Central

    2011-01-01

    Background There is little prior research on the burden of arthritis in the developing world. We sought to document how patients with advanced arthritis living in the Dominican Republic are affected by and cope with their disease. Methods We conducted semi-structured, one-to-one interviews with economically disadvantaged Dominican patients with advanced knee and/or hip arthritis in the Dominican Republic. The interviews, conducted in Spanish, followed a moderator's guide that included topics such as the patients' understanding of disease etiology, their support networks, and their coping mechanisms. The interviews were audiotaped, transcribed verbatim in Spanish, and systematically analyzed using content analysis. We assessed agreement in coding between two investigators. Results 18 patients were interviewed (mean age 60 years, median age 62 years, 72% women, 100% response rate). Patients invoked religious and environmental theories of disease etiology, stating that their illness had been caused by God's will or through contact with water. While all patients experienced pain and functional limitation, the social effects of arthritis were gender-specific: women noted interference with homemaking and churchgoing activities, while men experienced disruption with occupational roles. The coping strategies used by patients appeared to reflect their beliefs about disease causation and included prayer and avoidance of water. Conclusions Patients' explanatory models of arthritis influenced the psychosocial effects of the disease and coping mechanisms used. Given the increasing reach of global health programs, understanding these culturally influenced perceptions of disease will be crucial in successfully treating chronic diseases in the developing world. PMID:21985605

  20. Preclinical Development of New Therapy for Glycogen Storage Diseases

    PubMed Central

    Sun, Baodong; Brooks, Elizabeth D.; Koeberl, Dwight D.

    2015-01-01

    Glycogen storage disease (GSD) consists of more than 10 discrete conditions for which the biochemical and genetic bases have been determined, and new therapies have been under development for several of these conditions. Gene therapy research has generated proof-of-concept for GSD types I (von Gierke disease) and II (Pompe disease). Key features of these gene therapy strategies include the choice of vector and regulatory cassette, and recently adeno-associated virus (AAV) vectors containing tissue-specific promoters have achieved a high degree of efficacy. Efficacy of gene therapy for Pompe disease depend upon the induction of immune tolerance to the therapeutic enzyme. Efficacy of von Gierke disease is transient, waning gradually over the months following vector administration. Small molecule therapies have been evaluated with the goal of improving standard of care therapy or ameliorating the cellular abnormalities associated with specific GSDs. The receptor-mediated uptake of the therapeutic enzyme in Pompe disease was enhanced by administration of β2 agonists. Rapamycin reduced the liver fibrosis observed in GSD III. Further development of gene therapy could provide curative therapy for patients with GSD, if efficacy from preclinical research is observed in future clinical trials and these treatments become clinically available. PMID:26122079

  1. Preclinical Development of New Therapy for Glycogen Storage Diseases.

    PubMed

    Sun, Baodong; Brooks, Elizabeth D; Koeberl, Dwight D

    2015-01-01

    Glycogen storage disease (GSD) consists of more than 10 discrete conditions for which the biochemical and genetic bases have been determined, and new therapies have been under development for several of these conditions. Gene therapy research has generated proof-of-concept for GSD types I (von Gierke disease) and II (Pompe disease). Key features of these gene therapy strategies include the choice of vector and regulatory cassette, and recently adeno-associated virus (AAV) vectors containing tissue-specific promoters have achieved a high degree of efficacy. Efficacy of gene therapy for Pompe disease depend upon the induction of immune tolerance to the therapeutic enzyme. Efficacy of von Gierke disease is transient, waning gradually over the months following vector administration. Small molecule therapies have been evaluated with the goal of improving standard of care therapy or ameliorating the cellular abnormalities associated with specific GSDs. The receptor-mediated uptake of the therapeutic enzyme in Pompe disease was enhanced by administration of β2 agonists. Rapamycin reduced the liver fibrosis observed in GSD III. Further development of gene therapy could provide curative therapy for patients with GSD, if efficacy from preclinical research is observed in future clinical trials and these treatments become clinically available. PMID:26122079

  2. Proteomic analysis reveals suppression of bark chitinases and proteinase inhibitors in citrus plants affected by the citrus sudden death disease.

    PubMed

    Cantú, M D; Mariano, A G; Palma, M S; Carrilho, E; Wulff, N A

    2008-10-01

    Citrus sudden death (CSD) is a disease of unknown etiology that greatly affects sweet oranges grafted on Rangpur lime rootstock, the most important rootstock in Brazilian citriculture. We performed a proteomic analysis to generate information related to this plant pathogen interaction. Protein profiles from healthy, CSD-affected and CSD-tolerant stem barks, were generated using two-dimensional gel electrophoresis. The protein spots were well distributed over a pI range of 3.26 to 9.97 and a molecular weight (MW) range from 7.1 to 120 kDa. The patterns of expressed proteins on 2-DE gels made it possible to distinguish healthy barks from CSD-affected barks. Protein spots with MW around 30 kDa and pI values ranging from 4.5 to 5.2 were down-regulated in the CSD-affected root-stock bark. This set of protein spots was identified as chitinases. Another set of proteins, ranging in pI from 6.1 to 9.6 with an MW of about 20 kDa, were also suppressed in CSD-affected rootstock bark; these were identified as miraculin-like proteins, potential trypsin inhibitors. Down-regulation of chitinases and proteinase inhibitors in CSD-affected plants is relevant since chitinases are well-known pathogenesis-related protein, and their activity against plant pathogens is largely accepted. PMID:18943454

  3. Possible interaction between myxomatosis and calicivirosis related to rabbit haemorrhagic disease affecting the European rabbit.

    PubMed

    Marchandeau, S; Bertagnoli, S; Peralta, B; Boucraut-Baralon, C; Letty, J; Reitz, F

    2004-11-01

    Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD-like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996 and 1997 in two areas of France were analysed. For each disease, the effects of bodyweight, year, month and seropositivity for the other disease were modelled by using logistic regressions. In one area, a model including RHD seropositivity was selected to explain the myxoma virus seropositivity. Models including myxoma virus seropositivity were selected to explain the RHD seropositivity in both areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and 8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and seropositive to RHD. The year and bodyweight had significant effects for myxomatosis in one area and for RHD in both areas. PMID:15573951

  4. Gut microbiota and the development of pediatric diseases.

    PubMed

    Lu, Chun-Yi; Ni, Yen-Hsuan

    2015-07-01

    The human gut harbors a huge number of microbes, which are collectively named "microbiota." The dynamic composition of the human gut microbiota is determined by multiple factors, including mode of delivery, diet, environment, and antibiotics. A healthy gut microbiota is helpful to the host in many aspects, including providing nutrients, protection from pathogens, and maturation of immune responses. Dysbiosis plays important roles in various diseases in infancy and later life: necrotizing enterocolitis, inflammatory bowel disease, obesity, and atopic diseases are some examples. Studies of functional metagenomics by newly developed techniques, such as next-generation sequencing, will not only elucidate the molecular mechanisms underlying gut microbiota-host interactions but will also provide new possibilities for disease prevention and treatment. PMID:25917564

  5. Exploring the Role of Microorganisms in the Disease-Like Syndrome Affecting the Sponge Ianthella basta▿ †

    PubMed Central

    Luter, Heidi M.; Whalan, Steve; Webster, Nicole S.

    2010-01-01

    A disease-like syndrome is currently affecting a large percentage of the Ianthella basta populations from the Great Barrier Reef and central Torres Strait. Symptoms of the syndrome include discolored, necrotic spots leading to tissue degradation, exposure of the skeletal fibers, and disruption of the choanocyte chambers. To ascertain the role of microbes in the disease process, a comprehensive comparison of bacteria, viruses, fungi, and other eukaryotes was performed in healthy and diseased sponges using multiple techniques. A low diversity of microbes was observed in both healthy and diseased sponge communities, with all sponges dominated by an Alphaproteobacteria, a Gammaproteobacteria, and a group I crenarchaeota. Bacterial cultivation, community analysis by denaturing gradient gel electrophoresis (Bacteria and Eukarya), sequencing of 16S rRNA clone libraries (Bacteria and Archaea), and direct visual assessment by electron microscopy failed to reveal any putative pathogens. In addition, infection assays could not establish the syndrome in healthy sponges even after direct physical contact with affected tissue. These results suggest that microbes are not responsible for the formation of brown spot lesions and necrosis in I. basta. PMID:20622129

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

    PubMed

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

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease. PMID:27143113

  7. Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.

    PubMed

    Kho, Alvin T; Chhabra, Divya; Sharma, Sunita; Qiu, Weiliang; Carey, Vincent J; Gaedigk, Roger; Vyhlidal, Carrie A; Leeder, J Steven; Tantisira, Kelan G; Weiss, Scott T

    2016-06-01

    The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases. We analyzed whole-lung transcriptome profiles of 61 females and 78 males at 54-127 days postconception (dpc) from nonsmoking mothers using unsupervised principal component analysis and supervised linear regression models. We identified dominant transcriptomic correlates for postconception age and sex with corresponding gene sets that were enriched for developing lung structural and functional ontologies. We observed that the transcriptomic sex difference was not a uniform global time shift/lag, rather, lungs of males appear to be more mature than those of females before 96 dpc, and females appear to be more mature than males after 96 dpc. The age correlate gene set was consistently enriched for asthma and bronchopulmonary dysplasia genes, but the sex correlate gene sets were not. Despite sex differences in the developing fetal lung transcriptome, postconception age appears to be more dominant than sex in the effect of early fetal lung developments on disease risk during this early pseudoglandular phase of development. PMID:26584061

  8. Disease severity of organic rice as affected by host resistance, fertility and tillage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies were conducted to determine the effect of fertilizer inputs and tillage methods on disease incidence in an organic rice production system. The results of these studies suggest that organically produced rice is more vulnerable to infection of narrow brown leaf spot and brown spot. Thi...

  9. Differences in secondary metabolites in leaves from trees affected with the greening (HLB) disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Preliminary analyses by HPLC-MS of methanolic extracts of two sets of orange leaves that are symptomatic of the Greening Disease (HLB) have shown several consistent differences. The main flavonoids in symptomatic and nonsymptomatic leaves were monitored in the HPLC chromatograms at 330 nm, and signi...

  10. Imaging modalities and clinical assesment in men affected with Peyronie’s disease

    PubMed Central

    Pawłowska, Emilia; Bianek-Bodzak, Agnieszka

    2011-01-01

    Summary Background: Peyronie’s disease (PD) is characterized by the formation of fibrous tissue plaques within the tunica albuginea, usually causing a penile deformity and a subsequent erectile dysfunction. Diagnosis of PD is based on medical and sexual history, physical examination and imaging examinations, i.e.: ultrasound, color Doppler ultrasound, magnetic resonance and X-ray mammography. Material/Methods: Ultrasound appears superior to all other methods for depicting calcifications, with the detection rate of 100%. It is safe, non-invasive, repeatable and reliable. It should be a method of choice in most standard cases of Peyronie’s disease. With color Doppler ultrasound (CDU), one can find hyperperfusion around the plaques as a sign of inflammation in the active state of the disease. CDU is useful in diagnosing erectile dysfunction which is observed in most cases of PD. Results: MR is superior to US and X-ray as regards the detection of periplaque inflammation, though this information can be obtained from medical history and penile plaque palpation. MR, being an expensive imaging modality, should be reserved for special cases, i.e.: plaques located at the penile basis, a suspicion of malignant disease, and prior penile surgery. Conclusions: X-ray mammography is the most accurate in showing calcifications as well as the angle of penile curvature. However, the possibility of obtaining this information does not justify the use of ionizing radiation for that purpose. PMID:22802839

  11. Factors affecting milk ELISA scores of cows tested for Johne’s disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection with Mycobacterium avium subsp. paratuberculosis (Johne’s disease) has been estimated to cost dairy producers over $1.5 billion per year. The objective of this study was to examine the influence a number of environmental and genetic factors have on ELISA milk test scores for Johne’s diseas...

  12. Periodontal Health and Caries Prevalence Evaluation in Patients Affected by Parkinson's Disease

    PubMed Central

    Cicciù, Marco; Risitano, Giacomo; Lo Giudice, Giuseppe; Bramanti, Ennio

    2012-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder related to the loss or absence of dopaminergic neurons in the brain. These deficits result in slowness of movement, tremor, rigidity, and dysfunction of behaviour. These symptoms negatively influence the patient's capability to carry out the daily oral hygiene manoeuvres. The aim of this work is to record the oral health condition of PD patients evaluated at the IRCSS Bonino-Puleio in Messina. The oral health of 45 consecutive PD patients (study group) with neurologic diagnosis based on United Kingdom Brain Bank Criteria has been compared with that of another 45 no PD patients of the same age (control group). The evaluation of the general oral condition was recorded underlining tooth loss, active periodontal disease, and presence of untreated caries. The frequency of untreated caries, periodontal diseases, and missing teeth of the study group was significantly higher than in control group. Based on the data results, clinicians should direct high attention to the oral hygiene of patients with PD, above all at the early stages of the caries or periodontal disease, in order to prevent serious evolution of those pathologic dental conditions that may finally result in the tooth extraction event. PMID:23320249

  13. Fungicide applications affect fruit diseases and quality of muscadine grape (Vitis rotundifolia Michx.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungicides can significantly reduce losses due to disease in the yield and quality of muscadine grapes. In three studies fungicides were applied individually or as part of a full season schedule from early bloom until harvest of three muscadine cultivars. The objective was to compare the effect of a...

  14. POLYMORPHISMS IN CYTOPLASMIC SERINE HYDROXYMETHYLTRANSFERASE AND METHYLENETETRAHYDROFOLATE REDUCTASE AFFECT THE RISK OF CARDIOVASCULAR DISEASE IN MEN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic variation in folate-regulating enzymes contributes to the risk of cardiovascular disease (CVD). The cytoplasmic serine hydroxymethyltransferase (cSHMT) enzyme is proposed to regulate a key metabolic intersection in folate metabolism. We hypothesized that a variant in cSHMT (cSHMT 1420CT) aff...

  15. Evolutionary changes affecting rapid identification of 2008 Newcastle disease viruses isolated from double-crested cormorants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An outbreak of virulent Newcastle Disease Virus (NDV) in wild double-breasted cormorants (Phalacrocorax auritus) occurred in North America in the summer of 2008. All ten viruses isolated from cormorants were positively identified by the USDA validated real-time reverse transcriptase polymerase chai...

  16. TRIM-NHL proteins in development and disease.

    PubMed

    Tocchini, Cristina; Ciosk, Rafal

    2015-12-01

    TRIM-NHL proteins are key regulators of developmental transitions, for example promoting differentiation, while inhibiting cell growth and proliferation, in stem and progenitor cells. Abnormalities in these proteins have been also associated with human diseases, particularly affecting muscular and neuronal functions, making them potential targets for therapeutic intervention. The purpose of this review is to provide a systematic and comprehensive summary on the most studied TRIM-NHL proteins, highlighting examples where connections were established between structural features, molecular functions and biological outcomes. PMID:26514622

  17. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  18. Genetic variants in IL2RA and IL7R affect multiple sclerosis disease risk and progression.

    PubMed

    Traboulsee, Anthony L; Bernales, Cecily Q; Ross, Jay P; Lee, Joshua D; Sadovnick, A Dessa; Vilariño-Güell, Carles

    2014-08-01

    Multiple sclerosis (MS) is a common demyelinating neurodegenerative disease with a strong genetic component. Previous studies have associated genetic variants in IL2RA and IL7R in the pathophysiology of the disease. In this study, we describe the association between IL2RA (rs2104286) and IL7R (rs6897932) in the Canadian population. Genotyping 1,978 MS patients and 830 controls failed to identify any significant association between these variants and disease risk. However, stratified analysis for family history of disease and disease course identified a trend towards association for IL2RA in patients without a family history (p = 0.05; odds ratio = 0.77) and a significant association between IL7R and patients who developed progressive MS (PrMS) (p = 0.002; odds ratio = 0.73). Although not statistically significant, the effect of IL2RA (rs2104286) in patients without a family history of MS indicates that the genetic components for familial and sporadic disease are perhaps distinct. This data suggests that the onset of sporadic disease is likely determined by a large number of variants of small effect, whereas MS in patients with a family history of disease is caused by a few deleterious variants. In addition, the significant association between PrMS and rs6897932 indicates that IL7R may not be disease-causing but a determinant of disease course. Further characterization of the effect of IL2RA and IL7R genetic variants in defined MS subtypes is warranted to evaluate the effect of these genes on specific clinical outcomes and to further elucidate the mechanisms of disease onset and progression. PMID:24770783

  19. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    DOE PAGESBeta

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; et al

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  20. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    SciTech Connect

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; Perelson, Alan S.; Dahari, Harel

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver diseasemax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

  1. Development and Evaluation of the Protective Efficacy of Novel Marek's Disease Virus Rispens Vector Vaccines Against Infectious Bursal Disease.

    PubMed

    Ishihara, Yukari; Esaki, Motoyuki; Saitoh, Shuji; Sato, Takanori; Yasuda, Atsushi

    2016-09-01

    Infectious bursal disease (IBD) is a major disease affecting the poultry industry and is caused by infection with IBD virus (IBDV). To develop a novel vaccine to prevent IBD in chickens, recombinant Marek's disease virus Rispens viruses carrying the VP2 gene of IBDV driven by five different promoters (Rispens/IBD) were constructed using homologous recombination and a bacterial artificial chromosome (BAC). Rispens/IBD driven by the chicken beta-actin (Bac) promoter (Rispens/Bac-IBD), Rous sarcoma virus promoter, or simian virus 40 promoter were administered to 1-day-old SPF chicks, and the protective efficacy against IBDV was evaluated by challenging chicks with virulent IBDV. As a result, Rispens/Bac-IBD showed the best protection (87%). Next, we constructed the virus driven by the Bac-derived Coa5 promoter (Rispens/Coa5-IBD) for a secondary in vivo trial using commercial layer chickens since Rispens/Bac-IBD was thought to be genetically unstable. Rispens/Coa5-IBD showed stability in vitro and exhibited better antibody production and protection during challenge against virulent IBDV at both 5 (95%) and 7 wk of age (91%) compared with that of Rispens/Bac-IBD (90% at 5 wk of age and 84% at 7 wk of age). Thus, Rispens/Coa5-IBD may be a novel promising vaccine against IBD and virulent Marek's disease. PMID:27610721

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

    PubMed Central

    Zhang, Qing-Jun; Liu, Zhi-Ping

    2015-01-01

    Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases. PMID:25942538

  3. Biotechnology in the diagnosis of infectious diseases and vaccine development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molecular biological methods have become increasingly applicable to the diagnosis of infectious diseases and vaccine development. To become widely used the methods need to be easy, safe, sensitive, reproducible and eventually automated to facilitate the evaluation of large number of samples. The p...

  4. Development and Coherence of Beliefs Regarding Disease Causality and Prevention

    ERIC Educational Resources Information Center

    Sigelman, Carol K.

    2014-01-01

    Guided by a naïve theories perspective on the development of thinking about disease, this study of 188 children aged 6 to 18 examined knowledge of HIV/AIDS causality and prevention using parallel measures derived from open-ended and structured interviews. Knowledge of both risk factors and prevention rules, as well as conceptual understanding of…

  5. Factors Affecting Female Participation in Education in Seven Developing Countries. Second Edition. Education Research Paper.

    ERIC Educational Resources Information Center

    Brock, Colin; Cammish, Nadine

    Factors affecting female participation in education in seven developing countries were examined through field visits to the following countries: Bangladesh, Cameroon, India, Jamaica, Seychelles, Sierra Leone, and Vanuatu. In each country, researchers interviewed key personnel, consulted local documentation, and conducted two empirical surveys…

  6. Opinions of Primary School Science and Technology Teachers about Developing Students' Affective Competence

    ERIC Educational Resources Information Center

    Eristi, Bahadir; Tunca, Nihal

    2012-01-01

    The present study aimed to determine the primary school secondary level science and technology teachers' opinions about developing students' affective competence. It was designed as a case study with qualitative research method. The participants of the study consisted of 19 science and technology teachers with at least five years of experience,…

  7. The Effect of Differentiation Approach Developed on Creativity of Gifted Students: Cognitive and Affective Factors

    ERIC Educational Resources Information Center

    Altintas, Esra; Özdemir, Ahmet S.

    2015-01-01

    The aim of the study is to develop a differentiation approach for the mathematics education of gifted middle school students and to determine the effect of the differentiation approach on creative thinking skills of gifted students based on both cognitive and affective factors. In this context, the answer to the following question was searched:…

  8. Factors that Affect Emergent Literacy Development When Engaging with Electronic Books

    ERIC Educational Resources Information Center

    Salmon, Lynda G.

    2014-01-01

    This article reviews extant literature with the purpose of identifying factors that affect the potential efficacy of electronic books to support literacy development during early childhood. Selection criteria include experimental, quasi-experimental, and observational studies from peer-reviewed journals from 2000 to 2013 with a target population…

  9. Does Intellectual Disability Affect the Development of Dental Caries in Patients with Cerebral Palsy?

    ERIC Educational Resources Information Center

    Moreira, Rafaela Nogueira; Alcantara, Carlos Eduardo Pinto; Mota-Veloso, Isabella; Marinho, Sandra Aparecida; Ramos-Jorge, Maria L.; Oliveira-Ferreira, Fernanda

    2012-01-01

    The aim of this study was to evaluate if the severity of intellectual disability is a factor that affects the development of dental cavities in patients with cerebral palsy. This cross-sectional study was conducted on 165 individuals who were selected from a physical rehabilitation center, a special public school and a regular public school. Of…

  10. Interest Groups and the Development of Federal Legislation Affecting Older Americans.

    ERIC Educational Resources Information Center

    Harootyan, Robert A.

    Changes in the development of federal legislation affecting the elderly are analyzed in this study, which concentrates on the use of chronological and non-chronological eligibility criteria. Data for this research are contained in a computerized annotated index of federal legislation impacting on older Americans. The index covers seven major areas…

  11. Early Experiences Can Alter Gene Expression and Affect Long-Term Development. Working Paper #10

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2010

    2010-01-01

    New scientific research shows that environmental influences can actually affect whether and how genes are expressed. Thus, the old ideas that genes are "set in stone" or that they alone determine development have been disproven. In fact, scientists have discovered that early experiences can determine how genes are turned on and off and even…

  12. The Development of an Emotional Response to Literature Measure: The Affective Response to Literature Survey

    ERIC Educational Resources Information Center

    Fischer, Ronald G.; Fischer, Jerome M.

    2006-01-01

    Based on theories of emotional intelligence, adult education, psychology of reading, and emotions and literature, this study was designed to develop and validate the Affective Response to Literature Survey (ARLS), a psychological instrument used to measure an emotional response to literature. Initially, 27 items were generated by a review of…

  13. Factors Affecting Work Force Development in the People's Republic of China.

    ERIC Educational Resources Information Center

    Sredl, Henry J.

    Work force development in the Peoples' Republic of China (PRC) is affected by sundry but interrelated factors. Included among these are the following: (1) the PRC's population of one billion people; (2) a recent history of political turmoil and violence, resulting in profound changes in national leadership and vacillation in national policy; (3)…

  14. Variables Affecting the Effects of Recasts on L2 Pronunciation Development

    ERIC Educational Resources Information Center

    Saito, Kazuya

    2015-01-01

    The current study investigated how recasts can promote the L2 pronunciation development of word-initial /?/ by Japanese learners of English in relation to two developmental stages of English /?/ acquisition (i.e. change in second formant [F2] ? change in third formant [F3]) as well as four affecting variables (i.e. the amount of recasts and…

  15. Dogs in the Hall: A Case Study of Affective Skill Development in an Urban Veterinary Program

    ERIC Educational Resources Information Center

    Martin, Michael; Tummons, John; Ball, Anna; Bird, William

    2014-01-01

    The purpose of this bounded single case study was to explore how an urban high school veterinary program impacted students' affective skill development. The program was unique because students were required to participate in internships with local animal care businesses and care for animals within the school veterinary laboratory. The…

  16. A Sharing Experience: Development of a Group for Families Affected by HIV Infection.

    ERIC Educational Resources Information Center

    Melvin, Diane; Appleby, Sue

    1995-01-01

    Describes the establishment and development of a support group for the parents of children infected and/or affected by HIV infection. The group is hospital-based, meeting monthly since April 1992, facilitated by professionals but with a self-help and peer support emphasis. Explains the planning, setting, and running of the group. Identifies…

  17. The Federal Policy Landscape: A Look at How Legislation Affects Professional Development

    ERIC Educational Resources Information Center

    Islas, M. Rene

    2010-01-01

    Four years ago, Learning Forward established "affecting the policy context" as the first of five strategic priorities that would guide its efforts through 2011. Learning Forward believes that good policy promotes good practice and that laws and policies that promote and support effective professional development are needed to achieve the…

  18. On the Affective Challenges of Developing a Pedagogy of Teacher Education

    ERIC Educational Resources Information Center

    Ritter, Jason K.

    2011-01-01

    This article reports on the affective challenges I experienced while attempting to develop a pedagogy of teacher education during my first three years in teacher preparation. Data were collected systematically over the course of the study in the form of written interpretive accounts of my experiences. Analysis of these accounts revealed how…

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

    PubMed Central

    Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, BT; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto

    2013-01-01

    Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children’s Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA. PMID:23151163

  20. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    PubMed

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today. PMID:26573709

  1. Health innovation networks to help developing countries address neglected diseases.

    PubMed

    Morel, Carlos M; Acharya, Tara; Broun, Denis; Dangi, Ajit; Elias, Christopher; Ganguly, N K; Gardner, Charles A; Gupta, R K; Haycock, Jane; Heher, Anthony D; Hotez, Peter J; Kettler, Hannah E; Keusch, Gerald T; Krattiger, Anatole F; Kreutz, Fernando T; Lall, Sanjaya; Lee, Keun; Mahoney, Richard; Martinez-Palomo, Adolfo; Mashelkar, R A; Matlin, Stephen A; Mzimba, Mandi; Oehler, Joachim; Ridley, Robert G; Senanayake, Pramilla; Singer, Peter; Yun, Mikyung

    2005-07-15

    Gross inequities in disease burden between developed and developing countries are now the subject of intense global attention. Public and private donors have marshaled resources and created organizational structures to accelerate the development of new health products and to procure and distribute drugs and vaccines for the poor. Despite these encouraging efforts directed primarily from and funded by industrialized countries, sufficiency and sustainability remain enormous challenges because of the sheer magnitude of the problem. Here we highlight a complementary and increasingly important means to improve health equity: the growing ability of some developing countries to undertake health innovation. PMID:16020723

  2. Sonic Hedgehog Signaling in the Lung. From Development to Disease

    PubMed Central

    Joyner, Alexandra L.; Loomis, Cynthia A.; Munger, John S.

    2015-01-01

    Over the past two decades, the secreted protein sonic hedgehog (SHH) has emerged as a critical morphogen during embryonic lung development, regulating the interaction between epithelial and mesenchymal cell populations in the airway and alveolar compartments. There is increasing evidence that the SHH pathway is active in adult lung diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, and lung cancer, which raises two questions: (1) What role does SHH signaling play in these diseases? and (2) Is it a primary driver of the disease or a response (perhaps beneficial) to the primary disturbance? In this review we aim to fill the gap between the well-studied period of embryonic lung development and the adult diseased lung by reviewing the hedgehog (HH) pathway during the postnatal period and in adult uninjured and injured lungs. We elucidate the similarities and differences in the epithelial–mesenchymal interplay during the fibrosis response to injury in lung compared with other organs and present a critical appraisal of tools and agents available to evaluate HH signaling. PMID:25068457

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

    PubMed

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

    2016-01-01

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

  4. Understanding graft-versus-host disease. Preliminary findings regarding the effects of exercise in affected patients.

    PubMed

    Fiuza-Luces, Carmen; Garatachea, Nuria; Simpson, Richard J; Berger, Nathan A; Ramírez, Manuel; Lucia, Alejandro

    2015-01-01

    Advances in this century regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) have led to an expanding population of long-term survivors, many of whom suffer severe side effects, particularly those related to graft-versushost disease (GVHD), a potentially multi-systemic disorder caused by immunoeffector donor lymphocytes that destroy host tissues. The GVHD, especially in its chronic form (cGVHD), generates considerable morbidity and compromises the physical capacity of patients. We have reviewed the main pathophysiological aspects of the disease as well as the data available on the effects of exercise in GVHD, based on animal and human patient research. Although exercise training as an adjunct therapy to improve health outcomes after allo-HSCT shows promise (particularly, this lifestyle intervention can improve physical fitness and possibly immune function while attenuating fatigue), there is a need for more randomized control trials that focus specifically on GVHD. PMID:25826127

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

    PubMed Central

    Ajami, Sima; Askarianzadeh, Mahdi; Mortazavi, Mojgan

    2015-01-01

    Background: Disease registry is a database that includes information about people suffering a special kind of disease. The aim of this study was to first identify and compare the National Renal Disease Registry (NRDR) characteristics in some countries with Iran; and second, develop a provisional and NRDR for Iran. Materials and Methods: Retrieval of data of the NRDR was performed by scholars responsible in related agencies, including the Ministry of Health and Medical Education, Renal Disease charity, and data registries in the United States, United Kingdom, Malaysia, and Iran. This research was applied, and the study was descriptive-comparative. The study population consisted of the NRDR in selected countries in which data were collected by forms that were designed according to the study objectives. Sources of data were researchers, articles, books, journals, databases, websites, related documents, and people who are active in this regard, and related agencies, including the Ministry of Health and Medical Education, and patient support charity. The researchers collected data for each country based on the study objectives and then put them in comparative tables. Data were analyzed by descriptive, comparative, and theoretical methods. Results: Most of the renal transplant teams report their own results as a single center experiences. America and Britain have a preeminent national registry of renal disease compared to other countries. Conclusion: Given that control, prevention, and treatment of chronic renal diseases incur high expenses and the disease is one of leading mortality factors in Iran and across the world and since national registry system for chronic renal diseases can provide better tools and strategies to manage and evaluate patients’ characteristics as well as risk factors which eventually leads to making better decisions. PMID:26109970

  6. Socioeconomic status affects pulmonary hypertension disease severity at time of first evaluation

    PubMed Central

    Sahni, Sonu; Talwar, Ankoor; Kohn, Nina; Klinger, James R.

    2016-01-01

    Abstract A low socioeconomic status (SES) has been linked to disproportionate access to health care in many diseases, leading to worse disease severity at initial presentation. There is a paucity of these data in the pulmonary hypertension (PHTN) population. We studied the association of SES, as measured by zip code–based median annual household income, with World Health Organization functional class (WHO-FC) at time of first evaluation in PHTN patients. All patients evaluated at our center with a right heart catheterization revealing a mean pulmonary artery pressure of ≥25 mmHg within 12 months of initial evaluation were considered for the study. Demographics, WHO-FC, and zip codes were obtained from retrospective chart analysis. The 2010 US census was used to obtain zip code–based annual median income. The income groups were divided into quartiles. Patients were categorized by their WHO-FC and zip code–derived median income. Similar analyses were conducted for pulmonary arterial hypertension (PAH) patients. Survival was estimated with the Kaplan-Meier method. Data were analyzed in SAS, and P < 0.05 was considered significant. There were 228 PHTN patients (70 [30.7%] male, 158 [69.3%] female). As median income decreased, the FC at presentation increased, signifying higher disease severity (Spearman correlation: r = −0.161, P < 0.0515). This association between median income groups and WHO-FC at initial evaluation was significant (χ2 test: P < 0.0168). There were 116 PAH patients (32 [27.6%] male, 84 [72.4%] female). There was again a negative relationship between income and initial FC (Spearman correlation: r = −0.0307, P < 0.0007). A lower SES was associated with worse disease, as measured by WHO-FC. PMID:27252845

  7. How Ambient Humidity May Affect the Transmission of Viral Infectious Diseases

    NASA Astrophysics Data System (ADS)

    Yang, Wan; Marr, Linsey; Elankumaran, Subbiah

    2013-04-01

    Viral infectious diseases such as influenza have been a great burden to public health. The airborne transmission route is an important venue for the spread of many respiratory viral diseases. Many airborne viruses have been shown to be sensitive to ambient humidity, yet the mechanisms responsible for this phenomenon remain elusive. A thorough understanding of this phenomenon may provide insight into the temporal and spatial distribution of diseases. For instance, studies have repeatedly suggested ambient humidity as an important environmental determinant in the transmission of influenza in temperate regions. Further, knowing how to optimize humidity so as to minimize virus survival may have practical implications for disease prevention. In this talk, we will discuss multiple mechanisms that may account for the association between humidity and viability of viruses in aerosols, including water activity, surface inactivation, salt toxicity, and conformational changes to the virus in response to varying pH. As a case study, we will discuss our work on the effect of relative humidity (RH) on survival of influenza A virus (IAV) and how it may contribute to the transmission patterns of seasonal flu around the world. We measured the change in viability of IAV in droplets at various RHs. Results suggest three potential regimes defined by humidity: physiological (~100% RH) with high viability, concentrated (~50% to near 100% RH) with lower viability, and dry (<~50% RH) with high viability. Based on these results, we propose a mechanistic basis for the dependence of IAV's transmission on humidity. In temperate regions, the increase in influenza activity in winter may be due to enhanced transmission via the aerosol route thanks to IAV's higher viability in droplets at low RH. In tropical regions, transmission could be enhanced due to high viability of IAV at extremely high RH (rainy season), as observed in our study, possibly through both the aerosol route and the contact

  8. Socioeconomic status affects pulmonary hypertension disease severity at time of first evaluation.

    PubMed

    Talwar, Arunabh; Sahni, Sonu; Talwar, Ankoor; Kohn, Nina; Klinger, James R

    2016-06-01

    A low socioeconomic status (SES) has been linked to disproportionate access to health care in many diseases, leading to worse disease severity at initial presentation. There is a paucity of these data in the pulmonary hypertension (PHTN) population. We studied the association of SES, as measured by zip code-based median annual household income, with World Health Organization functional class (WHO-FC) at time of first evaluation in PHTN patients. All patients evaluated at our center with a right heart catheterization revealing a mean pulmonary artery pressure of ≥25 mmHg within 12 months of initial evaluation were considered for the study. Demographics, WHO-FC, and zip codes were obtained from retrospective chart analysis. The 2010 US census was used to obtain zip code-based annual median income. The income groups were divided into quartiles. Patients were categorized by their WHO-FC and zip code-derived median income. Similar analyses were conducted for pulmonary arterial hypertension (PAH) patients. Survival was estimated with the Kaplan-Meier method. Data were analyzed in SAS, and P < 0.05 was considered significant. There were 228 PHTN patients (70 [30.7%] male, 158 [69.3%] female). As median income decreased, the FC at presentation increased, signifying higher disease severity (Spearman correlation: r = -0.161, P < 0.0515). This association between median income groups and WHO-FC at initial evaluation was significant (χ(2) test: P < 0.0168). There were 116 PAH patients (32 [27.6%] male, 84 [72.4%] female). There was again a negative relationship between income and initial FC (Spearman correlation: r = -0.0307, P < 0.0007). A lower SES was associated with worse disease, as measured by WHO-FC. PMID:27252845

  9. Recent advances in prostate development and links to prostatic diseases.

    PubMed

    Powers, Ginny L; Marker, Paul C

    2013-01-01

    The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signaling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression, expression profiling microarrays, and other large-scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multilab projects including the Genitourinary Developmental Molecular Atlas Project has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases. PMID:23335485

  10. Congenital familial myasthenic syndromes: disease and course in an affected dizygotic twin pair

    PubMed Central

    Pavone, Piero; Praticò, Andrea Domenico; Pavone, Vito; Falsaperla, Raffaele

    2013-01-01

    The present report describes clinical variability in an affected dizygotic twin pair. Twin 1 showed classical features of the congenital myasthenic syndromes (CMS), that is, ptosis, dysphonia, asthenia and hypotonia. In twin 2, these clinical signs were less pronounced, but subtle resulting in severe lumbar hyperlordosis. Molecular analysis, performed for both twins, revealed the presence of three polymorphisms in the heterozygous form in RAPSN gene. The present report highlights the clinical variability of the CMS. PMID:23365176

  11. Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson's disease.

    PubMed

    Péron, Julie; Biseul, Isabelle; Leray, Emmanuelle; Vicente, Siobhan; Le Jeune, Florence; Drapier, Sophie; Drapier, Dominique; Sauleau, Paul; Haegelen, Claire; Vérin, Marc

    2010-01-01

    Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) can produce emotional disorders that have been linked to disturbance of the STN's limbic territory. The aim of this study was to confirm the impairment of the recognition of facial emotions (RFE) induced by STN DBS, not only ruling out the effect of the disease's natural progression in relation to the effect of DBS, but also assessing the influence of modifications in dopamine replacement therapy (DRT) following STN DBS. RFE was investigated in 24 PD patients who underwent STN DBS and 20 PD patients treated with apomorphine. They were assessed 3 months before and after treatment. The 2 patient groups were compared with a group of 30 healthy matched controls. The results showed that RFE for negative emotions (fear and sadness) was impaired in only the STN DBS group in the posttreatment condition and was unrelated to DRT. Results confirm the selective reduction of RFE induced by STN DBS, due neither to the disease's natural progression nor to modifications in DRT. PMID:20063943

  12. Transcriptome Changes Affecting Hedgehog and Cytokine Signalling in the Umbilical Cord: Implications for Disease Risk

    PubMed Central

    Stünkel, Walter; Tng, Emilia; Tan, Jun Hao; Chen, Li; Joseph, Roy; Cheong, Clara Y.; Ong, Mei-Lyn; Lee, Yung Seng; Chong, Yap-Seng; Saw, Seang Mei; Meaney, Michael J.; Kwek, Kenneth; Sheppard, Allan M.; Gluckman, Peter D.; Holbrook, Joanna D.

    2012-01-01

    Background Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA. Methods The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698–4151 g) and gestational ages (35–41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity. Results We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome. Conclusions We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk. PMID:22808055

  13. [Pneumonectomy for benign disease: indication and factors affecting the postoperative course].

    PubMed

    Arame, A; Rivera, C; Mordant, P; Pricopi, C; Foucault, C; Badia, A; Le Pimpec Barthes, F; Riquet, M

    2015-02-01

    Pneumonectomy for benign disease is rare but may generate more postoperative morbimortality than when performed for lung cancer. We questioned this assessment and retrospectively reviewed 1436 pneumonectomies and 54 completions of which 82 and 10 performed for benign disease (5.7% and 18.5%, respectively): left n=65 and right n=27. Indications were: post-tuberculosis destroyed lung (n=37), aspergilloma (n=18), bronchiectasis (n=19), infection (n=5), congenital malformations (n=5), inflammatory pseudotumor (n=3), trauma (n=2), post-radiation (n=2) and mucormycosis (n=1). Pneumonectomy consisted of 48 standard and 44 pleuro-pneumonectomies. Stump coverage by flaps was performed in 66.3% (61/92). Complications occurred in 21.7% (20/92) and postoperative deaths in 7.6% (7/92, of which 5 with fungal infections), which was not different than what was observed in lung cancer. There was no difference in fistula formation and mortality regarding the side, the type of resection and the protective role of stump coverage. Considering patients with fungal infections versus others, mortality was 26.3% (n=5/19) and 2.7% (n=2/74), respectively (P=0.0028). Pneumonectomy for benign disease achieves cure with acceptable mortality and morbidity. However, presence of fungal infection should raise the attention for possibility of increased postoperative risks. PMID:25131368

  14. Subregions of the inferior parietal lobule are affected in the progression to Alzheimer's disease.

    PubMed

    Greene, Sarah J; Killiany, Ronald J

    2010-08-01

    Changes in several regions within the brain have been associated with progression from healthy aging to Alzheimer's disease (AD), including the hippocampus, entorhinal cortex, and the inferior parietal lobule (IPL). In this study, the IPL was divided into three subregions: the gyrus, the banks of the sulcus, and the fundus to determine if these regions are independent of medial temporal regions in the progression of AD. Participants of the Alzheimer's disease Neuroimaging Initiative (Alzheimer's disease Neuroimaging initiative (ADNI); n = 54) underwent a structural magnetic resonance imaging (MRI) scan and neuropsychological examination, and were categorized as normal controls, mild cognitively impaired (MCI), or AD. FreeSurfer was initially used to identify the boundaries of the IPL. Each subregion was then manually traced based on FreeSurfer curvature intensities. Multivariate analyses of variance were used to compare groups. Results suggest that changes in thickness of the banks of the inferior parietal lobule are occurring early in the progression from normal to MCI, followed by changes in the gyrus and fundus, and these measures are related to neuropsychological performance. PMID:20570398

  15. Area-wide biological control of disease vectors and agents affecting wildlife.

    PubMed

    Reichard, R E

    2002-04-01

    Two examples of area-wide programmes, employing the sterile insect technique (SIT), which have eradicated a parasite and a disease vector common to domestic and wild animals are described. New World screwworm (NWS), Cochliomyia hominivorax, caused significant morbidity and mortality of livestock and wild mammals in tropical and subtropical areas of America before eradication was achieved in North America using the SIT and other components of an integrated pest management (IPM) programme. Movement of wild as well as domestic animals from an area which is infested with screwworm to a free area requires prophylactic treatment. Tsetse fly-borne trypanosomosis has an immense influence on the distribution of people and livestock in Africa. The immunotolerance of wildlife to the parasites is an important factor in maintaining some areas livestock free as wildlife refuges. Slaughter has ceased of wild hoofstock species considered to be disease reservoirs for control purposes. The SIT, combined with other IPM measures, has resulted in the eradication of the tsetse fly and trypanosomosis from Zanzibar. Other programmes in Africa are underway. Microbial 'biopesticides' have also been employed successfully against plant insect pests and some vectors of human disease. It seems likely that for the immediate future, wildlife may benefit from area-wide biological control programmes, intended mainly to protect humans and/or domestic animals. PMID:11974628

  16. [Mechanism of the development of neuromuscular disorders in Itsenko-Cushing disease].

    PubMed

    Agafonov, B V; Lahutina, T S; Deianova, A F

    1982-01-01

    The results of electromyographic studies indicate that the affection of the neuromuscular system is seen in all the patients with Icenko-Cushing's disease. Changes in different indices of the electromyogram (EMG), i.e. denervation activity, a character of the summary EMG alteration, mean duration of the motor unit action potentials (MUAP), the number of polyphase action potentials, their amplitude and the MUAP synchronization in different spheres indicate a neurogenic character of this affection. It was shown that both denervation and reinnervation processes are more pronounced in the foot muscles than in the hand ones. The denervation process is seemed to be primarily developed in the foot muscles, followed by the hand musculature injury. Therefore, the changes in several EMG parameters may be seen during several stages of the disease in some muscles and not to be observed in the others. PMID:7156070

  17. Genetic variation in lipid desaturases and its impact on the development of human disease

    PubMed Central

    2010-01-01

    Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management. PMID:20565855

  18. Non-coding RNAs in Mammary Gland Development and Disease.

    PubMed

    Sandhu, Gurveen K; Milevskiy, Michael J G; Wilson, Wesley; Shewan, Annette M; Brown, Melissa A

    2016-01-01

    Non-coding RNAs (ncRNAs) are untranslated RNA molecules that function to regulate the expression of numerous genes and associated biochemical pathways and cellular functions. NcRNAs include small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs). They participate in the regulation of all developmental processes and are frequently aberrantly expressed or functionally defective in disease. This Chapter will focus on the role of ncRNAs, in particular miRNAs and lncRNAs, in mammary gland development and disease. PMID:26659490

  19. Rare Mutations of CACNB2 Found in Autism Spectrum Disease-Affected Families Alter Calcium Channel Function

    PubMed Central

    Breitenkamp, Alexandra F. S.; Matthes, Jan; Nass, Robert Daniel; Sinzig, Judith; Lehmkuhl, Gerd; Nürnberg, Peter; Herzig, Stefan

    2014-01-01

    Autism Spectrum Disorders (ASD) are complex neurodevelopmental diseases clinically defined by dysfunction of social interaction. Dysregulation of cellular calcium homeostasis might be involved in ASD pathogenesis, and genes coding for the L-type calcium channel subunits CaV1.2 (CACNA1C) and CaVβ2 (CACNB2) were recently identified as risk loci for psychiatric diseases. Here, we present three rare missense mutations of CACNB2 (G167S, S197F, and F240L) found in ASD-affected families, two of them described here for the first time (G167S and F240L). All these mutations affect highly conserved regions while being absent in a sample of ethnically matched controls. We suggest the mutations to be of physiological relevance since they modulate whole-cell Ba2+ currents through calcium channels when expressed in a recombinant system (HEK-293 cells). Two mutations displayed significantly decelerated time-dependent inactivation as well as increased sensitivity of voltage-dependent inactivation. In contrast, the third mutation (F240L) showed significantly accelerated time-dependent inactivation. By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD. In conclusion, the results of our first-time biophysical characterization of these three rare CACNB2 missense mutations identified in ASD patients support the hypothesis that calcium channel dysfunction may contribute to autism. PMID:24752249

  20. [Factors affecting the control of blood pressure and lipid levels in patients with cardiovascular disease: the PREseAP Study].

    PubMed

    Orozco-Beltrán, Domingo; Brotons, Carlos; Moral, Irene; Soriano, Nuria; Del Valle, María A; Rodríguez, Ana I; Pepió, Josep M; Pastor, Ana

    2008-03-01

    The aim of this observational study was to identify factors influencing the control of blood pressure (i.e., <140/90 mmHg, or <130/80 mmHg in diabetic patients) and low-density lipoprotein (LDL) cholesterol level (<100 mg/dL) in 1223 patients with cardiovascular disease. Overall, 70.2% of patients were men, and their mean age was 66.4 years. Blood pressure was poorly controlled in 50.9% (95% confidence interval [CI], 46.9%-54.8%) and the LDL cholesterol level was poorly controlled in 60.1% (95% CI, 56.3%-63.9%). Determinants of poor blood pressure control were diabetes, hypertension, no previous diagnosis of heart failure, previous diagnosis of peripheral artery disease or stroke, obesity, and no lipid-lowering treatment. Determinants of poor LDL cholesterol control were no lipid-lowering treatment, no previous diagnosis of ischemic heart disease, no antihypertensive treatment, and dyslipidemia. The factors affecting blood pressure control were different from those affecting LDL cholesterol control, an observation that should be taken into account when implementing treatment recommendations for achieving therapeutic objectives in secondary prevention. PMID:18361907

  1. The Eyes Absent proteins in development and disease.

    PubMed

    Tadjuidje, Emmanuel; Hegde, Rashmi S

    2013-06-01

    The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings. PMID:22971774

  2. Language Development and Learning to Read: The Scientific Study of How Language Development Affects Reading Skill

    ERIC Educational Resources Information Center

    McGuinness, Diane

    2005-01-01

    Research on reading has tried, and failed, to account for wide disparities in reading skill even among children taught by the same method. Why do some children learn to read easily and quickly while others, in the same classroom and taught by the same teacher, don't learn to read at all? In "Language Development and Learning to Read", Diane…

  3. The relationship between affective and cognitive development in Down's Syndrome infants.

    PubMed

    Cicchetti, D; Sroufe, L A

    1976-12-01

    A close association between affective expression and cognitive development was demonstrated in a longitudinal study of 14 Down's syndrome infants. It was found that the Down's syndrome infants laughed to groups of stimulus items in the same order as did previous samples of normal infants. Although the process was delayed by several months, the retarded babies too laughed first at physically intrusive items and only later to items calling for greater cognitive sophistication. In addition, cognitive developmental status, assessed by the Bayley and Uzgiris-Hunt scales, paralleled and was predicted by the level of affective development. Predictive and concurrent correlations between Bayley mental scores and various indices of affectivity ranged from .68 to .92. There was striking individual consistency across affective, mental, and motor measures, suggesting the organized nature of retarded development. Finally, since Down's syndrome infants frequently smiled under conditions when normal babies would laugh, a role for tension production, in addition to cognitive factors, was suggested in accounting for the behavior of these infants. PMID:137105

  4. Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

    PubMed Central

    Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

    2015-01-01

    Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

  5. Tissue stiffness dictates development, homeostasis, and disease progression.

    PubMed

    Handorf, Andrew M; Zhou, Yaxian; Halanski, Matthew A; Li, Wan-Ju

    2015-01-01

    Tissue development is orchestrated by the coordinated activities of both chemical and physical regulators. While much attention has been given to the role that chemical regulators play in driving development, researchers have recently begun to elucidate the important role that the mechanical properties of the extracellular environment play. For instance, the stiffness of the extracellular environment has a role in orienting cell division, maintaining tissue boundaries, directing cell migration, and driving differentiation. In addition, extracellular matrix stiffness is important for maintaining normal tissue homeostasis, and when matrix mechanics become imbalanced, disease progression may ensue. In this article, we will review the important role that matrix stiffness plays in dictating cell behavior during development, tissue homeostasis, and disease progression. PMID:25915734

  6. Systems analysis of salivary gland development and disease

    PubMed Central

    Larsen, Melinda; Yamada, Kenneth M.; Musselmann, Kurt

    2012-01-01

    Branching morphogenesis is a crucial developmental process in which vertebrate organs generate extensive epithelial surface area while retaining a compact size. In the vertebrate submandibular salivary gland, branching morphogenesis is crucial for generation of the large surface area necessary to produce sufficient saliva. However, in many salivary gland diseases, saliva-producing acinar cells are destroyed, resulting in dry mouth and secondary health conditions. Systems-based approaches can provide insights into understanding salivary gland development, function, and disease. The traditional approach to understanding these processes is identification of molecular signals using reductionist approaches; we review current progress with such methods in understanding salivary gland development. Taking a more global approach, multiple groups are currently profiling the transcriptome, the proteome, and other “omes” in both developing mouse tissues and in human patient samples. Computational methods have been successful in deciphering large data sets, and mathematical models are starting to make predictions regarding the contribution of molecules to the physical processes of morphogenesis and of cellular function. A challenge for the future will be to establish comprehensive, publicly accessible salivary gland databases spanning the full range of genes and proteins; plans are underway to provide these resources to researchers in centralized repositories. The greatest challenge for the future will be to develop realistic models that integrate multiple types of data to both describe and predict embryonic development and human disease. PMID:20890964

  7. Deiodinase Knockdown during Early Zebrafish Development Affects Growth, Development, Energy Metabolism, Motility and Phototransduction

    PubMed Central

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M.; Esguerra, Camila V.; Blust, Ronny; Darras, Veerle M.; Knapen, Dries

    2015-01-01

    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  8. Anthropogenic changes in sodium affect neural and muscle development in butterflies.

    PubMed

    Snell-Rood, Emilie C; Espeset, Anne; Boser, Christopher J; White, William A; Smykalski, Rhea

    2014-07-15

    The development of organisms is changing drastically because of anthropogenic changes in once-limited nutrients. Although the importance of changing macronutrients, such as nitrogen and phosphorus, is well-established, it is less clear how anthropogenic changes in micronutrients will affect organismal development, potentially changing dynamics of selection. We use butterflies as a study system to test whether changes in sodium availability due to road salt runoff have significant effects on the development of sodium-limited traits, such as neural and muscle tissue. We first document how road salt runoff can elevate sodium concentrations in the tissue of some plant groups by 1.5-30 times. Using monarch butterflies reared on roadside- and prairie-collected milkweed, we then show that road salt runoff can result in increased muscle mass (in males) and neural investment (in females). Finally, we use an artificial diet manipulation in cabbage white butterflies to show that variation in sodium chloride per se positively affects male flight muscle and female brain size. Variation in sodium not only has different effects depending on sex, but also can have opposing effects on the same tissue: across both species, males increase investment in flight muscle with increasing sodium, whereas females show the opposite pattern. Taken together, our results show that anthropogenic changes in sodium availability can affect the development of traits in roadside-feeding herbivores. This research suggests that changing micronutrient availability could alter selection on foraging behavior for some roadside-developing invertebrates. PMID:24927579

  9. Anthropogenic changes in sodium affect neural and muscle development in butterflies

    PubMed Central

    Snell-Rood, Emilie C.; Espeset, Anne; Boser, Christopher J.; White, William A.; Smykalski, Rhea

    2014-01-01

    The development of organisms is changing drastically because of anthropogenic changes in once-limited nutrients. Although the importance of changing macronutrients, such as nitrogen and phosphorus, is well-established, it is less clear how anthropogenic changes in micronutrients will affect organismal development, potentially changing dynamics of selection. We use butterflies as a study system to test whether changes in sodium availability due to road salt runoff have significant effects on the development of sodium-limited traits, such as neural and muscle tissue. We first document how road salt runoff can elevate sodium concentrations in the tissue of some plant groups by 1.5–30 times. Using monarch butterflies reared on roadside- and prairie-collected milkweed, we then show that road salt runoff can result in increased muscle mass (in males) and neural investment (in females). Finally, we use an artificial diet manipulation in cabbage white butterflies to show that variation in sodium chloride per se positively affects male flight muscle and female brain size. Variation in sodium not only has different effects depending on sex, but also can have opposing effects on the same tissue: across both species, males increase investment in flight muscle with increasing sodium, whereas females show the opposite pattern. Taken together, our results show that anthropogenic changes in sodium availability can affect the development of traits in roadside-feeding herbivores. This research suggests that changing micronutrient availability could alter selection on foraging behavior for some roadside-developing invertebrates. PMID:24927579

  10. Association of a DNA virus with grapevines affected by red blotch disease in California.

    PubMed

    Al Rwahnih, Maher; Dave, Ashita; Anderson, Michael M; Rowhani, Adib; Uyemoto, Jerry K; Sudarshana, Mysore R

    2013-10-01

    In the Napa Valley of California, vineyards of 'Cabernet Franc' (CF) clone 214, 'Cabernet Sauvignon' clone 337, and 'Zinfandel' clone 1A (Z1A) with grapevines exhibiting foliar symptoms of red blotches, marginal reddening, and red veins that were accompanied by reduced sugar accumulation in fruit at harvest were initially suspected to be infected with leafroll-associated viruses. However, reverse-transcription polymerase chain reaction (PCR) tests were negative for all known leafroll-associated viruses, with the exception of Grapevine leafroll-associated virus 2 in Z1A. Metagenomic analysis of cDNA libraries obtained from double-stranded RNA enriched nucleic acid (NA) preparations from bark scrapings of dormant canes on an Illumina platform revealed sequences having a distant relationship with members of the family Geminiviridae. Sequencing of products obtained by PCR assays using overlapping primers and rolling circle amplification (RCA) confirmed the presence of a single circular genome of 3,206 nucleotides which was nearly identical to the genome of a recently reported Grapevine cabernet franc-associated virus found in declining grapevines in New York. We propose to call this virus "Grapevine red blotch-associated virus" (GRBaV) to describe its association with grapevine red blotch disease. Primers specific to GRBaV amplified a product of expected size (557 bp) from NA preparations obtained from petioles of several diseased source vines. Chip bud inoculations successfully transmitted GRBaV to test plants of CF, as confirmed by PCR analysis. This is the first report of a DNA virus associated with red blotch disease of grapevines in California. PMID:23656312

  11. Weaning Markedly Affects Transcriptome Profiles and Peyer’s Patch Development in Piglet Ileum

    PubMed Central

    Inoue, Ryo; Tsukahara, Takamitsu; Nakatani, Masako; Okutani, Mie; Nishibayashi, Ryoichiro; Ogawa, Shohei; Harayama, Tomoko; Nagino, Takayuki; Hatanaka, Hironori; Fukuta, Kikuto; Romero-Pérez, Gustavo A.; Ushida, Kazunari; Kelly, Denise

    2015-01-01

    Transcriptome analyses were conducted on the ileal mucosa of 14- to 35-day-old piglets to investigate postnatal gut development during suckling and postweaning. The transcriptome profiles of 14-day-old suckling piglets showed a considerably higher number of differentially expressed genes than did those of 21-, 28-, and 35-day olds, indicating an intensive gut development during the first 14–21 postnatal days. In addition, the analysis of biological pathways indicated that Chemotaxis Leucocyte chemotaxis was the most significantly affected pathway in suckling piglets between 14 and 21 days of age. Weaning negatively affected pathways associated with acquired immunity, but positively affected those associated with innate immunity. Interestingly, pathway Chemotaxis Leucocyte chemotaxis was found positively affected when comparing 14- and 21-day-old suckling piglets, but negatively affected in 28-day-old piglets weaned at 21 days of age, when compared with 28-day-old suckling piglets. Genes CXCL13, SLA-DOA (MHC class II), ICAM1, VAV1, and VCAM1 were involved in the pathway Chemotaxis Leukocyte chemotaxis and they were found to significantly change between 14- and 21-day-old suckling piglets and between groups of suckling and weaned piglets. The expression of these genes significantly declined after weaning at 14, 21, and 28 days of age. This decline indicated that CXCL13, SLA-DOA, ICAM1, VAV1, and VCAM1 may be involved in the development of Peyer’s patches (PP) because lower gene expression clearly corresponded with smaller areas of PP in the ileal mucosa of piglets. Moreover, weaning piglets prior to a period of intensive gut development, i.e., 14 days of age, caused significant adverse effects on the size of PP, which were not reverted even 14 days postweaning. PMID:26697021

  12. Derivation of Huntington Disease affected Genea091 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea091 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 98% SSEA4 and gave a Pluritest pluripotency score of 38.36, Novelty of 1.35. The cell line was negative for Mycoplasma and visible contamination. PMID:27346013

  13. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346012

  14. Derivation of Huntington Disease affected Genea089 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea089 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 41 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a PluriTest Pluripotency score of 39.28, Novelty of 1.2. The cell line was negative for Mycoplasma and visible contamination. PMID:27346008

  15. Derivation of Huntington Disease affected Genea090 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea090 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a pluritest pluripotency score of 30.91, novelty of 1.23. The cell line was negative for Mycoplasma and visible contamination. PMID:27346026

  16. Derivation of Huntington disease affected Genea020 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Peura, Teija; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346007

  17. Scientific literature on infectious diseases affecting livestock animals, longitudinal worldwide bibliometric analysis.

    PubMed

    Ducrot, Christian; Gautret, Marjolaine; Pineau, Thierry; Jestin, André

    2016-01-01

    The objectives of this bibliometric analysis of the scientific literature were to describe the research subjects and the international collaborations in the field of research on infectious diseases in livestock animals including fishes and honeybees. It was based on articles published worldwide from 2006 through 2013. The source of data was the Web of Science, Core collection(®) and only papers fully written in English were considered. Queries were built that combined 130 descriptors related to animal species and 1213 descriptors related to diseases and pathogens. To refine and assess the accuracy of the extracted database, supplementary filters were applied to discard non-specific terms and neighbouring topics, and numerous tests were carried out on samples. For pathogens, annotation was done using a thematic terminology established to link each disease with its corresponding pathogen, which was in turn classified according to its family. A total of 62,754 articles were published in this field during this 8-year period. The average annual growth rate of the number of papers was 5%. This represents the reference data to which we compared the average annual growth rate of articles produced in each of the sub-categories that we defined. Thirty-seven percent of the papers were dedicated to ruminant diseases. Poultry, pigs and fishes were covered by respectively 21, 13 and 14% of the total. Thirty-seven percent of papers concerned bacteria, 33% viruses, 19% parasites, 2% prions, the remaining being multi-pathogens. Research on virology, especially on pigs and poultry, is increasing faster than the average. There also is increasing interest in monogastric species, fish and bees. The average annual growth rate for Asia was 10%, which is high compared to 3% for Europe and 2% for the Americas, indicating that Asia is currently playing a leading role in this field. There is a well established network of international collaborations. For 75% of the papers, the co

  18. [Infections related to central venous catheters in children affected from malignant diseases].

    PubMed

    Handrup, Mette Møller; Møller, Jens Kjølseth; Schrøder, Henrik

    2011-06-27

    Central venous catheters (CVC) are an essential part of the treatment of children with haematological and oncological diseases. Unfortunately, CVC also represent a major risk factor of bloodstream infections. Catheter-related bloodstream infections (CRBSI) in children are often diagnosed based on blood cultures from the CVC only. Most CRBSI can be treated without catheter removal. On suspicion of CRBSI empirical antibiotic treatment with piperacillin-tazobactam, meropenem or ampicillin in combination with gentamicin is recommended. The systemic treatment can be combined with catheter-lock therapy. PMID:21712011

  19. Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutation

    PubMed Central

    Han, Yongmei; Ripley, Barry; Serada, Satoshi; Naka, Tetsuji; Fujimoto, Minoru

    2016-01-01

    Background & Aim Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease. Recent evidence indicates that inflammation is associated with many neurodegenerative diseases including ALS. Previously, abnormal levels of inflammatory cytokines including IL-1β, IL-6 and TNF-α were described in ALS patients and/or in mouse ALS models. In addition, one study showed that blocking IL-1β could slow down progression of ALS-like symptoms in mice. In this study, we examined a role for IL-6 in ALS, using an animal model for familial ALS. Methods Mice with mutant SOD1 (G93A) transgene, a model for familial ALS, were used in this study. The expression of the major inflammatory cytokines, IL-6, IL-1β and TNF-α, in spinal cords of these SOD1 transgenic (TG) mice were assessed by real time PCR. Mice were then crossed with IL-6(-/-) mice to generate SOD1TG/IL-6(-/-) mice. SOD1 TG/IL-6(-/-) mice (n = 17) were compared with SOD1 TG/IL-6(+/-) mice (n = 18), SOD1 TG/IL-6(+/+) mice (n = 11), WT mice (n = 15), IL-6(+/-) mice (n = 5) and IL-6(-/-) mice (n = 8), with respect to neurological disease severity score, body weight and the survival. We also histologically compared the motor neuron loss in lumber spinal cords and the atrophy of hamstring muscles between these mouse groups. Results Levels of IL-6, IL-1β and TNF-α in spinal cords of SOD1 TG mice was increased compared to WT mice. However, SOD1 TG/IL-6(-/-) mice exhibited weight loss, deterioration in motor function and shortened lifespan (167.55 ± 11.52 days), similarly to SOD1 TG /IL-6(+/+) mice (164.31±12.16 days). Motor neuron numbers and IL-1β and TNF-α levels in spinal cords were not significantly different in SOD1 TG /IL-6(-/-) mice and SOD1 TG /IL-6 (+/+) mice. Conclusion These results provide compelling preclinical evidence indicating that IL-6 does not directly contribute to motor neuron disease caused by SOD1 mutations. PMID:27070121

  20. [Determination of an ELISA test on tissues of grapevine affected by yellow disease].

    PubMed

    Caudwell, A; Kuszala, C

    1992-10-01

    We report here results concerning the best part of the grapevine to section, the best sampling period and an important adaptation of the extraction media for the diagnosis of a grapevine yellow disease by ELISA. The addition of Triton-X100, or better of Chaps enabled us to get clear results for the sensitive Vitis vinifera scion varieties. Until now, results have not been obtained for the symptomless root stock varieties. However, antigen concentration by molecular filtration may be a way to solve the problem of assaying root stocks. PMID:1298032

  1. Advances in pediatric rhabdomyosarcoma characterization and disease model development

    PubMed Central

    Brien, Dennis O’; Jacob, Aishwarya G.; Qualman, Stephen J.; Chandler, Dawn S.

    2014-01-01

    Summary Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor Xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades. PMID:22127592

  2. Oxidative Stress and Therapeutic Development in Lung Diseases

    PubMed Central

    Villegas, Leah; Stidham, Timothy; Nozik-Grayck, Eva

    2016-01-01

    Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies. PMID:27019769

  3. Fabry Disease – Current Treatment and New Drug Development

    PubMed Central

    Motabar, Omid; Sidransky, Ellen; Goldin, Ehud; Zheng, Wei

    2010-01-01

    Fabry disease is a rare inherited lysosomal storage disorder caused by a partial or complete deficiency of α-galactosidase A (GLA), resulting in the storage of excess cellular glycosphingolipids. Enzyme replacement therapy is available for the treatment of Fabry disease, but it is a costly, intravenous treatment. Alternative therapeutic approaches, including small molecule chaperone therapy, are currently being explored. High throughput screening (HTS) technologies can be utilized to discover other small molecule compounds, including non-inhibitory chaperones, enzyme activators, molecules that reduce GLA substrate, and molecules that activate GLA gene promoters. This review outlines the current therapeutic approaches, emerging treatment strategies, and the process of drug discovery and development for Fabry disease. PMID:21127742

  4. Inhibition of Comt with tolcapone slows progression of polycystic kidney disease in the more severely affected PKD/Mhm (cy/+) substrain of the Hannover Sprague-Dawley rat

    PubMed Central

    Boehn, Susanne N.E.; Spahn, Sonja; Neudecker, Sabine; Keppler, Andrea; Bihoreau, Marie-Thérèse; Kränzlin, Bettina; Pandey, Priyanka; Hoffmann, Sigrid C.; Li, Li; Torres, Vicente E.; Gröne, Hermann-Josef; Gretz, Norbert

    2013-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human inherited diseases. Modifier genes seem to modulate the disease progression and might therefore be promising drug targets. Although a number of modifier loci have been already identified, no modifier gene has been proven to be a real modifier yet. Methods Gene expression profiling of two substrains of the Han:SPRD rat, namely PKD/Mhm and PKD/US, both harboring the same mutation, was conducted in 36-day-old animals. Catechol-O-methyltransferase (Comt) was identified as a potential modifier gene. A 3-month treatment with tolcapone, a selective inhibitor of Comt, was carried out in PKD/Mhm and PKD/US (cy/+) animals. Results Comt is localized within a known modifier locus of PKD (MOP2). The enzyme encoding gene was found upregulated in the more severely affected PKD/Mhm substrain and was hence presumed to be a putative modifier gene of PKD. The treatment with tolcapone markedly attenuated the loss of renal function, inhibited renal enlargement, shifted the size distribution of renal cysts and retarded cell proliferation, apoptosis, inflammation and fibrosis development in affected (cy/+) male and female PKD/Mhm and PKD/US rats. Conclusions Comt has been confirmed to be the first reported modifier gene for PKD and tolcapone offers a promising drug for treating PKD. PMID:23543593

  5. A PCR-based diagnostic assay for the detection of Roseovarius crassostreae in Crassostrea virginica affected by juvenile oyster disease (JOD)

    USGS Publications Warehouse

    Maloy, A.P.; Barber, B.J.; Boettcher, K.J.

    2005-01-01

    We have developed a PCR-assay for the diagnosis of juvenile oyster disease (JOD) based on the detection of Roseovarius crassostreae directly from affected oysters. Species-specific primers are used to amplify the 16S-23S rDNA internal transcribed spacer (ITS) of R. crassostreae, and confirmation of product identity is accomplished by restriction enzyme analysis. No false positives were obtained with either closely related bacterial species or from other DNAs present in oyster samples. The assay has the potential to detect as few as 10 cells of R. crassostreae per oyster when samples are taken from the inner valve surfaces of the animal. Inclusion of material from soft body surfaces is not necessary, and may reduce sensitivity approximately 10-fold. In a JOD-affected population, a positive PCR result was obtained from all oysters from which these bacteria were subsequently cultured. The assay also detected the presence of R. crassostreae in 2 oysters from which no R. crassostreae isolates were recovered. No R. crassostreae was detected by either PCR or bacteriology in oysters from a population that was not exhibiting JOD-signs. This assay is expected to advance regional disease management efforts and provide valuable insights into the disease process and epizootiology of JOD. ?? Inter-Research 2005.

  6. Fixing the Problem With Empathy: Development and Validation of the Affective and Cognitive Measure of Empathy.

    PubMed

    Vachon, David D; Lynam, Donald R

    2016-04-01

    Low empathy is a criterion for most externalizing disorders, and empathy training is a regular component of treatment for aggressive people, from school bullies to sex offenders. However, recent meta-analytic evidence suggests that current measures of empathy explain only 1% of the variance in aggressive behavior. A new assessment of empathy was developed to more fully represent the empathy construct and better predict important outcomes-particularly aggressive behavior and externalizing psychopathology. Across three independent samples (N = 210-708), the 36-item Affective and Cognitive measure of Empathy (ACME) was internally consistent, structurally reliable, and invariant across sex. The ACME bore significant associations to important outcomes, which were incremental relative to other measures of empathy and generalizable across sex. Importantly, the affective scales of the ACME-particularly a new "Affective Dissonance" scale-yielded moderate to strong associations with aggressive behavior and externalizing disorders. The ACME is a short, reliable, and useful measure of empathy. PMID:25612628

  7. The EYA-SO/SIX complex in development and disease.

    PubMed

    Xu, Pin-Xian

    2013-06-01

    Eyes absent (EYA) and Sine oculis (SO/SIX) proteins function as transcriptional activation complexes and play essential roles in organogenesis during embryonic development in regulating cell proliferation and survival and coordination of particular differentiation programs. Mutations of the Eya and So/Six genes cause profound developmental defects in organisms as diverse as flies, frogs, fish, mice, and humans. EYA proteins also possess an intrinsic phosphatase activity, which is essential for normal development. Here, we review crucial roles of EYA and SO/SIX in development and disease in mice and humans. PMID:22806561

  8. Proteome analysis of the macroscopically affected colonic mucosa of Crohn’s disease and intestinal tuberculosis

    PubMed Central

    Rukmangadachar, Lokesh A.; Makharia, Govind K.; Mishra, Asha; Das, Prasenjit; Hariprasad, Gururao; Srinivasan, Alagiri; Gupta, Siddhartha Datta; Ahuja, Vineet; Acharya, Subrat K.

    2016-01-01

    Differentiation between intestinal tuberculosis (ITB) and Crohn’s disease (CD) is challenging in geographical regions where both these diseases are prevalent. There is a need of biomarkers for differentiation between these two disorders. Colonic biopsies from inflamed mucosa of treatment-naive patients with ITB, CD and controls were used for analysis. Protein extracted from biopsies was digested with trypsin and resulting peptides were labeled with iTRAQ reagents. The peptides were subsequently analyzed using LC-MS/MS for identification and quantification. Gene ontology annotation for proteins was analyzed in PANTHER. Validation experiments were done for six differentially expressed proteins using immunohistochemistry. 533 proteins were identified and 241 proteins were quantified from 5 sets of iTRAQ experiments. While 63 were differentially expressed in colonic mucosa of patients with CD and ITB in at least one set of iTRAQ experiment, 11 proteins were differentially expressed in more than one set of experiments. Six proteins used for validation using immunohistochemistry in a larger cohort of patients; none of them however was differentially expressed in patients with ITB and CD. There are differentially expressed proteins in tissue proteome of CD and ITB. Further experiments are required using a larger cohort of homogeneous tissue samples. PMID:26988818

  9. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease

    PubMed Central

    Kim, Sokho; Park, Surim; Kim, Bumseok; Kwon, Jungkee

    2016-01-01

    Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway’s IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD. PMID:27279075

  10. Do malignant diseases affect semen quality? Sperm parameters of men with cancers.

    PubMed

    Caponecchia, L; Cimino, G; Sacchetto, R; Fiori, C; Sebastianelli, A; Salacone, P; Marcucci, I; Tomassini, S; Rago, R

    2016-04-01

    The advent of modern treatments together with the improvement of the surgical techniques has significantly increased 5-year survival rates of young patients with cancer. Although the deleterious effects of chemotherapy and radiation are well documented, controversies exist about the effect of cancer itself on semen parameters before treatment. We collected data on 236 patients representative of different types of cancers reoffered at our institution for sperm cryopreservation with the aim to correlate the pre-freeze semen parameters with type of cancer, disease stage and with semen quality of 102 fertile and healthy men. The median baseline semen parameters of all our patients with cancer are placed above the 5th percentile of the World Health Organization reference value, but the type of cancer may impact the sperm parameters. In testicular tumours and in Hodgkin lymphoma, we show a semen concentration statistically lower than in the fertile population, while in patients with other cancers, there is no difference with the healthy men. We found no correlation between semen quality and disease stage. Eighty-six per cent of our patients do not have children at the time of semen cryopreservation, and the only established clinical option for preserving fertility of these men is cryopreservation of spermatozoa. PMID:26173956

  11. Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease.

    PubMed

    Jundi, Karim; Greene, Catherine M

    2015-01-01

    Interleukin-8 (IL-8) is a neutrophil chemokine that is encoded on the CXCL8 gene. Normally CXCL8 expression is repressed due to histone deacetylation, octamer-1 binding to the promoter and the inhibitory effect of nuclear factor-κB repressing factor (NRF). However, in response to a suitable stimulus, the human CXCL8 gene undergoes transcription due to its inducible promoter that is regulated by the transcription factors nuclear factor-κB (NF-κB), activating protein (AP-1), CAAT/enhancer-binding protein β (C/EBPβ, also known as NF-IL-6), C/EBP homologous protein (CHOP) and cAMP response element binding protein (CREB). CXCL8 mRNA is then stabilised by the activity of p38 mitogen-activated protein kinase (p38 MAPK). Cystic fibrosis (CF) lung disease is characterised by a neutrophil-dominated airway inflammatory response. A major factor contributing to the large number of neutrophils is the higher than normal levels of IL-8 that are present within the CF lung. Infection and inflammation, together with intrinsic alterations in CF airway cells are responsible for the abnormally high intrapulmonary levels of IL-8. Strategies to inhibit aberrantly high CXCL8 expression hold therapeutic potential for CF lung disease. PMID:26140537

  12. Development of CAD prototype system for Crohn's disease

    NASA Astrophysics Data System (ADS)

    Oda, Masahiro; Kitasaka, Takayuki; Furukawa, Kazuhiro; Watanabe, Osamu; Ando, Takafumi; Goto, Hidemi; Mori, Kensaku

    2010-03-01

    The purpose of this paper is to present a CAD prototype system for Crohn's disease. Crohn's disease causes inflammation or ulcers of the gastrointestinal tract. The number of patients of Crohn's disease is increasing in Japan. Symptoms of Crohn's disease include intestinal stenosis, longitudinal ulcers, and fistulae. Optical endoscope cannot pass through intestinal stenosis in some cases. We propose a new CAD system using abdominal fecal tagging CT images for efficient diagnosis of Crohn's disease. The system displays virtual unfolded (VU), virtual endoscopic, curved planar reconstruction, multi planar reconstruction, and outside views of both small and large intestines. To generate the VU views, we employ a small and large intestines extraction method followed by a simple electronic cleansing method. The intestine extraction is based on the region growing process, which uses a characteristic that tagged fluid neighbor air in the intestine. The electronic cleansing enables observation of intestinal wall under tagged fluid. We change the height of the VU views according to the perimeter of the intestine. In addition, we developed a method to enhance the longitudinal ulcer on views of the system. We enhance concave parts on the intestinal wall, which are caused by the longitudinal ulcer, based on local intensity structure analysis. We examined the small and the large intestines of eleven CT images by the proposed system. The VU views enabled efficient observation of the intestinal wall. The height change of the VU views helps finding intestinal stenosis on the VU views. The concave region enhancement made longitudinal ulcers clear on the views.

  13. The unfolded protein response is activated in disease-affected brain regions in progressive supranuclear palsy and Alzheimer’s disease

    PubMed Central

    2013-01-01

    Background Progressive supranuclear palsy (PSP) is a neurodegenerative disorder pathologically characterized by intracellular tangles of hyperphosphorylated tau protein distributed throughout the neocortex, basal ganglia, and brainstem. A genome-wide association study identified EIF2AK3 as a risk factor for PSP. EIF2AK3 encodes PERK, part of the endoplasmic reticulum’s (ER) unfolded protein response (UPR). PERK is an ER membrane protein that senses unfolded protein accumulation within the ER lumen. Recently, several groups noted UPR activation in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, multiple system atrophy, and in the hippocampus and substantia nigra of PSP subjects. Here, we evaluate UPR PERK activation in the pons, medulla, midbrain, hippocampus, frontal cortex and cerebellum in subjects with PSP, AD, and in normal controls. Results We found UPR activation primarily in disease-affected brain regions in both disorders. In PSP, the UPR was primarily activated in the pons and medulla and to a much lesser extent in the hippocampus. In AD, the UPR was extensively activated in the hippocampus. We also observed UPR activation in the hippocampus of some elderly normal controls, severity of which positively correlated with both age and tau pathology but not with Aβ plaque burden. Finally, we evaluated EIF2AK3 coding variants that influence PERK activation. We show that a haplotype associated with increased PERK activation is genetically associated with increased PSP risk. Conclusions The UPR is activated in disease affected regions in PSP and the genetic evidence shows that this activation increases risk for PSP and is not a protective response. PMID:24252572

  14. Newcastle disease: progress and gaps in the development of vaccines and diagnostic tools.

    PubMed

    Afonso, C L; Miller, P J

    2013-01-01

    Newcastle disease (ND) is a contagious disease of birds that can have severe economic consequences for poultry producers, including a serious impact on the international trade of poultry and eggs. Newcastle disease virus (NDV) isolates are also called avian paramyxovirus serotype-1 isolates, but only infection with virulent NDV (vNDV) causes the disease. Virulent Newcastle disease virus (vNDV) isolates are distributed worldwide and have a high capacity to mutate, allowing the development of multiple vNDV genotypes evolving simultaneously at different locations. Large gaps in existing knowledge in the areas of epidemiology and evolution limit the possibilities to control the disease. Recurrent infection of poultry and wild birds allows the maintenance of a reservoir for the viruses; however, the role of wild birds and poultry in vNDV evolution is largely unknown. In the area of diagnostics, the performance of fast and accurate diagnostics methods is often affected by the evolution of viral genomes. Therefore, there is a need for the validation of multiple recently developed experimental tests and a need to develop additional fast and inexpensive diagnostic tests to be used in the field. In the area of vaccination, the development of inexpensive thermostable NDV vaccines and the development of vaccines capable of preventing viral replication are the highest priorities for endemic countries. In countries considered free of vNDV the development of low- cost vaccines that produce minimal vaccine reactions to prevent decreased productivity are higher priorities. Worldwide, better strategies that replace the culling of infected birds are needed to control outbreaks. PMID:23689887

  15. Enteric nervous system development: migration, differentiation, and disease

    PubMed Central

    Lake, Jonathan I.

    2013-01-01

    The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations. PMID:23639815

  16. Not all sounds sound the same: Parkinson's disease affects differently emotion processing in music and in speech prosody.

    PubMed

    Lima, César F; Garrett, Carolina; Castro, São Luís

    2013-01-01

    Does emotion processing in music and speech prosody recruit common neurocognitive mechanisms? To examine this question, we implemented a cross-domain comparative design in Parkinson's disease (PD). Twenty-four patients and 25 controls performed emotion recognition tasks for music and spoken sentences. In music, patients had impaired recognition of happiness and peacefulness, and intact recognition of sadness and fear; this pattern was independent of general cognitive and perceptual abilities. In speech, patients had a small global impairment, which was significantly mediated by executive dysfunction. Hence, PD affected differently musical and prosodic emotions. This dissociation indicates that the mechanisms underlying the two domains are partly independent. PMID:23477505

  17. The Structure and Validity of Self-reported Affect in Mild Cognitive Impairment and Mild Alzheimer’s Disease

    PubMed Central

    Ready, Rebecca E.; Carvalho, Janessa O.; Green, Robert C.; Gavett, Brandon E.; Stern, Robert A.

    2013-01-01

    Background This study determined the reliability, validity, and factor structure of self-report emotions in persons with mild Alzheimer’s disease (AD) and mild cognitive impairment (MCI) relative to controls. Methods Participants (mild AD, n = 73; MCI, n = 159; controls, n = 96) rated current emotions with the Visual Analogue Mood Scales (Stern, 1997). Results Internal consistency reliabilities were comparable across groups, as were the factor structures of emotion. Persons with AD reported more negative affect (NA) than persons with MCI and controls. The emotion that most differentiated groups was confusion. NA and PA may be more bipolar in persons with AD than for persons with MCI and controls. Conclusions The underlying structure of affect was similar in persons with mild AD, MCI, and controls. Further, persons with MCI appeared to be “transitional” between cognitive health and dementia with regard to mood and affect. That is, participants with MCI tended to have affect scores that were intermediate between those with AD and controls. Implications for interventions to improve emotional well-being in AD and MCI are discussed. PMID:21429280

  18. The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size.

    PubMed Central

    Brinkman, R R; Mezei, M M; Theilmann, J; Almqvist, E; Hayden, M R

    1997-01-01

    Prior studies describing the relationship between CAG size and the age at onset of Huntington disease (HD) have focused on affected persons. To further define the relationship between CAG repeat size and age at onset of HD, we now have analyzed a large cohort of affected and asymptomatic at-risk persons with CAG expansion. This cohort numbered 1,049 persons, including 321 at-risk and 728 affected individuals with a CAG size of 29-121 repeats. Kaplan-Meier analysis has provided curves for determining the likelihood of onset at a given age, for each CAG repeat length in the 39-50 range. The curves were significantly different (P < .0005), with relatively narrow 95% confidence intervals (95% CI) (+/-10%). Penetrance of the mutation for HD also was examined. Although complete penetrance of HD was observed for CAG sizes of > or = 42, only a proportion of those with a CAG repeat length of 36-41 showed signs or symptoms of HD within a normal life span. These data provide information concerning the likelihood of being affected, by a specific age, with a particular CAG size, and they may be useful in predictive-testing programs and for the design of clinical trials for persons at increased risk for HD. PMID:9150168

  19. Diagnostic assays developed for the control of foot-and-mouth disease in India

    PubMed Central

    Sharma, Gaurav Kumar; Mahajan, Sonalika; Matura, Rakesh; Subramaniam, Saravanan; Ranjan, Rajeev; Biswal, Jitendra; Rout, Manoranjan; Mohapatra, Jajati Keshari; Dash, Bana Bihari; Sanyal, Aniket; Pattnaik, Bramhadev

    2015-01-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of livestock, primarily affecting cattle, buffalo and pigs. FMD virus serotypes O, A and Asia1 are prevalent in India and systematic efforts are on to control and eventually eradicate the disease from the country. FMD epidemiology is complex due to factors like co-circulation, extinction, emergence and re-emergence of genotypes/lineages within the three serotypes, animal movement, diverse farm practices and large number of susceptible livestock in the country. Systematic vaccination, prompt diagnosis, strict biosecurity measures, and regular monitoring of vaccinal immunity and surveillance of virus circulation are indispensible features for the effective implementation of the control measures. Availability of suitable companion diagnostic tests is very important in this endeavour. In this review, the diagnostic assays developed and validated in India and their contribution in FMD control programme is presented. PMID:26279990

  20. Diagnostic assays developed for the control of foot-and-mouth disease in India.

    PubMed

    Sharma, Gaurav Kumar; Mahajan, Sonalika; Matura, Rakesh; Subramaniam, Saravanan; Ranjan, Rajeev; Biswal, Jitendra; Rout, Manoranjan; Mohapatra, Jajati Keshari; Dash, Bana Bihari; Sanyal, Aniket; Pattnaik, Bramhadev

    2015-08-12

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of livestock, primarily affecting cattle, buffalo and pigs. FMD virus serotypes O, A and Asia1 are prevalent in India and systematic efforts are on to control and eventually eradicate the disease from the country. FMD epidemiology is complex due to factors like co-circulation, extinction, emergence and re-emergence of genotypes/lineages within the three serotypes, animal movement, diverse farm practices and large number of susceptible livestock in the country. Systematic vaccination, prompt diagnosis, strict biosecurity measures, and regular monitoring of vaccinal immunity and surveillance of virus circulation are indispensible features for the effective implementation of the control measures. Availability of suitable companion diagnostic tests is very important in this endeavour. In this review, the diagnostic assays developed and validated in India and their contribution in FMD control programme is presented. PMID:26279990

  1. Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson’s Disease?

    PubMed Central

    Ferrazzoli, Davide; Ortelli, Paola; Maestri, Roberto; Bera, Rossana; Giladi, Nir; Ghilardi, Maria Felice; Pezzoli, Gianni; Frazzitta, Giuseppe

    2016-01-01

    Background: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson’s disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. Objective: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD. Methods: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1—normal cognition (score 27–30), group 2—mild cognitive impairment (score 21–26), group 3—moderate or severe cognitive impairment (score ≤ 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score ≥13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS). Results: All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score. Conclusions: Patients gain benefit in the rehabilitative outcomes, regardless of cognition

  2. Histopathological investigation of clinically non-affected perilesional scalp in alopecias detected unexpected spread of disease activities.

    PubMed

    Watanabe-Okada, Emiko; Amagai, Masayuki; Ohyama, Manabu

    2014-09-01

    Histopathological comparison between clinically affected and intact regions in alopecia patients has been considered to facilitate better understanding of the pathophysiology of ongoing disease. Theoretically, adjacent intact regions should provide ideal controls as they should share close histological characteristics, however, to what extent clinically non-affected neighboring regions maintain their pathological integrity has not been fully assessed. The goal of this study is to delineate histopathological characteristics of clinically intact perilesional regions in the patients with various forms of alopecia. Transverse sections of 4-mm punch biopsy at the levels of isthmus and suprabulbar portion were obtained from seemingly unimpaired perilesional scalp of 50 Japanese alopecia patients (16 alopecia areata [AA] multiplex, 19 scarring alopecia [SA], 15 other conditions) and subject to histopathological investigation. Initial screening detected decrease in anagen (anagen : telogen ratio = 82.4:17.6) when compared with previously reported standard hair counts in normal Asian scalp. This finding prompted further investigation. Unexpectedly, 33 (66%) specimens demonstrated some microscopic abnormalities, 10 (62.5%) AA specimens showed increase in telogen ratio, vellus hair count and miniaturization, while perifollicular inflammatory cell infiltration was detected in 5 (26.3%) SA cases. Exclusion of histologically affected specimens yielded average hair count numbers resembling those reported in Koreans, supporting the pathological integrity of selected samples and, more importantly, indicating normal hair counts in east Asians. These findings indicated a less recognized significance of histopathological investigation of clinically non-affected perilesional scalp in alopecias for better assessment of the spread of disease activities, which should enable better management of hair loss conditions. PMID:25156442

  3. Do laboratory rearing conditions affect auditory and mechanosensory development of zebrafish (Danio rerio)?

    NASA Astrophysics Data System (ADS)

    Poling, Kirsten R.; Jaworski, Eva; Fantetti, Kristen R.; Higgs, Dennis M.

    2005-04-01

    The effect of anthropogenic noise on the fish auditory system has become of increasing concern due to possible detrimental effects of intense sounds on auditory function and structures. This is especially problematic when raising fish in laboratory and aquaculture settings using filtration and aeration, which increase sound levels. To assess the effects of laboratory rearing conditions, one group of zebrafish (Danio rerio) embryos (``controls'') were placed into aerated aquaria in a normal laboratory rearing environment. A second set of embryos (``quiet'') were reared in aquaria with no aeration or filtration in a sound-resistant room. The intensity difference between the two sets of tanks was over 30 dB. Preliminary data show that there was no affect of differential rearing environments on saccular hair cell numbers or on hearing ability in fish up to 25 mm total length. However, rearing environment did affect neuromast number. ``Quiet'' fish had higher numbers of both cephalic and trunk superficial neuromasts, relative to controls. This difference was maintained up to 11 mm total length (the size at which canal formation begins). This suggests that acoustic environments normally found in the laboratory do not affect development of hearing in zebrafish, although laboratory acoustics may affect mechanosensory development.

  4. Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases

    PubMed Central

    Lamontagne, Jason; Steel, Laura F; Bouchard, Michael J

    2015-01-01

    Chronic infection with the hepatitis B virus (HBV) is the leading risk factor for the development of hepatocellular carcinoma (HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, microRNAs (miRNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of miRNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between miRNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some miRNAs, such as miR-122, and miR-125 and miR-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and miRNAs, including how HBV affects cellular miRNAs, how these miRNAs impact HBV replication, and the relationship between HBV-mediated miRNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and miRNAs, and propose potential applications of miRNA-related techniques that could enhance our understanding of the role miRNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes. PMID:26139985

  5. Derivation of Huntington Disease affected Genea017 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346022

  6. Derivation of Huntington Disease affected Genea018 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1.45, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346005

  7. Which factors affect the choice of the inhaler in chronic obstructive respiratory diseases?

    PubMed

    Scichilone, Nicola; Benfante, Alida; Bocchino, Marialuisa; Braido, Fulvio; Paggiaro, Pierluigi; Papi, Alberto; Santus, Pierachille; Sanduzzi, Alessandro

    2015-04-01

    Inhalation is the preferred route of drug administration in chronic respiratory diseases because it optimises delivery of the active compounds to the targeted site and minimises side effects from systemic distribution. The choice of a device should be made after careful evaluation of the patient's clinical condition (degree of airway obstruction, comorbidities), as well as their ability to coordinate the inhalation manoeuvre and to generate sufficient inspiratory flow. These patient factors must be aligned with the specific advantages and limitations of each inhaler when making this important choice. Finally, adherence to treatment is not the responsibility of the patient alone, but should be shared also by clinicians. Clinicians have access to a wide selection of pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) that can be used effectively when matched to the needs of individual patients; this should be perceived as an opportunity rather than a limitation. PMID:25724817

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

    PubMed

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

    2016-03-01

    Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development. PMID:27025078

  9. TREM-1 Deficiency Can Attenuate Disease Severity without Affecting Pathogen Clearance

    PubMed Central

    Weber, Benjamin; Schuster, Steffen; Zysset, Daniel; Rihs, Silvia; Dickgreber, Nina; Schürch, Christian; Riether, Carsten; Siegrist, Mark; Schneider, Christoph; Pawelski, Helga; Gurzeler, Ursina; Ziltener, Pascal; Genitsch, Vera; Tacchini-Cottier, Fabienne; Ochsenbein, Adrian; Hofstetter, Willy; Kopf, Manfred; Kaufmann, Thomas; Oxenius, Annette; Reith, Walter; Saurer, Leslie; Mueller, Christoph

    2014-01-01

    Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock or microbial sepsis have so far mostly relied on the administration of TREM-1 fusion proteins or peptides representing part of the extracellular domain of TREM-1. However, binding of these agents to the yet unidentified TREM-1 ligand could also impact signaling through alternative receptors. More importantly, controversial results have been obtained regarding the requirement of TREM-1 for microbial control. To unambiguously investigate the role of TREM-1 in homeostasis and disease, we have generated mice deficient in Trem1. Trem1−/− mice are viable, fertile and show no altered hematopoietic compartment. In CD4+ T cell- and dextran sodium sulfate-induced models of colitis, Trem1−/− mice displayed significantly attenuated disease that was associated with reduced inflammatory infiltrates and diminished expression of pro-inflammatory cytokines. Trem1−/− mice also exhibited reduced neutrophilic infiltration and decreased lesion size upon infection with Leishmania major. Furthermore, reduced morbidity was observed for influenza virus-infected Trem1−/− mice. Importantly, while immune-associated pathologies were significantly reduced, Trem1−/− mice were equally capable of controlling infections with L. major, influenza virus, but also Legionella pneumophila as Trem1+/+ controls. Our results not only demonstrate an unanticipated pathogenic impact of TREM-1 during a viral and parasitic infection, but also indicate that therapeutic blocking of TREM-1 in distinct inflammatory disorders holds considerable promise by blunting excessive inflammation while preserving the capacity

  10. Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease

    PubMed Central

    Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan; Arboleda, Gonzalo; Singh, Inderjit; Singh, Avtar Kaur

    2010-01-01

    Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied their femora. This study reports that twi femora are smaller than of those of wild type (wt), and present with abnormality of marrow cellularity, bone deposition (osteoblastic function), and osteoclastic activity. Furthermore, lipidomic analysis indicates altered sphingolipid homeostasis, but without significant changes in the levels of sphingolipid-derived intermediates of cell death (ceramide) or the levels of the osteoclast-osteoblast coupling factor (sphingosine-1-phosphate). However, there was significant accumulation of psychosine in the femora of adult twi animals as compared to wt, without induction of tumor necrosis factor-alpha or interleukin-6. Analysis of insulin-like growth factor-1 (IGF-1) plasma levels, a liver secreted hormone known to play a role in bone growth, indicated a drastic reduction in twi animals when compared to wt. To identify the cause of the decrease, we examined the IGF-1 mRNA expression and protein levels in the liver. The results indicated a significant reduction of IGF-1 mRNA as well as protein levels in the liver from twi as compared to wt littermates. Our data suggest that a combination of endogenous (psychosine) and endocrine (IGF-1) factors play a role in the inhibition of postnatal bone growth in twi mice; and further suggest that derangements of liver function may be contributing, at least in part, to this alteration. PMID:20441793

  11. Generation of Human Induced Pluripotent Stem Cells from Extraembryonic Tissues of Fetuses Affected by Monogenic Diseases.

    PubMed

    Spitalieri, Paola; Talarico, Rosa V; Botta, Annalisa; Murdocca, Michela; D'Apice, Maria Rosaria; Orlandi, Augusto; Giardina, Emiliano; Santoro, Massimo; Brancati, Francesco; Novelli, Giuseppe; Sangiuolo, Federica

    2015-08-01

    The generation of human induced pluripotent stem cells (hiPSCs) derived from an autologous extraembryonic fetal source is an innovative personalized regenerative technology that can transform own-self cells into embryonic stem-like ones. These cells are regarded as a promising candidate for cell-based therapy, as well as an ideal target for disease modeling and drug discovery. Thus, hiPSCs enable researchers to undertake studies for treating diseases or for future applications of in utero therapy. We used a polycistronic lentiviral vector (hSTEMCCA-loxP) encoding OCT4, SOX2, KLF4, and cMYC genes and containing loxP sites, excisible by Cre recombinase, to reprogram patient-specific fetal cells derived from prenatal diagnosis for several genetic disorders, such as myotonic dystrophy type 1 (DM1), β-thalassemia (β-Thal), lymphedema-distichiasis syndrome (LDS), spinal muscular atrophy (SMA), cystic fibrosis (CF), as well as from wild-type (WT) fetal cells. Because cell types tested to create hiPSCs influence both the reprogramming process efficiency and the kinetics, we used chorionic villus (CV) and amniotic fluid (AF) cells, demonstrating how they represent an ideal cell resource for a more efficient generation of hiPSCs. The successful reprogramming of both CV and AF cells into hiPSCs was confirmed by specific morphological, molecular, and immunocytochemical markers and also by their teratogenic potential when inoculated in vivo. We further demonstrated the stability of reprogrammed cells over 10 and more passages and their capability to differentiate into the three embryonic germ layers, as well as into neural cells. These data suggest that hiPSCs-CV/AF can be considered a valid cellular model to accomplish pathogenesis studies and therapeutic applications. PMID:26474030

  12. Factors Affecting the Designation of Cerebrovascular Diseases as Work-Related in Administrative Litigation

    PubMed Central

    Kim, Hyeongsu; Rim, Hwayoung; Chang, Sounghoon; Lee, Kunsei

    2008-01-01

    The purpose of this study was to identify factors that could be used as standardized criteria for evaluating occupational diseases in initial assessments or requests for examination. Using 100 administrative litigation cases on the work-relatedness of cerebrovascular diseases (CVDs) by the Seoul Branch of the Korea Labor Welfare Corporation (KLWC) from 1997 to 2002, we estimated the relationship between the investigated variables and designation of the work-relatedness of the CVD. As for the age, the odds ratio of the acceptance rate of a case as work-related in subjects over 60 yr of age was 0.08 (95% CI, 0.01-0.75), which was compared to subjects under 30 yr of age. Regarding working hours, the odds ratio of the acceptance rate of a case as work-related in CVDs in those over 56 hr was 9.50 (95% CI, 1.92-47.10) when compared to those less than 56 hr. As for the benefit type, the odds ratio of the acceptance rate of a case as work-related in medical benefits was 5.74 (95% CI, 1.29-25.54), compared to survivor benefits. As for the criteria for defining situations as work overload, the odds ratio of the acceptance rate of a case as work-related in injured workers was 12.06 (95% CI, 3.12-46.62), compared to that in non-injured workers. Our findings show that the criteria for defining situations of work overload played an important role in assessing the work-relatedness of CVDs in administrative litigation, and it is necessary to make the scientific evidence on judgement of work-relatedness on overwork. PMID:18437006

  13. Quantification of Cylindrocarpon in roots of almond and peach trees from orchards affected by Prunus replant disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prunus replant disease (PRD) is a poorly understood soilborne complex that suppresses replanted almond and peach orchards in California. Using culture-dependent and culture-independent approaches, we found Cylindrocarpon (Cyl) macrodidymum among microorganisms associated with PRD. We developed a qPC...

  14. Molecular motors in neuronal development, intracellular transport and diseases.

    PubMed

    Hirokawa, Nobutaka; Takemura, Reiko

    2004-10-01

    Molecular motors such as kinesin superfamily proteins (KIFs), dynein superfamily proteins and myosin superfamily proteins have diverse and fundamental roles in many cellular processes, including neuronal development and the pathogenesis of neuronal diseases. During neuronal development, KIFs take significant roles in the regulation of axon-collateral branch extension, which is essential for brain wiring. Cytoplasmic dynein together with LIS1 takes pivotal roles in neocortical layer formation. In axons, anterograde transport is mediated by KIFs, whereas retrograde transport is mediated mainly by cytoplasmic dynein, and dysfunction of motors results in neurodegenerative diseases. In dendrites, the transport of NMDA and AMPA receptors is mediated by KIFs, and the motor has been shown to play a significant part in establishing learning and memory. PMID:15464889

  15. Altered cytokine network in gestational diabetes mellitus affects maternal insulin and placental-fetal development.

    PubMed

    Wedekind, Lauren; Belkacemi, Louiza

    2016-01-01

    Pregnancy is characterized by an altered inflammatory profile, compared to the non-pregnant state with an adequate balance between pro-and anti-inflammatory cytokines needed for normal development. Cytokines are small secreted proteins expressed mainly in immunocompetent cells in the reproductive system. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines. The placental production of cytokines may affect mother and fetus independently. In turn because of this unique position at the maternal fetal interface, the placenta is also exposed to the regulatory influence of cytokines from maternal and fetal circulations, and hence, may be affected by changes in any of these. Gestational diabetes mellitus (GDM) is associated with an overall alteration of the cytokine network. This review discusses the changes that occur in cytokines post GDM and their negative effects on maternal insulin and placental-fetal development. PMID:27230834

  16. Genetic Analysis of 63 Mutations Affecting Maize Kernel Development Isolated from Mutator Stocks

    PubMed Central

    Scanlon, M. J.; Stinard, P. S.; James, M. G.; Myers, A. M.; Robertson, D. S.

    1994-01-01

    Sixty-three mutations affecting development of the maize kernel were isolated from active Robertson's Mutator (Mu) stocks. At least 14 previously undescribed maize gene loci were defined by mutations in this collection. Genetic mapping located 53 of these defective kernel (dek) mutations to particular chromosome arms, and more precise map determinations were made for 21 of the mutations. Genetic analyses identified 20 instances of allelism between one of the novel mutations and a previously described dek mutation, or between new dek mutations identified in this study; phenotypic variability was observed in three of the allelic series. Viability testing of homozygous mutant kernels identified numerous dek mutations with various pleiotropic effects on seedling and plant development. The mutations described here presumably arose by insertion of a Mu transposon within a dek gene; thus, many of the affected loci are expected to be accessible to molecular cloning via transposon-tagging. PMID:8138165

  17. A Comprehensive Review of Novel Drug-Disease Models in Diabetes Drug Development.

    PubMed

    Gaitonde, Puneet; Garhyan, Parag; Link, Catharina; Chien, Jenny Y; Trame, Mirjam N; Schmidt, Stephan

    2016-07-01

    Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, which affects millions of people worldwide. The disease is characterized by chronically elevated blood glucose concentrations (hyperglycaemia), which result in comorbidities and multi-organ dysfunction. This is due to a gradual loss of glycaemic control as a result of increasing insulin resistance, as well as decreasing β-cell function. The objective of T2DM drug interventions is, therefore, to reduce fasting and postprandial blood glucose concentrations to normal, healthy levels without hypoglycaemia. Several classes of novel antihyperglycaemic drugs with various mechanisms of action have been developed over the past decades or are currently under clinical development. The development of these drugs is routinely supported by the application of pharmacokinetic/pharmacodynamic modelling and simulation approaches. They integrate information on the drug's pharmacokinetics, clinically relevant biomarker information and disease progression into a single, unifying approach, which can be used to inform clinical study design, dose selection and drug labelling. The objective of this review is to provide a comprehensive overview of the quantitative approaches that have been reported since the 2008 review by Landersdorfer and Jusko in an increasing order of complexity, starting with glucose homeostasis models. Each of the presented approaches is discussed with respect to its strengths and limitations, and respective knowledge gaps are highlighted as potential opportunities for future drug-disease model development in the area of T2DM. PMID:26798033

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

    PubMed

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

    2014-01-01

    Downy mildew caused by Peronospora sparsa has resulted in serious production losses in boysenberry (Rubus hybrid), blackberry (Rubus fruticosus), and rose (Rosa sp.) in New Zealand, Mexico, and the United States and the United Kingdom, respectively. Development of a model to predict downy mildew risk would facilitate development and implementation of a disease warning system for efficient fungicide spray application in the crops affected by this disease. Because detailed disease observation data were not available, a two-step approach was applied to develop an empirical risk prediction model for P. sparsa. To identify the weather patterns associated with a high incidence of downy mildew berry infections (dryberry disease) and derive parameters for the empirical model, classification and regression tree (CART) analysis was performed. Then, fuzzy sets were applied to develop a simple model to predict the disease risk based on the parameters derived from the CART analysis. High-risk seasons with a boysenberry downy mildew incidence >10% coincided with months when the number of hours per day with temperature of 15 to 20°C averaged >9.8 over the month and the number of days with rainfall in the month was >38.7%. The Fuzzy Peronospora Sparsa (FPS) model, developed using fuzzy sets, defined relationships among high-risk events, temperature, and rainfall conditions. In a validation study, the FPS model provided correct identification of both seasons with high downy mildew risk for boysenberry, blackberry, and rose and low risk in seasons when no disease was observed. As a result, the FPS model had a significant degree of agreement between predicted and observed risks of downy mildew for those crops (P = 0.002). PMID:23883152

  19. Fibroblast growth factor signaling in skeletal development and disease

    PubMed Central

    Ornitz, David M.; Marie, Pierre J.

    2015-01-01

    Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored. PMID:26220993

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

    PubMed Central

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

    2014-01-01

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

  1. Identification of Novel Mutations in HEXA Gene in Children Affected with Tay Sachs Disease from India

    PubMed Central

    Sheth, Frenny; Sanghavi, Daksha; Kondurkar, Pratima; Patil, Swapnil; Idicula-Thomas, Susan; Gupta, Sarita; Sheth, Jayesh

    2012-01-01

    Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G (p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W). The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V. PMID:22723944

  2. How Does Lumbar Degenerative Disc Disease Affect the Disc Deformation at the Cephalic Levels In Vivo?

    PubMed Central

    Wang, Shaobai; Xia, Qun; Passias, Peter; Li, Weishi; Wood, Kirkham; Li, Guoan

    2013-01-01

    Study Design Case-control study. Objective . To evaluate the effect of lumbar degenerative disc disease (DDD) on the disc deformation at the adjacent level and at the level one above the adjacent level during end ranges of lumbar motion. Summary of Background Data It has been reported that in patients with DDD, the intervertebral discs adjacent to the diseased levels have a greater tendency to degenerate. Although altered biomechanics have been suggested to be the causative factors, few data have been reported on the deformation characteristics of the adjacent discs in patients with DDD. Methods Ten symptomatic patients with discogenic low back pain between L4 and S1 and with healthy discs at the cephalic segments were involved. Eight healthy subjects recruited in our previous studies were used as a reference comparison. The in vivo kinematics of L3–L4 (the cephalic adjacent level to the degenerated discs) and L2–L3 (the level one above the adjacent level) lumbar discs of both groups were obtained using a combined magnetic resonance imaging and dual fluoroscopic imaging technique at functional postures. Deformation characteristics, in terms of areas of minimal deformation (defined as less than 5%), deformations at the center of the discs, and maximum tensile and shear deformations, were compared between the two groups at the two disc levels. Results In the patients with DDD, there were significantly smaller areas of minimal disc deformation at L3–L4 and L2–L3 than the healthy subjects (18% compared with 45% of the total disc area, on average). Both L2–L3 and L3–L4 discs underwent larger tensile and shear deformations in all postures than the healthy subjects. The maximum tensile deformations were higher by up to 23% (of the local disc height in standing) and the maximum shear deformations were higher by approximately 25% to 40% (of the local disc height in standing) compared with those of the healthy subjects. Conclusion Both the discs of the adjacent

  3. Identification of novel mutations in HEXA gene in children affected with Tay Sachs disease from India.

    PubMed

    Mistri, Mehul; Tamhankar, Parag M; Sheth, Frenny; Sanghavi, Daksha; Kondurkar, Pratima; Patil, Swapnil; Idicula-Thomas, Susan; Gupta, Sarita; Sheth, Jayesh

    2012-01-01

    Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Mutations were confirmed in parents and looked up in public databases. In silico analysis for mutations was carried out using SIFT, Polyphen2, MutationT@ster and Accelrys Discovery Studio softwares. Fifteen families were included in the study. We identified six novel missense mutations, c.340 G>A (p.E114K), c.964 G>A (p.D322N), c.964 G>T (p.D322Y), c.1178C>G (p.R393P) and c.1385A>T (p.E462V), c.1432 G>A (p.G478R) and two previously reported mutations. c.1277_1278insTATC and c.508C>T (p.R170W). The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. Mutations could not be identified in one family. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V. PMID:22723944

  4. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    PubMed Central

    Dean, Afshan; van den Driesche, Sander; Wang, Yili; McKinnell, Chris; Macpherson, Sheila; Eddie, Sharon L.; Kinnell, Hazel; Hurtado-Gonzalez, Pablo; Chambers, Tom J.; Stevenson, Kerrie; Wolfinger, Elke; Hrabalkova, Lenka; Calarrao, Ana; Bayne, Rosey AL; Hagen, Casper P.; Mitchell, Rod T.; Anderson, Richard A.; Sharpe, Richard M.

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters. PMID:26813099

  5. Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development

    PubMed Central

    Trotter, Caroline L.; Ramsay, Mary E.; Chandra, Manosree; Jolley, Keith A.; van der Ende, Arie; Carion, Françoise; Berthelsen, Lene; Hoffmann, Steen; Harðardóttir, Hjördís; Vazquez, Julio A.; Murphy, Karen; Toropainen, Maija; Caniça, Manuela; Ferreira, Eugenia; Diggle, Mathew; Edwards, Giles F.; Taha, Muhamed-Kheir; Stefanelli, Paola; Kriz, Paula; Gray, Steve J.; Fox, Andrew J.; Jacobsson, Susanne; Claus, Heike; Vogel, Ulrich; Tzanakaki, Georgina; Heuberger, Sigrid; Caugant, Dominique A.; Frosch, Matthias; Maiden, Martin C. J.

    2014-01-01

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups. PMID:24695776

  6. ARTIE: An Integrated Environment for the Development of Affective Robot Tutors

    PubMed Central

    Imbernón Cuadrado, Luis-Eduardo; Manjarrés Riesco, Ángeles; De La Paz López, Félix

    2016-01-01

    Over the last decade robotics has attracted a great deal of interest from teachers and researchers as a valuable educational tool from preschool to highschool levels. The implementation of social-support behaviors in robot tutors, in particular in the emotional dimension, can make a significant contribution to learning efficiency. With the aim of contributing to the rising field of affective robot tutors we have developed ARTIE (Affective Robot Tutor Integrated Environment). We offer an architectural pattern which integrates any given educational software for primary school children with a component whose function is to identify the emotional state of the students who are interacting with the software, and with the driver of a robot tutor which provides personalized emotional pedagogical support to the students. In order to support the development of affective robot tutors according to the proposed architecture, we also provide a methodology which incorporates a technique for eliciting pedagogical knowledge from teachers, and a generic development platform. This platform contains a component for identiying emotional states by analysing keyboard and mouse interaction data, and a generic affective pedagogical support component which specifies the affective educational interventions (including facial expressions, body language, tone of voice,…) in terms of BML (a Behavior Model Language for virtual agent specification) files which are translated into actions of a robot tutor. The platform and the methodology are both adapted to primary school students. Finally, we illustrate the use of this platform to build a prototype implementation of the architecture, in which the educational software is instantiated with Scratch and the robot tutor with NAO. We also report on a user experiment we carried out to orient the development of the platform and of the prototype. We conclude from our work that, in the case of primary school students, it is possible to identify, without

  7. ARTIE: An Integrated Environment for the Development of Affective Robot Tutors.

    PubMed

    Imbernón Cuadrado, Luis-Eduardo; Manjarrés Riesco, Ángeles; De La Paz López, Félix

    2016-01-01

    Over the last decade robotics has attracted a great deal of interest from teachers and researchers as a valuable educational tool from preschool to highschool levels. The implementation of social-support behaviors in robot tutors, in particular in the emotional dimension, can make a significant contribution to learning efficiency. With the aim of contributing to the rising field of affective robot tutors we have developed ARTIE (Affective Robot Tutor Integrated Environment). We offer an architectural pattern which integrates any given educational software for primary school children with a component whose function is to identify the emotional state of the students who are interacting with the software, and with the driver of a robot tutor which provides personalized emotional pedagogical support to the students. In order to support the development of affective robot tutors according to the proposed architecture, we also provide a methodology which incorporates a technique for eliciting pedagogical knowledge from teachers, and a generic development platform. This platform contains a component for identiying emotional states by analysing keyboard and mouse interaction data, and a generic affective pedagogical support component which specifies the affective educational interventions (including facial expressions, body language, tone of voice,…) in terms of BML (a Behavior Model Language for virtual agent specification) files which are translated into actions of a robot tutor. The platform and the methodology are both adapted to primary school students. Finally, we illustrate the use of this platform to build a prototype implementation of the architecture, in which the educational software is instantiated with Scratch and the robot tutor with NAO. We also report on a user experiment we carried out to orient the development of the platform and of the prototype. We conclude from our work that, in the case of primary school students, it is possible to identify, without

  8. Parents and Early Life Environment Affect Behavioral Development of Laying Hen Chickens

    PubMed Central

    de Haas, Elske N.; Bolhuis, J. Elizabeth; Kemp, Bas; Groothuis, Ton G. G.; Rodenburg, T. Bas

    2014-01-01

    Severe feather pecking (SFP) in commercial laying hens is a maladaptive behavior which is associated with anxiety traits. Many experimental studies have shown that stress in the parents can affect anxiety in the offspring, but until now these effects have been neglected in addressing the problem of SFP in commercially kept laying hens. We therefore studied whether parental stock (PS) affected the development of SFP and anxiety in their offspring. We used flocks from a brown and white genetic hybrid because genetic background can affect SFP and anxiety. As SFP can also be influenced by housing conditions on the rearing farm, we included effects of housing system and litter availability in the analysis. Forty-seven rearing flocks, originating from ten PS flocks were followed. Behavioral and physiological parameters related to anxiety and SFP were studied in the PS at 40 weeks of age and in the rearing flocks at one, five, ten and fifteen weeks of age. We found that PS had an effect on SFP at one week of age and on anxiety at one and five weeks of age. In the white hybrid, but not in the brown hybrid, high levels of maternal corticosterone, maternal feather damage and maternal whole-blood serotonin levels showed positive relations with offsprings’ SFP at one week and offsprings’ anxiety at one and five weeks of age. Disruption and limitation of litter supply at an early age on the rearing farms increased SFP, feather damage and fearfulness. These effects were most prominent in the brown hybrid. It appeared that hens from a brown hybrid are more affected by environmental conditions, while hens from a white hybrid were more strongly affected by parental effects. These results are important for designing measures to prevent the development of SFP, which may require a different approach in brown and white flocks. PMID:24603500

  9. Agonistic Anti-TIGIT Treatment Inhibits T Cell Responses in LDLr Deficient Mice without Affecting Atherosclerotic Lesion Development

    PubMed Central

    Foks, Amanda C.; Ran, Ingrid A.; Frodermann, Vanessa; Bot, Ilze; van Santbrink, Peter J.; Kuiper, Johan; van Puijvelde, Gijs H. M.

    2013-01-01

    Objective Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT) directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. Methods and Results TIGIT was upregulated on CD4+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr−/− mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. Conclusions Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells. PMID:24376654

  10. Alzheimer's disease, but not ageing or depression, affects dual-tasking.

    PubMed

    Kaschel, Reiner; Logie, Robert H; Kazén, Miguel; Della Sala, Sergio

    2009-11-01

    Two experiments are reported that assess dual task performance in Alzheimer's disease (AD), in chronic depression and in healthy old age. Results suggest that dual task impairments are present in AD but are not shown in depression. This is true even when episodic memory performance is equated between the groups. These results, together with those of previous studies, point to dual task performance as an aid to diagnosis of AD relative to depression. This is of particular relevance when episodic memory tests cannot distinguish between the two conditions. The dual task paradigm appears to have considerable promise in assisting the early detection of the specific cognitive deficits associated with AD, and in monitoring their progression, both in the laboratory setting and in everyday tasks. Results also are of theoretical interest in pointing to a specific dual task coordination function in the healthy human cognitive system that allows for the coordination of two tasks performed simultaneously and which is damaged in AD but not in depression. PMID:19543789

  11. The distribution of parasite strains among hosts affects disease spread in a social insect.

    PubMed

    Ulrich, Yuko; Schmid-Hempel, Paul

    2015-06-01

    Social insects present highly interesting and experimentally amenable systems for the study of disease transmission because they naturally live in dense groups of frequently interacting individuals. Using experimental inoculations of five trypanosomatid strains into groups of its natural host, the bumblebee Bombus terrestris, we investigate the effects of the initial parasite strain distribution across group members on the establishment and transmission success of the different strains to new hosts. For a given number of parasite strains circulating within a host group, transmission to new hosts was increased when the strains were initially inoculated as mixed infections (as opposed to separate single infections), presumably because mixed infections generally favored fast replicating strains. In contrast, separate single infections reduced transmission at least in part through a precedence effect, whereby weak strains appeared to persist by making their host unavailable to superinfection. These results suggest that host groups could benefit from 'compartmentalizing' infections by different parasite strains across different group members, which might be achieved in social insects, for example, by division of labor. PMID:25858120

  12. Brain parcellation choice affects disease-related topology differences increasingly from global to local network levels.

    PubMed

    Lord, Anton; Ehrlich, Stefan; Borchardt, Viola; Geisler, Daniel; Seidel, Maria; Huber, Stefanie; Murr, Julia; Walter, Martin

    2016-03-30

    Network-based analyses of deviant brain function have become extremely popular in psychiatric neuroimaging. Underpinning brain network analyses is the selection of appropriate regions of interest (ROIs). Although ROI selection is fundamental in network analysis, its impact on detecting disease effects remains unclear. We investigated the impact of parcellation choice when comparing results from different studies. We investigated the effects of anatomical (AAL) and literature-based (Dosenbach) parcellation schemes on comparability of group differences in 35 female patients with anorexia nervosa and 35 age- and sex-matched healthy controls. Global and local network properties, including network-based statistics (NBS), were assessed on resting state functional magnetic resonance imaging data obtained at 3T. Parcellation schemes were comparably consistent on global network properties, while NBS and local metrics differed in location, but not metric type. Location of local metric alterations varied for AAL (parietal and cingulate cortices) versus Dosenbach (insula, thalamus) parcellation approaches. However, consistency was observed for the occipital cortex. Patient-specific global network properties can be robustly observed using different parcellation schemes, while graph metrics characterizing impairments of individual nodes vary considerably. Therefore, the impact of parcellation choice on specific group differences varies depending on the level of network organization. PMID:27000302

  13. Dopamine Does Not Appear to Affect Mental Rotation in Parkinson’s Disease

    PubMed Central

    Crucian, Gregory P.; Armaghani, Sheyan; Armaghani, Avan; Foster, Paul S.; Burks, David W.; Skoblar, Barry; Drago, Valeria; Heilman, Kenneth M.

    2014-01-01

    Objective Patients with Parkinson’s disease (PD) often have deficits with mental rotation (MR). The neuropathological factors underlying these deficits, however, remain to be elucidated. One hypothesis suggests that dopamine depletion in nigro-striatal systems adversely influences MR. Another hypothesis suggests that deterioration of cortical (fronto-temporo-parietal basal ganglia) networks that mediate this function are responsible for this deficit. The goal of this study was to test the dopamine hypothesis by determining if dopamine abstinence negatively influences MR performance. Methods Thirty three non-demented right-handed individuals with PD were assess for their ability to perform a pencil and paper MR test while “on” and “off” dopaminergic medications. Dopamine abstinence followed the typical overnight withdrawal procedures. Results No differences in mental rotation abilities were found between “on” and “off” dopaminergic medications. Conclusions These results suggest that other neuropathological factors, such as cortical-basal ganglia neurodegeneration, or dysfunction of other neurotransmitters systems, might account for these cognitive deficits and future research will have to test these alternative hypotheses. PMID:25360231

  14. Do Beliefs of Inner-City Parents About Disease and Vaccine Risks Affect Immunization?

    PubMed Central

    Trauth, Jeanette M.; Zimmerman, Richard K.; Musa, Donald; Mainzer, Hugh; Nutini, Jean F.

    2003-01-01

    Objective. The objective of this study was to understand how low income, inner-city parents of preschool children think about childhood diseases and prevention and the impact that this has on late receipt of vaccines. Methods. Parents of all children born between 1/1/91 and 5/31/95, whose child received medical assistance and their health care at one of four inner-city, primary care clinics in Pittsburgh, PA., completed a telephone interview and gave consent for a vaccine record review. The main outcome measures were lateness for first and third diphtheria and tetanus toxoids and pertussis vaccines (DTP) and not receiving at least 4 DTP, 3 polio virus containing and 1 measles, mumps and rubella (MMR) doses by 19 months. Results. 483 parents participated. Fifteen percent of children were late for the first DTP, 52% for the third DTP and, 40% had not received at least 4 DTP, 3 polio and 1 MMR by 19 months of age. Statistically significant factors associated with lateness at 19 months included: having three or more children, having two children, beliefs regarding the severity of immunization side effects and, being African American. Conclusions. The results of this study indicate that a combination of life circumstances as well as cognitive factors were associated with late immunization.

  15. Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease.

    PubMed

    Habak, Claudine; Noreau, Anne; Nagano-Saito, Atsuko; Mejía-Constaín, Beatriz; Degroot, Clotilde; Strafella, Antonio P; Chouinard, Sylvain; Lafontaine, Anne-Louise; Rouleau, Guy A; Monchi, Oury

    2014-11-01

    Parkinson's disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the SLC6A3 gene (formerly named DAT1) and its polymorphisms, which have been largely overlooked in Parkinson's disease. Thirty patients (ages 53-68 years; 19 males, 11 females) at early stages of Parkinson's disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the SLC6A3/DAT1 gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the SLC6A3/DAT1 genotype has a significant effect on fronto-striatal activation and performance in Parkinson's disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism's effect on the clinical evolution of patients with Parkinson's disease, especially with cognitive decline. PMID:25212851

  16. Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes

    SciTech Connect

    Kremer, B.; Theilmann, J.; Spence, N.

    1995-08-01

    A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in {approximately}70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r{sup 2}=.19). The size of the CAG repeat influenced larger intergenerational expansions (>7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (>7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P<10{sub -7}), while offspring of affected mothers are more likely to show no change (P=.01) or contractions in CAG size (P=.002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability. 22 refs., 4 figs., 3 tabs.

  17. Strategies to Enhance the Effectiveness of Adult Stem Cell Therapy for Ischemic Heart Diseases Affecting the Elderly Patients

    PubMed Central

    Khatiwala, Roshni

    2016-01-01

    Myocardial infarctions and chronic ischemic heart disease both commonly and disproportionately affect elderly patients more than any other patient population. Despite available treatments, heart tissue is often permanently damaged as a result of cardiac injury. This review aims to summarize recent literature proposing the use of modified autologous adult stem cells to promote healing of post-infarct cardiac tissue. This novel cellular treatment involves isolation of adult stem cells from the patient, in vitro manipulation of these stem cells, and subsequent transplantation back into the patient’s own heart to accelerate healing. One of the hindrances affecting this process is that cardiac issues are increasingly common in elderly patients, and stem cells recovered from their tissues tend to be pre-senescent or already in senescence. As a result, harsh in vitro manipulations can cause the aged stem cells to undergo massive in vivo apoptosis after transplantation. The consensus in literature is that inhibition or reversal of senescence onset in adult stem cells would be of utmost benefit. In fact, it is believed that this strategy may lower stem cell mortality and coerce aged stem cells into adopting more resilient phenotypes similar to that of their younger counterparts. This review will discuss a selection of the most efficient and most-recent strategies used experimentally to enhance the effectiveness of current stem cell therapies for ischemic heart diseases. PMID:26779896

  18. Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens.

    PubMed Central

    Vallejo, R L; Bacon, L D; Liu, H C; Witter, R L; Groenen, M A; Hillel, J; Cheng, H H

    1998-01-01

    Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 6(3) (MD resistant) and 7(2) (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32-68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility. PMID:9475745

  19. Origin of porcine circovirus type 2 (PCV2) from swine affected by PCV2-associated diseases in Croatia.

    PubMed

    Novosel, D; Tuboly, T; Csagola, A; Lorincz, M; Cubric-Curik, V; Jungic, A; Curik, I; Segalés, J; Cortey, M; Lipej, Z

    2014-04-26

    Porcine circovirus type 2 (PCV2) causes some of the most significant economic losses in pig production. Several multisystemic syndromes have been attributed to PCV2 infection, which are known as PCV2-associated diseases (PCVDs). This study investigated the origin and evolution of PCV2 sequences in domestic pigs and wild boars affected by PCVDs in Croatia. Viral sequences were recovered from three wild boars diagnosed with PCV2-systemic disease (PCV2-SD), 63 fetuses positive for PCV2 DNA as determined by PCR, 14 domestic pigs affected with PCV2-SD (displaying severe interstitial nephritis) and five domestic pigs with proliferative and necrotising pneumonia. Seventeen complete PCV2 genomes were recovered. Phylogenetic and evolutionary analyses based on median-joining phylogenetic networks, amino acid alignments and principal coordinate analysis were performed using complete genomes, as well as complete and partial ORF sequences for ORF1 and ORF2. Two of the 17 PCV2 sequences belonged to PCV2a, 14 to PCV2b and one was unclustered. PCV2b was the predominant genotype in Croatia and has been linked to international trade as a route of introduction. Correlation between particular viral strains with PCVDs is lacking. PMID:24591478

  20. Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy.

    PubMed

    Brooks-Kayal, Amy R; Bath, Kevin G; Berg, Anne T; Galanopoulou, Aristea S; Holmes, Gregory L; Jensen, Frances E; Kanner, Andres M; O'Brien, Terence J; Whittemore, Vicky H; Winawer, Melodie R; Patel, Manisha; Scharfman, Helen E

    2013-08-01

    Many symptoms of neurologic or psychiatric illness--such as cognitive impairment, depression, anxiety, attention deficits, and migraine--occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure. PMID:23909853

  1. Does bacteria disease control affect UV reflective mulch for thrips and tospovirus control in tomatoes?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetable growers continue to be encouraged to adopt Integrated Pest Management (IPM) practices as a means to make vegetable production more economical, sustainable and environmentally benign. Over the years, researchers have developed many highly effective programs to manage specific pests. Howeve...

  2. Advances in the Development of Vaccines for Alzheimer's Disease

    PubMed Central

    Lambracht-Washington, Doris; Rosenberg, Roger N.

    2013-01-01

    One of the challenges of our society is to find a treatment or cure for Alzheimer's disease (AD). AD is the leading form of age-related dementia and with the increase of life expectancy worldwide, the social and economic burden from this disease will increase dramatically. It is a progressive and, in regard to clinical scores, a highly variable disease. AD pathogenesis has been associated with the accumulation, aggregation, and deposition of amyloid beta (Abeta) peptides in the brain. Hallmarks of AD are the amyloid plaques consisting of fibrillar Abeta and neurofibrillary tangles which are intracellular fibrils of hyperphosphorylated tau protein that develop later in this disease. The amyloid cascade hypothesis postulates that Abeta deposition is an initial event in the multifactorial pathogenesis and Abeta deposition may precede AD symptoms in some patients by at least 20 years. Amyloid beta therapy with active and passive immunizations against Abeta has a high possibility to be effective in removing Abeta from brain and might thus prevent the downstream pathology. Since 2000 a number of clinical trials for AD immunotherapy have started, have failed, and are continuing to be pursued. This article will review these clinical trials and ongoing research in this regard. PMID:23725605

  3. Stress factors in the development of coronary artery disease.

    PubMed

    Dorian, B; Taylor, C B

    1984-10-01

    The epidemiologic evidence that stress contributes to cardiovascular disease is reviewed. No one characterization of stress has been associated with all manifestations of cardiovascular disease, yet specific characterizations have been associated with particular manifestations of disease. Type A behavior pattern is a risk factor for coronary artery disease (CAD) and is correlated with the severity and progression of atherosclerosis demonstrated angiographically. Work overload with job dissatisfaction also predisposes to CAD. Socioeconomic disadvantage in a society of urbanization and industrialization increases the risk of hypertension and CAD, while chronic states of anxiety, depression, and helplessness are associated with angina and sudden death. Traumatic life events, especially involving loss of or threat to self-esteem, may precipitate sudden death in patients with preexisting CAD. There is evidence that the mechanism linking the experience of stress and the development of acute coronary events is exposure to sympathetic hyperarousal and a deficit in soothing. Research is needed to determine if work environments can be designed to minimize hyperarousal and provide protective outlets for individuals experiencing such arousal. PMID:6387069

  4. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  5. Disease surveillance at district level: a model for developing countries.

    PubMed

    John, T J; Samuel, R; Balraj, V; John, R

    1998-07-01

    For over a decade we have maintained within a district of 5 million people, a system of prompt reporting of cases of childhood vaccine-preventable diseases, encephalitis, meningitis, hepatitis, and rabies; together with a sentinel laboratory surveillance of cholera, typhoid fever, malaria, HIV infection and antimicrobial-resistance patterns of selected pathogens. The system combined government and private sectors, with every hospital enrolled and participating. Reports were scanned daily on a computer for any clustering of cases. Interventions included investigations, immunisation, antimicrobial treatment, health education, and physical rehabilitation of children with paralysis. All vaccine-preventable diseases have declined markedly, whilst malaria and HIV infections have increased steadily. Annual expense was less than one US cent per head. The reasons for the success and sustainability of this model include simplicity or reporting procedure, low budget, private-sector participation, personal rapport with people in the network, regular feedback of information through a monthly bulletin, and the visible interventions consequent upon reporting. This district-level disease surveillance model is replicable in developing countries for evaluating polio eradication efforts, monitoring immunisation programmes, detecting outbreaks of old or new diseases, and for evaluating control measures. PMID:9800768

  6. Nitroxide pharmaceutical development for age-related degeneration and disease

    PubMed Central

    Zarling, Jacob A.; Brunt, Vienna E.; Vallerga, Anne K.; Li, Weixing; Tao, Albert; Zarling, David A.; Minson, Christopher T.

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  7. [Clinical study on development of nontuberculous mycobacterial lung disease].

    PubMed

    Kurashima, Atsuyuki

    2004-12-01

    DEVELOPEMENT OF MAC LUNG DISEASE: An increase of nodular bronchiectatic type of MAC lung disease becomes a problem among respiratory physician today. The reason is still unknown, but it seems to be globally recognized that this type of MAC disease is developing particularly in middle-aged woman. Some papers mentioned the existence of such type of MAC lung disease already early in the 70s, in Japan. Yamamoto described that 17 cases of middle lobe type lung disease out of 154 non-photochoromogen cases, and 76.5% were female, in 1970. Shimoide also pointed such type of 39 cases out of 240 MAC lung disease and 84.6% were female, in 1980. Prince reported MAC lung disease seen in old and middle age female of 21 cases including lethality example of 4 cases without a precedent disease in 1989. After his report, the international consensus of this peculiar type of MAC lung disease seems to be spread. In 1989, we compared 72 cases of nodular bronchiectatic type of MAC lung disease and 56 cases of diffuse panbronchiolitis (DPB) that was a most typical chronic airway disease at that time in Japan. The average age of disease onset of DPB group was 37.0 +/- 16.3 years old and that of MAC group was 54.5 +/- 16.3 years old. The percentage of female was 32% in DPB group and 87.5% in MAC group. It was highly possible that two groups belong different parent population. We could grasp that nodular bronchiectatic type of MAC lung disease patients is a unique group. We observed the serial films of 21 cases of nodular bronchiectatic MAC lung disease, and divide the progression of the disease to sequential 7 steps as Fig. 1. Small nodules progress to cavities in mean about 10 years. However, why is MAC which is opportunistic pathogen with weak virulence, able to form a lesion at unimpaired lung parenchyma? Is there really normal site? Why dose it start from lingula? Why is MAC seen a lot in woman? While it is extremely pathognomonic clinical picture, and, is an extremely interesting

  8. Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis

    PubMed Central

    Wang, Guang; Li, Yan; Wang, Xiao-Yu; Chuai, Manli; Yeuk-Hon Chan, John; Lei, Jian; Münsterberg, Andrea; Lee, Kenneth Ka Ho; Yang, Xuesong

    2015-01-01

    The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7+ somite development and directly increased HNK-1+ neural crest cell (NCC) migration and TuJ-1+ neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development. PMID:25568339

  9. Prepubertal tamoxifen treatment affects development of heifer reproductive tissues and related signaling pathways.

    PubMed

    Al Naib, A; Tucker, H L M; Xie, G; Keisler, D H; Bartol, F F; Rhoads, R P; Akers, R M; Rhoads, M L

    2016-07-01

    Prepubertal exposure of the developing ovaries and reproductive tract (RT) to estrogen or xenoestrogens can have acute and long-term consequences that compromise the reproductive performance of cattle. This research examined effects of the selective estrogen receptor modulator tamoxifen (TAM) on gene and protein abundance in prepubertal ovaries and RT, with a particular focus on signaling pathways that affect morphology. Tamoxifen was administered to Holstein heifer calves (n=8) daily (0.3mg/kg subcutaneously) from 28 to 120 d of age, when tissues were collected. Control calves (n=7) received an equal volume of excipient. Weight, gross measurements, and samples of reproductive tissues were collected, and protein and mRNA were extracted from snap-frozen samples of vagina, cervix, uterus, oviduct, ovary, and liver. Neither estradiol nor insulin-like growth factor I (IGFI) concentrations in the serum were affected by TAM treatment. Tamoxifen treatment reduced ovarian weight independently from effects on antral follicle populations, as there was no difference in visible antral follicle numbers on the day of collection. Estrogen receptor α (ESR1) and β (ESR2) mRNA, ESR1 protein, IGFI, progesterone receptor, total growth hormone receptor, WNT4, WNT5A, and WNT7A mRNA, in addition to mitogen-activated protein kinase (MAPK) and phosphorylated MAPK proteins were affected differently depending on the tissue examined. However, neither IGFI receptor mRNA nor protein abundance were affected by TAM treatment. Results indicate that reproductive development in prepubertal Holstein heifer calves is TAM-sensitive, and that bovine RT and ovarian development are supported, in part, by estrogen receptor-dependent mechanisms during the period studied here. Potential long-term consequences of such developmental disruption remain to be defined. PMID:27085397

  10. Coronary artery disease affects cortical circuitry associated with brain-heart integration during volitional exercise

    PubMed Central

    Norton, Katelyn N.; Badrov, Mark B.; Barron, Carly C.; Suskin, Neville; Heinecke, Armin

    2015-01-01

    This study tested the hypothesis that coronary artery disease (CAD) alters the cortical circuitry associated with exercise. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 23 control subjects [control; 8 women; 63 ± 11 yr; mean arterial pressure (MAP): 90 ± 9 mmHg] (mean ± SD) and 17 similarly aged CAD patients (4 women; 59 ± 9 yr; MAP: 87 ± 10 mmHg). Four repeated bouts each of 30%, 40%, and 50% of maximal voluntary contraction (MVC) force (LAB session), and seven repeated bouts of isometric handgrip (IHG) at 40% MVC force (fMRI session), were performed, with each contraction lasting 20 s and separated by 40 s of rest. There was a main effect of group (P = 0.03) on HR responses across all IHG intensities. Compared with control, CAD demonstrated less task-dependent deactivation in the posterior cingulate cortex and medial prefrontal cortex, and reduced activation in the right anterior insula, bilateral precentral cortex, and occipital lobe (P < 0.05). When correlated with HR, CAD demonstrated reduced activation in the bilateral insula and posterior cingulate cortex, and reduced deactivation in the dorsal anterior cingulate cortex, and bilateral precentral cortex (P < 0.05). The increased variability in expected autonomic regions and decrease in total cortical activation in response to the IHG task are associated with a diminished HR response to volitional effort in CAD. Therefore, relative to similarly aged and healthy individuals, CAD impairs the heart rate response and modifies the cortical patterns associated with cardiovascular control during IHG. PMID:25972576

  11. Meteorological factors affect the hand, foot, and mouth disease epidemic in Qingdao, China, 2007-2014.

    PubMed

    Jiang, F C; Yang, F; Chen, L; Jia, J; Han, Y L; Hao, B; Cao, G W

    2016-08-01

    Hand, foot, and mouth disease (HFMD) has caused public health concerns worldwide. We aimed to investigate the effect of meteorological factors on the HFMD epidemic in Qingdao, a port city in China. A total of 78641 cases were reported in Qingdao between January 2007 and December 2014. Of those, 71084 (90·39%) occurred in children aged 0-5 years, with an incidence of 1691·2/100000. The incidence increased from early spring, peaked between spring and summer, and decreased in late summer. Aetiological agents in all severe cases and selected mild cases were characterized by examining throat swabs. Except for enterovirus 71 (EV71) and coxsackievirus A16 (CA16), other EVs caused >50% of the HFMD cases between 2011 and 2014. EV71 was more frequent in the off-peak months than in the peak months and prone to causing more severe cases compared to CA16 (χ 2 = 46·3, P < 0·001). CA10 caused more severe HFMD than did CA6 (χ 2 = 20·49, P < 0·001) and all non-CA10 EVs (χ 2 = 41·01, P < 0·001). Community-derived HFMD cases accounted for 65·11%. Spearman rank correlation analysis showed that HFMD incidence in children aged 0-5 years was positively correlated with atmospheric temperature (r s = 0·77, P < 0·001), relative humidity (r s = 0·507, P < 0·001), and precipitation (r s = 0·328, P < 0·001). Climate changes and CA10 surveillance in communities should be integrated into the current prophylactic programme. PMID:27018924

  12. Dopaminergic therapy affects learning and impulsivity in Parkinson’s disease

    PubMed Central

    Hiebert, Nole M; Seergobin, Ken N; Vo, Andrew; Ganjavi, Hooman; MacDonald, Penny A

    2014-01-01

    Objective The aim was to examine the effect of dopaminergic medication on stimulus-response learning versus performing decisions based on learning. Method To see the effect of dopaminergic therapy on stimulus-response learning and response selection, participants with Parkinson’s disease (PD) were either tested on and/or off their prescribed dose of dopaminergic therapy during different testing days. Forty participants with PD and 34 healthy controls completed the experiment on consecutive days. On Day 1, participants learned to associate abstract images with spoken, “right” or “left” responses via feedback (Session 1). On Day 2, participants recalled these responses (Session 2) and indicated the location (i.e., right or left of center) of previously studied images intermixed with new images (Session 3). Results Participants with PD off medication learned stimulus-response associations equally well compared to healthy controls. Learning was impaired by dopaminergic medication. Regardless of medication status, patients recalled the stimulus-response associations from Day 1 as well as controls. In Session 3 off medication, patients demonstrated enhanced facilitation relative to controls and patients on medication, when the stimulus location was congruent with the spoken response that was learned for the stimulus in Session 1. Interpretation Learning in PD was comparable to that of healthy controls off medication. Learning was worsened by dopaminergic therapy in PD. We interpret greater facilitation in participants with PD off medication for congruent responses as evidence of greater impulsivity. This motor or reflexive impulsivity was normalized by medication in PD. These findings shed light on the cognitive profile of PD and have implications for dopaminergic treatment. PMID:25493274

  13. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease.

    PubMed

    Pan, Xiaoxia; Ouyang, Yan; Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  14. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

    PubMed Central

    Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  15. Dopamine depletion affects communicative intentionality in Parkinson's disease patients: Evidence from action kinematics.

    PubMed

    Straulino, Elisa; Scaravilli, Tomaso; Castiello, Umberto

    2016-04-01

    Appropriate communication is at the heart of successful, healthy social interactions in humans. Deficits in social communication are a hallmark of several neurological and psychiatric disorders. Yet, very little research has been devoted to understanding the mechanisms underlying these issues. It has been suggested that dopamine is a candidate neurotransmitter system involved in stimulating communication in individuals that are not highly motivated to communicate. A typical model to study dopaminergic dysfunctions in humans is represented by Parkinson's disease (PD) patients, who show motor, cognitive and motivational symptoms. Our study aimed to investigate the effects of social communication on actions in non-demented PD patients receiving dopamine replacement therapy (Levodopa = l-Dopa) and in neurologically healthy control participants. Patients' ability to modulate motor patterning depending on the communicative intention motivating the action to be performed was evaluated both in "on" (with l-Dopa) and "off" (without l-Dopa) states. In two main conditions, participants were requested to reach towards, grasp an object, and either simply lift it (individual condition) or lift it with the intent to communicate a meaning to a partner (communicative condition). Movements' kinematics was recorded using a three-dimensional motion analysis system. The results indicate that kinematics is sensitive to communicative intention and that l-Dopa treatment has positive effects on translating communicative intentions into specific motor patterns in PD patients. Although the to-be-grasped object remained the same both the controls and the PD patients in an 'on' state adopted different kinematic patterning for the 'individual' and the 'communication' conditions. The PD patients in the 'off' state, instead, were unable to kinematically differentiate between the two conditions. We contend that social and communicative impairments are associated with abnormalities in

  16. Disruption of Amyloid Plaques Integrity Affects the Soluble Oligomers Content from Alzheimer Disease Brains

    PubMed Central

    Moyano, Javier; Sanchez-Mico, María; Torres, Manuel; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

    2014-01-01

    The implication of soluble Abeta in the Alzheimer’s disease (AD) pathology is currently accepted. In fact, the content of soluble extracellular Abeta species, such as monomeric and/or oligomeric Abeta, seems to correlate with the clinico-pathological dysfunction observed in AD patients. However, the nature (monomeric, dimeric or other oligomers), the relative abundance, and the origin (extra-/intraneuronal or plaque-associated), of these soluble species are actually under debate. In this work we have characterized the soluble (defined as soluble in Tris-buffered saline after ultracentrifugation) Abeta, obtained from hippocampal samples of Braak II, Braak III–IV and Braak V–VI patients. Although the content of both Abeta40 and Abeta42 peptides displayed significant increase with pathology progression, our results demonstrated the presence of low, pg/µg protein, amount of both peptides. This low content could explain the absence (or below detection limits) of soluble Abeta peptides detected by western blots or by immunoprecipitation-western blot analysis. These data were in clear contrast to those published recently by different groups. Aiming to explain the reasons that determine these substantial differences, we also investigated whether the initial homogenization could mobilize Abeta from plaques, using 12-month-old PS1xAPP cortical samples. Our data demonstrated that manual homogenization (using Dounce) preserved the integrity of Abeta plaques whereas strong homogenization procedures (such as sonication) produced a vast redistribution of the Abeta species in all soluble and insoluble fractions. This artifact could explain the dissimilar and somehow controversial data between different groups analyzing human AD samples. PMID:25485545

  17. Early-Life Environmental Variation Affects Intestinal Microbiota and Immune Development in New-Born Piglets

    PubMed Central

    Zhang, Ling-li; Vastenhouw, Stéphanie A.; Heilig, Hans G. H. J.; Smidt, Hauke; Rebel, Johanna M. J.; Smits, Mari A.

    2014-01-01

    Background Early-life environmental variation affects gut microbial colonization and immune competence development; however, the timing and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development. Methodology/Principal Findings To investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited. Conclusions/Significance We provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances. PMID:24941112

  18. The Use of Narrative in Understanding how Cancer Affects Development: The Stories of One Cancer Survivor

    PubMed Central

    LEE, CHRISTINA SUNMI

    2010-01-01

    Although cancer disrupts development, the experience of having cancer is often understood using developmental theories that do not assume serious illness at an early age. This article presents a narrative analysis of one patient’s story of survivorship. She tells three interrelated stories: how others have reacted to her illness; her struggles to understand her illness; and how it has changed her priorities. Taken together, her stories comprise an account of how the experience has affected her development. Her story is an example of how individuals integrate unusual life events into their development. It suggests that focusing more on how unusual life experiences contribute to development may expand and enrich our understanding of developmental processes. PMID:21151860

  19. The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis.

    PubMed

    Fassio, A; Idolazzi, L; Jaber, M A; Dartizio, C; Viapiana, O; Rossini, M; Gatti, D

    2016-01-01

    Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself. PMID:27608794

  20. Technology innovation for infectious diseases in the developing world.

    PubMed

    So, Anthony D; Ruiz-Esparza, Quentin

    2012-01-01

    Enabling innovation and access to health technologies remains a key strategy in combating infectious diseases in low- and middle-income countries (LMICs). However, a gulf between paying markets and the endemicity of such diseases has contributed to the dearth of R&D in meeting these public health needs. While the pharmaceutical industry views emerging economies as potential new markets, most of the world's poorest bottom billion now reside in middle-income countries--a fact that has complicated tiered access arrangements. However, product development partnerships--particularly those involving academic institutions and small firms--find commercial opportunities in pursuing even neglected diseases; and a growing pharmaceutical sector in BRICS countries offers hope for an indigenous base of innovation. Such innovation will be shaped by 1) access to building blocks of knowledge; 2) strategic use of intellectual property and innovative financing to meet public health goals; 3) collaborative norms of open innovation; and 4) alternative business models, some with a double bottom line. Facing such resource constraints, LMICs are poised to develop a new, more resource-effective model of innovation that holds exciting promise in meeting the needs of global health. PMID:23849080