WorldWideScience

Sample records for cell disorder perspectives

  1. Perspectives for computational modeling of cell replacement for neurological disorders

    Directory of Open Access Journals (Sweden)

    James B Aimone

    2013-11-01

    Full Text Available Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

  2. Perspectives for computational modeling of cell replacement for neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Aimone, James B.; Weick, Jason P.

    2013-01-01

    Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

  3. Perspectives for computational modeling of cell replacement for neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Aimone, James B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Weick, Jason P. [Univ. of New Mexico, Albuquerque, NM (United States)

    2013-01-01

    In mathematical modeling of anatomically-constrained neural networks we provide significant insights regarding the response of networks to neurological disorders or injury. Furthermore, a logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

  4. Stem cell therapy for Alzheimer's disease and related disorders: current status and future perspectives.

    Science.gov (United States)

    Tong, Leslie M; Fong, Helen; Huang, Yadong

    2015-03-13

    Underlying cognitive declines in Alzheimer's disease (AD) are the result of neuron and neuronal process losses due to a wide range of factors. To date, all efforts to develop therapies that target specific AD-related pathways have failed in late-stage human trials. As a result, an emerging consensus in the field is that treatment of AD patients with currently available drug candidates might come too late, likely as a result of significant neuronal loss in the brain. In this regard, cell-replacement therapies, such as human embryonic stem cell- or induced pluripotent stem cell-derived neural cells, hold potential for treating AD patients. With the advent of stem cell technologies and the ability to transform these cells into different types of central nervous system neurons and glial cells, some success in stem cell therapy has been reported in animal models of AD. However, many more steps remain before stem cell therapies will be clinically feasible for AD and related disorders in humans. In this review, we will discuss current research advances in AD pathogenesis and stem cell technologies; additionally, the potential challenges and strategies for using cell-based therapies for AD and related disorders will be discussed.

  5. Perspectives on Oppositional Defiant Disorder, Conduct Disorder, and Psychopathic Features

    Science.gov (United States)

    Loeber, Rolf; Burke, Jeffrey; Pardini, Dustin A.

    2009-01-01

    This paper presents a few perspectives on oppositional defiant disorder (ODD), conduct disorder (CD), and early forms of psychopathy. The developmental changes and stability of each, and the interrelationship between the three conditions are reviewed, and correlates and predictors are highlighted. The paper also examines effective interventions…

  6. Autologous Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders – Recent Progress and Perspective for Clinical Application

    Directory of Open Access Journals (Sweden)

    Kuroda S

    2011-01-01

    Full Text Available There is increasing evidence that the transplanted BMSC significantly promote functional recovery after CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, traumatic brain injury and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with CNS disorders. In this review, therefore, we discuss what we should clarify to establish cell transplantation therapy as the scientifically proven entity in clinical situation and describe our recent works for this purpose. The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. The BMSC can be expanded in vitro using the animal serum-free medium. Pharmacological modulation may accelerate the in vitro proliferation of the BMSC. Using in vivo optical imaging technique, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future.

  7. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F; Wevers, CWJ; Wintzen, AR; Busch, HFM; Howeler, CJ; deJager, AEJ; Padberg, GW; deVisser, M; Wokke, JHJ

    1997-01-01

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  8. Multicultural Perspectives in Communication Disorders.

    Science.gov (United States)

    Screen, Robert Martin; Anderson, Noma Bennett

    This text provides information about the impact of multiculturalism on services for individuals with communication disorders. It examines the involvement of the American Speech-Language-Hearing Association (ASHA) and multicultural speech, language, and hearing organizations as they respond to the challenges created by multiculturalism. An…

  9. Language disorder: a functional linguistic perspective.

    Science.gov (United States)

    Armstrong, E

    2005-01-01

    This paper explores the issues involved in the linguistic characterisation of disordered discourse and the ways in which a Systemic Functional Linguistic framework addresses these issues. For many years, language disorders were described in terms of formal grammars, with "breakdown" discussed in terms of one or more of the traditional levels of language, i.e., phonology, syntax, and semantics. While it was acknowledged that an individual could have difficulty at one or more of these levels, each was viewed quite separately, with semantics viewed largely from a referential perspective. More recent approaches using functional grammar have broadened this view of language and have provided a model of language that re-conceptualizes the notion of meaning and embraces context as integral to its organisation. Such a model has introduced a different perspective on language into clinical fields, and has enabled researchers and clinicians to explore the skills of speakers with language disorders across a variety of situations and contextual variables, examining the linguistic resources still available to them. This paper introduces principles involved in a functional framework and provides an overview of how these principles have been applied to language disorders to date. In addition, the notion of "disorder" itself is discussed as it is situated in this alternative model.

  10. Personality disorders from a phenomenological perspective.

    Science.gov (United States)

    Dörr Zengers, O

    2008-01-01

    Different studies have questioned the capacity of the categorical diagnostics to establish a clear distinction between the existence or not of a determined personality disorder. The dimensional perspective would approach more to reality, in the measure that it tries to measure the different intensity degrees in which these disorders are present in the patients. But its application is very laborious and besides, presupposes that those categories whose nuances it pretends to measure really exist. The foresaid leads us to appeal to phenomenological perspective, which seems to be more adequate for the study of complex realities, as it is the case of the personality and its disorders. The essential features of the phenomenological method in the sense of Husserl are described, as well as his contribution to the study of personality disorders. This can be summarized in three fundamental points: the ideal types, introduced in psychiatry by Karl Jaspers, the existential types, by Ludwig Binswanger, and the dialectic typologies and polarities, by Wolfgang Blankenburg and the undersigned. This author defines and develops each one of these concepts, aiming to show their advantages with respect to the categorical and dimensional systems.

  11. White Blood Cell Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  12. [Obsessive-compulsive disorders and religion in contemporary perspective].

    Science.gov (United States)

    Baumann, K

    2007-10-01

    After a retrospect on former viewpoints about the relationship between psychiatry and religion, especially concerning obsessive-compulsive disorders (S. Freud; "Ekklesiogenic Neurosis") a contemporary perspective shows: religion is hardly mentioned in German-speaking psychiatry textbooks. Pathogenic interaction between religion and psychological disorders is discussed in plurifactorial perspective. Religious views can be distorted by psychic disorders and adapted to the disorders. Starting from an anthropological definition of religion (C. Geertz), the paper presents three functions of religion and explains the relationship of Christian faith and obsessions/compulsions. Teaching programs for students and psychiatrists seem indicated for a better understanding of religion (and its absence) in the context of psychological disorders.

  13. Personality disorder: a new global perspective

    DEFF Research Database (Denmark)

    Tyrer, Peter; Mulder, Roger; Crawford, Mike

    2010-01-01

    Personality disorder is now being accepted as an important condition in mainstream psychiatry acreoss the world. Although it often remains unrecognized in ordinary practice, research studies have shown it is common, creates considerable morbidity, is associated with high costs to services...... incerasing evidence that some teratments, manilyl psychological, are of value in this group of disorders. What is now needed is a new classification that is of greater value to clinicians, and the WPA Section on Personality Disorders is currently undertaking this task....... and to society, and interferes, usually negatively, with progress in the treatment of other mental disorders. We now have evidence that personality disorder, as currently classified, affects around 6% of the world population, and the differences between countries show no consistent variation. We are also getting...

  14. Parenting among Mothers with Bipolar Disorder: Children's Perspectives

    Science.gov (United States)

    Venkataraman, Meenakshi

    2011-01-01

    Four children from three families in which the mother had a bipolar disorder were interviewed to understand their perspectives on their mothers' parenting. Children identified strengths in their mother's parenting, such as helping them with homework and moods and providing for their wants. They also identified challenges, such as mothers sleeping…

  15. Children's Perspectives on Disorder and Violence in Urban Neighbourhoods

    Science.gov (United States)

    de Carvalho, Maria Joao Leote

    2013-01-01

    Based on the analysis of 312 children's neighbourhood drawings and narratives, this article discusses children's socialization in six public housing neighbourhoods in Portugal, through children's personal accounts of their lives. It then examines their perspectives on disorder and violence. Most complained about living in their neighbourhoods,…

  16. Transcendental meditation for autism spectrum disorders? A perspective

    Directory of Open Access Journals (Sweden)

    David O. Black

    2015-12-01

    Full Text Available Anecdotal reports suggest that Transcendental Meditation (TM may be helpful for some children and young adults with autism spectrum disorders (ASDs. In this perspective piece, we present six carefully evaluated individuals with diagnosed ASDs, who appear to have benefitted from TM, and offer some thoughts as to how this technique might help such individuals.

  17. Alexithymia in Eating Disorders: a transcultural perspective

    Directory of Open Access Journals (Sweden)

    Stefania Roma

    2010-06-01

    Full Text Available The role of alexithymia in eating disorders has been exstensively studied in Western cultures. On the contrary, studies on alexithymia in the Far East are rare, and its possible role in eating disorders is yet unstudied. After discussing the history and the meaning of the concept of alexithymia in Western cultures, the present paper poses the anthropological question whether alexithymia has a different meaning in Western and Eastern cultures. The sinologist literature on the topic of emotions in China is fi rstly addressed, followed by a review of empirical studies on eating disorders in China. Finally, the results of a preliminary study that compared the role of alexithymia in Italian and Chinese eating disorders are discussed, stressing that the signifi cantly lower alexithymia scores in Chinese eating disorders might be interpreted as strictly connected with the native culture, that is the tendency of Chinese girls to give socially desirable answers. Accordingly, a relevant pathoplastic role of the native culture not only on symptoms, but even on basic traits like alexithymia is suggested.

  18. Narcissistic personality disorder: a clinical perspective.

    Science.gov (United States)

    Ronningstam, Elsa

    2011-03-01

    Narcissistic traits and narcissistic personality disorder (NPD) present specific diagnostic challenges. While they are often readily and straightforwardly identified, their presentation in some patients and the reasons for which such patients seek treatment may conceal significant narcissistic pathology. Recently, several empirical studies have confirmed that the phenotypic range of people with NPD includes individuals with insecure, shy, and hypersensitive traits with prominent internalized narcissistic features and functioning. Other studies have confirmed that internal emotional distress, interpersonal vulnerability, fear, pain, anxiety, a sense of inadequacy, and depressivity can also co-occur with narcissistic personality functioning. This paper focuses on integrating these findings into the diagnostic evaluation and initial negotiation of treatment for NPD. In patients with narcissistic traits or NPD, it is important to give attention to the two sides of character functioning, which include both self-serving and self-enhancing manifestations as well as hypersensitivity, fluctuations in self-esteem, and internal pain and fragility. This article highlights some of these seemingly incompatible clinical presentations of narcissistic traits and NPD, especially as they co-occur with depressivity and perfectionism, and it discusses implications for building a treatment alliance with a patient with such a predominant disorder of character functioning. The article also discusses the importance of retaining the NPD diagnosis as a separate type of personality disorder, with this range of features, in the upcoming fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DMS-5).

  19. Autism Spectrum Disorder: the Present Perspective

    Directory of Open Access Journals (Sweden)

    S Chaudhuri

    2015-06-01

    Full Text Available The last decade has witnessed a surge of awareness about autism among the public and professionals. Much revealing research is being done on this issue and the knowledge base has improved substantially and a set of professionals are specializing on the subject, focusing on its causative factors and management. Autism being a disorder stemming from early childhood and the prevalence rate rising alarmingly over the years, Pediatricians are expected to play a vital role in early detection and early intervention in management of the problem. But, unfortunately, autism is not yet considered to be under the purview of pediatricians. As pediatricians, we are often perplexed when faced with such a different child in our office and either overlook the problem or hurry to hand him over to a psychiatrist, not trying to really identify and understand the problem as a medical entity ourselves. Hence better awareness among pediatricians is the need of the day. As specialists have worked with autism over the decades, it has become clear that: autism is a disorder that involves early development, presently there is no medical answer to autism, and the only management strategy hinges largely on effective training. The earlier the training begins the better it is for the child. It is of paramount importance to start training and bring about changes by the time the child is 18 months old. This throws up interesting new challenges to the profession of pediatrics. To identify the early warning signs of autism, it is important that Pediatricians are able to recognize the signs and symptoms of autistic spectrum disorders (ASD, have a strategy for assessing them systematically, be familiar with available tools for screening as well as developmental and educational resources.DOI: http://dx.doi.org/10.3126/jcmsn.v10i3.12775 Journal of College of Medical Sciences-Nepal, 2014, Vol-10, No-3, 37-47

  20. Thyroid disorders in India: An epidemiological perspective

    Directory of Open Access Journals (Sweden)

    Ambika Gopalakrishnan Unnikrishnan

    2011-01-01

    Full Text Available Thyroid diseases are common worldwide. In India too, there is a significant burden of thyroid diseases. According to a projection from various studies on thyroid disease, it has been estimated that about 42 million people in India suffer from thyroid diseases. This review will focus on the epidemiology of five common thyroid diseases in India: (1 hypothyroidism, (2 hyperthyroidism, (3 goiter and iodine deficiency disorders, (4 Hashimoto′s thyroiditis, and (5 thyroid cancer. This review will also briefly cover the exciting work that is in progress to ascertain the normal reference range of thyroid hormones in India, especially in pregnancy and children.

  1. A Global Workspace perspective on mental disorders

    Directory of Open Access Journals (Sweden)

    Wallace Rodrick

    2005-12-01

    Full Text Available Abstract Background Recent developments in Global Workspace theory suggest that human consciousness can suffer interpenetrating dysfunctions of mutual and reciprocal interaction with embedding environments which will have early onset and often insidious staged developmental progression, possibly according to a cancer model, in which a set of long-evolved control strategies progressively fails. Methods and results A rate distortion argument implies that, if an external information source carries a damaging 'message', then sufficient exposure to it, particularly during critical developmental periods, is sure to write a sufficiently accurate image of it on mind and body in a punctuated manner so as to initiate or promote similarly progressively punctuated developmental disorder, in essence either a staged failure affecting large-scale brain connectivity, which is the sine qua non of human consciousness, or else damaging the ability of embedding goal contexts to contain conscious dynamics. Conclusion The key intervention, at the population level, is clearly to limit exposure to factors triggering developmental disorders, a question of proper environmental sanitation, in a large sense, primarily a matter of social justice which has long been known to be determined almost entirely by the interactions of cultural trajectory, group power relations, and economic structure, with public policy. Intervention at the individual level appears limited to triggering or extending periods of remission, representing reestablishment of an extensive, but largely unexplored, spectrum of evolved control strategies, in contrast with the far better-understood case of cancer.

  2. NUTRITIONAL DEFICIENCY DISORDERS IN PAEDIATRICS: AN AYURVEDIC PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Tikole Rushikesh V.

    2013-08-01

    Full Text Available Nutrition is major concern for the mankind. Food determines body condition right from the womb to tomb; it is main source of energy. Abnormal nutrition may cause both over and under nutrition hazards. It causes more than half of the nearly 11 million deaths each year among children under age five. Nutritional deficiency disorders are viewed under Apatarpanajanya vyadhis. Ancient Acharyas explained diseases related to nutritional deficiency such as Phakka, Parigarbhika, Bala shosha etc in different samhitas. This paper highlights Ayurvedic perspective of nutritional deficiency related disorders.

  3. Mesenchymal stem cells in diabetes treatment: progress and perspectives

    Directory of Open Access Journals (Sweden)

    Yu CHENG

    2016-08-01

    Full Text Available Diabetes is a chronic metabolic disorder caused by relative or absolute insulin deficient or reduced sensitivity of target cells to insulin. Mesenchymal stem cells (MSCs are adult stem cells with multiple differentiation potential, self-renewable and immunoregulatory properties. Accumulating evidences from clinic or animal experiments recent years showed that MSCs infusion could ameliorate hyperglycemia in diabetes. The research progress of MSCs in diabetes treatment is summarized and a corresponding perspective is herewith proposed in present paper. DOI: 10.11855/j.issn.0577-7402.2016.07.16

  4. A Review of Visual Perspective taking in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Amy ePearson

    2013-10-01

    Full Text Available Impairments in social cognition are a key symptom of Autism Spectrum Disorder. People with autism have great difficulty with understanding the beliefs and desires of other people. In recent years literature has begun to examine the link between impairments in social cognition and abilities which demand the use of spatial and social skills, such as visual perspective taking (VPT. Flavell (1977 defined two levels of perspective taking: VPT level 1 is the ability to understand that other people have a different line of sight to ourselves, whereas VPT level 2 is the understanding that two people viewing the same item from different points in space may see different things. So far, literature on whether either level of VPT is impaired or intact in autism is inconsistent. Here we review studies which have examined VPT levels 1 and 2 in people with autism with a focus on the methods that have been used to measure perspective taking. We conclude the review with an evaluation of the findings into VPT in autism and give recommendations for future research which may give a clearer insight into whether perspective taking is truly impaired in autism.

  5. Polymers in cell encapsulation from an enveloped cell perspective.

    Science.gov (United States)

    de Vos, Paul; Lazarjani, Hamideh Aghajani; Poncelet, Denis; Faas, Marijke M

    2014-04-01

    In the past two decades, many polymers have been proposed for producing immunoprotective capsules. Examples include the natural polymers alginate, agarose, chitosan, cellulose, collagen, and xanthan and synthetic polymers poly(ethylene glycol), polyvinyl alcohol, polyurethane, poly(ether-sulfone), polypropylene, sodium polystyrene sulfate, and polyacrylate poly(acrylonitrile-sodium methallylsulfonate). The biocompatibility of these polymers is discussed in terms of tissue responses in both the host and matrix to accommodate the functional survival of the cells. Cells should grow and function in the polymer network as adequately as in their natural environment. This is critical when therapeutic cells from scarce cadaveric donors are considered, such as pancreatic islets. Additionally, the cell mass in capsules is discussed from the perspective of emerging new insights into the release of so-called danger-associated molecular pattern molecules by clumps of necrotic therapeutic cells. We conclude that despite two decades of intensive research, drawing conclusions about which polymer is most adequate for clinical application is still difficult. This is because of the lack of documentation on critical information, such as the composition of the polymer, the presence or absence of confounding factors that induce immune responses, toxicity to enveloped cells, and the permeability of the polymer network. Only alginate has been studied extensively and currently qualifies for application. This review also discusses critical issues that are not directly related to polymers and are not discussed in the other reviews in this issue, such as the functional performance of encapsulated cells in vivo. Physiological endocrine responses may indeed not be expected because of the many barriers that the metabolites encounter when traveling from the blood stream to the enveloped cells and back to circulation. However, despite these diffusion barriers, many studies have shown optimal

  6. Collective cell migration: a mechanistic perspective.

    Science.gov (United States)

    Vedula, Sri Ram Krishna; Ravasio, Andrea; Lim, Chwee Teck; Ladoux, Benoit

    2013-11-01

    Collective cell migration is fundamental to gaining insights into various important biological processes such as wound healing and cancer metastasis. In particular, recent in vitro studies and in silico simulations suggest that mechanics can explain the social behavior of multicellular clusters to a large extent with minimal knowledge of various cellular signaling pathways. These results suggest that a mechanistic perspective is necessary for a comprehensive and holistic understanding of collective cell migration, and this review aims to provide a broad overview of such a perspective.

  7. Eating disorders in adolescence: attachment issues from a developmental perspective.

    Science.gov (United States)

    Gander, Manuela; Sevecke, Kathrin; Buchheim, Anna

    2015-01-01

    In the present article we review findings from an emerging body of research on attachment issues in adolescents with eating disorders from a developmental perspective. Articles for inclusion in this review were identified from PsychINFO (1966-2013), Sciencedirect (1970-2013), Psychindex (1980-2013), and Pubmed (1980-2013). First, we will outline the crucial developmental changes in the attachment system and discuss how they might be related to the early onset of the disease. Then we will report on the major results from attachment studies using self-report and narrative instruments in that age group. Studies with a developmental approach on attachment will be analyzed in more detail. The high incidence of the unresolved attachment pattern in eating disorder samples is striking, especially for patients with anorexia nervosa. Interestingly, this predominance of the unresolved category was also found in their mothers. To date, these transgenerational aspects are still poorly understood and therefore represent an exciting research frontier. Future studies that include larger adolescent samples and provide a more detailed description including symptom severity and comorbidity would contribute to a better understanding of this complex and painful condition.

  8. Eating disorders in adolescence: attachment issues from a developmental perspective

    Directory of Open Access Journals (Sweden)

    Manuela eGander

    2015-08-01

    Full Text Available In the present article we review findings from an emerging body of research on attachment issues in adolescents with eating disorders from a developmental perspective. First, we will outline the crucial developmental changes in the attachment system and discuss how they might be related to the early onset of the disease. Then we will report on the major results from attachment studies using self-report and narrative instruments in that age group. Studies with a developmental approach on attachment will be analyzed in more detail. The high incidence of the unresolved attachment pattern in eating disorder samples is striking, especially for patients with anorexia nervosa. Interestingly, this predominance of the unresolved category was also found in their mothers. To date, these transgenerational aspects are still poorly understood and therefore represent an exciting research frontier. Future studies that include larger adolescent samples and provide a more detailed description including symptom severity and comorbidity would contribute to a better understanding of this complex and painful condition.

  9. Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders.

    Science.gov (United States)

    Yoo, Ji Youn; Kim, Sung Soo

    2016-03-18

    Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

  10. Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Ji Youn Yoo

    2016-03-01

    Full Text Available Metabolic disorders, including type 2 diabetes (T2DM and cardiovascular disease (CVD, present an increasing public health concern and can significantly undermine an individual’s quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity. The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

  11. Pediatric red cell disorders and pure red cell aplasia.

    Science.gov (United States)

    Perkins, Sherrie L

    2004-12-01

    Anemia in children may arise from a wide variety of pathogenetic mechanisms that include congenital and acquired disorders. Often the diagnostic considerations include disorders that are not seen commonly in adults and lifelong disorders that arise in children and persist throughout life. Consideration of diverse causes of anemia such as red cell membrane disorders, red cell enzymopathies, congenital dyserythropoietic anemias, congenital sideroblastic anemias, and hereditary pure red cell aplasia (Diamond-Blackfan anemia), as well as infectious causes such as parvovirus B19 infection, often is required when diagnosing anemia in an infant or young child. Knowledge of these entities that are important causes of anemia in the pediatric population, including clinical manifestations and laboratory workup, will aid in recognition of the specific disease entities and effective workup of pediatric red cell disorders.

  12. A Multi-Perspective Collaborative on Teacher Learning for Teachers of Students with Autism Spectrum Disorder

    Science.gov (United States)

    West, Elizabeth A.; Jones, Phyllis; Chambers, Dianne; Whitehurst, Teresa

    2012-01-01

    The purpose of this multi-perspective collaborative research activity was to analyze moments of teacher learning as perceived by a group of teachers who educate students with the label of Autism Spectrum Disorder (ASD). The researchers in this project acknowledge the value of hearing teachers' perspectives on what works for them in their…

  13. Orphan drugs in development for urea cycle disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Häberle J

    2014-09-01

    Full Text Available Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of ammonia. The resulting hyperammonemia causes severe brain injury unless aggressive steps are taken to reduce the accumulation of ammonia, which is thought to be the most toxic metabolite. This review describes the current state of chronic management of urea cycle disorders, focusing on new and emerging therapies. Management strategies include the mainstay of treatment, namely dietary protein restriction and supplementation with l-arginine or l-citrulline. Several currently approved medications utilize and enhance alternative pathways of waste nitrogen excretion (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate in several formulations, and glycerol phenylbutyrate, working through conjugation of the drug to either glycine (in the case of benzoate or glutamine, the products of which are excreted in the urine. Carglumic acid activates the first committed step of conversion of ammonia to urea, carbamoylphosphate synthetase, and thus effectively treats defective synthesis of the endogenous activator, N-acetylglutamate, whether due to genetic defects or biochemical inhibition of the N-acetylglutamate synthase enzyme. Approaches to neuroprotection during episodes of hyperammonemia are discussed, including the use of controlled hypothermia (brain cooling, as well as proposed, but as yet untested, pharmacologic therapies. Finally, cell-based therapies, including liver transplantation, infusion of fresh or cryopreserved hepatocytes, use of stem cells, and new approaches to gene

  14. Embryonic stem cell differentiation: a chromatin perspective.

    Science.gov (United States)

    Rasmussen, Theodore P

    2003-11-13

    Embryonic stem (ES) cells hold immense promise for the treatment of human degenerative disease. Because ES cells are pluripotent, they can be directed to differentiate into a number of alternative cell-types with potential therapeutic value. Such attempts at "rationally-directed ES cell differentiation" constitute attempts to recapitulate aspects of normal development in vitro. All differentiated cells retain identical DNA content, yet gene expression varies widely from cell-type to cell-type. Therefore, a potent epigenetic system has evolved to coordinate and maintain tissue-specific patterns of gene expression. Recent advances show that mechanisms that govern epigenetic regulation of gene expression are rooted in the details of chromatin dynamics. As embryonic cells differentiate, certain genes are activated while others are silenced. These activation and silencing events are exquisitely coordinated with the allocation of cell lineages. Remodeling of the chromatin of developmentally-regulated genes occurs in conjunction with lineage commitment. Oocytes, early embryos, and ES cells contain potent chromatin-remodeling activities, an observation that suggests that chromatin dynamics may be especially important for early lineage decisions. Chromatin dynamics are also involved in the differentiation of adult stem cells, where the assembly of specialized chromatin upon tissue-specific genes has been studied in fine detail. The next few years will likely yield striking advances in the understanding of stem cell differentiation and developmental biology from the perspective of chromatin dynamics.

  15. Embryonic stem cell differentiation: A chromatin perspective

    Directory of Open Access Journals (Sweden)

    Rasmussen Theodore P

    2003-11-01

    Full Text Available Abstract Embryonic stem (ES cells hold immense promise for the treatment of human degenerative disease. Because ES cells are pluripotent, they can be directed to differentiate into a number of alternative cell-types with potential therapeutic value. Such attempts at "rationally-directed ES cell differentiation" constitute attempts to recapitulate aspects of normal development in vitro. All differentiated cells retain identical DNA content, yet gene expression varies widely from cell-type to cell-type. Therefore, a potent epigenetic system has evolved to coordinate and maintain tissue-specific patterns of gene expression. Recent advances show that mechanisms that govern epigenetic regulation of gene expression are rooted in the details of chromatin dynamics. As embryonic cells differentiate, certain genes are activated while others are silenced. These activation and silencing events are exquisitely coordinated with the allocation of cell lineages. Remodeling of the chromatin of developmentally-regulated genes occurs in conjunction with lineage commitment. Oocytes, early embryos, and ES cells contain potent chromatin-remodeling activities, an observation that suggests that chromatin dynamics may be especially important for early lineage decisions. Chromatin dynamics are also involved in the differentiation of adult stem cells, where the assembly of specialized chromatin upon tissue-specific genes has been studied in fine detail. The next few years will likely yield striking advances in the understanding of stem cell differentiation and developmental biology from the perspective of chromatin dynamics.

  16. Sickle Cell Disease as a Neurodevelopmental Disorder

    Science.gov (United States)

    Schatz, Jeffrey; McClellan, Catherine B.

    2006-01-01

    Sickle cell disease (SCD) is a blood disorder; however, the central nervous system (CNS) is one of the organs frequently affected by the disease. Brain disease can begin early in life and often leads to neurocognitive dysfunction. Approximately one-fourth to one-third of children with SCD have some form of CNS effects from the disease, which…

  17. Fetal Alcohol Spectrum Disorders: an overview from the glia perspective

    Directory of Open Access Journals (Sweden)

    Clare J. Wilhelm

    2016-01-01

    Full Text Available Alcohol consumption during pregnancy can produce a variety of central nervous system abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD. Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS, as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the

  18. Clinical and scientific perspectives on movement disorders: Stanley Fahn's contributions.

    Science.gov (United States)

    Jankovic, Joseph; Bressman, Susan; Dauer, William; Kang, Un Jung

    2015-12-01

    Dr. Stanley Fahn, the H. Houston Merritt Professor of Neurology and Director Emeritus of the Center for Parkinson's Disease and Other Movement Disorders at Columbia University, one of the founders of the field of movement disorders, was the first president of the Movement Disorders Society (subsequently renamed as the International Parkinson and Movement Disorder Society). Together with his friend and colleague, Professor David Marsden, he also served as the first co-editor of the journal Movement Disorders. By emphasizing phenomenology as the key element in differentiating various hypokinetic and hyperkinetic movement disorders, Dr. Fahn drew attention to the clinical history and the power of observation in the diagnosis of movement disorders. Dr. Fahn had major influence on the development of classifications and assessments of various movement disorders and in organizing various research groups such as the Parkinson Study Group. As the founder and president of the World Parkinson Coalition and an organizer of the initial three World Parkinson Congresses, he has demonstrated his long-standing commitment to the cause of including patients as partners. The primary goal and objective of this invited review is to highlight some of Dr. Fahn's most impactful scientific and clinical contributions to the understanding and treatment of Parkinson's disease, dystonia, and other movement disorders.

  19. Assessment and Treatment of Personality Disorders: A Behavioral Perspective

    Science.gov (United States)

    Nelson-Gray, Rosemery O.; Lootens, Christopher M.; Mitchell, John T.; Robertson, Christopher D.; Hundt, Natalie E.; Kimbrel, Nathan A.

    2009-01-01

    Personality disorders are complex and highly challenging to treatment providers; yet, for clients with these problems, there exist very few treatment options that have been supported by research. Given the lack of empirically-supported therapies for personality disorders, it can be difficult to make treatment decisions for this population. The…

  20. Eating Disorders: National Institute of Mental Health's Perspective

    Science.gov (United States)

    Chavez, Mark; Insel, Thomas R.

    2007-01-01

    The mission of the National Institute of Mental Health (NIMH) is to reduce the burden of mental and behavioral disorders through research, and eating disorders embody an important fraction of this burden. Although past and current research has provided important knowledge regarding the etiology, classification, pathophysiology, and treatment of…

  1. Comorbidity in "DSM" Childhood Mental Disorders: A Functional Perspective

    Science.gov (United States)

    Cipani, Ennio

    2014-01-01

    In this article, I address the issue of comorbidity and its prevalence in the prior "Diagnostic and Statistical Manual of Mental Disorders" ("DSM") classification systems. The focus on the topography or form of presenting problems as the venue for determining mental disorders is scrutinized as the possible cause. Addressing the…

  2. Perspective-taking deficits in people with schizophrenia spectrum disorders: a prospective investigation

    DEFF Research Database (Denmark)

    Schiffman, Jason; Lam, Cecilia W; Jiwatram, Tina

    2004-01-01

    BACKGROUND: This study examined data from a Danish prospective longitudinal project in attempt to address the state/trait controversy regarding theory of mind deficits in schizophrenia. Deficits in perspective-taking--a component of theory of mind--were investigated prospectively among children who......-psychotic disorder. CONCLUSIONS: Deficits in perspective-taking among children who later developed schizophrenia spectrum disorders suggest that a facet of theory of mind is impaired prior to development of schizophrenia. Our findings lend support to the hypothesis that theory of mind deficits in schizophrenia...... developed schizophrenia spectrum disorders as adults in comparison to children who did not develop schizophrenia spectrum disorders. METHOD: A total of 265 high risk and control subjects were studied in 1972. At the time of initial assessment, the Role-Taking Task (RTT) was administered. Two hundred...

  3. Perspectives of induced pluripotent stem cells for cardiovascular system regeneration

    Science.gov (United States)

    Csöbönyeiová, Mária; Polák, Štefan

    2015-01-01

    Induced pluripotent stem cells (iPSCs) hold great promise for basic research and regenerative medicine. They offer the same advantages as embryonic stem cells (ESCs) and moreover new perspectives for personalized medicine. iPSCs can be generated from adult somatic tissues by over-expression of a few defined transcription factors, including Oct4, Sox2, Klf4, and c-myc. For regenerative medicine in particular, the technology provides great hope for patients with incurable diseases or potentially fatal disorders such as heart failure. The endogenous regenerative potentials of adult hearts are extremely limited and insufficient to compensate for myocardial loss occurring after myocardial infarction. Recent discoveries have demonstrated that iPSCs have the potential to significantly advance future cardiovascular regenerative therapies. Moreover, iPSCs can be generated from somatic cells of patients with genetic basis for their disease. This human iPSC derivates offer tremendous potential for new disease models. This paper reviews current applications of iPSCs in cardiovascular regenerative medicine and discusses progress in modeling cardiovascular diseases using iPSCs-derived cardiac cells. PMID:25595188

  4. Major Channels Involved In Neuropsychiatric Disorders And Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Paola eImbrici

    2013-05-01

    Full Text Available Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders or schizophrenia. Moreover, point mutations in calcium, sodium and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium and potassium channels in bipolar disorder, schizophrenia and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.

  5. An integrative perspective on psychotherapeutic treatments for borderline personality disorder

    NARCIS (Netherlands)

    de Groot, E.R.; Verheul, R.; Trijsburg, R.W.

    2008-01-01

    Although there is an abundance of literature on the psychotherapeutic treatment of borderline pathology, little is known about differences and similarities between treatments of borderline personality disorder (BPD). Potential differences and similarities are especially important in the absence of e

  6. Substance use disorder and the family: An Indian perspective

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2016-01-01

    Full Text Available The substance use disorder not only impacts the patient himself/herself, but also affects family members. This is more relevant in a country like India where the familial ties are stronger with family members playing a significant role in the treatment process. This narrative review takes an overview of the inter-relationship between substance use disorder and the family. The domestic violence and adverse familial circumstances, both often arise as a consequence of substance use. Although the spouses of substance users experience greater rates of psychopathology and distress, children of patients with substance user disorders demonstrate higher levels of behavioral disturbances. Codependence often develops in the familial relationship, which perpetuates the substance use disorder. Substance use places quite a burden on the family, both psychologically as well as in terms of resources. Nonetheless, family members provide motivation, emotional support, and practical help during the treatment of substance use disorders and hence need to be engaged in the therapeutic process. Finally, the changing family structure and family dynamics in India might influence the in the future both the effect of substance use disorder on the family, and the familial resource available for treatment.

  7. Are Mental Disorders Brain Diseases, and What Does This Mean? A Clinical-Neuropsychological Perspective.

    Science.gov (United States)

    Frisch, Stefan

    Neuroscientific research has substantially increased our knowledge about mental disorders in recent years. Along with these benefits, radical postulates have been articulated according to which understanding and treatment of mental disorders should generally be based on biological terms, such as neurons/brain areas, transmitters, genes etc. Proponents of such a 'biological psychiatry' claim that mental disorders are analogous to neurological disorders and refer to neurology and neuropsychology to corroborate their claims. The present article argues that, from a clinical-neuropsychological perspective, 'biological psychiatry' is based on a mechanistic, 'cerebrocentric' framework of brain (dys-)function which has its roots in experimental neuroscience but runs up against narrow limits in clinical neurology and neuropsychology. In fact, understanding and treating neurological disorders generally demands a systems perspective including brain, organism and environment as intrinsically entangled. In this way, 'biological' characterizes a 'holistic', nonreductionist level of explanation, according to which the significance of particular mechanisms can only be estimated in the context of the organism (or person). This is evident in the common observation that local brain damage does not just lead to an isolated loss of function, but to multiple attempts of reorganization and readaptation; it initiates new developments. Furthermore, treating brain disorders necessarily includes aspects of individuality and subjectivity, a conclusion that contradicts the purely 'objectivist', third-person stance put forward by some proponents of biological psychiatry. In sum, understanding and treating brain damage sequelae in the clinical neurosciences demands a biopsychosocial perspective, for both conceptual and historical reasons. The same may hold for psychiatry when adopting a brain-based view on mental disorders. In such a perspective, biological psychiatry seems an interesting

  8. Peeling the Onion of Auditory Processing Disorder: A Language/Curricular-Based Perspective

    Science.gov (United States)

    Wallach, Geraldine P.

    2011-01-01

    Purpose: This article addresses auditory processing disorder (APD) from a language-based perspective. The author asks speech-language pathologists to evaluate the functionality (or not) of APD as a diagnostic category for children and adolescents with language-learning and academic difficulties. Suggestions are offered from a…

  9. Integrating Recovery and the Narrative Attachment Systems Perspective to Working through Borderline Personality Disorder

    Science.gov (United States)

    Bernardon, Stephanie; Pernice-Duca, Francesca

    2012-01-01

    Borderline personality disorder (BPD) presents a number of symptoms and adjustment issues for individuals, but it is also associated with a myriad of risks for the larger family system. A systemic perspective is crucial to comprehending the development of BPD. Promoting healthy relationships with one or more supportive adult enables the child to…

  10. Self-Presentation and the Role of Perspective Taking and Social Motivation in Autism Spectrum Disorder

    Science.gov (United States)

    Scheeren, Anke M.; Banerjee, Robin; Koot, Hans M.; Begeer, Sander

    2016-01-01

    We compared self-presentation abilities of 132 children and adolescents with autism spectrum disorders (ASD) to those of 41 typically developing (TD) peers, and examined the potential link with their social motivation and perspective taking. Participants introduced themselves to an interviewer in a baseline condition (without incentive) and a…

  11. Endocrine disruptors and metabolic and reproductive disorders: Future perspectives

    Directory of Open Access Journals (Sweden)

    Jaime Mendiola Olivares

    2014-06-01

    Full Text Available There is increasing evidence of the relation between environmental exposures [mainly to endocrine disrupting chemicals (EDC] and human health impairment. These compounds include a wide assortment of chemicals used in agriculture (organophosphate and organochlorine compounds, fungicides, etc. and industrial and commercial applications (bisphenol A, phthalates, perfluorinated compounds, etc.. Currently, the main research areas into this relation are related to neurodevelopmental disorders or cancer, and hormonal, metabolic or reproductive disorders or diseases. The incidence rates of metabolic disorders or conditions–obesity, metabolic syndrome or diabetes–and reproductive or infertility problems are on the rise in human populations. However, the already known risk factors do not fully explain the documented trends for these disorders and diseases. In general, it would be highly advisable to increase the number of epidemiological studies in humans and of mechanistic studies in preclinical and/or cellular models to better understand the links between environmental exposure to EDCs and metabolic disorders or conditions such as obesity, metabolic syndrome, diabetes or infertility, including epigenetic aspects as well.

  12. Eating disorders and attachment: a contemporary psychodynamic perspective.

    Science.gov (United States)

    Tasca, Giorgio A; Balfour, Louise

    2014-06-01

    A contemporary psychodynamic framework can add much to our understanding of eating disorders. Eating disorders are associated with complex comorbidities, high levels of mortality, and therapist countertransferences that can complicate psychological treatments. Mainstream models currently focus on cognitive, biological, or cultural factors to the near exclusion of attachment functioning, and the individual's dynamics. As such, standard models appear to exclude person-centred and developmental considerations when providing treatments. In this article, we describe a contemporary psychodynamic model that understands eating disorder symptoms as a consequence of vulnerability to social pressures to be thin and biological predispositions to body weight. Individual vulnerabilities are rooted in unmet attachment needs causing negative affect, and subsequent maladaptive defenses and eating disorder symptoms as a means of coping. We describe how this model can inform transdiagnostic eating disorder treatment that focuses on symptoms as well as specific attachment functions including: interpersonal style, affect regulation, reflective functioning, and coherence of mind. Two clinical examples are presented to illustrate case formulations and psychological treatments informed by these conceptualizations.

  13. Limbal stem cell transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Atallah MR

    2016-04-01

    the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers the best results. Future studies aim at improving cellular expansion and finding different sources of stem cells. Keywords: limbal stem cell deficiency (LSCD, simple limbal epithelial transplantation (SLET, cultivated limbal epithelial transplantation (CLET, keratolimbal allograft (KLAL

  14. Understanding and coping with binge eating disorder: the patient's perspective.

    Science.gov (United States)

    McElroy, Susan L; Guerdjikova, Anna I

    2015-08-01

    Binge eating disorder (BED) is the most common of the 6 feeding and eating disorders recognized by the DSM-5 and a significant public health problem that can be successfully managed with appropriate help. Many patients, however, are hesitant to discuss the symptoms of BED with their providers because of embarrassment or because they simply do not recognize the behavior as a problem behavior. Clinicians need to increase their awareness of BED, its warning signs, and how and why patients might try to hide it leading to increased BED recognition and timely diagnosis. Then, given the right tools, clinicians can help patients to not only accept the diagnosis and look into various treatment options but also to move beyond it to recognize if any comorbid disorders are present and in need of treatment.

  15. Animal models of tic disorders: a translational perspective.

    Science.gov (United States)

    Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco

    2014-12-30

    Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders.

  16. Dopamine in Socioecological and Evolutionary Perspectives: Implications for Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Yoshie eYamaguchi

    2015-06-01

    Full Text Available Dopamine (DA transmission in brain areas such as the prefrontal cortex (PFC and nucleus accumbens (NAcc plays important roles in cognitive and affective function. As such, DA deficits have been implicated in a number of psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder (ADHD. Accumulating evidence suggests that DA is also involved in social behavior of animals and humans. Although most animals organize and live in social groups, how the DA system functions in such social groups of animals, and its dysfunction causes compromises in the groups has remained less understood. Here we propose that alterations of DA signaling and associated genetic variants and behavioral phenotypes, which have been normally considered as deficits in investigation at an individual level, may not necessarily yield disadvantages, and even work advantageously, depending on social contexts in subjects with such DA alterations living in social groups. This hypothesis could provide a novel insight into our understanding of the biological mechanisms of psychiatric disorders, and a potential explanation that disadvantageous phenotypes associated with DA deficits in psychiatric disorders have remained in humans through evolution.

  17. Outcomes in Adults with Autism Spectrum Disorders: A Historical Perspective

    Science.gov (United States)

    Henninger, Natalie A.; Taylor, Julie Lounds

    2013-01-01

    In this review, we examine the ways in which researchers have defined successful adult outcomes for individuals with autism spectrum disorders (ASDs) from the first systematic follow-up reports to the present day. The earliest outcome studies used vague and unreliable outcome criteria, and institutionalization was a common marker of poor outcomes.…

  18. Nanotechnology Based Treatments for Neurological Disorders from Genetics Perspective

    Directory of Open Access Journals (Sweden)

    Nicholas S. Kurek

    2013-02-01

    Full Text Available Nanotechology involves the application, analysis and manipulation of nanomaterials. These materials have unique and medically useful properties due to their nanoscale parameters. Nanotechnology based treatments and diagnostics might eventually bring great relief to people suffering from neurological disorders including autism spectrum disorders, Alzheimer’s disease and Parkinson’s disorders. A large variety of nonmaterials such as viruses, carbon nanotubes, gold and silica nanoparticles, nanoshells, quantum dots, genetic material and proteins as well as hordes of other forms of nanotechnology have been researched in order to determine their potential in enhancing disease treatments and diagnostics. Nanotechnology has shown countless applications and might eventually be used in every biotech/health industry. Nevertheless, many nanomaterials may pose some safety risks and whether their benefits overweigh the risk is still being debated. Once the proper ethical and safety protocols are established and enough research is completed, nanotechnology is expected to benefit the mankind enormously. In this article, we will discuss and analyze many ways in which, nanotechnology based treatments and diagnostics will be used to help people with neurological disorders through the methods that we currently have at our disposal. [Archives Medical Review Journal 2013; 22(1.000: 12-32

  19. Attachment and Externalizing Disorders: A Developmental Psychopathology Perspective

    Science.gov (United States)

    Guttmann-Steinmetz, Sarit; Crowell, Judith A.

    2006-01-01

    Objective: Attachment theory offers an intriguing formulation of protection and risk that ties together key aspects of behavior, emotion, and cognition. The authors present links among attachment status, other developmental domains, and the development and maintenance of externalizing disorders to illustrate an approach to integrating attachment…

  20. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective.

    Science.gov (United States)

    Pauls, David L; Abramovitch, Amitai; Rauch, Scott L; Geller, Daniel A

    2014-06-01

    Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.

  1. Endocrinological disorders affecting neurosurgical patients: An intensivists perspective

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa

    2014-01-01

    Full Text Available Management of critically ill neurosurgical patients is often complicated by the presence or development of endocrinological ailments which complicate the clinical scenario and adversely affect the prognosis of these patients. The anatomical proximity to the vital centers regulating the endocrinological physiology and alteration in the neurotransmitter release causes disturbances in the hormonal homeostasis. This paves the way for development of diverse disorders where single or multiple hormones may be involved which can have deleterious effect on the different organ system. Understanding and awareness of these disorders is important for the treating intensivist to recognize these changes early in their course, so that appropriate and timely therapeutic measures can be initiated along with the treatment of the primary malady.

  2. The APA classification of mental disorders: future perspectives.

    Science.gov (United States)

    Regier, Darrel A; Narrow, William E; First, Michael B; Marshall, Tina

    2002-01-01

    After 8-10 years of experience with the fourth edition of the Diagnostic and Statistical Manual (DSM-IV) and the tenth edition of the International Classification of Diseases (ICD-10), it is an ideal time to begin looking at the clinical and research consequences of these diagnostic systems. The American Psychiatric Association, in conjunction with the National Institutes of Health, has initiated a research development process intended to accelerate an evaluation of existing criteria while developing and testing hypotheses that would improve the validity of our diagnostic concepts. Over the past year, a multidisciplinary, international panel has developed a series of six white papers which define research opportunities in the following broad areas: Nomenclature, Disability and Impairment, Personality Disorders, Relational Disorders, Developmental Psychopathology, Neuroscience, and Cross-Cultural aspects of Psychopathology. Recommendations for future national and international research in each of these areas will be discussed.

  3. Perspectives on sensory processing disorder: a call for translational research

    Directory of Open Access Journals (Sweden)

    Lucy J Miller

    2009-09-01

    Full Text Available This article explores the convergence of two fields, which have similar theoretical origins: a clinical field originally known as sensory integration and a branch of neuroscience that conducts research in an area also called sensory integration. Clinically, the term was used to identify a pattern of dysfunction in children and adults, as well as a related theory, assessment, and treatment method for children who have atypical responses to ordinary sensory stimulation. Currently the term for the disorder is Sensory Processing Disorder (SPD. In neuroscience, the term sensory integration refers to converging information in the brain from one or more sensory domains. A recent subspecialty in neuroscience labeled multisensory integration (MSI refers to the neural process that occurs when sensory input from two or more different sensory modalities converge. Understanding the specific meanings of the term sensory integration intended by the clinical and neuroscience fields and the term multisensory integration in neuroscience is critical. A translational research approach would improve exploration of crucial research questions in both the basic science and clinical science. Refinement of the conceptual model of the disorder and the related treatment approach would help prioritize which specific hypotheses should be studied in both the clinical and neuroscience fields. The issue is how we can facilitate a translational approach between researchers in the two fields. Multidisciplinary, collaborative studies would increase knowledge of brain function and could make a significant contribution to alleviating the impairments of individuals with SPD and their families.

  4. Functional neurosurgery for movement disorders: a historical perspective.

    Science.gov (United States)

    Benabid, Alim Louis; Chabardes, Stephan; Torres, Napoleon; Piallat, Brigitte; Krack, Paul; Fraix, Valerie; Pollak, Pierre

    2009-01-01

    Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become

  5. Etiology of autism spectrum disorder: a genomics perspective.

    Science.gov (United States)

    Connolly, John J; Hakonarson, Hakon

    2014-11-01

    In recent years, considerable progress has been made in understanding the genomic basis of autism spectrum disorder (ASD). Hundreds of variants have been proposed as predisposing to ASD, and the challenge now is to validate candidates and to understand how gene networks interact to produce ASD phenotypes. Genome-wide association and second-generation sequencing studies in particular have provided important indications about how to understand ASD on a molecular level, and we are beginning to see these experimental approaches translate into novel treatments and diagnostic tests. We review key studies in the field over the past five years and discuss some of the remaining technological and methodological challenges that remain.

  6. Empathy in narcissistic personality disorder: from clinical and empirical perspectives.

    Science.gov (United States)

    Baskin-Sommers, Arielle; Krusemark, Elizabeth; Ronningstam, Elsa

    2014-07-01

    Narcissistic personality disorder (NPD) is associated with an assortment of characteristics that undermine interpersonal functioning. A lack of empathy is often cited as the primary distinguishing feature of NPD. However, clinical presentations of NPD suggest that empathy is not simply deficient in these individuals, but dysfunctional and subject to a diverse set of motivational and situational factors. Consistent with this presentation, research illustrates that empathy is multidimensional, involving 2 distinct emotional and cognitive processes associated with a capacity to respectively understand and respond to others' mental and affective states. The goal of this practice review is to bridge the gap between our psychobiological understanding of empathy and its clinical manifestations in NPD. We present 3 case studies highlighting the variability in empathic functioning in people with NPD. Additionally, we summarize the literature on empathy and NPD, which largely associates this disorder with deficient emotional empathy, and dysfunctional rather than deficient cognitive empathy. Because this research is limited, we also present empathy-based findings for related syndromes (borderline and psychopathy). Given the complexity of narcissism and empathy, we propose that multiple relationships can exist between these constructs. Ultimately, by recognizing the multifaceted relationship between empathy and narcissism, and moving away from an all or nothing belief that those with NPD simply lack empathy, therapists may better understand narcissistic patients' behavior and motivational structure.

  7. Insights from ERPs into Emotional Disorders: An affective neuroscience perspective

    Directory of Open Access Journals (Sweden)

    Salvatore Campanella

    2006-03-01

    Full Text Available Affective neuroscience disposes of complementary imaging tools, some identifying which neural regions are involved in a specific cognitive function, others defining the temporal sequences of these activations with an optimal temporal resolution. The aim of the present manuscript is to show how event-related potentials (ERPs may help us to enhance our understanding of psychopathological conditions. To do so, three experiments from our laboratory will be presented. An emotional oddball design was used, in which participants are confronted with frequent stimuli (neutral faces and deviant stimuli (emotional faces which they have to detect as quickly as possible. These studies address anxiety, the long-term consequences of ecstasy consumption and schizophrenia. Our main purpose is to show that, if previous studies have shown for generalised anxiety disorder, as well as for drug abuse or schizophrenia, P300 alterations, the impaired processes leading to such an identical disturbance are different from one population to the other.

  8. A statistical perspective on association studies of psychiatric disorders

    DEFF Research Database (Denmark)

    Foldager, Leslie

    2014-01-01

    and 2 were motivated by the hypothesis that defects of the immune system may increase risk of psychiatric disorders. We consider two components from the lectin pathway of activation: mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) via continuous traits (protein level...... accepted genome-wide threshold for single-marker association tests has become 5e-8 but searching for interactions genome-wide results in drastically many more tests and thus the need of an even lower p-value threshold. Lowering the threshold comes at the unfortunate but inevitable expense of increasing...... for significance. Yet, in paper 6 we propose the Landscape method to summarise a series of sequentially ordered test values without the need of more or less arbitrary prior grouping....

  9. Communication accommodation and managing musculoskeletal disorders: doctors' and patients' perspectives.

    Science.gov (United States)

    Baker, Susan C; Gallois, Cindy; Driedger, S Michelle; Santesso, Nancy

    2011-06-01

    This study examined the ways in which health care providers (general practitioners and specialists) and patients communicate with each other about managing musculoskeletal (MSK) disorders, a major cause of long-term pain and physical disability. In managing their illness, patients must interact closely with health care providers, who play a large role in transferring knowledge to them. In-depth interviews with patients, general practitioners, and specialist rheumatologists in Australia and Canada were analyzed using Leximancer (a text-mining tool). Results indicated that, in their communication, doctors subtly emphasized accepting and adjusting to the illness ("new normal"), whereas patients emphasized pain relief and getting "back to normal." These results suggest that doctors and patients should accommodate in their communication across subtle and often unexpressed differences in the priorities of provider and patient, or they are likely to be at cross purposes and thus less effective.

  10. Computational Biomechanics of Human Red Blood Cells in Hematological Disorders.

    Science.gov (United States)

    Li, Xuejin; Li, He; Chang, Hung-Yu; Lykotrafitis, George; Em Karniadakis, George

    2017-02-01

    We review recent advances in multiscale modeling of the biomechanical characteristics of red blood cells (RBCs) in hematological diseases, and their relevance to the structure and dynamics of defective RBCs. We highlight examples of successful simulations of blood disorders including malaria and other hereditary disorders, such as sickle-cell anemia, spherocytosis, and elliptocytosis.

  11. Microparticles: A New Perspective in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Stephanie M. Schindler

    2014-01-01

    Full Text Available Microparticles (MPs are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer’s disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS.

  12. Neurodevelopmental Plasticity in Pre- and Postnatal Environmental Interactions: Implications for Psychiatric Disorders from an Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Young-A Lee

    2015-01-01

    Full Text Available Psychiatric disorders are disadvantageous behavioral phenotypes in humans. Accordingly, a recent epidemiological study has reported decreased fecundity in patients with psychiatric disorders, such as schizophrenia and autism spectrum disorders. Moreover, the fecundity of the relatives of these patients is not exceedingly higher compared to the fecundity of the relatives of normal subjects. Collectively, the prevalence of psychiatric disorders among humans is expected to decrease over generations. Nevertheless, in reality, the prevalence rates of psychiatric disorders in humans either have been constant over a long period of time or have even increased more recently. Several attempts to explain this fact have been made using biological mechanisms, such as de novo gene mutations or variants, although none of these explanations is fully comprehensive. Here, we propose a hypothesis towards understanding the biological mechanisms of psychiatric disorders from evolutionary perspectives. This hypothesis considers that behavioral phenotypes associated with psychiatric disorders might have emerged in the evolution of organisms as a neurodevelopmental adaptation against adverse environmental conditions associated with stress.

  13. Red blood cells in retinal vascular disorders.

    Science.gov (United States)

    Agrawal, Rupesh; Sherwood, Joseph; Chhablani, Jay; Ricchariya, Ashutosh; Kim, Sangho; Jones, Philip H; Balabani, Stavroula; Shima, David

    2016-01-01

    Microvascular circulation plays a vital role in regulating physiological functions, such as vascular resistance, and maintaining organ health. Pathologies such as hypertension, diabetes, or hematologic diseases affect the microcirculation posing a significant risk to human health. The retinal vasculature provides a unique window for non-invasive visualisation of the human circulation in vivo and retinal vascular image analysis has been established to predict the development of both clinical and subclinical cardiovascular, metabolic, renal and retinal disease in epidemiologic studies. Blood viscosity which was otherwise thought to play a negligible role in determining blood flow based on Poiseuille's law up to the 1970s has now been shown to play an equally if not a more important role in controlling microcirculation and quantifying blood flow. Understanding the hemodynamics/rheology of the microcirculation and its changes in diseased states remains a challenging task; this is due to the particulate nature of blood, the mechanical properties of the cells (such as deformability and aggregability) and the complex architecture of the microvasculature. In our review, we have tried to postulate a possible role of red blood cell (RBC) biomechanical properties and laid down future framework for research related to hemorrheological aspects of blood in patients with retinal vascular disorders.

  14. Clinical Holistic Medicine: Mental Disorders in a Holistic Perspective

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2005-01-01

    Full Text Available From a holistic perspective, psychiatric diseases are caused by the patient’s unwillingness to assume responsibility for his life, existence, and personal relations. The loss of responsibility arises from the repression of the fundamental existential dimensions of the patients. Repression of love and purpose causes depersonalization (i.e., a lack of responsibility for being yourself and for the contact with others, loss of direction and purpose in life. Repression of strength in mind and emotions leads to derealization (the breakdown of the reality testing, often with mental delusions and hallucinations. The repression of joy and gender leads to devitalization (emotional emptiness, loss of joy, personal energy, sexuality, and pleasure in life.The losses of existential dimensions are invariably connected to traumas with life-denying decisions. Healing the wounds of the soul by holding and processing will lead to the recovery of the person's character, purpose of life, and existential responsibility. It can be very difficult to help a psychotic patient. The physician must first love his patient unconditionally and then fully understand the patient in order to meet and support the patient to initiate the holistic process of healing. It takes motivation and willingness to suffer on behalf of the patients in order to heal, as the existential and emotional pain of the traumas resulting in insanity is often overwhelming. We believe that most psychiatric diseases can be alleviated or cured by the loving and caring physician who masters the holistic toolbox. Further research is needed to document the effect of holistic medicine in psychiatry.

  15. Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

    Directory of Open Access Journals (Sweden)

    Abrams TE

    2015-10-01

    Full Text Available Thad E Abrams,1,2 Amy Blevins,1,3 Mark W Vander Weg1,2,4 1Department of Internal Medicine, University of Iowa, 2Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, 3Hardin Health Sciences Library, 4Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Background: Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature.Objectives: The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1 determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2 identify targeted areas for further research.Methods: A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1 the co-occurrence of COPD and PTSD and 2 the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology.Results: A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD

  16. Satanism, ritual abuse, and multiple personality disorder: a sociohistorical perspective.

    Science.gov (United States)

    Mulhern, S

    1994-10-01

    During the past decade in North America, a growing number of mental health professionals have reported that between 25% and 50% of their patients in treatment for multiple personality disorder (MPD) have recovered early childhood traumatic memories of ritual torture, incestuous rape, sexual debauchery, sacrificial murder, infanticide, and cannibalism perpetrated by members of clandestine satanic cults. Although hundreds of local and federal police investigations have failed to corroborate patients' therapeutically constructed accounts, because the satanic etiology of MPD is logically coherent with the neodissociative, traumatic theory of psychopathology, conspiracy theory has emerged as the nucleus of a consistent pattern of contemporary clinical interpretation. Resolutely logical and thoroughly operational, ultrascientific psychodemonology remains paradoxically oblivious to its own irrational premises. When the hermetic logic of conspiracy theory is stripped away by historical and socio/psychological analysis, however, the hypothetical perpetrators of satanic ritual abuse simply disappear, leaving in their wake the very real human suffering of all those who have been caught up in the social delusion.

  17. Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Neal EG

    2014-04-01

    Full Text Available Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatment for intractable seizures in children, these ketone-generating diets are increasingly also being used in adults. They are the treatment of choice in glucose transporter type 1 deficiency syndrome and pyruvate dehydrogenase deficiency. Evidence for the potential of KD therapy to be included within the treatment options for cancer and neurodegenerative disorders is more limited, albeit an exciting area of research with future clinical potential. This review discusses the key aspects of KD therapy, including the efficacy of treatments and clinical implementation. The importance of appropriate initiation, adequate clinical supervision, regular monitoring, and assessment of nutritional needs is highlighted. Keywords: diet, seizures, ketosis

  18. Proprioceptive rehabilitation of upper limb dysfunction in movement disorders: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Giovanni eAbbruzzese

    2014-11-01

    Full Text Available Movement disorders are frequently associated with sensory abnormalities. In particular, proprioceptive deficits have been largely documented in both hypokinetic (Parkinson’s disease and hyperkinetic conditions (dystonia suggesting a possible role in their pathophysiology. Proprioceptive feedback is a fundamental component of sensorimotor integration allowing effective planning and execution of voluntary movements. Rehabilitation has become an essential element in the management of patients with movement disorders and there is a strong rationale to include proprioceptive training in rehabilitation protocols focused on mobility problems of the upper limbs. Proprioceptive training is aimed at improving the integration of proprioceptive signals using task intrinsic or augmented feedback. This perspective article reviews the available evidences on the effects of proprioceptive stimulation in improving upper limb mobility in patients with movement disorders and highlights the emerging innovative approaches targeted to maximizing the benefits of exercise by means of enhanced proprioception.

  19. Perspective-taking deficits in people with schizophrenia spectrum disorders: a prospective investigation

    DEFF Research Database (Denmark)

    Schiffman, Jason; Lam, Cecilia W; Jiwatram, Tina;

    2004-01-01

    developed schizophrenia spectrum disorders as adults in comparison to children who did not develop schizophrenia spectrum disorders. METHOD: A total of 265 high risk and control subjects were studied in 1972. At the time of initial assessment, the Role-Taking Task (RTT) was administered. Two hundred......BACKGROUND: This study examined data from a Danish prospective longitudinal project in attempt to address the state/trait controversy regarding theory of mind deficits in schizophrenia. Deficits in perspective-taking--a component of theory of mind--were investigated prospectively among children who...... and forty-two of these children were evaluated in 1992 during follow-up examinations. Sixteen developed schizophrenia, 10 developed a schizophrenia spectrum disorder, 70 had outcomes of other psychopathology, and 146 did not develop a mental illness. RESULTS: Children who later developed schizophrenia...

  20. Cultural aspects of major mental disorders: a critical review from an Indian perspective.

    Science.gov (United States)

    Viswanath, Biju; Chaturvedi, Santosh K

    2012-10-01

    Major mental disorders such as schizophrenia and affective disorders are highly disabling illnesses. The cultural factors that influence the diagnosis and treatment of these disorders are of paramount clinical significance. We attempted to critically review the cultural factors in relation to the epidemiology, phenomenology, treatment, and outcome of major mental disorders from an Indian perspective, and tried to compare these with the cultural factors identified in major international studies. The clinical expression of major mental disorders was noted to vary across cultures in the review. In addition, the outcome of major mental disorders is reported to be better in developing nations than in the developed countries. Transcultural variations are also noted to exist in pharmacokinetics, pharmacodynamics, traditional healing practices, and psychotherapeutic approaches. The role of cultural factors in severe mental illnesses needs adequate attention from mental health professionals. Continued research on the cultural aspects is required to understand the interplay of all social, cultural, and biological factors. It is important to consider other cultural, traditional, and folk methods for understanding and management of mental illnesses.

  1. Language cannot be reduced to biology: Perspectives from neuro-developmental disorders affecting language learning

    Indian Academy of Sciences (India)

    D Vasanta

    2005-02-01

    The study of language knowledge guided by a purely biological perspective prioritizes the study of syntax. The essential process of syntax is recursion – the ability to generate an infinite array of expressions from a limited set of elements. Researchers working within the biological perspective argue that this ability is possible only because of an innately specified genetic makeup that is specific to human beings. Such a view of language knowledge may be fully justified in discussions on biolinguistics, and in evolutionary biology. However, it is grossly inadequate in understanding language-learning problems, particularly those experienced by children with neurodevelopmental disorders such as developmental dyslexia, Williams syndrome, specific language impairment and autism spectrum disorders. Specifically, syntax-centered definitions of language knowledge completely ignore certain crucial aspects of language learning and use, namely, that language is embedded in a social context; that the role of envrironmental triggering as a learning mechanism is grossly underestimated; that a considerable extent of visuo-spatial information accompanies speech in day-to-day communication; that the developmental process itself lies at the heart of knowledge acquisition; and that there is a tremendous variation in the orthographic systems associated with different languages. All these (socio-cultural) factors can influence the rate and quality of spoken and written language acquisition resulting in much variation in phenotypes associated with disorders known to have a genetic component. Delineation of such phenotypic variability requires inputs from varied disciplines such as neurobiology, neuropsychology, linguistics and communication disorders. In this paper, I discuss published research that questions cognitive modularity and emphasises the role of the environment for understanding linguistic capabilities of children with neuro-developmental disorders. The discussion

  2. Bipolar disorder: a neural network perspective on a disorder of emotion and motivation.

    Science.gov (United States)

    Wessa, Michèle; Kanske, Philipp; Linke, Julia

    2014-01-01

    Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.

  3. Embryonic stem cell differentiation: A chromatin perspective

    OpenAIRE

    Rasmussen Theodore P

    2003-01-01

    Abstract Embryonic stem (ES) cells hold immense promise for the treatment of human degenerative disease. Because ES cells are pluripotent, they can be directed to differentiate into a number of alternative cell-types with potential therapeutic value. Such attempts at "rationally-directed ES cell differentiation" constitute attempts to recapitulate aspects of normal development in vitro. All differentiated cells retain identical DNA content, yet gene expression varies widely from cell-type to ...

  4. A unified cell biological perspective on axon-myelin injury.

    Science.gov (United States)

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin

    2014-08-04

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon-myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a local inflammatory disease process early in MS into the global progressive disorder seen during later stages. This mode of spreading could also apply to other neurological disorders.

  5. B cells as therapeutic targets in autoimmune neurological disorders.

    Science.gov (United States)

    Dalakas, Marinos C

    2008-10-01

    B cells have a fundamental role in the pathogenesis of various autoimmune neurological disorders, not only as precursors of antibody-producing cells, but also as important regulators of the T-cell activation process through their participation in antigen presentation, cytokine production, and formation of ectopic germinal centers in the intermeningeal spaces. Two B-cell trophic factors-BAFF (B-cell-activating factor) and APRIL (a proliferation-inducing ligand)-and their receptors are strongly upregulated in many immunological disorders of the CNS and PNS, and these molecules contribute to clonal expansion of B cells in situ. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules and trophic factors provides a rational approach to the treatment of autoimmune neurological diseases. This article reviews the role of B cells in autoimmune neurological disorders and summarizes the experience to date with rituximab, a B-cell-depleting monoclonal antibody against CD20, for the treatment of relapsing-remitting multiple sclerosis, autoimmune neuropathies, neuromyelitis optica, paraneoplastic neurological disorders, myasthenia gravis, and inflammatory myopathies. It is expected that ongoing controlled trials will establish the efficacy and long-term safety profile of anti-B-cell agents in several autoimmune neurological disorders, as well as exploring the possibility of a safe and synergistic effect with other immunosuppressants or immunomodulators.

  6. Strategies to Fight Stigma toward People with Mental Disorders: Perspectives from Different Stakeholders

    Directory of Open Access Journals (Sweden)

    Marc Corbière

    2012-01-01

    Full Text Available This study aims to provide a more complete and exhaustive perspective on the whole range of potential strategies to fight stigma by considering the perspectives of different stakeholders. Delegates to a Canadian conference were invited to participate in a survey that focused on stigma, from which the responses to the following question were analyzed: tell us briefly what you do to reduce prejudice and stigma toward people with a diagnosis of mental disorder? From 253 participants, 15 categories of strategies to fight stigma were identified from the verbatim (e.g., sharing/encouraging disclosure. These categories fell under six main themes: education, contact, protestation, person centered, working on recovery and social inclusion, and reflexive consciousness. The occurrence of these themes was different among stakeholders (clinical, organizational, and experiential knowledge. For example, people with mental disorders (experiential knowledge often mentioned contact and person centered strategies, while mental health professionals (clinical knowledge preferred education and working on recovery and social inclusion strategies. The results from this study highlight the need to pay more attention to the concept of disclosure of mental disorders in the process for de-stigmatization. Future studies are needed to assess the impact of the emerging strategies to fight stigma in the community.

  7. Induced Pluripotent Stem Cells: Characteristics and Perspectives

    Science.gov (United States)

    Cantz, Tobias; Martin, Ulrich

    The induction of pluripotency in somatic cells is widely considered as a major breakthrough in regenerative medicine, because this approach provides the basis for individualized stem cell-based therapies. Moreover, with respect to cell transplantation and tissue engineering, expertise from bioengineering to transplantation medicine is now meeting basic research of stem cell biology.

  8. Expansion of hematopoietic stem cells for transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Schuster Jessica A

    2012-05-01

    Full Text Available Abstract Hematopoietic stem cells (HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The expansion of HSCs has remained an important goal to develop advanced cell therapies for bone marrow transplantation and many blood disorders. Over the last several decades, there have been numerous attempts to expand HSCs in vitro using purified growth factors that are known to regulate HSCs. However, these attempts have been met with limited success for clinical applications. New developments in the HSC expansion field coupled with gene therapy and stem cell transplant should encourage progression in attractive treatment options for many disorders including hematologic conditions, immunodeficiencies, and genetic disorders.

  9. Difficulties in everyday life: Young persons with attention-deficit/hyperactivity disorder and autism spectrum disorders perspectives. A chat-log analysis

    OpenAIRE

    Ahlström, Britt H; Wentz, Elisabet

    2014-01-01

    This study focuses on the everyday life of young persons with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). There are follow-up studies describing ADHD, and ASD in adults, and residual impairments that affect life. Few qualitative studies have been conducted on the subject of their experiences of everyday life, and even fewer are from young persons’ perspectives. This study’s aim was to describe how young persons with ADHD and ASD function and how they ma...

  10. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

    OpenAIRE

    Ioana Mozos

    2015-01-01

    The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular dise...

  11. Caregiver perspectives on unintentional injury risk in children with an autism spectrum disorder.

    Science.gov (United States)

    Cavalari, Rachel N S; Romanczyk, Raymond G

    2012-12-01

    Unintentional injury risk research for children with an autism spectrum disorder (ASD) is currently limited. This article presents findings from a two-phase investigation of caregiver perspectives regarding unintentional injury risk in children with an ASD. Results indicate that children with an ASD exhibit elevated rates of risk-taking behaviors compared with peers, which increases the likelihood of more frequent and severe injuries. In addition, although ASD symptom severity positively correlated with risk-taking behavior and frequency of injury, children with an ASD were rarely rated as high risks for injury by caregivers. Implications are discussed in the context of pediatric health service provision.

  12. Substance use disorder in the context of LGBT health: a social work perspective.

    Science.gov (United States)

    Silvestre, Anthony; Beatty, Rodger L; Friedman, M Reuel

    2013-01-01

    The impacts of public and private funding of lesbian, gay, bisexual, and transgender (LGBT) health research, the state of integration of LGBT health issues into the academic and professional training programs of health care practitioners, and the larger social reality experienced by LGBT people profoundly affect substance use and substance use disorders in those populations. This analysis uses a social work perspective and considers the current state of research, professional training, and social oppression as they affect the health of LGBT people. Suggestions for action are offered that may improve the health of LGBT peoples and the practice of social work.

  13. Cell biology perspectives in phage biology.

    Science.gov (United States)

    Ansaldi, Mireille

    2012-01-01

    Cellular biology has long been restricted to large cellular organisms. However, as the resolution of microscopic methods increased, it became possible to study smaller cells, in particular bacterial cells. Bacteriophage biology is one aspect of bacterial cell biology that has recently gained insight from cell biology. Despite their small size, bacteriophages could be successfully labeled and their cycle studied in the host cells. This review aims to put together, although non-extensively, several cell biology studies that recently pushed the elucidation of key mechanisms in phage biology, such as the lysis-lysogeny decision in temperate phages or genome replication and transcription, one step further.

  14. Stem cells: a plant biology perspective

    NARCIS (Netherlands)

    Scheres, B.J.G.

    2005-01-01

    A recent meeting at the Juan March Foundation in Madrid, Spain brought together plant biologists to discuss the characteristics of plant stem cells that are unique and those that are shared by stem cells from the animal kingdom

  15. Induced pluripotent stem cells: origins, applications, and future perspectives.

    Science.gov (United States)

    Zhao, Jing; Jiang, Wen-jie; Sun, Chen; Hou, Cong-zhe; Yang, Xiao-Mei; Gao, Jian-gang

    2013-12-01

    Embryonic stem (ES) cells are widely used for different purposes, including gene targeting, cell therapy, tissue repair, organ regeneration, and so on. However, studies and applications of ES cells are hindered by ethical issues regarding cell sources. To circumvent ethical disputes, great efforts have been taken to generate ES cell-like cells, which are not derived from the inner cell mass of blastocyst-stage embryos. In 2006, Yamanaka et al. first reprogrammed mouse embryonic fibroblasts into ES cell-like cells called induced pluripotent stem (iPS) cells. About one year later, Yamanaka et al. and Thomson et al. independently reprogrammed human somatic cells into iPS cells. Since the first generation of iPS cells, they have now been derived from quite a few different kinds of cell types. In particular, the use of peripheral blood facilitates research on iPS cells because of safety, easy availability, and plenty of cell sources. Now iPS cells have been used for cell therapy, disease modeling, and drug discovery. In this review, we describe the generations, applications, potential issues, and future perspectives of iPS cells.

  16. Understanding schizophrenia as a disorder of consciousness: biological correlates and translational implications from quantum theory perspectives.

    Science.gov (United States)

    Venkatasubramanian, Ganesan

    2015-04-30

    From neurophenomenological perspectives, schizophrenia has been conceptualized as "a disorder with heterogeneous manifestations that can be integrally understood to involve fundamental perturbations in consciousness". While these theoretical constructs based on consciousness facilitate understanding the 'gestalt' of schizophrenia, systematic research to unravel translational implications of these models is warranted. To address this, one needs to begin with exploration of plausible biological underpinnings of "perturbed consciousness" in schizophrenia. In this context, an attractive proposition to understand the biology of consciousness is "the orchestrated object reduction (Orch-OR) theory" which invokes quantum processes in the microtubules of neurons. The Orch-OR model is particularly important for understanding schizophrenia especially due to the shared 'scaffold' of microtubules. The initial sections of this review focus on the compelling evidence to support the view that "schizophrenia is a disorder of consciousness" through critical summary of the studies that have demonstrated self-abnormalities, aberrant time perception as well as dysfunctional intentional binding in this disorder. Subsequently, these findings are linked with 'Orch-OR theory' through the research evidence for aberrant neural oscillations as well as microtubule abnormalities observed in schizophrenia. Further sections emphasize the applicability and translational implications of Orch-OR theory in the context of schizophrenia and elucidate the relevance of quantum biology to understand the origins of this puzzling disorder as "fundamental disturbances in consciousness".

  17. Stem cells news update: a personal perspective.

    Science.gov (United States)

    Wong, Sc

    2013-12-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy.

  18. Stem cells and the reproductive system: historical perspective and future directions.

    Science.gov (United States)

    Duke, Cindy M P; Taylor, Hugh S

    2013-11-01

    Recent findings in stem cell biology have presented new perspectives and opportunities for the treatment of reproductive disease. In a departure from the long held dogma of embryologically fixed numbers of oocytes, current literature suggests that human ovaries contain stem cells which form new oocytes even in adulthood and that these stem cells can be cultured in vitro to develop into mature oocytes. These findings have provided new hope and broader options for fertility preservation. Evidence of endometrial regeneration by bone marrow stem cells in endometrial tissue of women who received bone marrow transplant highlight potential for the novel treatments of uterine disorders and supports new theories for the etiology of endometriosis - ectopic transdifferentiation of stem cells. Further, endometrial derived stem cells have been demonstrated to be useful in the treatment of several chronic and often debilitating diseases, including Parkinson's Disease and Diabetes. Other cells that may present future therapeutic benefits for a myriad of disease states include placental and fetal cells which enter maternal circulation during pregnancy and can later promote parenchymal regeneration in maternal tissue. These findings highlight novel functions of the uterus and ovaries. They demonstrate that the uterus is a dynamic organ permeable to fetal stem cells capable of transdifferentiation as well as a renewable source of multipotent stem cells. While we still have much to understand about stem cells, their potential applications in reproductive biology and medicine are countless.

  19. In vitro development of resistance to arsenite and chromium-VI in Lactobacilli strains as perspective attenuation of gastrointestinal disorder.

    Science.gov (United States)

    Upreti, Raj K; Sinha, Vartika; Mishra, Ritesh; Kannan, Ambrose

    2011-05-01

    Inadvertent intake of inorganic arsenic and chromium through drinking water and food causing their toxic insults is a major health problem. Intestinal bacteria including Lactobacilli play important regulatory roles on intestinal homeostasis, and their loss is known to cause gastrointestinal (GI) disorders. Probiotic Lactobacilli resistance to arsenite and chromium-VI could be an importantfactorfor the perspective attenuation of Gl-disorders caused by these toxic metals/metalloid. In the present study resistance of arsenite (up to 32 ppm), Cr-VI (up to 64 ppm), and arsenite plus Cr-VI (32 ppm each) were developed under in vitro condition following chronological chronic exposures in Lactobacilli strains. Comparative study of biochemical parameters such as membrane transport enzymes and structural constituents; dehydrogenase and esterase activity tests, which are respective indicators for respiratory and energy producing processes, and the general heterotrophic activity of cells, of resistant strains showed similarities with their respective normal parent strains. The resistant strains were also found to be sensitive to antibiotics. Findings indicate that these resistant probiotic Lactobacilli would be useful in the prophylactic interventions of arsenic and chromium GI-toxicity.

  20. Human embryonic stem cells: preclinical perspectives

    Directory of Open Access Journals (Sweden)

    Sarda Kanchan

    2008-01-01

    Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

  1. Clinical translation of stem cells in neurodegenerative disorders.

    Science.gov (United States)

    Lindvall, Olle; Barker, Roger A; Brüstle, Oliver; Isacson, Ole; Svendsen, Clive N

    2012-02-01

    Stem cells and their derivatives show tremendous potential for treating many disorders, including neurodegenerative diseases. We discuss here the challenges and potential for the translation of stem-cell-based approaches into treatments for Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.

  2. Clinical Translation of Stem Cells in Neurodegenerative Disorders

    Science.gov (United States)

    Lindvall, Olle; Barker, Roger A.; Brüstle, Oliver; Isacson, Ole; Svendsen, Clive N.

    2014-01-01

    Stem cells and their derivatives show tremendous potential for treating many disorders, including neurode-generative diseases. We discuss here the challenges and potential for the translation of stem-cell-based approaches into treatments for Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. PMID:22305565

  3. DOE perspective on fuel cells in transportation

    Energy Technology Data Exchange (ETDEWEB)

    Kost, R.

    1996-04-01

    Fuel cells are one of the most promising technologies for meeting the rapidly growing demand for transportation services while minimizing adverse energy and environmental impacts. This paper reviews the benefits of introducing fuel cells into the transportation sector; in addition to dramatically reduced vehicle emissions, fuel cells offer the flexibility than use petroleum-based or alternative fuels, have significantly greater energy efficiency than internal combustion engines, and greatly reduce noise levels during operation. The rationale leading to the emphasis on proton-exchange-membrane fuel cells for transportation applications is reviewed as are the development issues requiring resolution to achieve adequate performance, packaging, and cost for use in automobiles. Technical targets for power density, specific power, platinum loading on the electrodes, cost, and other factors that become increasingly more demanding over time have been established. Fuel choice issues and pathways to reduced costs and to a renewable energy future are explored. One such path initially introduces fuel cell vehicles using reformed gasoline while-on-board hydrogen storage technology is developed to the point of allowing adequate range (350 miles) and refueling convenience. This scenario also allows time for renewable hydrogen production technologies and the required supply infrastructure to develop. Finally, the DOE Fuel Cells in Transportation program is described. The program, whose goal is to establish the technology for fuel cell vehicles as rapidly as possible, is being implemented by means of the United States Fuel Cell Alliance, a Government-industry alliance that includes Detroit`s Big Three automakers, fuel cell and other component suppliers, the national laboratories, and universities.

  4. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W

    2015-01-01

    tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC...... disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation....

  5. Stem cells in neurology - current perspectives

    Directory of Open Access Journals (Sweden)

    Chary Ely Marquez Batista

    2014-06-01

    Full Text Available Central nervous system (CNS restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective : The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method : Literature review of animal and human clinical experimental trials, using the following key words: “stem cell”, “neurogenesis”, “Parkinson”, “Huntington”, “amyotrophic lateral sclerosis”, “traumatic brain injury”, “spinal cord injury”, “ischemic stroke”, and “demyelinating diseases”. Conclusion : Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.

  6. [Stem cell perspectives in myocardial infarctions].

    Science.gov (United States)

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  7. Artificial Dendritic Cells: Multi-faceted Perspectives

    CERN Document Server

    Greensmith, Julie

    2009-01-01

    Dendritic cells are the crime scene investigators of the human immune system. Their function is to correlate potentially anomalous invading entities with observed damage to the body. The detection of such invaders by dendritic cells results in the activation of the adaptive immune system, eventually leading to the removal of the invader from the host body. This mechanism has provided inspiration for the development of a novel bio-inspired algorithm, the Dendritic Cell Algorithm. This algorithm processes information at multiple levels of resolution, resulting in the creation of information granules of variable structure. In this chapter we examine the multi-faceted nature of immunology and how research in this field has shaped the function of the resulting Dendritic Cell Algorithm. A brief overview of the algorithm is given in combination with the details of the processes used for its development. The chapter is concluded with a discussion of the parallels between our understanding of the human immune system a...

  8. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

    Skakkebaek, N E; Rajpert-De Meyts, E; Jørgensen, N;

    1998-01-01

    in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which...... is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated......Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads...

  9. Th17 cells in neuromyelitis optica spectrum disorder: a review.

    Science.gov (United States)

    Lin, Jie; Li, Xiang; Xia, Junhui

    2016-12-01

    Neuromyelitis optica spectrum disorder (NMOSD) has been identified as a central nervous system (CNS) autoimmune inflammatory disorder, which has been recognized as a B cell-mediated humoral immune disease. However, cases have been reported indicating that some of the neuromyelitis optica (NMO) patients have been resistant to B cell-related treatments. Recently, more and more evidence has shown that T cell-mediated immunity may take part in the pathogenesis of NMOSD, especially in the Th17 phenotype. In our PUBMED search, we used the following keywords: Th17 cell, Th17 cell-related cytokines, T cells, B cells, B cell-related productions, NMO, NMOSD, recurrent/bilateral optic neuritis, recurrent transverse myelitis and longitudinally extensive transverse myelitis. We systemically reviewed the role of Th17 cells and Th17 cell-related cytokines in NMOSD. We found that Th17 cells and Th17-related cytokines, such as IL-6, IL-1β, IL-17, IL-21, IL-22, IL-23 and TGF-β, are not only directly involved in the pathogenesis but also collaborated with B cells and B cell-related antibody production to induce CNS lesions. Th17 cell-related therapy has also been reviewed in this article, and the data suggested that Th17 may be a new therapeutic target of NMOSD.

  10. Stem Cell Therapies in Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Aakriti Garg

    2017-02-01

    Full Text Available Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

  11. Stem cells for the treatment of neurological disorders

    Science.gov (United States)

    Lindvall, Olle; Kokaia, Zaal

    2006-06-01

    Many common neurological disorders, such as Parkinson's disease, stroke and multiple sclerosis, are caused by a loss of neurons and glial cells. In recent years, neurons and glia have been generated successfully from stem cells in culture, fuelling efforts to develop stem-cell-based transplantation therapies for human patients. More recently, efforts have been extended to stimulating the formation and preventing the death of neurons and glial cells produced by endogenous stem cells within the adult central nervous system. The next step is to translate these exciting advances from the laboratory into clinically useful therapies.

  12. Hürthle cell carcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Ahmadi S

    2016-11-01

    Full Text Available Sara Ahmadi,1 Michael Stang,2 Xiaoyin “Sara” Jiang,3 Julie Ann Sosa2,4,5 1Division of Endocrinology, Department of Medicine, 2Section of Endocrine Surgery, Department of Surgery, 3Department of Pathology, Duke University Medical Center, 4Duke Cancer Institute, 5Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA Abstract: Hürthle cell carcinoma (HCC can present either as a minimally invasive or as a widely invasive tumor. HCC generally has a more aggressive clinical behavior compared with the other differentiated thyroid cancers, and it is associated with a higher rate of distant metastases. Minimally invasive HCC demonstrates much less aggressive behavior; lesions <4 cm can be treated with thyroid lobectomy alone, and without radioactive iodine (RAI. HCC has been observed to be less iodine-avid compared with other differentiated thyroid cancers; however, recent data have demonstrated improved survival with RAI use in patients with HCC >2 cm and those with nodal and distant metastases. Patients with localized iodine-resistant disease who are not candidates for a wait-and-watch approach can be treated with localized therapies. Systemic therapy is reserved for patients with progressive, widely metastatic HCC. Keywords: thyroid cancer, thyroid nodule, follicular cell carcinoma, Hurthle cell lesion, minimally invasive HCC

  13. A unified cell biological perspective on axon-myelin injury

    OpenAIRE

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin

    2014-01-01

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon–myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a loc...

  14. Meeting the Educational and Social Needs of Children with Language Impairment or Autism Spectrum Disorder: The Parents' Perspectives

    Science.gov (United States)

    Lindsay, Geoff; Ricketts, Jessie; Peacey, Lindy V.; Dockrell, Julie E.; Charman, Tony

    2016-01-01

    Background: There is increasing interest in examining the perspectives of parents of children with special educational needs (SEN). Exploring the view of parents of a child with language impairment (LI) or autism spectrum disorder (ASD) is particularly important because of their high prevalence, at over 30% of children with SEN in England, and the…

  15. Personality Disorder Patients' Perspectives on the Introduction of Imagery within Schema Therapy: A Qualitative Study of Patients' Experiences

    Science.gov (United States)

    ten Napel-Schutz, Marieke C.; Abma, Tineke A.; Bamelis, Lotte; Arntz, Arnoud

    2011-01-01

    A qualitative study was done on patients' perspectives on the first phases of imagery work in the context of schema therapy (ST) for personality disorders. Patients participated in a multi-center randomized controlled study of the effectiveness of ST. Patients' experiences and opinions were collected with semistructured in-depth interviews at the…

  16. Towards a New Definition of Return-to-Work Outcomes in Common Mental Disorders from a Multi-Stakeholder Perspective

    NARCIS (Netherlands)

    Hees, Hiske L.; Nieuwenhuijsen, Karen; Koeter, Maarten W. J.; Bultmann, Ute; Schene, Aart H.

    2012-01-01

    Objectives: To examine the perspectives of key stakeholders involved in the return-to-work (RTW) process regarding the definition of successful RTW outcome after sickness absence related to common mental disorders (CMD's). Methods: A mixed-method design was used: First, we used qualitative methods (

  17. Induced pluripotent stem cells:origins, applications, and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Jing ZHAO; Wen-jie JIANG; Chen SUN; Cong-zhe HOU; Xiao-mei YANG; Jian-gang GAO

    2013-01-01

    Embryonic stem (ES) cells are widely used for different purposes, including gene targeting, celltherapy, tissue repair, organ regeneration, and so on. However, studies and applications of ES cells are hindered by ethical issues regarding cellsources. To circumvent ethical disputes, great efforts have been taken to generate ES cel-like cells, which are not derived from the inner cellmass of blastocyst-stage embryos. In 2006, Yamanaka et al. first re-programmed mouse embryonic fibroblasts into ES cell-like cells cal ed induced pluripotent stem (iPS) cells. About one year later, Yamanaka et al. and Thomson et al. independently reprogrammed human somatic cells into iPS cells. Since the first generation of iPS cells, they have now been derived from quite a few different kinds of celltypes. In particular, the use of peripheral blood facilitates research on iPS cells because of safety, easy availability, and plenty of cellsources. Now iPS cells have been used for celltherapy, disease modeling, and drug discovery. In this review, we describe the generations, applications, potential issues, and future perspectives of iPS cells.

  18. The study of temporomandibular disorders and orofacial pain from the perspective of the predoctoral dental curriculum.

    Science.gov (United States)

    Attanasio, Ron

    2002-01-01

    This paper addresses questions 2 to 6 posed in the charge to the conference to discuss the study of temporomandibular disorders (TMD) and orofacial pain from the perspective of the predoctoral dental curriculum. This paper lends itself to an additional query: how much diagnostic and therapeutic skill relative to TMD and orofacial pain should a new graduate possess and demonstrate to be deemed competent in accordance with the definition of competence of the American Dental Association's Commission on Dental Accreditation? Although much of the content of this and the accompanying articles from the conference pertain to the TMD and orofacial pain curricula of dental schools in North America, most of what is presented here is universal to the teaching of the subject matter; therefore, it could be applied to educational institutions in other parts of the world. Indeed, an international survey relative to the teaching of TMD and orofacial pain would be of interest and value to dental schools worldwide.

  19. Proprioceptive rehabilitation of upper limb dysfunction in movement disorders: a clinical perspective.

    Science.gov (United States)

    Abbruzzese, Giovanni; Trompetto, Carlo; Mori, Laura; Pelosin, Elisa

    2014-01-01

    Movement disorders (MDs) are frequently associated with sensory abnormalities. In particular, proprioceptive deficits have been largely documented in both hypokinetic (Parkinson's disease) and hyperkinetic conditions (dystonia), suggesting a possible role in their pathophysiology. Proprioceptive feedback is a fundamental component of sensorimotor integration allowing effective planning and execution of voluntary movements. Rehabilitation has become an essential element in the management of patients with MDs, and there is a strong rationale to include proprioceptive training in rehabilitation protocols focused on mobility problems of the upper limbs. Proprioceptive training is aimed at improving the integration of proprioceptive signals using "task-intrinsic" or "augmented feedback." This perspective article reviews the available evidence on the effects of proprioceptive stimulation in improving upper limb mobility in patients with MDs and highlights the emerging innovative approaches targeted to maximizing the benefits of exercise by means of enhanced proprioception.

  20. Stem Cell Transplantation for Treatment of Primary Immunodeficiency Disorders

    Directory of Open Access Journals (Sweden)

    Susanna M. Müller Wilhelm Friedrich

    2005-03-01

    Full Text Available Primary Immunodeficiencies constitute a group of highly complex congenital disorders most of which are characterized by a very poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT has become an established curative treatment approach in many of these disorders, which may be permanently corrected. In this presentation basic and practical aspects of HSCT are presented, with an emphasis on its application in lymphocyte disorders such as severe combined immunodeficiency (SCID. Optimal results and outcome of HSCT are highly dependant on early and correct diagnosis of these rare disorders, and HSCT should usually be applied early in the course of the disease in order to prevent irreversible complications from infections. Clinical results will be summarized based on recent analysis performed in large patient cohorts, which have shown steady improvements and have led to a marked change in the prognosis of patients with primary immunodeficiencies.

  1. Pure red cell aplasia and lymphoproliferative disorders: an infrequent association.

    Science.gov (United States)

    Vlachaki, Efthymia; Diamantidis, Michael D; Klonizakis, Philippos; Haralambidou-Vranitsa, Styliani; Ioannidou-Papagiannaki, Elizabeth; Klonizakis, Ioannis

    2012-01-01

    Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.

  2. Corneal stem cells and tissue engineering: Current advancesand future perspectives

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Major advances are currently being made in regenerativemedicine for cornea. Stem cell-based therapiesrepresent a novel strategy that may substituteconventional corneal transplantation, albeit there aremany challenges ahead given the singularities of eachcellular layer of the cornea. This review recapitulatesthe current data on corneal epithelial stem cells,corneal stromal stem cells and corneal endothelialcell progenitors. Corneal limbal autografts containingepithelial stem cells have been transplanted in humansfor more than 20 years with great successful rates,and researchers now focus on ex vivo cultures andother cell lineages to transplant to the ocular surface.A small population of cells in the corneal endotheliumwas recently reported to have self-renewal capacity,although they do not proliferate in vivo . Two mainobstacles have hindered endothelial cell transplantationto date culture protocols and cell delivery methods tothe posterior cornea in vivo . Human corneal stromalstem cells have been identified shortly after therecognition of precursors of endothelial cells. Stromalstem cells may have the potential to provide a directcell-based therapeutic approach when injected tocorneal scars. Furthermore, they exhibit the ability todeposit organized connective tissue in vitro and maybe useful in corneal stroma engineering in the future.Recent advances and future perspectives in the field arediscussed.

  3. Plant thin cell layers: update and perspectives

    Directory of Open Access Journals (Sweden)

    Teixeira da Silva Jaime A.

    2015-12-01

    Full Text Available Thin cell layers (TCLs are small and versatile explants for the in vitro culture of plants. At face value, their morphogenic productivity may appear to be less than conventional explants, but once the plant growth correction factor and geometric factor have been applied, the true (potential productivity exceeds that of a conventional explant. It is for this reason that for almost 45 years, TCLs have been applied to the in vitro culture of almost 90 species or hybrids, mainly ornamentals and orchids, but also to field and vegetable crops and medicinal plants. Focusing on 12 new studies that have emerged in the recent past (2013-2015, this paper brings promise to other horticultural species that could benefit from the use of TCLs.

  4. Online biomedical resources for malaria-related red cell disorders.

    Science.gov (United States)

    Piel, Frédéric B; Howes, Rosalind E; Nyangiri, Oscar A; Moyes, Catherine L; Williams, Thomas N; Weatherall, David J; Hay, Simon I

    2013-07-01

    Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.

  5. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.

  6. Mechanisms linking red blood cell disorders and cardiovascular diseases.

    Science.gov (United States)

    Mozos, Ioana

    2015-01-01

    The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.

  7. Mixed methods study examining work reintegration experiences from perspectives of Veterans with mental health disorders.

    Science.gov (United States)

    Kukla, Marina; Rattray, Nicholas A; Salyers, Michelle P

    2015-01-01

    Recent findings have demonstrated that reintegration for Veterans is often challenging. One difficult aspect of reintegration—transitioning into the civilian workplace—has not been fully explored in the literature. To address this gap and examine work reintegration, this mixed methods study examined the perspectives of Veterans with mental health disorders receiving Department of Veterans Affairs healthcare. Forty Veterans rated factors that affect work success; participants also provided narratives on their most and least successful work experiences. We used t-tests and qualitative analysis to compare participants who did and did not serve in combat. Several themes relevant to work reintegration emerged in the narratives, particularly for Veterans who served in combat. An array of work difficulties were reported in the months following military discharge. In addition, Veterans who served in combat reported significantly more work barriers than Veterans who did not serve in combat, particularly health-related barriers. In conclusion, Veterans with mental health disorders who served in combat experienced more work reintegration difficulty than their counterparts who did not serve in combat. The role of being a Veteran affected how combat Veterans formed their self-concept, which also shaped their work success and community reintegration, especially during the early transition period.

  8. Bovine mammary stem cells: new perspective for dairy science.

    Science.gov (United States)

    Martignani, E; Cravero, D; Miretti, S; Accornero, P; Baratta, M

    2014-01-01

    Mammary stem cells provide opportunities for the cyclic remodelling of the bovine mammary gland. Therefore, understanding the character and regulation of mammary stem cells is important for increasing animal health and productivity. The exciting possibility that stem cell expansion can influence milk production is currently being investigated by several researchers. In fact, appropriate regulation of mammary stem cells could hopefully benefit milk yield, persistency of lactation, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and regulate the function of bovine mammary stem cells. However, research on mammary stem cells requires tissue biopsies, which represents a limitation for the management of animal welfare. Interestingly, different studies recently reported the identification of putative mammary stem cells in human breast milk. The possible identification of primitive cell types within cow's milk may provide a non-invasive source of relevant mammary cells for a wide range of applications. In this review, we have summarized the main achievements in this field for dairy cow science and described the interesting perspectives open to manipulate milk persistency during lactation and to cope with oxidative stress during the transition period by regulating mammary stem cells.

  9. Lentiviral hematopoietic stem cell gene therapy in inherited metabolic disorders

    NARCIS (Netherlands)

    G. Wagemaker (Gerard)

    2014-01-01

    textabstractAfter more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This brief review summarizes the development and applications, focusing on the lysosomal enzyme

  10. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders.

    Science.gov (United States)

    Da Costa, Lydie; Galimand, Julie; Fenneteau, Odile; Mohandas, Narla

    2013-07-01

    Hereditary spherocytosis and elliptocytosis are the two most common inherited red cell membrane disorders resulting from mutations in genes encoding various red cell membrane and skeletal proteins. Red cell membrane, a composite structure composed of lipid bilayer linked to spectrin-based membrane skeleton is responsible for the unique features of flexibility and mechanical stability of the cell. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Both these diseases can be readily diagnosed by various laboratory approaches that include red blood cell cytology, flow cytometry, ektacytometry, electrophoresis of the red cell membrane proteins, and mutational analysis of gene encoding red cell membrane proteins.

  11. Cell Wall Biology: Perspectives from Cell Wall Imaging

    Institute of Scientific and Technical Information of China (English)

    Kieran J.D.Lee; Susan E.Marcus; J.Paul Knox

    2011-01-01

    Polysaccharide-rich plant cell walls are important biomaterials that underpin plant growth,are major repositories for photosynthetically accumulated carbon,and,in addition,impact greatly on the human use of plants. Land plant cell walls contain in the region of a dozen major polysaccharide structures that are mostly encompassed by cellulose,hemicelluloses,and pectic polysaccharides. During the evolution of land plants,polysaccharide diversification appears to have largely involved structural elaboration and diversification within these polysaccharide groups. Cell wall chemistry is well advanced and a current phase of cell wall science is aimed at placing the complex polysaccharide chemistry in cellular contexts and developing a detailed understanding of cell wall biology. Imaging cell wall glycomes is a challenging area but recent developments in the establishment of cell wall molecular probe panels and their use in high throughput procedures are leading to rapid advances in the molecular understanding of the spatial heterogeneity of individual cell walls and also cell wall differences at taxonomic levels. The challenge now is to integrate this knowledge of cell wall heterogeneity with an understanding of the molecular and physiological mechanisms that underpin cell wall properties and functions.

  12. Cell therapy for neurological disorders: The elusive goal

    Directory of Open Access Journals (Sweden)

    Prakash N Tandon

    2016-01-01

    Full Text Available The positive outcomes of the transplantation of fetal neural tissue in adult rat models of a variety of neurological disorders, particularly Parkinson's disease, in the 1970s, and its translation to humans in the 1980s, raised great hopes for patients suffering from these incurable disorders. This resulted in a frantic research globally to find more suitable, reliable, and ethically acceptable alternatives. The discovery of adult stem cells, embryonic stem cells, and more recently, the induced pluripotent cells further raised our expectations. The useful functional recovery in animal models using these cell transplantation techniques coupled with the desperate needs of such patients prompted many surgeons to “jump from the rat-to-man” without scientifically establishing a proof of their utility. Each new development claimed to overcome the limitations, shortcomings, safety, and other technical problems associated with the earlier technique, yet newer difficulties prevented evidence-based acceptance of their clinical use. However, thousands of patients across the globe have received these therapies without a scientifically acceptable proof of their reliability. The present review is an attempt to summarize the current status of cell therapy for neurological disorders.

  13. [Neuropsychological treatment of cognitive deficits in substance abuse disorders, affective disorders, anxiety disorders and obsessive-compulsive disorders - current status and perspectives].

    Science.gov (United States)

    Buschert, V C; Zwanzger, P; Brunnauer, A

    2015-05-01

    Neuropsychological treatment represents a promising therapeutic approach in the amelioration of cognitive deficits in many neuropsychiatric disorders. Cognitive impairment constitutes a core feature that often persists beyond psychopathological symptoms having a significant impact on psychosocial functioning. However, research interest and evidence of efficacy vary considerably between disease groups. Although neuropsychological treatment is frequently used in clinical practice, there are, with the exception of schizophrenia, relatively few studies on its effectiveness.

  14. Modulation of GABAergic Transmission in Development and Neurodevelopmental Disorders: Investigating Physiology and Pathology to Gain Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Gabriele eDeidda

    2014-05-01

    Full Text Available During mammalian ontogenesis, the neurotransmitter GABA is a fundamental regulator of neuronal networks. In neuronal development, GABAergic signaling regulates neural proliferation, migration, differentiation, and neuronal-network wiring. In the adult, GABA orchestrates the activity of different neuronal cell-types largely interconnected, by powerfully modulating synaptic activity. GABA exerts these functions by binding to chloride-permeable ionotropic GABAA receptors and metabotropic GABAB receptors. According to its functional importance during development, GABA is implicated in a number of neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis.The strength and polarity of GABAergic transmission is continuously modulated during physiological, but also pathological conditions. For GABAergic transmission through GABAA receptors, strength regulation is achieved by different mechanisms such as modulation of GABAA receptors themselves, variation of intracellular chloride concentration, and alteration in GABA metabolism. In the never-ending effort to find possible treatments for GABA-related neurological diseases, of great importance would be modulating GABAergic transmission in a safe and possibly physiological way, without the dangers of either silencing network activity or causing epileptic seizures. In this review, we will discuss the different ways to modulate GABAergic transmission normally at work both during physiological and pathological conditions. Our aim is to highlight new research perspectives for therapeutic treatments that reinstate natural and physiological brain functions in neuro-pathological conditions.

  15. A different perspective on bipolar disorder? : epidemiology, consequences, concept, and recognition of bipolar spectrum disorder in the general population

    NARCIS (Netherlands)

    Regeer, Eline Janet

    2008-01-01

    Bipolar disorder, or manic-depressive illness, is a mood disorder in which episodes of mania, hypomania and depression occur in alternation with intervals of normal mood. Bipolar disorder is typically a recurrent illness and may have serious consequences such as poor social and occupational function

  16. The use of stem cells to study autism spectrum disorder.

    Science.gov (United States)

    Ardhanareeswaran, Karthikeyan; Coppola, Gianfilippo; Vaccarino, Flora

    2015-03-01

    Autism spectrum disorder (ASD) affects as many as 1 in 68 children and is said to be the fastest-growing serious developmental disability in the United States. There is currently no medical cure or diagnostic test for ASD. Furthermore, the U.S. Food and Drug Administration has yet to approve a single drug for the treatment of autism's core symptoms. Despite numerous genome studies and the identification of hundreds of genes that may cause or predispose children to ASD, the pathways underlying the pathogenesis of idiopathic ASD still remain elusive. Post-mortem brain samples, apart from being difficult to obtain, offer little insight into a disorder that arises through the course of development. Furthermore, ASD is a disorder of highly complex, human-specific behaviors, making it difficult to model in animals. Stem cell models of ASD can be generated by performing skin biopsies of ASD patients and then dedifferentiating these fibroblasts into human-induced pluripotent stem cells (hiPSCs). iPSCs closely resemble embryonic stem cells and retain the unique genetic signature of the ASD patient from whom they were originally derived. Differentiation of these iPSCs into neurons essentially recapitulates the ASD patient's neuronal development in a dish, allowing for a patient-specific model of ASD. Here we review our current understanding of the underlying neurobiology of ASD and how the use of stem cells can advance this understanding, possibly leading to new therapeutic avenues.

  17. Human embryonic stem cells carrying mutations for severe genetic disorders.

    Science.gov (United States)

    Frumkin, Tsvia; Malcov, Mira; Telias, Michael; Gold, Veronica; Schwartz, Tamar; Azem, Foad; Amit, Ami; Yaron, Yuval; Ben-Yosef, Dalit

    2010-04-01

    Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il.

  18. Diagnosis and treatment of mast cell disorders: practical recommendations.

    Science.gov (United States)

    Sandes, Alex Freire; Medeiros, Raphael Salles Scortegagna; Rizzatti, Edgar Gil

    2013-01-01

    CONTEXT AND OBJECTIVE The term mastocytosis covers a group of rare disorders characterized by neoplastic proliferation and accumulation of clonal mast cells in one or more organs. The aim of this study was to assess the principal elements for diagnosing and treating these disorders. DESIGN AND SETTING Narrative review of the literature conducted at Grupo Fleury, São Paulo, Brazil. METHODS This study reviewed the scientific papers published in the PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) and Cochrane Library databases that were identified using the search term "mastocytosis." RESULTS The clinical presentation of mastocytosis is remarkably heterogeneous and ranges from skin lesions that may regress spontaneously to aggressive forms associated with organ failure and short survival. Currently, seven subtypes of mastocytosis are recognized through the World Health Organization classification system for hematopoietic tumors. These disorders are diagnosed based on clinical manifestations and on identification of neoplastic mast cells using morphological, immunophenotypic, genetic and molecular methods. Abnormal mast cells display atypical and frequently spindle-shaped morphology, and aberrant expression of the CD25 and CD2 antigens. Elevation of serum tryptase is a common finding in some subtypes, and more than 90% of the patients present the D816V KIT mutation in mast cells. CONCLUSION Here, we described the most common signs and symptoms among patients with mastocytosis and suggested a practical approach for the diagnosis, classification and initial clinical treatment of mastocytosis.

  19. Hypnosis Without Empathy? Perspectives From Autistic Spectrum Disorder and Stage Hypnosis.

    Science.gov (United States)

    Reid, David B

    2016-01-01

    Despite volumes of published studies supporting the efficacy of hypnosis for ego-strengthening, performance, and physical and psychological disorders, the precise nature of hypnosis, and in particular, the neurobiological underpinnings of trance-phenomenon, remains tenuous at best. With his empathic involvement theory of hypnosis, Wickramasekera II (2015) brings us closer to an understanding of the elusive nature of hypnotic processes by proposing a bridging of two long-standing and seemingly incongruent theories of hypnosis (i.e., neodissociative versus socio-cognitive). Borrowing from neuroscientific studies of empathy, the empathic involvement theory maintains that empathy, beyond any other human dynamic (including emotions, behavior, personality, and imagination), facilitates and enhances hypnotic experiences for both recipient and provider alike. By the same token, one can reasonably infer from the empathic involvement theory that non-empathic individuals are less likely to benefit from hypnosis. With this perspective in mind, the empathic involvement theory's identification of empathy as an apparent "Holy Grail" of the neural underpinnings and precise nature of hypnosis may be challenged on a number of grounds. Individuals with autistic spectrum disorder, especially those suffering from alexithymia, have been identified as empathy deficient, and therefore according to the empathic involvement theory would be classified as "low-hypnotizable," yet empirical studies, albeit limited in number, suggest otherwise. Furthermore, hypnotic inductions of audience volunteers by stage hypnotists challenge the empathic involvement theory's supposition that empathy is a required component of hypnosis. It is this author's contention that empathy is a beneficial, though not essential, element of successful hypnosis.

  20. Role of stem/progenitor cells in reparative disorders

    Directory of Open Access Journals (Sweden)

    Pretheeban Thavaneetharajah

    2012-12-01

    Full Text Available Abstract Adult stem cells are activated to proliferate and differentiate during normal tissue homeostasis as well as in disease states and injury. This activation is a vital component in the restoration of function to damaged tissue via either complete or partial regeneration. When regeneration does not fully occur, reparative processes involving an overproduction of stromal components ensure the continuity of tissue at the expense of its normal structure and function, resulting in a “reparative disorder”. Adult stem cells from multiple organs have been identified as being involved in this process and their role in tissue repair is being investigated. Evidence for the participation of mesenchymal stromal cells (MSCs in the tissue repair process across multiple tissues is overwhelming and their role in reparative disorders is clearly demonstrated, as is the involvement of a number of specific signaling pathways. Transforming growth factor beta, bone morphogenic protein and Wnt pathways interact to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells (TSCs, determining whether functional regeneration or the formation of scar tissue follows an injury. A growing understanding of both TSCs, MSCs and the complex cascade of signals regulating both cell populations have, therefore, emerged as potential therapeutic targets to treat reparative disorders. This review focuses on recent advances on the role of these cells in skeletal muscle, heart and lung tissues.

  1. Chromosome replication, cell growth, division and shape: a personal perspective

    Directory of Open Access Journals (Sweden)

    Arieh eZaritsky

    2015-08-01

    Full Text Available The origins of Molecular Biology and Bacterial Physiology are reviewed, from our personal standpoints, emphasizing the coupling between bacterial growth, chromosome replication and cell division, dimensions and shape. Current knowledge is discussed with historical perspective, summarizing past and present achievements and enlightening ideas for future studies. An interactive simulation program of the Bacterial Cell Division Cycle (BCD, described as The Central Dogma in Bacteriology, is briefly represented. The coupled process of transcription/translation of genes encoding membrane proteins and insertion into the membrane (so-called transertion is invoked as the functional relationship between the only two unique macromolecules in the cell, DNA and peptidoglycan embodying the nucleoid and the sacculus respectively. We envision that nucleoid complexity, defined as the weighted-mean DNA content associated with the replication terminus, is directly related to cell shape through the transertion process. Accordingly, the primary signal for cell division transmitted by DNA dynamics (replication, transcription and segregation to the peptidoglycan biosynthetic machinery is of a physico-chemical nature, eg stress in the plasma membrane, relieving nucleoid occlusion in the cell's center hence enabling the divisome to assemble and function between segregated daughter nucleoids.

  2. Meeting the educational and social needs of children with language impairment or autism spectrum disorder : the parents’ perspectives

    OpenAIRE

    Lindsay, Geoff; Ricketts, Jessie; Peacey, Lindy V.; Dockrell, Julie E.; Charman, Tony

    2016-01-01

    Background\\ud \\ud There is increasing interest in examining the perspectives of parents of children with special educational needs (SEN). Exploring the view of parents of a child with language impairment (LI) or autism spectrum disorder (ASD) is particularly important because of their high prevalence, at over 30% of children with SEN in England, and the increasing evidence of overlapping profiles of their needs.\\ud \\ud Aims\\ud \\ud To examine the similarities and differences between the perspe...

  3. Involvement of Programmed Cell Death in Neurotoxicity of Metallic Nanoparticles: Recent Advances and Future Perspectives

    Science.gov (United States)

    Song, Bin; Zhou, Ting; Liu, Jia; Shao, LongQuan

    2016-11-01

    The widespread application of metallic nanoparticles (NPs) or NP-based products has increased the risk of exposure to NPs in humans. The brain is an important organ that is more susceptible to exogenous stimuli. Moreover, any impairment to the brain is irreversible. Recently, several in vivo studies have found that metallic NPs can be absorbed into the animal body and then translocated into the brain, mainly through the blood-brain barrier and olfactory pathway after systemic administration. Furthermore, metallic NPs can cross the placental barrier to accumulate in the fetal brain, causing developmental neurotoxicity on exposure during pregnancy. Therefore, metallic NPs become a big threat to the brain. However, the mechanisms underlying the neurotoxicity of metallic NPs remain unclear. Programmed cell death (PCD), which is different from necrosis, is defined as active cell death and is regulated by certain genes. PCD can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. It is involved in brain development, neurodegenerative disorders, psychiatric disorders, and brain injury. Given the pivotal role of PCD in neurological functions, we reviewed relevant articles and tried to summarize the recent advances and future perspectives of PCD involvement in the neurotoxicity of metallic NPs, with the purpose of comprehensively understanding the neurotoxic mechanisms of NPs.

  4. Update on iron metabolism and molecular perspective of common genetic and acquired disorder, hemochromatosis.

    Science.gov (United States)

    Yun, Seongseok; Vincelette, Nicole D

    2015-07-01

    Iron is an essential component of erythropoiesis and its metabolism is tightly regulated by a variety of internal and external cues including iron storage, tissue hypoxia, inflammation and degree of erythropoiesis. There has been remarkable improvement in our understanding of the molecular mechanisms of iron metabolism past decades. The classical model of iron metabolism with iron response element/iron response protein (IRE/IRP) is now extended to include hepcidin model. Endogenous and exogenous signals funnel down to hepcidin via wide range of signaling pathways including Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3), Bone Morphogenetic Protein/Hemojuvelin/Mothers Against Decapentaplegic Homolog (BMP/HJV/SMAD), and Von Hippel Lindau/Hypoxia-inducible factor/Erythropoietin (VHL/HIF/EPO), then relay to ferroportin, which directly regulates intra- and extracellular iron levels. The successful molecular delineation of iron metabolism further enhanced our understanding of common genetic and acquired disorder, hemochromatosis. The majority of the hereditary hemochromatosis (HH) patients are now shown to have mutations in the genes coding either upstream or downstream proteins of hepcidin, resulting in iron overload. The update on hepcidin centered mechanisms of iron metabolism and their clinical perspective in hemochromatosis will be discussed in this review.

  5. Neuroscientific and neuroanthropological perspectives in music therapy research and practice with patients with disorders of consciousness

    Directory of Open Access Journals (Sweden)

    Julia eVogl

    2015-08-01

    Full Text Available A growing understanding of music therapy with patients with disorders of consciousness has developed from observing behavioral changes and using these to gain new ways of experiencing this research environment and setting. Neuroscience provides further insight into the effects of music therapy; however, various studies with similar protocols show different results.The neuroanthropological approach is informed by anthropological and philosophical frameworks. It puts emphasis on a research with and not just on human beings concerning the subject/object question within a research process. It examines relational aspects and outcomes in the context of working in an interdisciplinary team. This allows a broader view of music therapy in a reflective process and leads to a careful interpretation of behavioral reactions and imaging results.This article discusses the importance of the neuroanthropological perspective on our way of obtaining knowledge and its influence on therapeutic practice. It is important to consider how knowledge is generated as it influences the results. Data from two cases will be presented to illustrate the neuroanthropological approach by comparing quantitative PET data with qualitative results of video analyses.

  6. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Directory of Open Access Journals (Sweden)

    Natalie Kaminsky

    2016-06-01

    Full Text Available The DNA damage response (DDR is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes. Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a “hostile” environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  7. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Institute of Scientific and Technical Information of China (English)

    Natalie Kaminsky; Ofer Bihari; Sivan Kanner; Ari Barzilai

    2016-01-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to geno-mic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degener-ative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evi-dence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a‘‘hostile”environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  8. Changing Perspectives: Exploring a pedagogy to examine other perspectives about stem cell research

    Science.gov (United States)

    France, Bev; Mora, Helen A.; Bay, Jacquie L.

    2012-03-01

    This study explores how teachers developed and critically evaluated a range of teaching strategies that could support the discussion of a socio-scientific issue (SSI) that had the potential to be controversial. The issue was stem cell research and six New Zealand teachers of senior biology students (grades 12/13) took part in an action research project that was situational, collaborative and self-evaluative. The focus of the research was to identify communication barriers that interfered with classroom discussion and how teachers could help students cross cultural borders when they discussed SSIs that were outside their life worlds. The barriers to communication were access to relevant science knowledge, religion, language, an inability to question issues and cultural expectations of girls. Teachers trialled and adapted two discussion strategies, 'Drawing the Line' and 'Diamond Ranking' that provided a vehicle for their students to explore and discuss this issue from a range of perspectives. These discussion strategies enabled their students to take part in a dialogue where reciprocal conversation could occur because they had opportunities not only to explore their own perspectives but also other people's viewpoints.

  9. Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders

    Institute of Scientific and Technical Information of China (English)

    Shaoping Hou; Paul Lu

    2016-01-01

    Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important fron-tier ifelds in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cellsin vitro andin vivo and their potential treatments of neurological disorders.

  10. The promises of stem cells: stem cell therapy for movement disorders.

    Science.gov (United States)

    Mochizuki, Hideki; Choong, Chi-Jing; Yasuda, Toru

    2014-01-01

    Despite the multitude of intensive research, the exact pathophysiological mechanisms underlying movement disorders including Parkinson's disease, multiple system atrophy and Huntington's disease remain more or less elusive. Treatments to halt these disease progressions are currently unavailable. With the recent induced pluripotent stem cells breakthrough and accomplishment, stem cell research, as the vast majority of scientists agree, holds great promise for relieving and treating debilitating movement disorders. As stem cells are the precursors of all cells in the human body, an understanding of the molecular mechanisms that govern how they develop and work would provide us many fundamental insights into human biology of health and disease. Moreover, stem-cell-derived neurons may be a renewable source of replacement cells for damaged neurons in movement disorders. While stem cells show potential for regenerative medicine, their use as tools for research and drug testing is thought to have more immediate impact. The use of stem-cell-based drug screening technology could be a big boost in drug discovery for these movement disorders. Particular attention should also be given to the involvement of neural stem cells in adult neurogenesis so as to encourage its development as a therapeutic option.

  11. State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

    Science.gov (United States)

    Wagle Shukla, Aparna; Okun, Michael S

    2016-01-01

    Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

  12. Hereditary red cell membrane disorders and laboratory diagnostic testing.

    Science.gov (United States)

    King, M-J; Zanella, A

    2013-06-01

    This overview describes two groups of nonimmune hereditary hemolytic anemias caused by defects in membrane proteins located in distinct layers of the red cell membrane. Hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) represent disorders of the red cell cytoskeleton. Hereditary stomatocytoses represents disorders of cation permeability in the red cell membrane. The current laboratory screening tests for HS are the osmotic fragility test, acid glycerol lysis time test (AGLT), cryohemolysis test, and eosin-5'-maleimide (EMA)-binding test. For atypical HS, SDS-polyacrylamide gel electrophoresis of erythrocyte membrane proteins is carried out to confirm the diagnosis. The diagnosis of HE/HPP is based on abnormal red cell morphology and the detection of protein 4.1R deficiency or spectrin variants using gel electrophoresis. None of screening tests can detect all HS cases. Some testing centers (a survey of 25 laboratories) use a combination of tests (e.g., AGLT and EMA). No specific screening test for hereditary stomatocytoses is available. The preliminary diagnosis is based on presenting a compensated hemolytic anemia, macrocytosis, and a temperature or time dependent pseudohyperkalemia in some patients. Both the EMA-binding test and the osmotic fragility test may help in differential diagnosis of HS and hereditary stomatocytosis.

  13. Update on eating disorders: current perspectives on avoidant/restrictive food intake disorder in children and youth

    Directory of Open Access Journals (Sweden)

    Norris ML

    2016-01-01

    Full Text Available Mark L Norris,1 Wendy J Spettigue,2 Debra K Katzman3 1Division of Adolescent Medicine, Department of Pediatrics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada; 2Department of Psychiatry, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada; 3Division of Adolescent Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Abstract: Avoidant/restrictive food intake disorder (ARFID is a new eating disorder diagnosis that was introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM fifth edition. The fourth edition of the DSM had failed to adequately capture a cohort of children, adolescents, and adults who are unable to meet appropriate nutritional and/or energy needs, for reasons other than drive for thinness, leading to significant medical and/or psychological sequelae. With the introduction of ARFID, researchers are now starting to better understand the presentation, clinical characteristics, and complexities of this disorder. This article outlines the diagnostic criteria for ARFID with specific focus on children and youth. A case example of a patient with ARFID, factors that differentiate ARFID from picky eating, and the estimated prevalence in pediatric populations are discussed, as well as clinical and treatment challenges that impact health care providers providing treatment for patients. Keywords: avoidant/restrictive food intake disorder, ARFID, eating disorder, picky eating, prevalence, treatment

  14. Pacific paradigms of environmentally-induced neurological disorders: Clinical, epidemiological and molecular perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Garruto, R.M. (Laboratory of Central Nervous System Studies, National Institutes of Health, Bethesda, MD (Unites States))

    During the past quarter century biomedical scientists have begun to recognize the unique opportunities for studying disease etiology and mechanisms of pathogenesis in non-Western anthropological populations with focal, endemic diseases. The systematic search for etiological factors and mechanisms of pathogenesis of neurodegenerative disorders is perhaps nowhere better exemplified than in the western Pacific. During the past three decades, the opportunistic and multidisciplinary study of hyperendemic foci of amyotrophic lateral sclerosis and parkinsonism-dementia which occur in different cultures, in different ecological zones and among genetically divergent populations have served as natural models that have had a major impact on our thinking and enhanced our understanding of these and other neurodegenerative disorders such as Alzheimer disease and the process of early neuronal aging. Our cross-disciplinary approach to these intriguing neurobiological problems and the accumulated epidemiological, genetic, cellular and molecular evidence strongly implicates environmental factors in their causation, specifically the role of aluminum and its interaction with calcium in neuronal degeneration. As a direct consequence of our studies in these Pacific populations, we have undertaken the long-term development of experimental models of neuronal degeneration, in an attempt to understand the cellular and molecular mechanisms by which these toxicants affect the central nervous system. Our experimental studies have resulted in the establishment of an aluminum-induced chronic myelopathy in rabbits and the development of neurofilamentous lesions after low-dose aluminum administration in cell culture.

  15. In-cell NMR of intrinsically disordered proteins in prokaryotic cells.

    Science.gov (United States)

    Ito, Yutaka; Mikawa, Tsutomu; Smith, Brian O

    2012-01-01

    In-cell NMR, i.e., the acquisition of heteronuclear multidimensional NMR of biomacromolecules inside living cells, is, to our knowledge, the only method for investigating the three-dimensional structure and dynamics of proteins at atomic detail in the intracellular environment. Since the inception of the method, intrinsically disordered proteins have been regarded as particular targets for in-cell NMR, due to their expected sensitivity to the molecular crowding in the intracellular environment. While both prokaryotic and eukaryotic cells can be used as host cells for in-cell NMR, prokaryotic in-cell NMR, particularly employing commonly used protein overexpression systems in Escherichia coli cells, is the most accessible approach. In this chapter we describe general procedures for obtaining in-cell NMR spectra in E. coli cells.

  16. The indeterminate cell proliferative disorder: report of a case manifesting as an unusual cutaneous histiocytosis.

    Science.gov (United States)

    Wood, G S; Hu, C H; Beckstead, J H; Turner, R R; Winkelmann, R K

    1985-11-01

    A patient with an unusual, distinctive cutaneous histiocytosis is described. Extensive morphologic, antigenic, and enzymatic studies indicate that this histiocytosis represents a proliferative disorder of cutaneous indeterminate cells. Features that distinguish this disorder from other histiocytoses are discussed.

  17. The Genito-Pelvic Pain/Penetration Disorder Paradigm and Beyond : Theoretical and empirical perspectives

    NARCIS (Netherlands)

    Spoelstra, Symen Kornelis

    2017-01-01

    In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)the female sexual pain disorders vaginismus and dyspareunia have been merged into the genito-pelvic pain/penetration disorder (GPPPD). The major reason behind this merging is that in clinical practice it always

  18. Spermatogonial Stem Cells: Implications for Genetic Disorders and Prevention

    Science.gov (United States)

    Yamada, Makiko; De Chiara, Letizia

    2016-01-01

    Spermatogonial stem cells (SSCs) propagate mammalian spermatogenesis throughout male reproductive life by continuously self-renewing and differentiating, ultimately, into sperm. SSCs can be cultured for long periods and restore spermatogenesis upon transplantation back into the native microenvironment in vivo. Conventionally, SSC research has been focused mainly on male infertility and, to a lesser extent, on cell reprogramming. With the advent of genome-wide sequencing technology, however, human studies have uncovered a wide range of pathogenic alleles that arise in the male germ line. A subset of de novo point mutations was shown to originate in SSCs and cause congenital disorders in children. This review describes both monogenic diseases (eg, Apert syndrome) and complex disorders that are either known or suspected to be driven by mutations in SSCs. We propose that SSC culture is a suitable model for studying the origin and mechanisms of these diseases. Lastly, we discuss strategies for future clinical implementation of SSC-based technology, from detecting mutation burden by sperm screening to gene correction in vitro. PMID:27596369

  19. Hydrogen inhibits cytotrophoblast cells apoptosis in hypertensive disorders complicating pregnancy.

    Science.gov (United States)

    Guo, L; Guan, Z; Li, H; Yang, X

    2016-05-30

    Hypertensive disorders complicating pregnancy (HDCP) is one of the most serious medical disorders during pregnancy. Hydrogen is a therapeutic antioxidant and used to treat HDCP effectively. However, the molecular mechanism about the effect of hydrogen on HDCP still remains unclear. In this study, we found ROS content in HDCP group was significantly higher than that in the control and was reduced markedly in the presence of 100μmol/L hydrogen. IL6, Caspase3, Bax1, P-JAK2, P-Stat3 and P-p38 expression was much higher than the control, and was notably decreasedby the application of 100μmol/L hydrogen. Bcl2 expression in HDCP group was notably lower than the control and was increased by 100 μmol/L hydrogen. The apoptosis rate of cytotrophoblast cells was decreased, andratio of cytotrophoblast cells at G1 and G2 phase was increased and decreased by hydrogen, respectively. All those data indicated a potential molecular mechanism of hydrogen-mediated treatment in HDCP.

  20. Perspectives of family and veterans on family programs to support reintegration of returning veterans with posttraumatic stress disorder.

    Science.gov (United States)

    Fischer, Ellen P; Sherman, Michelle D; McSweeney, Jean C; Pyne, Jeffrey M; Owen, Richard R; Dixon, Lisa B

    2015-08-01

    Combat deployment and reintegration are challenging for service members and their families. Although family involvement in mental health care is increasing in the U.S. Department of Veterans Affairs (VA) system, little is known about family members' preferences for services. This study elicited the perspectives of returning Afghanistan and Iraq war veterans with posttraumatic stress disorder and their families regarding family involvement in veterans' mental health care. Semistructured qualitative interviews were conducted with 47 veterans receiving care for posttraumatic stress disorder at the Central Arkansas Veterans Healthcare System or Oklahoma City VA Medical Center and 36 veteran-designated family members. Interviews addressed perceived needs related to veterans' readjustment to civilian life, interest in family involvement in joint veteran/family programs, and desired family program content. Interview data were analyzed using content analysis and constant comparison. Both groups strongly supported inclusion of family members in programs to facilitate veterans' postdeployment readjustment and reintegration into civilian life. Both desired program content focused on information, practical skills, support, and gaining perspective on the other's experience. Although family and veteran perspectives were similar, family members placed greater emphasis on parenting-related issues and the kinds of support they and their children needed during and after deployment. To our knowledge, this is the first published report on preferences regarding VA postdeployment reintegration support that incorporates the perspectives of returning male and female veterans and those of their families. Findings will help VA and community providers working with returning veterans tailor services to the needs and preferences of this important-to-engage population.

  1. Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.

    Directory of Open Access Journals (Sweden)

    Esther R Berko

    Full Text Available DNA mutational events are increasingly being identified in autism spectrum disorder (ASD, but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement

  2. Current status and perspectives of cell therapy in Chagas disease

    Directory of Open Access Journals (Sweden)

    Milena Botelho Pereira Soares

    2009-07-01

    Full Text Available One century after its discovery, Chagas disease, caused by the protozoan, Trypanosoma cruzi, remains a major health problem in Latin America. Mortality and morbidity are mainly due to chronic processes that lead to dysfunction of the cardiac and digestive systems. About one third of the chronic chagasic individuals have or will develop the symptomatic forms of the disease, with cardiomyopathy being the most common chronic form. This is a progressively debilitating disease for which there are no currently available effective treatments other than heart transplantation. Like in other cardiac diseases, tissue engineering and cell therapy have been investigated in the past few years as a means of recovering the heart function lost as a consequence of chronic damage caused by the immune-mediated pathogenic mechanisms elicited in individuals with chronic chagasic cardiomyopathy. Here we review the studies of cell therapy in animal models and patients with chronic Chagas disease and the perspectives of the recovery of the heart function lost due to infection with T. cruzi.

  3. Language Disorders from a Developmental Perspective: Essays in Honor of Robin S. Chapman. New Directions in Communication Disorders Research

    Science.gov (United States)

    Paul, Rhea, Ed.

    2006-01-01

    The last 25 years have witnessed an explosion of research at the intersection of typical language development and child language disorders. A pioneer in bringing these fields of study together is Robin S. Chapman, Emerita, University of Wisconsin. This contributed volume honors her with chapters written by former students and colleagues, who track…

  4. A dynamic course of T cell defects in individuals at risk for mood disorders

    NARCIS (Netherlands)

    Snijders, G.; Schiweck, C.; Mesman, E.; Grosse, L.; De Wit, H.; Nolen, W. A.; Drexhage, H. A.; Hillegers, M. H. J.

    2016-01-01

    Objectives: T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk

  5. Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder.

    Science.gov (United States)

    Magro, Cynthia; Crowson, A Neil; Kovatich, Al; Burns, Frank

    2002-08-01

    Pityriasis lichenoides (PL) is a papulosquamous disorder often considered a form of reactive dermatosis and classified with small plaque parapsoriasis (digitate dermatosis). However, some patients with PL have developed large plaque parapsoriasis (LPP) and mycosis fungoides (MF), and lymphoid atypia and T-cell clonality have been reported in lesions of PL. We set out to explore the possibility that PL is a form of T-cell dyscrasia. Cases were selected by natural language search from an outpatient dermatopathology database; 35 cases were reviewed and clinicians and patients were contacted. Hematoxylin and eosin-stained sections were examined and immunophenotyping was carried out on paraffin-embedded, formalin-fixed tissue using antibodies to CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and CD56. In paraffin-embedded tissue, T-cell receptor (TCR)-gamma chain rearrangement was sought through polymerase chain reaction single stranded conformational polymorphism analysis. There were 14 males and 21 females with a mean age of 40 years held clinically to have PL chronica (PLC) (28 cases) and/or PL et varioliformis acuta (PLEVA) (7 cases). Five patients developed large atrophic poikilodermatous and/or annular plaques compatible with MF and/or LPP in a background of typical PLC. All biopsies showed tropism of lymphocytes to an epidermis manifesting psoriasiform hyperplasia, dyskeratosis, parakeratosis, and intraepithelial collections of Langerhans' cells and lymphocytes mimicking Pautrier's microabascesses. Epidermal atrophy, dermal fibroplasia, poikilodermatous alterations, and a dominance of intraepidermal cerebriform cells were seen only in patients with chronic persistent disease (i.e., PLC) and in some cases corresponded with clinical progression to MF. All cases had a T cell-dominant infiltrate, with a CD7 deletion in 21 of 32 biopsies examined; the CD7-negative cells were typically the largest and most atypical forms, often in a cohesive array within the upper layers of

  6. Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive-compulsive disorder: Perspectives from impulsivity and compulsivity

    Science.gov (United States)

    Kim, Minah; Lee, Tak Hyung; Choi, Jung-Seok; Kwak, Yoo Bin; Hwang, Wu Jeong; Kim, Taekwan; Lee, Ji Yoon; Lim, Jae-A; Park, Minkyung; Kim, Yeon Jin; Kim, Sung Nyun; Kim, Dai Jin; Kwon, Jun Soo

    2017-01-01

    Although internet gaming disorder (IGD) and obsessive-compulsive disorder (OCD) represent opposite ends of the impulsivity and compulsivity dimensions, the two disorders share common neurocognitive deficits in response inhibition. However, the similarities and differences in neurophysiological features of altered response inhibition between IGD and OCD have not been investigated sufficiently. In total, 27 patients with IGD, 24 patients with OCD, and 26 healthy control (HC) subjects participated in a Go/NoGo task with electroencephalographic recordings. N2-P3 complexes elicited during Go and NoGo condition were analyzed separately and compared among conditions and groups. NoGo-N2 latency at the central electrode site was delayed in IGD group versus the HC group and correlated positively with the severity of internet game addiction and impulsivity. NoGo-N2 amplitude at the frontal electrode site was smaller in OCD patients than in IGD patients. These findings suggest that prolonged NoGo-N2 latency may serve as a marker of trait impulsivity in IGD and reduced NoGo-N2 amplitude may be a differential neurophysiological feature between OCD from IGD with regard to compulsivity. We report the first differential neurophysiological correlate of the altered response inhibition in IGD and OCD, which may be a candidate biomarker for impulsivity and compulsivity. PMID:28134318

  7. New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders

    Institute of Scientific and Technical Information of China (English)

    Nigel; Irwin; Peter; R; Flatt

    2015-01-01

    The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucoselowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1(GLP-1), glucose-dependent insulinotropic polypeptide(GIP), oxyntomodulin(OXM) and cholecystokinin(CCK) for obesity-related diabetes.Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered.

  8. Understanding obsessive-compulsive personality disorder in adolescence: a dimensional personality perspective

    OpenAIRE

    Aelterman, Nathalie; Decuyper, Mieke; Fruyt, Filip De

    2010-01-01

    The validity of the Axis II Obsessive-Compulsive Personality Disorder (OCPD) category and its position within the Cluster C personality disorder (PDs) section of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, APA, 2000) continues to be a source of much debate. The present study examines the associations between general and maladaptive personality traits and OCPD symptoms, prior to and after controlling for co-occurring PD variance, in a general population sample of 274 Fle...

  9. Interfacial Materials for Organic Solar Cells: Recent Advances and Perspectives.

    Science.gov (United States)

    Yin, Zhigang; Wei, Jiajun; Zheng, Qingdong

    2016-08-01

    Organic solar cells (OSCs) have shown great promise as low-cost photovoltaic devices for solar energy conversion over the past decade. Interfacial engineering provides a powerful strategy to enhance efficiency and stability of OSCs. With the rapid advances of interface layer materials and active layer materials, power conversion efficiencies (PCEs) of both single-junction and tandem OSCs have exceeded a landmark value of 10%. This review summarizes the latest advances in interfacial layers for single-junction and tandem OSCs. Electron or hole transporting materials, including metal oxides, polymers/small-molecules, metals and metal salts/complexes, carbon-based materials, organic-inorganic hybrids/composites, and other emerging materials, are systemically presented as cathode and anode interface layers for high performance OSCs. Meanwhile, incorporating these electron-transporting and hole-transporting layer materials as building blocks, a variety of interconnecting layers for conventional or inverted tandem OSCs are comprehensively discussed, along with their functions to bridge the difference between adjacent subcells. By analyzing the structure-property relationships of various interfacial materials, the important design rules for such materials towards high efficiency and stable OSCs are highlighted. Finally, we present a brief summary as well as some perspectives to help researchers understand the current challenges and opportunities in this emerging area of research.

  10. Interfacial Materials for Organic Solar Cells: Recent Advances and Perspectives

    Science.gov (United States)

    Yin, Zhigang; Wei, Jiajun

    2016-01-01

    Organic solar cells (OSCs) have shown great promise as low‐cost photovoltaic devices for solar energy conversion over the past decade. Interfacial engineering provides a powerful strategy to enhance efficiency and stability of OSCs. With the rapid advances of interface layer materials and active layer materials, power conversion efficiencies (PCEs) of both single‐junction and tandem OSCs have exceeded a landmark value of 10%. This review summarizes the latest advances in interfacial layers for single‐junction and tandem OSCs. Electron or hole transporting materials, including metal oxides, polymers/small‐molecules, metals and metal salts/complexes, carbon‐based materials, organic‐inorganic hybrids/composites, and other emerging materials, are systemically presented as cathode and anode interface layers for high performance OSCs. Meanwhile, incorporating these electron‐transporting and hole‐transporting layer materials as building blocks, a variety of interconnecting layers for conventional or inverted tandem OSCs are comprehensively discussed, along with their functions to bridge the difference between adjacent subcells. By analyzing the structure–property relationships of various interfacial materials, the important design rules for such materials towards high efficiency and stable OSCs are highlighted. Finally, we present a brief summary as well as some perspectives to help researchers understand the current challenges and opportunities in this emerging area of research.

  11. Towards a new definition of return-to-work outcomes in common mental disorders from a multi-stakeholder perspective.

    Directory of Open Access Journals (Sweden)

    Hiske L Hees

    Full Text Available OBJECTIVES: To examine the perspectives of key stakeholders involved in the return-to-work (RTW process regarding the definition of successful RTW outcome after sickness absence related to common mental disorders (CMD's. METHODS: A mixed-method design was used: First, we used qualitative methods (focus groups, interviews to identify a broad range of criteria important for the definition of successful RTW (N = 57. Criteria were grouped into content-related clusters. Second, we used a quantitative approach (online questionnaire to identify, among a larger stakeholder sample (N = 178, the clusters and criteria most important for successful RTW. RESULTS: A total of 11 clusters, consisting of 52 unique criteria, were identified. In defining successful RTW, supervisors and occupational physicians regarded "Sustainability" and "At-work functioning" most important, while employees regarded "Sustainability," "Job satisfaction," "Work-home balance," and "Mental Functioning" most important. Despite agreement on the importance of certain criteria, considerable differences among stakeholders were observed. CONCLUSIONS: Key stakeholders vary in the aspects and criteria they regard as important when defining successful RTW after CMD-related sickness absence. Current definitions of RTW outcomes used in scientific research may not accurately reflect these key stakeholder perspectives. Future studies should be more aware of the perspective from which they aim to evaluate the effectiveness of a RTW intervention, and define their RTW outcomes accordingly.

  12. Neuronal cell adhesion genes: Key players in risk for schizophrenia, bipolar disorder and other neurodevelopmental brain disorders?

    Science.gov (United States)

    Corvin, Aiden P

    2010-01-01

    The major mental disorders, schizophrenia and bipolar disorder are substantially heritable. Recent genomic studies have identified a small number of common and rare risk genes contributing to both disorders and support epidemiological evidence that genetic susceptibility overlaps between them. Prompted by the question of whether risk genes cluster in specific molecular pathways or implicate discrete mechanisms we and others have developed hypothesis-free methods of investigating genome-wide association datasets at a pathway-level. The application of our method to the 212 experimentally-derived pathways in the Kyoto Encycolpaedia of Genes and Genomes (KEGG) database identified significant association between the cell adhesion molecule (CAM) pathway and both schizophrenia and bipolar disorder susceptibility across three GWAS datasets. Interestingly, a similar approach applied to an autistic spectrum disorders (ASDs) sample identified a similar pathway and involved many of the same genes. Disruption of a number of these genes (including NRXN1, CNTNAP2 and CASK) are known to cause diverse neurodevelopmental brain disorder phenotypes including schizophenia, autism, learning disability and specific language disorder. Taken together these studies bring the CAM pathway sharply into focus for more comprehensive DNA sequencing to identify the critical genes, and investigate their relationships and interaction with environmental risk factors in the expression of many seemingly different neurodevelopmental disorders.

  13. Personalized Medicine: Review and Perspectives of Promising Baseline EEG Biomarkers in Major Depressive Disorder and Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Olbrich, Sebastian; van Dinteren, Rik; Arns, Martijn

    2015-01-01

    Personalized medicine in psychiatry is in need of biomarkers that resemble central nervous system function at the level of neuronal activity. Electroencephalography (EEG) during sleep or resting-state conditions and event-related potentials (ERPs) have not only been used to discriminate patients from healthy subjects, but also for the prediction of treatment outcome in various psychiatric diseases, yielding information about tailored therapy approaches for an individual. This review focuses on baseline EEG markers for two psychiatric conditions, namely major depressive disorder and attention deficit hyperactivity disorder. It covers potential biomarkers from EEG sleep research and vigilance regulation, paroxysmal EEG patterns and epileptiform discharges, quantitative EEG features within the EEG main frequency bands, connectivity markers and ERP components that might help to identify favourable treatment outcome. Further, the various markers are discussed in the context of their potential clinical value and as research domain criteria, before giving an outline for future studies that are needed to pave the way to an electrophysiological biomarker-based personalized medicine.

  14. The Effect of Post Traumatic Stress Disorder on Military Leadership: An Historical Perspective

    Science.gov (United States)

    2011-05-19

    Post Traumatic Stress Disorder and Operations Enduring Freedom and Iraqi Freedom: Progress in the Time of Controversy,” Clinical Psychology Review 29...Posttraumatic Stress Disorder and Operating Enduring Freedom and Iraqi Freedom: Progress in a Time of Controversy.” Clinical Psychology Review 29

  15. Developing scales measuring disorder-specific intolerance of uncertainty (DSIU) : a new perspective on transdiagnostic

    NARCIS (Netherlands)

    Thibodeau, Michel A; Carleton, R Nicholas; McEvoy, Peter M; Zvolensky, Michael J; Brandt, Charles P; Boelen, Paul A; Mahoney, Alison E J; Deacon, Brett J; Asmundson, Gordon J G

    2015-01-01

    Intolerance of uncertainty (IU) is a construct of growing prominence in literature on anxiety disorders and major depressive disorder. Existing measures of IU do not define the uncertainty that respondents perceive as distressing. To address this limitation, we developed eight scales measuring disor

  16. Emerging Adulthood in Developmental Co-Ordination Disorder: Parent and Young Adult Perspectives

    Science.gov (United States)

    Kirby, A.; Edwards, L.; Sugden, D.

    2011-01-01

    Recent research widely acknowledges that developmental co-ordination disorder (DCD) is a pervasive and enduring disorder, which persists into adolescence and adulthood ([Cousins and Smyth, 2003] and [Kirby et al., 2008]). However, few studies have given detailed consideration to the range and level of functioning difficulties in emerging adults…

  17. The Pathogenesis of Childhood Anxiety Disorders: Considerations from a Developmental Psychopathology Perspective

    Science.gov (United States)

    Muris, Peter

    2006-01-01

    Anxiety disorders are among the most prevalent psychiatric problems in children and adolescents. The present article summarizes the main evidence that has accumulated on the pathogenesis of childhood anxiety disorders during the past two decades. Various risk and vulnerability factors (e.g., genetics, behavioral inhibition, disgust sensitivity,…

  18. Repetitive Behaviors in Autism and Obsessive-Compulsive Disorder: New Perspectives from a Network Analysis

    Science.gov (United States)

    Ruzzano, Laura; Borsboom, Denny; Geurts, Hilde M.

    2015-01-01

    The association between autism and obsessive-compulsive disorder (OCD) seems largely dependent upon observed similarities in the repetitive behaviors that manifest in both disorders. The aim of this study was to use a network approach to explore the interactions between these behaviors. We constructed a network based on clinician's…

  19. Early Intervention for Children with Autism Spectrum Disorders in China: A Family Perspective

    Science.gov (United States)

    Su, Xueyun; Long, Toby; Chen, Lianjun; Fang, Junming

    2013-01-01

    Autism spectrum disorders (ASD) were first reported in China in 1982. Since then, autism and other related disorders have been recognized by both the public and professionals. The importance of early intervention for children with ASD is becoming more accepted throughout China. A survey was designed to investigate the status of early intervention…

  20. Therapeutic potential of human adipose-derived stem cells in neurological disorders.

    Science.gov (United States)

    Chang, Keun-A; Lee, Jun-Ho; Suh, Yoo-Hun

    2014-01-01

    Stem cell therapy has been noted as a novel strategy to various diseases including neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and Huntington's disease that have no effective treatment available to date. The adipose-derived stem cells (ASCs), mesenchymal stem cells (MSCs) isolated from adipose tissue, are well known for their pluripotency with the ability to differentiate into various types of cells and immuno-modulatory property. These biological features make ASCs a promising source for regenerative cell therapy in neurological disorders. Here we discuss the recent progress of regenerative therapies in various neurological disorders utilizing ASCs.

  1. Perspectives

    Science.gov (United States)

    Tarone, Elaine

    2013-01-01

    The topic of this "Perspectives" column is "Requiring a Proficiency Level as a Requirement for U.S. K-12 Teacher Licensure." In 1998, the American Council of Teachers of Foreign Languages (ACTFL) began to work with the National Council for Accreditation of Teacher Education (NCATE), which accredits teacher education programs…

  2. Path to facilitate the prediction of functional amino acid substitutions in red blood cell disorders--a computational approach.

    Directory of Open Access Journals (Sweden)

    Rajith B

    Full Text Available BACKGROUND: A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs that affect protein functions and relate to disease is an important task. PRINCIPAL FINDINGS: In this study, we performed a comprehensive analysis of deleterious SNPs at both functional and structural level in the respective genes associated with red blood cell metabolism disorders using bioinformatics tools. We analyzed the variants in Glucose-6-phosphate dehydrogenase (G6PD and isoforms of Pyruvate Kinase (PKLR & PKM2 genes responsible for major red blood cell disorders. Deleterious nsSNPs were categorized based on empirical rule and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for evaluation of protein structure stability. SIGNIFICANCE: We argue here that bioinformatics tools can play an important role in addressing the complexity of the underlying genetic basis of Red Blood Cell disorders. Based on our investigation, we report here the potential candidate SNPs, for future studies in human Red Blood Cell disorders. Current study also demonstrates the presence of other deleterious mutations and also endorses with in vivo experimental studies. Our approach will present the application of computational tools in understanding functional variation from the perspective of structure, expression, evolution and phenotype.

  3. Current perspectives on deep brain stimulation for severe neurological and psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Kocabicak E

    2015-04-01

    Full Text Available Ersoy Kocabicak,1–3 Yasin Temel,1,2 Anke Höllig,4 Björn Falkenburger,5 Sonny KH Tan2,4 1Department of Neurosurgery, Maastricht University Medical Centre, 2Department of Neuroscience, Maastricht University, Maastricht, the Netherlands; 3Department of Neurosurgery, Ondokuz Mayis University, Samsun, Turkey; 4Department of Neurosurgery, 5Department of Neurology, RWTH Aachen University, Aachen, Germany Abstract: Deep brain stimulation (DBS has become a well-accepted therapy to treat movement disorders, including Parkinson’s disease, essential tremor, and dystonia. Long-term follow-up studies have demonstrated sustained improvement in motor symptoms and quality of life. DBS offers the opportunity to selectively modulate the targeted brain regions and related networks. Moreover, stimulation can be adjusted according to individual patients’ demands, and stimulation is reversible. This has led to the introduction of DBS as a treatment for further neurological and psychiatric disorders and many clinical studies investigating the efficacy of stimulating various brain regions in order to alleviate severe neurological or psychiatric disorders including epilepsy, major depression, and obsessive–compulsive disorder. In this review, we provide an overview of accepted and experimental indications for DBS therapy and the corresponding anatomical targets. Keywords: deep brain stimulation, movement disorders, neurological disorders, psychiatric disorders, Parkinson’s disease

  4. Histaminergic system in brain disorders: lessons from the translational approach and future perspectives.

    Science.gov (United States)

    Baronio, Diego; Gonchoroski, Taylor; Castro, Kamila; Zanatta, Geancarlo; Gottfried, Carmem; Riesgo, Rudimar

    2014-01-01

    Histamine and its receptors were first described as part of immune and gastrointestinal systems, but their presence in the central nervous system and importance in behavior are gaining more attention. The histaminergic system modulates different processes including wakefulness, feeding, and learning and memory consolidation. Histamine receptors (H1R, H2R, H3R, and H4R) belong to the rhodopsin-like family of G protein-coupled receptors, present constitutive activity, and are subjected to inverse agonist action. The involvement of the histaminergic system in brain disorders, such as Alzheimer's disease, schizophrenia, sleep disorders, drug dependence, and Parkinson's disease, is largely studied. Data obtained from preclinical studies point antagonists of histamine receptors as promising alternatives to treat brain disorders. Thus, clinical trials are currently ongoing to assess the effects of these drugs on humans. This review summarizes the role of histaminergic system in brain disorders, as well as the effects of different histamine antagonists on animal models and humans.

  5. "A terror to their neighbors": beliefs about mental disorder and violence in historical and cultural perspective.

    Science.gov (United States)

    Monahan, J

    1992-01-01

    This tribute to the enduring legacy of Bernard Diamond explores public perceptions of a link between mental disorder and violent behavior. Research on contemporary American beliefs is summarized and compared both to historical accounts of public perceptions in Western cultures and to anthropological investigations of public perceptions in non-Western cultures. The conclusion of these reviews is that the belief that mental disorder bears some moderate association with violent behavior is both historically invariant and culturally universal.

  6. Primary headache disorder in the emergency department: perspective from a general neurology outpatient clinic

    OpenAIRE

    Gahir, K K; Larner, A J

    2006-01-01

    Over a six month period, 22% of patients with headache seen in general neurology outpatient clinics reported prior attendance at an emergency department because of their headache; 9% of the headache cohort had been admitted to hospital. All had primary headache disorders according to International Headache Society diagnostic criteria. Improved primary care services for headache patients are required to reduce the burden of primary headache disorders seen in emergency departments.

  7. Addiction in developmental perspective: influence of conduct disorder severity, subtype, and attention-deficit hyperactivity disorder on problem severity and comorbidity in adults with opioid dependence.

    NARCIS (Netherlands)

    Carpentier, P.J.; Knapen, L.J.; Gogh, M.T. van; Buitelaar, J.K.; Jong, C.A.J. de

    2012-01-01

    This retrospective cross-sectional study examines whether conduct disorder and attention deficit hyperactivity disorder are associated with problem severity and psychiatric comorbidity in 193 middle-aged, opioid-dependent patients. Conduct disorder history, attention deficit hyperactivity disorder,

  8. ADHD and Comorbid Psychiatric Disorders: Adult Student Perspectives on Learning Needs and Academic Support

    Science.gov (United States)

    Hubbard, Laura E.

    2011-01-01

    The focus of this study is to understand, from their own perspective, the learning needs of adult college students with comorbid attention deficits and psychiatric disabilities, and to identify services and practices that support their success in the college environment. Adult students with comorbid attention deficits and psychiatric disorders…

  9. Eating Disorder Public Service Announcements: Analyzing Effects from an Intergroup Affect and Stereotype Perspective

    Science.gov (United States)

    Iles, Irina A.; Seate, Anita Atwell; Waks, Leah

    2016-01-01

    Purpose: Previous studies have documented that exposure to stereotypical information about certain social groups leads to unfavorable perceptions and feelings toward that group. Integrating insights from the mental illness stigma and the social identity perspective literatures, the purpose of this paper is to explore the effects of eating disorder…

  10. Merkel Cells as Putative Regulatory Cells in Skin Disorders: An In Vitro Study

    OpenAIRE

    Nicholas Boulais; Ulysse Pereira; Nicolas Lebonvallet; Eric Gobin; Germaine Dorange; Nathalie Rougier; Christophe Chesne; Laurent Misery

    2009-01-01

    Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factor...

  11. PANCREATIC AND EXTRA-PANCREATIC EFFECTS OF INCRETINS AND PERSPECTIVES FOR STUDYING ENTEROINSULIN HORMONAL SYSTEM DURING GESTATIONAL DISORDER OF CARBOHYDRATE METABOLISM

    Directory of Open Access Journals (Sweden)

    T. V. Saprina

    2013-01-01

    Full Text Available The absence of an ideal medicine for the treatment of patients with type 2 diabetes, that would be able to provide not only high quality and constant monitoring of glycemia without increasing body weight, with no risk of hypoglycemia, with no negative impact on the heart, kidneys, liver, but could also ensure the preservation of the secretory function of β-cells, makes scientists continue to search for new opportunities to influence the occurrence and progression of T2D.Gastric inhibitory polypeptide (GIP and glucagon-like peptide-1 (GLP-1 are the two primary incretin hormones secreted from the intestine on ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β-cells. Within the pancreas, GIP and GLP-1 together promote β-cell proliferation and inhibit apoptosis, thereby expanding pancreatic β-cell mass, while GIP enhances postprandial glucagon response and GLP-1 suppresses it. In adipose tissues, GIP but not GLP-1 facilitates fat deposition. In bone, GIP promotes bone formation while GLP-1 inhibits bone absorption. In the brain, both GIP and GLP-1 are thought to be involved in memory formation as well as the control of appetite. In addition to these differences, secretion of GIP and GLP-1 and their insulinotropic effects on β-cells have been shown to differ in patients with type 2 diabetes compared to healthy subjects.Enteroinsulin hormones' role in the development of gestational disorder of carbohydrate metabolism is poorly understood.In a review article we analyze the publications that summarize what is known about the pancreatic and extra-pancreatic GIP and GLP-1-effects compared with healthy subjects and type 2 diabetes patients. The aspects of gestational diabetes pathophysiology and the perspectives for studying enteroinsulin hormonal system during pregnancy are also discussed in the article.

  12. Teachers' Perspectives of Research-Based Instructional Strategies and Implementation to Promote Literacy Skills for Students with Autism Spectrum Disorders: A Collection of Case Studies

    Science.gov (United States)

    Pinto, Prasopsuk Y.

    2014-01-01

    The purpose of this collection of multiple case studies was to examine teachers' perspectives and practices to determine whether instructional strategies implemented in their classrooms to promote literacy skills for students with autism spectrum disorders were described as research-based practices. Although extensive research has been conducted…

  13. Moving the field forward: commentary for the special series "Narcissistic personality disorder--new perspectives on diagnosis and treatment".

    Science.gov (United States)

    Kealy, David; Hadjipavlou, George A; Ogrodniczuk, John S

    2014-10-01

    Comments on the articles by A. E. Skodol et al. (see record 2013-24395-001), E. Ronningstam (see record 2014-42878-005), D. Diamond et al. (see record 2014-42878-004), and A. L. Pincus et al. (see record 2014-01439-001). These articles in this special issue, "Narcissistic personality disorder--new perspectives on diagnosis and treatment", provide useful guidance for all clinicians working with patients with narcissistic pathology, particularly those who may not have considered narcissism as an underlying cause of a patient's presenting difficulties or as a contributor to therapeutic impasse. Taken together, they offer a more conceptually sophisticated approach to NPD than the constraining criteria of the DSM, and make a compelling case that it is time for NPD and pathological narcissism to receive greater clinical and research attention.

  14. The use of medication against attention deficit/hyperactivity disorder in Denmark: a drug use study from a national perspective

    DEFF Research Database (Denmark)

    Pottegård, Anton; Bjerregaard, Bine Kjøller; Glintborg, Dorte

    2012-01-01

    Purpose The purpose of the study was to characterize the utilization of medication against attention deficit hyperactivity disorder (ADHD) in Denmark between 1995 and 2011 from a national perspective, by using population-based prescription data. Methods National data on drug use in Denmark between....... Methylphenidate accounted for 92.6 % of DDDs used. The general practitioner (GP) rarely initiated treatment, although treatment initiation based on the GP’s advice increased with older age of the patient. Maintenance treatment was found to be distributed roughly equally between prescriber types...... and lacking evidence of heavy users. However, the prescriber profile for incident users and the large regional variances raise concerns. It is therefore vital that the use of ADHD drugs is closely monitored....

  15. Client-centred therapy, post-traumatic stress disorder and post-traumatic growth: theoretical perspectives and practical implications.

    Science.gov (United States)

    Joseph, Stephen

    2004-03-01

    In practice it is not unusual for client-centred therapists to work with people who have experienced traumatic events. However, client-centred therapy is not usually considered within texts on traumatic stress and questions have been raised over the appropriateness of client-centred therapy with trauma survivors. The present study shows how, although he was writing well before the introduction of the term 'post-traumatic stress disorder', Carl Rogers provided a theory of therapy and personality that contains an account of threat-related psychological processes largely consistent with contemporary trauma theory. Rogers' theory provides the conceptual underpinnings to the client-centred and experiential ways of working with traumatized people. Furthermore, Rogers' theory provides an understanding of post-traumatic growth processes, and encourages therapists to adopt a more positive psychological perspective to their understanding of how people adjust to traumatic events.

  16. Neuromuscular disorders in zebrafish: state of the art and future perspectives.

    Science.gov (United States)

    Pappalardo, Andrea; Pitto, Letizia; Fiorillo, Chiara; Alice Donati, M; Bruno, Claudio; Santorelli, Filippo M

    2013-06-01

    Neuromuscular disorders are a broad group of inherited conditions affecting the structure and function of the motor system with polymorphic clinical presentation and disease severity. Although individually rare, collectively neuromuscular diseases have an incidence of 1 in 3,000 and represent a significant cause of disability of the motor system. The past decade has witnessed the identification of a large number of human genes causing muscular disorders, yet the underlying pathogenetic mechanisms remain largely unclear, limiting the developing of targeted therapeutic strategies. To overcome this barrier, model systems that replicate the different steps of human disorders are increasingly being developed. Among these, the zebrafish (Danio rerio) has emerged as an excellent organism for studying genetic disorders of the central and peripheral motor systems. In this review, we will encounter most of the available zebrafish models for childhood neuromuscular disorders, providing a brief overview of results and the techniques, mainly transgenesis and chemical biology, used for genetic manipulation. The amount of data collected in the past few years will lead zebrafish to became a common functional tool for assessing rapidly drug efficacy and off-target effects in neuromuscular diseases and, furthermore, to shed light on new etiologies emerging from large-scale massive sequencing studies.

  17. Paraneoplastic neurologic disorders in small cell lung carcinoma

    Science.gov (United States)

    Woodhall, Mark; Chapman, Caroline; Nibber, Anjan; Waters, Patrick; Vincent, Angela; Lang, Bethan; Maddison, Paul

    2015-01-01

    Objective: To determine the frequency and range of paraneoplastic neurologic disorders (PNDs) and neuronal antibodies in small cell lung carcinoma (SCLC). Methods: Two hundred sixty-four consecutive patients with biopsy-proven SCLC were recruited at the time of tumor diagnosis. All patients underwent full neurologic examination. Serum samples were taken prior to chemotherapy and analyzed for 15 neuronal antibodies. Thirty-eight healthy controls were analyzed in parallel. Results: PNDs were quite prevalent (n = 24, 9.4%), most frequently Lambert-Eaton myasthenic syndrome (3.8%), sensory neuronopathy (1.9%), and limbic encephalitis (1.5%). Eighty-seven percent of all patients with PNDs had antibodies to SOX2 (62.5%), HuD (41.7%), or P/Q VGCC (50%), irrespective of their syndrome. Other neuronal antibodies were found at lower frequencies (GABAb receptor [12.5%] and N-type VGCC [20.8%]) or very rarely (GAD65, amphiphysin, Ri, CRMP5, Ma2, Yo, VGKC complex, CASPR2, LGI1, and NMDA receptor [all <5%]). Conclusions: The spectrum of PNDs is broader and the frequency is higher than previously appreciated, and selected antibody tests (SOX2, HuD, VGCC) can help determine the presence of an SCLC. PMID:26109714

  18. POSTRAUMATIC STRESS DISORDERS (PTSD) FROM DIFFERENT PERSPECTIVES: A TRANSDISCIPLINARY INTEGRATIVE APPROACH

    OpenAIRE

    Jakovljević, Miro; Brajković, Lovorka; Jakšić, Nenad; Lončar, Mladen; Aukst-Margetić, Branka; Lasić, Davor

    2012-01-01

    Background: Psychotraumatization continues to be a pervasive aspect of life in the 21st century all over the world so we should better understand psychological trauma and PTSD for the sake of prevention and healing. Method: We have made an overview of available literature on PTSD to identify explanatory models, hypotheses and theories. Results: In this paper we describe our transdisciplinary multiperspective integrative model of PTSD based on the seven perspective explanatory appr...

  19. Perspective

    DEFF Research Database (Denmark)

    Kussmann, Martin; Morine, Melissa J; Hager, Jörg

    2013-01-01

    We review here the status of human type 2 diabetes studies from a genetic, epidemiological, and clinical (intervention) perspective. Most studies limit analyses to one or a few omic technologies providing data of components of physiological processes. Since all chronic diseases are multifactorial...... of the complexity of T2DM, we propose a systems biology approach to advance the understanding of origin, onset, development, prevention, and treatment of this complex disease. This systems-based strategy is based on new study design principles and the integrated application of omics technologies: we pursue...

  20. Current perspectives on Internet delivered cognitive behavioral therapy for adults with anxiety and related disorders

    Directory of Open Access Journals (Sweden)

    Mewton L

    2014-01-01

    Full Text Available Louise Mewton, Jessica Smith, Pieter Rossouw, Gavin Andrews Clinical Research Unit for Anxiety and Depression, St Vincent’s Hospital, Sydney, NSW, Australia Abstract: The aim of the current review is to provide a summary of research into Internet-delivered cognitive behavioral therapy (iCBT for anxiety disorders. We include 37 randomized controlled trials that examined the efficacy of iCBT programs in adults (aged over 18 years, as compared with waiting list or active control. The included studies were identified from Medline searches and from reference lists, and only published data were included. Several trials of iCBT for generalized anxiety disorder, panic disorder, and social phobia were identified. Two trials of iCBT for obsessive-compulsive disorder were identified, whilst one trial each was identified for hypochondriasis, specific phobia (spiders, and post-traumatic stress disorder. Finally, there were five trials that focused on transdiagnostic therapy for either a range of comorbid anxiety disorders or comorbid anxiety and depression. Between-group effect sizes were moderate to large for all disorders, and ranged from 0.30 to 2.53. iCBT was found to be commensurate with face-to-face cognitive behavioral therapy whether delivered individually or in group format. Guidance may not be necessary for iCBT to be effective for immediate gains, but may be more important in longer-term maintenance of symptom improvement and maximizing patient adherence. The clinical experience of the individual providing guidance does not appear to impact treatment outcomes. Future research needs to focus on the optimal level of guidance required to generate maximum patient benefits, whilst balancing the efficient use of clinician time and resources. Evidence-based contraindications to iCBT should also be developed so that the choice of treatment modality accurately reflects patients’ needs. Further research should be conducted into the effective elements of

  1. Derivation of autism spectrum disorder-specific induced pluripotent stem cells from peripheral blood mononuclear cells.

    Science.gov (United States)

    DeRosa, Brooke A; Van Baaren, Jessica M; Dubey, Gaurav K; Lee, Joycelyn M; Cuccaro, Michael L; Vance, Jeffery M; Pericak-Vance, Margaret A; Dykxhoorn, Derek M

    2012-05-10

    Induced pluripotent stem cells (iPSCs) hold tremendous potential both as a biological tool to uncover the pathophysiology of disease by creating relevant cell models and as a source of stem cells for cell-based therapeutic applications. Typically, iPSCs have been derived by the transgenic overexpression of transcription factors associated with progenitor cell or stem cell function in fibroblasts derived from skin biopsies. However, the need for skin punch biopsies to derive fibroblasts for reprogramming can present a barrier to study participation among certain populations of individuals, including children with autism spectrum disorders (ASDs). In addition, the acquisition of skin punch biopsies in non-clinic settings presents a challenge. One potential mechanism to avoid these limitations would be the use of peripheral blood mononuclear cells (PBMCs) as the source of the cells for reprogramming. In this article we describe, for the first time, the derivation of iPSC lines from PBMCs isolated from the whole blood of autistic children, and their subsequent differentiation in GABAergic neurons.

  2. Content of intrinsic disorder influences the outcome of cell-free protein synthesis.

    Science.gov (United States)

    Tokmakov, Alexander A; Kurotani, Atsushi; Ikeda, Mariko; Terazawa, Yumiko; Shirouzu, Mikako; Stefanov, Vasily; Sakurai, Tetsuya; Yokoyama, Shigeyuki

    2015-09-11

    Cell-free protein synthesis is used to produce proteins with various structural traits. Recent bioinformatics analyses indicate that more than half of eukaryotic proteins possess long intrinsically disordered regions. However, no systematic study concerning the connection between intrinsic disorder and expression success of cell-free protein synthesis has been presented until now. To address this issue, we examined correlations of the experimentally observed cell-free protein expression yields with the contents of intrinsic disorder bioinformatically predicted in the expressed sequences. This analysis revealed strong relationships between intrinsic disorder and protein amenability to heterologous cell-free expression. On the one hand, elevated disorder content was associated with the increased ratio of soluble expression. On the other hand, overall propensity for detectable protein expression decreased with disorder content. We further demonstrated that these tendencies are rooted in some distinct features of intrinsically disordered regions, such as low hydrophobicity, elevated surface accessibility and high abundance of sequence motifs for proteolytic degradation, including sites of ubiquitination and PEST sequences. Our findings suggest that identification of intrinsically disordered regions in the expressed amino acid sequences can be of practical use for predicting expression success and optimizing cell-free protein synthesis.

  3. Parent Perspectives on Sources of Information about Autism Spectrum Disorder Interventions in Australia

    Science.gov (United States)

    Carlon, Sarah; Stephenson, Jennifer; Carter, Mark

    2015-01-01

    Extant research on sources of information about interventions used by parents of children with autism spectrum disorder (ASD) has provided a general overview of sources used. However, it has provided little insight into why parents view certain sources as reliable or trustworthy, or how useful parents found the information provided to them by the…

  4. Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Warfield, Marji Erickson; Crossman, Morgan K.; Delahaye, Jennifer; Der Weerd, Emma; Kuhlthau, Karen A.

    2015-01-01

    We conducted in-depth case studies of 10 health care professionals who actively provide primary medical care to adults with autism spectrum disorders. The study sought to understand their experiences in providing this care, the training they had received, the training they lack and their suggestions for encouraging more physicians to provide this…

  5. Trauma Spectrum Disorders: Emerging Perspectives on the Impact on Military and Veteran Families

    Science.gov (United States)

    O'Donnell, Lolita; Begg, Lisa; Lipson, Linda; Elvander, Erika

    2011-01-01

    This article summarizes the findings from the Second Annual Trauma Spectrum Disorders Conference, which was held in December 2009 and was sponsored by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury in conjunction with the Department of Veterans Affairs and the National Institutes of Health. The conference…

  6. A behavioural neuroscience perspective on the aetiology and treatment of anxiety disorders

    NARCIS (Netherlands)

    Kindt, M.

    2014-01-01

    Over the past decades, behaviour and cognitive psychology have produced fruitful and mutually converging theories from which hypotheses could be derived on the nature and origin of fear and anxiety disorders. Notwithstanding the emergence of effective treatments, there are still many questions that

  7. Emerging clinical trends and perspectives on comorbid patterns of mental disorders in research

    DEFF Research Database (Denmark)

    Fava, Giovanni A; Tossani, Eliana; Bech, Per;

    2014-01-01

    Comorbidity is a well-established and documented phenomenon in mental disorders and medicine with heuristic value. The concept of comorbidity remains however poorly defined and lacks a comprehensive and coherent theoretical framework. There is a need to develop coherent methodological strategies...

  8. Assessing behavioural and cognitive domains of autism spectrum disorders in rodents: current status and future perspectives

    NARCIS (Netherlands)

    Kas, M.J.; Glennon, J.C.; Buitelaar, J.; Ey, E.; Biemans, B.; Crawley, J.; Ring, R.H.; Lajonchere, C.; Esclassan, F.; Talpos, J.; Noldus, L.P.; Burbach, J.P.H.; Steckler, T.

    2014-01-01

    The establishment of robust and replicable behavioural testing paradigms with translational value for psychiatric diseases is a major step forward in developing and testing etiology-directed treatment for these complex disorders. Based on the existing literature, we have generated an inventory of ap

  9. Assessing behavioural and cognitive domains of autism spectrum disorders in rodents : current status and future perspectives

    NARCIS (Netherlands)

    Kas, Martien J; Glennon, Jeffrey C; Buitelaar, Jan; Ey, Elodie; Biemans, Barbara; Crawley, Jacqueline; Ring, Robert H; Lajonchere, Clara; Esclassan, Frederic; Talpos, John; Noldus, Lucas P J J; Burbach, J Peter H; Steckler, Thomas

    2014-01-01

    The establishment of robust and replicable behavioural testing paradigms with translational value for psychiatric diseases is a major step forward in developing and testing etiology-directed treatment for these complex disorders. Based on the existing literature, we have generated an inventory of ap

  10. Siblings of Youth with Autism Spectrum Disorders: Theoretical Perspectives on Sibling Relationships and Individual Adjustment

    Science.gov (United States)

    McHale, Susan M.; Updegraff, Kimberly A.; Feinberg, Mark E.

    2016-01-01

    A burgeoning research literature investigates the sibling relationships of youth with autism spectrum disorder (ASD) and their implications for individual adjustment. Focusing on four relationship domains--behaviors, emotions, cognitions and involvement--and toward advancing this generally atheoretical literature, we review and apply tenets from a…

  11. Video Modeling and Children with Autism Spectrum Disorder: A Survey of Caregiver Perspectives

    Science.gov (United States)

    Cardon, Teresa A.; Guimond, Amy; Smith-Treadwell, Amanda M.

    2015-01-01

    Video modeling (VM) has shown promise as an effective intervention for individuals with autism spectrum disorder (ASD); however, little is known about what may promote or prevent caregivers' use of this intervention. While VM is an effective tool to support skill development among a wide range of children in research and clinical settings, VM is…

  12. Crisis on Campus: Eating Disorder Intervention from a Developmental-Ecological Perspective

    Science.gov (United States)

    Taylor, Julia V.; Gibson, Donna M.

    2016-01-01

    Objective: The purpose of this article is to review a crisis intervention using the developmental-ecological protocol (Collins and Collins, 2005) with a college student presenting with symptomatology of an active eating disorder. Participants: Participants included University Wellness Center employees responding to the crisis. Methods: Methods…

  13. Sickness absence due to mental health disorders-a societal perspective

    NARCIS (Netherlands)

    Roelen, C. A. M.; van Rhenen, W.; Koopmans, P. C.; Bultmann, U.; Groothoff, J. W.; van der Klink, J. J. L.

    2012-01-01

    Background Sickness absence (SA) is affected by societal factors. Increasing socioeconomic stress may cause or worsen mental health disorders, which are among the most frequent causes of SA. Employees may also be more cautious about being absent, for example in times of poor economy. Aims To monitor

  14. A behavioural neuroscience perspective on the aetiology and treatment of anxiety disorders.

    Science.gov (United States)

    Kindt, Merel

    2014-11-01

    Over the past decades, behaviour and cognitive psychology have produced fruitful and mutually converging theories from which hypotheses could be derived on the nature and origin of fear and anxiety disorders. Notwithstanding the emergence of effective treatments, there are still many questions that remain to be answered. Here, I will argue that the burgeoning field of behavioural neuroscience may advance our understanding of fear, anxiety disorders and its treatments. Decades of fear-conditioning research across species have begun to elucidate the neurobiological mechanisms underlying associative fear learning and memory. The fear-conditioning paradigm provides a well-controlled and fine-grained research platform to examine these processes. Although the traditional fear conditioning paradigm was originally designed to unveil general principles of fear (un)learning, it is well-suited to understand the transition from normal fear to pathological fear and the mechanisms of change. This paper presents 1) a selection of fear conditioning studies on the generalization and persistence of associative fear memory as intermediate phenotypes of fear and anxiety disorders, and 2) insights from neuroscience on the malleability of fear memory with the potential to provide a long-term cure for anxiety and related disorders.

  15. Recognising Autism Spectrum Disorders in Primary Care: Perspectives of Speech and Language Therapists

    Science.gov (United States)

    Cameron, Helen; Muskett, Tom

    2014-01-01

    Understanding the process of recognising autism spectrum disorders (ASD) in children is important, both for achieving timely identification of children's difficulties and for ensuring positive experiences for families. Professionals working in primary care services are suitably positioned to identify children requiring referral for diagnostic…

  16. What counts as effective genetic counselling for presymptomatic testing in late-onset disorders? A study of the consultand's perspective.

    Science.gov (United States)

    Guimarães, Lídia; Sequeiros, Jorge; Skirton, Heather; Paneque, Milena

    2013-08-01

    Genetic counselling must be offered in the context of presymptomatic testing (PST) for severe late-onset diseases; however, effective genetic counselling is not well defined, and measurement tools that allow a systematic evaluation of genetic practice are still not available. The aims of this qualitative study were to (1) recognize relevant aspects across the whole process of genetic counselling in PST for late-onset neurodegenerative disorders that might indicate effective practice from the consultand's perspective; and (2) analyse aspects of current protocols of counselling that might be relevant for successful practice. We interviewed 22 consultands undergoing PST for late-onset neurological disorders (Huntington disease, spinocerebellar ataxias and familial amyloid polyneuropathy ATTRV30M) in the three major counselling services for these diseases in Portugal. The main themes emerging from the content analysis were (1) the consultand's general assessment of the PST process in genetic services; (2) appropriateness and adaptation of the protocol to the consultand's personal expectations and needs; and (3) consultand's experience of the decision-making process and the role of engagement and counselling skills of the counsellor. Participants also provided a set of recommendations and constructive criticisms relating to the length of the protocol, the time gap between consultations and the way results were delivered. These issues and the construction of the relationship between counsellor and counselee should be further investigated and used for the improvement of current protocols of counselling.

  17. Investigating evolutionary perspective of carcinogenesis with single-cell transcriptome analysis

    Institute of Scientific and Technical Information of China (English)

    Xi Zhang; Cheng Zhang; Zhongjun Li; Jiangjian Zhong; Leslie P. Weiner; Jiang F. Zhong

    2013-01-01

    We developed phase-switch microfluidic devices for molecular profiling of a large number of single cells. Whole genome microarrays and RNA-sequencing are commonly used to determine the expression levels of genes in cell lysates (a physical mix of millions of cells) for inferring gene functions. However, cellular heterogeneity becomes an inherent noise in the measurement of gene expression. The unique molecular characteristics of individual cells, as well as the temporal and quantitative information of gene expression in cells, are lost when averaged among all cells in cell lysates. Our single-cell technology overcomes this limitation and enables us to obtain a large number of single-cell transcriptomes from a population of cells. A collection of single-cell molecular profiles allows us to study carcinogenesis from an evolutionary perspective by treating cancer as a diverse population of cells with abnormal molecular characteristics. Because a cancer cellpopulation contains cells at various stages of development toward drug resistance, clustering similar single-cell molecular profiles could reveal how drug-resistant sub-clones evolve during cancer treatment. Here, we discuss how single-celltranscriptome analysis technology could enable the study of carcinogenesis from an evolutionary perspective and the development of drug-resistance in leukemia. The single-cell transcriptome analysis reported here could have a direct and significant impact on current cancer treatments and future personalized cancer therapies.

  18. B cells in the pathophysiology of autoimmune neurological disorders: a credible therapeutic target.

    Science.gov (United States)

    Dalakas, Marinos C

    2006-10-01

    There is evidence that B cells are involved in the pathophysiology of many neurological diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. Clonal expansion of B cells either in situ or intrathecally and circulating autoantibodies are critical elements in multiple sclerosis (MS), Devic's disease, paraneoplastic central nervous system disorders, stiff-person syndrome, myasthenia gravis, autoimmune demyelinating neuropathies and dermatomyositis. The pathogenic role of B cells and autoantibodies in central and peripheral nervous system disorders, as reviewed here, provides a rationale for investigating whether depletion of B cells with new agents can improve clinical symptomatology and, potentially, restore immune function. Preliminary results from several clinical studies and case reports suggest that B cell depletion may become a viable alternative approach to the treatment of autoimmune neurological disorders.

  19. The Expression of Caspases Is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients

    Science.gov (United States)

    Siniscalco, Dario; Sapone, Anna; Giordano, Catia; Cirillo, Alessandra; de Novellis, Vito; de Magistris, Laura; Rossi, Francesco; Fasano, Alessio; Maione, Sabatino; Antonucci, Nicola

    2012-01-01

    Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and…

  20. Lower risk of atopic disorders in whole cell pertussis-vaccinated children

    NARCIS (Netherlands)

    R.M.D. Bernsen (Roos); J.C. de Jongste (Johan); J.C. van der Wouden (Hans)

    2003-01-01

    textabstractThis study addressed whether whole cell pertussis-vaccinated children have a different risk of atopic disorders compared with children who did not receive this vaccination. Data on vaccination status, atopic disorders and child and family characteristics of the children

  1. Parental perspectives on the causes of an autism spectrum disorder in their children.

    Science.gov (United States)

    Mercer, L; Creighton, S; Holden, J J A; Lewis, M E S

    2006-02-01

    Autism Spectrum Disorders (ASDs) are complex neurodevelopmental disorders with many biological causes, including genetic, syndromic and environmental. Such etiologic heterogeneity impacts considerably upon parents' needs for understanding their child's diagnosis. A descriptive survey was designed to investigate parental views on the cause(s) of ASD in their child. Among the 41 parents who replied to the questionnaire, genetic influences (90.2%), perinatal factors (68.3%), diet (51.2%), prenatal factors (43.9%) and vaccines (40.0%) were considered to be the most significant contributory factors. Parents reported inaccurately high recurrence risks, misperceptions of the contribution of various putative factors, feelings of guilt and blame regarding their child's diagnosis, as well as a lack of advocacy for genetic counseling by non-geneticist professionals. This study offers clinicians and researchers further insight into what parents believe contributed to their child's diagnosis of ASD and will help facilitate genetic counseling for these families.

  2. [Social companies and solidary economy: perspectives for the work inclusion of individuals with mental disorders].

    Science.gov (United States)

    Lussi, Isabela Aparecida de Oliveira; Pereira, Maria Alice Ornellas

    2011-04-01

    The psychiatric reform process requires the implementation of public policies that guarantee the work inclusion of individuals with mental disorders. To do this, work must be understood as a promoter of autonomy, emancipation and citizenship. The objective of this study is to reflect on the theoretical concepts related to social insertion through work, with the purpose of exploring the inclusion of individuals with mental disorders in the work market. The concepts social company and solidary economy where selected as fundamental for the study. In the social company, the subject is considered to be a social being, focusing on the development process towards emancipation. In solidary economy, the objective is to develop an economy that is more just, equal and solidary. Further discussions on these concepts should be developed to support the implementation of projects for social inclusion through work.

  3. The Positive Illusory Bias in Children with ADHD: A Perspective from Bipolar Disorder

    OpenAIRE

    2016-01-01

    Since the 1990’s, many researchers have clarified that children with Attention DeficitHyperactivity Disorder (ADHD) had unrealistically positive self-perception (positive illusorybias; PIB). That is, children with ADHD consistently have shown high self-perception despitethe fact that they could only achieve low performance. For the mechanism of the PIB, someexplanations have been made, such as cognitive immature, neuropsychological deficits,ignorance of incompetence, or self-protection. Addit...

  4. The Assessment of Habit Disorders: A Tripartite Perspective in Measuring Change.

    Science.gov (United States)

    1982-08-01

    subscores. The revised Janis-Field Feelings of Inadequay Scale (Eagly, 1967) is a 20-question test aimed at direct inquiry of positive and negative ...34like me" or "unlike me." Although this test ,%as originally fornulated for children, Coopersmith has produced an adult version. Self- derogation ... multidimensional measures of change. Nowhere is this trend more evident than in habit disorder research. To establish a philosophic foundation, Plato’s

  5. A Review of Autism Spectrum Disorders (ASD) from A Perspective of Classical Chinese Medicine (CCM)

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun

    2010-01-01

    @@ Introduction Autism is a complex developmental disability that typically appears during the first two years of man's life and is the result of a neurological disorder that affects the functioning of the brain, and the development in social interaction and communication skills. Both children and adults along the autistic spectrum typically show difficulties in verbal and non-verbal communication, social interactions, and leisure or play activities.

  6. A review of attention-deficit/hyperactivity disorder from the perspective of brain networks

    Directory of Open Access Journals (Sweden)

    Angelica eDe La Fuente

    2013-05-01

    Full Text Available Attention-Deficit/Hyperactivity disorder (ADHD is the most commonly diagnosed neurodevelopmental disorder in childhood, which affects more than 5% of the population worldwide. ADHD is characterized by developmentally inappropriate behaviors of inattention, and/or impulsivity and hyperactivity. These behavioral manifestations contribute to diminished academic, occupational and social functioning, and have neurobiological bases. Neuronal deficits, especially in the attention and executive function processing networks, have been implicated in both children and adults with ADHD by using sophisticated structural and functional neuroimaging approaches. These structural and functional abnormalities in the brain networks have been associated with the impaired cognitive, affective, and motor behaviors seen in the disorder. The goal of this review is to summarize and integrate emerging themes from the existing neuroimaging connectivity studies based on advanced imaging techniques, applied in data of structural Magnetic Resonance Imaging (MRI, functional MRI (fMRI, Diffusion Tensor Imaging (DTI, Electroencephalography (EEG and Event Related Potential (ERP; and to discuss the results of these studies when considering future directions for understanding pathophysiological mechanisms and developmental trajectories of the behavioral manifestations in ADHD. We conclude this review by suggesting that future research should put more effort on understanding the roles of the subcortical structures and their structural/functional pathways in ADHD.

  7. A perspective on the role of microRNA-128 regulation in mental and behavioral disorders

    Directory of Open Access Journals (Sweden)

    Ai Sze eChing

    2015-12-01

    Full Text Available MiRNAs are short, non-coding RNA molecules that regulate gene expression post-transcriptionally. Over the past decade, misregulated miRNA pathways have been associated with various diseases such as cancer, neurodegenerative diseases and neurodevelopmental disorders. In this article, we aim to discuss the role played by miR-128 in neuropsychiatric disorders, and highlight potential target genes from an in silico analysis of predicted miR-128 targets. We also discuss the differences of target gene determination based on a bioinformatics or empirical approach. Using data from TargetScan and published reports, we narrowed the miR-128 target gene list to those that are known to be associated with neuropsychiatric disorders, and found that these genes can be classified into 29 gene clusters and are mostly enriched in cancer and MAPK signaling pathways. We also highlight some recent studies on several of the miR-128 targets which should be investigated further as potential candidate genes for therapeutic interventions.

  8. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells.

    Science.gov (United States)

    Sanberg, Paul R; Eve, David J; Willing, Alison E; Garbuzova-Davis, Svitlana; Tan, Jun; Sanberg, Cyndy D; Allickson, Julie G; Cruz, L Eduardo; Borlongan, Cesar V

    2011-01-01

    Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

  9. Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective.

    Science.gov (United States)

    Ono, Masahiro; Tanaka, Reiko J

    2016-01-01

    Thymus-derived regulatory T cells (Tregs) are considered to be a distinct T-cell lineage that is genetically programmed and specialised for immunosuppression. This perspective is based on the key evidence that CD25(+) Tregs emigrate to neonatal spleen a few days later than other T cells and that thymectomy of 3-day-old mice depletes Tregs only, causing autoimmune diseases. Although widely believed, the evidence has never been reproduced as originally reported, and some studies indicate that Tregs exist in neonates. Thus we examine the consequences of the controversial evidence, revisit the fundamental issues of Tregs and thereby reveal the overlooked relationship of T-cell activation and Foxp3-mediated control of the T-cell system. Here we provide a new model of Tregs and Foxp3, a feedback control perspective, which views Tregs as a component of the system that controls T-cell activation, rather than as a distinct genetically programmed lineage. This perspective provides new insights into the roles of self-reactivity, T cell-antigen-presenting cell interaction and T-cell activation in Foxp3-mediated immune regulation.

  10. Single-cell analysis: Advances and future perspectives

    Directory of Open Access Journals (Sweden)

    Emir Hodzic

    2016-11-01

    Full Text Available The last several years have seen rapid development of technologies and methods that permit a detailed analysis of the genome and transcriptome of a single cell. Recent evidence from studies of single cells reveals that each cell type has a distinct lineage and function. The lineage and stage of development of each cell determine how they respond to each other and the environment. Experimental approaches that utilize single-cell analysis are effective means to understand how cell networks work in concert to coordinate a response at the population level; recent progress in single-cell analysis is offering a glimpse at the future.

  11. Perspectives and controversies in the field of stem cell research.

    Science.gov (United States)

    Romano, Gaetano

    2006-09-01

    The fourth annual meeting of the International Society for Stem Cell Research focused on a number of pressing issues, including: (I) the need to better characterize the biology of stem cells; (II) the need to exploit and optimize the great therapeutic potential of stem cells in tissue regeneration; (III) ethical and safety considerations related to the use of human embryonic stem cells; (IV) the contribution of adult stem cells to carcinogenesis; (V) the need to investigate the biology of cancer stem cells. The purpose of this report is to summarize the current status of stem cell research, as surmised by the proceedings of this meeting.

  12. Perspectives in inflammation, neoplasia, and vascular cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Edgington, T.S.; Ross, R.; Silverstein, S.C.

    1987-01-01

    This book contains 25 selections. Some of the titles are: Characterization of cDNAs for the Human Interleukin-2 Receptor; Regulation of the Epidermal Growth Factor Receptor by Phosphorylation; Endothelial Cell Proteases and Cellular Invasion; Structure and Chromosomal Localization of the Human Lymphotoxin Gene; and Vascular Endothelial Cells in Cell-Mediated Immunity: Adoptive Transfer with In Vitro Conditioned Cells is Genetically Restricted at the Endothelial Cell Barrier.

  13. Poverty as the Prime Source of World Disorder - Global and Regional Migration in a Development Perspective

    DEFF Research Database (Denmark)

    Schmidt, Johannes Dragsbæk

    2008-01-01

    to the emerging regionalism in the North and notice that labor exporting countries in the South are debating various coherent regional and sub-regional responses in fear of rising regionalism, protectionism and bans on immigration in the United States and Europe. The paper also touches on the impact of the 1997......The intention of this paper is to provide a tentative perspective on attempts to theorize and conceptualize various understandings of regionalization and regionalism in relation to labor market regulation and global migration. The paper explores the link between national and collective responses...... Asian financial crisis on regional labor market regulation, migration and social policy. The paper ends up by exploring the new regimes of governance concerning labor migration in light of the recent rise of terror and rightwing policies in the North....

  14. Genetic analysis in inherited metabolic disorders--from diagnosis to treatment. Own experience, current state of knowledge and perspectives.

    Science.gov (United States)

    Wertheim-Tysarowska, Katarzyna; Gos, Monika; Sykut-Cegielska, Jolanta; Bal, Jerzy

    2015-01-01

    Inherited metabolic disorders, also referred to as inborn errors of metabolism (IEM), are a group of congenital disorders caused by mutation in genomic or mitochondrial DNA. IEM are mostly rare disorders with incidence ranging from 1/50,000-1/150,000), however in total IEM may affect even 1/1000 people. A particular mutation affects specific protein or enzyme that improper function leads to alterations in specific metabolic pathway. Inborn errors of metabolism are monogenic disorders that can be inherited in autosomal recessive manner or, less frequently, in autosomal dominant or X-linked patterns. Some exceptions to Mendelian rules of inheritance have also been described. Vast majority of mutations responsible for IEM are small DNA changes affecting single or several nucleotides, although larger rearrangements were also identified. Therefore, the methods used for the identification of pathogenic mutations are mainly based on molecular techniques, preferably on Sanger sequencing. Moreover, the next generation sequencing technique seems to be another prospective method that can be successfully implemented for the diagnosis of inborn errors of metabolism. The identification of the genetic defect underlying the disease is not only indispensable for genetic counseling, but also might be necessary to apply appropriate treatment to the patient. Therapeutic strategies for IEM are continuously elaborated and tested (eg. enzyme replacement therapy, specific cells or organ transplantation or gene therapy, both in vivo and ex vivo) and have already been implemented for several disorders. In this article we present current knowledge about various aspects of IEM on the basis of our own experience and literature review.

  15. Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Vladislav Volarevic

    2014-01-01

    Full Text Available Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

  16. Family burden, quality of life and disability in obsessive compulsive disorder: An Indian perspective

    Directory of Open Access Journals (Sweden)

    Gururaj G

    2008-01-01

    Full Text Available Background: Obsessive compulsive disorder (OCD is a psychiatric disorder that often tends to run a chronic course. The lifetime prevalence of OCD is around 1-3%, which is twice as prevalent as schizophrenia and bipolar disorder. Aim: To asses the family burden, quality of life (QoL and disability in patients suffering from at least moderately ill OCD and then to compare them with schizophrenia patients of comparable severity. Settings and Design: We recruited 70 consecutive subjects (OCD=35, schizophrenia=35 who met study criteria between March 2005 and March 2006 from the psychiatric services of the National Institute of Mental Health and Neuro Sciences, Bangalore, India. Materials and Methods: The severity of illness was rated using the Clinical Global Impression-Severity (CGI-S. Instruments used in the current study were the Family Burden Schedule, the World Health Organization (WHO QoL (Bref and the WHO - Disability Assessment Schedule (DAS. Statistical Analysis: The Fisher′s exact test/chi-square test was used to compare categorical variables and the independent sample t test was used to analyze continuous variables. Analysis of covariance (ANCOVA was used to compare the groups after controlling for potential confounding variables. Pearson′s correlation was used for correlation analysis. Results: Overall family burden, financial burden and disruption of family routines were significantly higher in schizophrenia patients compared to OCD although the groups did not differ with respect to other domains of family burden. On the WHO QoL, OCD patients were comparable to schizophrenia patients with respect to the psychological and social domains. On the WHO - DAS, both the groups were similar in all the domains except getting around. Conclusion: Severe OCD is associated with significant disability, poor QoL and high family burden, often comparable to schizophrenia. Therefore, there is an urgent need to increase the sensitivity among healthcare

  17. Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders

    Directory of Open Access Journals (Sweden)

    Nathan Gerald Skene

    2016-01-01

    Full Text Available The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesised that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.

  18. Introduction to the special series on "Narcissistic personality disorder--new perspectives on diagnosis and treatment".

    Science.gov (United States)

    Ronningstam, Elsa

    2014-10-01

    The first aim for this Special Series on "Narcissistic personality disorder--new perspecitves on diagnosis and treatment" is to further the dimensional self-regulatory diagnostic approach for identifying NPD by integrating range of functioning, co-occurring grandiosity and vulnerability, compromised empathic ability, self-enhancing interpersonal strategies and relatedness, and overt and covert expressions of pathological narcissism. A second aim is to broaden the conceptualization of pathological narcissism by identifying it in terms of attachment and mentalization/reflective function. The third aim is to apply the combined dimensional and trait diagnostic approach to clinical practice, both diagnostic evaluation and treatment.

  19. A feminist perspective on risk factor research and on the prevention of eating disorders.

    Science.gov (United States)

    Piran, Niva

    2010-01-01

    This review utilizes a feminist lens to discuss risk factor research and prevention work in the field of eating disorders. The article suggests that feminist informed risk factor research needs to consider gender as it intersects with other social variables as a relevant higher level risk factor and examine its relationship to individual level risk factors such as the internalization of thinness or negative body image. The article also highlights the key elements of participatory approaches and systemic changes to feminist informed prevention work. Prevention work conducted to date suggests the relevance of these elements to achieving behavioral changes in prevention work.

  20. Interleukin-1 as a Common Denominator from Autoinflammatory to Autoimmune Disorders: Premises, Perils, and Perspectives

    Science.gov (United States)

    Lopalco, Giuseppe; Cantarini, Luca; Vitale, Antonio; Iannone, Florenzo; Anelli, Maria Grazia; Andreozzi, Laura; Lapadula, Giovanni; Galeazzi, Mauro; Rigante, Donato

    2015-01-01

    A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet's disease, gout, Sjögren's syndrome, interstitial lung diseases, and Still's disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems. PMID:25784780

  1. The perspective of parents on the functional consequences of Developmental Coordination Disorder (DCD: a literature review

    Directory of Open Access Journals (Sweden)

    Beatriz de Arruda Pereira Galvão

    2014-04-01

    Full Text Available In general, the difficulties presented by children diagnosed with Developmental Coordination Disorder (DCD are first noticed by parents in the daily routine. Although the discussion about the functional impact of DCD is expanding in some countries, it is still poorly explored in Brazil. The purpose of this study was to review the literature that describes the perception of parents concerning the impact of DCD on the daily life of these children and their families. An electronic search for the evidence available in the literature was conducted in major databases using, as keywords, the terms commonly adopted by researchers and practitioners working with children with DCD. The inclusion criteria were articles that used qualitative methodology, studies published from January 1995 to February 2012, and data collected through interviews with parents and/or caregivers, which described children with specific signs of DCD. Of the 594 articles found, only eight used qualitative methodology - all in English. The data presented in these articles show the concern of parents regarding the socialization process of their children with DCD and the lack of preparation of the educational system to deal with the motor difficulties that characterize this disorder. In conclusion, it is essential, especially for rehabilitation professionals who deal with children with DCD, to value how parents perceive the motor coordination difficulties of their children in order to develop actions and services that are adequate to the reality of Brazilian families.

  2. Interleukin-1 as a Common Denominator from Autoinflammatory to Autoimmune Disorders: Premises, Perils, and Perspectives

    Directory of Open Access Journals (Sweden)

    Giuseppe Lopalco

    2015-01-01

    Full Text Available A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet’s disease, gout, Sjögren’s syndrome, interstitial lung diseases, and Still’s disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems.

  3. Underlying Factors Behind the Low Prevalence of Autism Spectrum Disorders in Oman; Sociocultural perspective

    Directory of Open Access Journals (Sweden)

    Allal Ouhtit

    2015-05-01

    Full Text Available Epidemiological surveys from various countries indicate an increased prevalence of autism spectrum disorders (ASD, leading researchers to debate whether there are now ‘more affected’ or ‘more detected’. The epidemiology of ASD in developing countries, such as Oman, has generally indicated a lower prevalence compared to developed countries in the West. In Oman, the prevalence is low; however, this article highlights some of the factors that could contribute to the appearance of a low ASD rate: cross-cultural variations in the presentation of distress; a lack of reliable biological markers for diagnosing ASD, and a lack of health services for children with ASD, thus limiting the number of participants in epidemiological surveys. While the defining features of ASD have yet to be established, pilot studies in Oman indicate a substantial number of children with these disorders. Therefore, it is important that these discrepancies be addressed and the need for appropriate services for this patient population in Oman be highlighted.

  4. Bipolar Disorder: Clinical Perspectives and Implications with Cognitive Dysfunction and Dementia

    Directory of Open Access Journals (Sweden)

    R. Lopes

    2012-01-01

    Full Text Available Introduction. Cognitive dysfunction as a core feature in the course of bipolar affective disorder (BPD is a current subject of debate and represents an important source of psychosocial and functional burden. Objectives. To stand out the connection and clinical implications between cognitive dysfunction, dementia, and BPD. Methods. A nonsystematic review of all English language PubMed articles published between 1995 and 2011 using the terms “bipolar disorder,” “cognitive dysfunction,” and “dementia”. Discussion. As a manifestation of an affective trait or stage, both in the acute phases and in remission, the domains affected include attention, executive function, and verbal memory. The likely evolution or overlap with the behavioural symptoms of an organic dementia allows it to be considered as a dementia specific to BPD. This is named by some authors, as BPD type VI, but others consider it a form of frontotemporal dementia. It is still not known if this process is neurodevelopmental or neurodegenerative in nature, or both simultaneously. The assessment should consider the iatrogenic effects of medication, the affective symptoms, and a neurocognitive evaluation. Conclusion. More specific neuropsychological tests and functional imaging studies are needed and will assume an important role in the near future for diagnosis and treatment.

  5. Difficulties in everyday life: Young persons with attention-deficit/hyperactivity disorder and autism spectrum disorders perspectives. A chat-log analysis

    Directory of Open Access Journals (Sweden)

    Britt H. Ahlström

    2014-05-01

    Full Text Available This study focuses on the everyday life of young persons with attention-deficit/hyperactivity disorder (ADHD and autism spectrum disorder (ASD. There are follow-up studies describing ADHD, and ASD in adults, and residual impairments that affect life. Few qualitative studies have been conducted on the subject of their experiences of everyday life, and even fewer are from young persons’ perspectives. This study's aim was to describe how young persons with ADHD and ASD function and how they manage their everyday life based on analyses of Internet-based chat logs. Twelve young persons (7 males and 5 females aged 15–26 diagnosed with ADHD and ASD were included consecutively and offered 8 weeks of Internet-based Support and Coaching (IBSC. Data were collected from 12 chat logs (445 pages of text produced interactively by the participants and the coaches. Qualitative content analysis was applied. The text was coded and sorted into subthemes and further interpreted into themes. The findings revealed two themes: “fighting against an everyday life lived in vulnerability” with the following subthemes: “difficult things,” “stress and rest,” and “when feelings and thoughts are a concern”; and the theme “struggling to find a life of one's own” with the following subthemes: “decide and carry out,” “making life choices,” and “taking care of oneself.” Dealing with the problematic situations that everyday encompasses requires personal strength and a desire to find adequate solutions, as well as to discover a role in society. This study, into the provision of support and coaching over the Internet, led to more in-depth knowledge about these young persons’ everyday lives and revealed their ability to use IBSC to express the complexity of everyday life for young persons with ADHD and ASD. The implications of the findings are that using online coaching makes available new opportunities for healthcare professionals to acknowledge

  6. Stem cells as promising therapeutic options for neurological disorders.

    Science.gov (United States)

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  7. Altered effects of perspective-taking on functional connectivity during self- and other-referential processing in adults with autism spectrum disorder.

    Science.gov (United States)

    Hashimoto, Ryu-Ichiro; Itahashi, Takashi; Ohta, Haruhisa; Yamada, Takashi; Kanai, Chieko; Nakamura, Motoaki; Watanabe, Hiromi; Kato, Nobumasa

    2016-08-30

    In interactive social situations, it is often crucial to be able to take another person's perspective when evaluating one's own or another person's specific trait; individuals with autism spectrum disorder (ASD) critically lack this social skill. To examine how perspective-dependent self- and other-evaluation processes modulate functional connectivity in ASD, we conducted a functional magnetic resonance imaging study in which 26 high-functioning adults with ASD and 24 typically developed (TD) controls were asked to decide whether an adjective describing a personality trait correctly described the participant himself/herself ("self") or the participant's mother ("other") by taking either the first (1P) or third person (3P) perspective. We observed that functional connectivity between the left sensorimotor cortex and the left middle cingulate cortex was enhanced in TD control individuals taking the 3P perspective, this enhancement was significantly reduced in ASD, and the degree of reduction was significantly correlated with the severity of autistic traits. Furthermore, the self-reference effect on functional connectivity between the left inferior frontal cortex and frontopolar cortices was significantly enhanced in TD control individuals taking the 3P perspective, whereas such effect was reversed in ASD. These findings indicate altered effects of perspective on the functional connectivity, which may underlie the deficits in social interaction and communication observed in individuals with ASD.

  8. The Mesenchymal Stem Cells From The Veterinary Sciences Perspective

    Directory of Open Access Journals (Sweden)

    Nancy B. Riaño G.

    2007-06-01

    Full Text Available The characteristics of a stem cell are determined by being undifferentiated, auto renewable, and because of having the capacity of generating cells for multiple cellular lineages, with the capacity to proliferate indefinitely in cultures. The origin of the stem cells can be embryonic (blastomers and cells of the internal mass of the blastocyst or somatic (pluripotential cells from adult tissues. The source of the somatic stem cells is the bone marrow, in which the hematopoietic stem cells and the mesenchymals (MSCs are found. Diverse studies in animal models have demonstrated that MSCs constitute a potential tool for the establishment of regenerative therapies in injured tissues. This article reviews the properties of the stem cells, their potentials, their advantages and limitations in several animal models.

  9. Myoepithelial cells: Current perspectives in salivary gland tumors

    Directory of Open Access Journals (Sweden)

    C Pramod Redder

    2013-01-01

    Full Text Available Myoepithelial cells are normal constituent of the salivary acini and smaller ducts, and are found between the epithelial cells and the basement membrane. Microscopic examination shows that myoepithelial cells are thin and spindle-shaped and situated between the basement membrane and epithelial cells. Ultrastructurally they possess a number of cytoplasmic processes that extend between and over the acinar and ductal-lining cells. They display features of both smooth muscle and epithelium, such as numerous microfilaments with focal densities in the cytoplasmic processes, and desmosomes which attach the myoepithelial to the epithelial cells. Neoplastic myoepithelial cells in both benign and malignant tumors can take several forms, including epithelioid, spindle, plasmacytoid, and clear, and this variability largely accounts for difficulties in histopathological diagnosis. This review article highlights the role of myoepithelial cells in salivary gland tumors.

  10. Hilar mossy cells of the dentate gyrus: a historical perspective

    Directory of Open Access Journals (Sweden)

    Helen E Scharfman

    2013-01-01

    Full Text Available The circuitry of the dentate gyrus of the hippocampus is unique compared to other hippocampal subfields because there are two glutamatergic principal cells instead of one: granule cells, which are the vast majority of the cells in the dentate gyrus, and the so-called ‘mossy cells.’ The distinctive appearance of mossy cells, the extensive divergence of their axons, and their vulnerability to excitotoxicity relative to granule cells has led to a great deal of interest in mossy cells. Nevertheless, there is no consensus about the normal functions of mossy cells and the implications of their vulnerability. There even seems to be some ambiguity about exactly what mossy cells are. Here we review initial studies of mossy cells, characteristics that define them, and suggest a practical definition to allow investigators to distinguish mossy cells from other hilar neurons even if all morphological and physiological information is unavailable due to technical limitations of their experiments. In addition, hypotheses are discussed about the role of mossy cells in the dentate gyrus network, reasons for their vulnerability and their implications for disease.

  11. [Clinical features, biology and neuropsychology of the autistic disorder: towards an integrative perspective].

    Science.gov (United States)

    Cukier, Sebastián H

    2005-01-01

    Autism constitutes one of the most investigated disorders in child psychiatry. The heterogeneous clinical phenomena that characterize it have been exhaustibly described along the last 62 years. Multiple aetiological hypothesis, neuropsychological theories and physiopathological mechanisms, sometimes complementary and other times mutually exclusive, and different descriptions of neurobiological alterations that resulted, in general, of low replicability, have attempted to account for the marked variability of its manifestations. An integration of these different levels of analysis results even harder than the comprehension of each of them separately. In this article the author revises the three aspects considered the most characteristic of the syndrome (social interaction, communication and flexibility) and tries to integrate its clinical manifestations with some neuropsychological variables and the neurobiological substrates.

  12. HANNIBAL REVISITED: ANTISOCIAL PERSONALITY DISORDER VERSUS PSYCHOPATHY--MEDICO-LEGAL PERSPECTIVES FROM SOUTH AFRICA.

    Science.gov (United States)

    Stevens, Philip

    2014-07-01

    Psychopathy and its relation to criminal behaviour has been the focus of clinical research for many years. Within the context of South African criminal law, the impact of psychopathy on criminal liability has been addressed in numerous decisions with varying outcomes all indicative of the reality that psychopathy will at most serve as a factor in mitigation of sentence, but will not exonerate an accused of criminal responsibility. In this contribution, the author reflects on the diagnostic entities of psychopathy and antisocial personality disorder against the backdrop of South African criminal law cases in terms of which either of these entities were raised in support of mitigation of sentence and/or as extenuating circumstances.

  13. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

    OpenAIRE

    Giordani Rodrigues Dos Passos; Douglas Kazutoshi Sato; Jefferson Becker; Kazuo Fujihara

    2016-01-01

    Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of e...

  14. Tratamento farmacológico do transtorno de ansiedade generalizada: perspectivas futuras Pharmacological treatment of generalized anxiety disorder: future perspectives

    Directory of Open Access Journals (Sweden)

    Roberto Andreatini

    2001-12-01

    Full Text Available O presente artigo apresenta uma visão atualizada e ampla do tratamento farmacológico do transtorno de ansiedade generalizada (TAG. São revistos os medicamentos com eficácia comprovada em estudos controlados e atualmente disponíveis na clínica (benzodiazepínicos, buspirona, antidepressivos, betabloqueadores, antipsicóticos e extrato de kava-kava. A seguir, baseados nesses dados, propõe-se um algoritmo de tratamento do TAG. São apresentadas as principais linhas de pesquisa de novos fármacos ansiolíticos, descrevendo os principais achados clínicos e pré-clínicos.This article presents an updated and broad perspective of the pharmacological treatment of generalized anxiety disorder (GAD. Medications proven to be efficacious in controlled studies and available in the clinic setting were reviewed (benzodiazepines, buspirone, antidepressives, beta-blocking agents, antipsychotics and kava-kava extract. From this data, an algorithm for GAD treatment is proposed. In addition, the main research lines on new anxiolytic drugs and their stage of clinical or pre-clinical development are presented.

  15. Prescribing Clinicians’ Perspectives on Evidence-Based Psychotherapy for Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Erin R. Barnett

    2014-10-01

    Full Text Available Evidence-based psychotherapies (EBP for Posttraumatic Stress Disorder are not utilized to their full extent within the Department of Veterans Affairs (VA. VA provides care to many persons with PTSD and has been in the forefront of clinical practice guidelines and EBP training and dissemination. Yet VA continues to find EBP implementation difficult. Veterans with PTSD often initially present to prescribing clinicians, who then help make care decisions. It is therefore critical that these clinicians correctly screen and triage appropriate mental health care. The purpose of this study was to assess VA prescribing clinicians’ knowledge, perceptions, and referral behaviors related to EBPs for PTSD and to identify facilitators and barriers to implementing EBPs within VA. We conducted qualitative interviews with 26 VA prescribing clinicians. Limited access to EBPs was the most commonly noted barrier. The clinicians we interviewed also held specific beliefs and behaviors that may delay or deter EBPs. Strategies to improve utilization also emerged. Findings suggest the need for increased access to EBPs, training to optimize the role of prescribing clinicians in helping Veterans with PTSD make appropriate care decisions, and specific organizational changes to facilitate access and effective referral systems for EBPs.

  16. [Perspectives of genetic research in eating disorders using the example of anorexia nervosa].

    Science.gov (United States)

    Hinney, Anke; Volckmar, Anna-Lena

    2015-01-01

    Genetic mechanisms are relevant for both body weight regulation and eating disorders (e.g. anorexia nervosa, AN). Although genome-wide association studies (GWAS) have so far identified about 100 chromosomal regions that influence body weight, only a small part of the variance could be explained by molecular genetic factors. For AN GWAS up to now did not reveal genome-wide significant loci. There are first hints for epigenetic mechanisms involved in the described phenotypes. Epigenomics can improve our understanding of the regulation of body weight including hunger (AN) and overnutrition (obesity). Since the prenatal phase is characterized by dramatic epigenetic changes, it can be regarded as vulnerable period for the epigenotype. Adult health and disease depend on prenatal and early postnatal development. Gene expression markers that are imprinted during this phase can be heritable at the cellular level. These markers can be altered by environmental factors. Altered epigenetic profiles had been described for obese individuals. In mice it was shown that an epigenetic modification of an obesity gene locus had been transferred to the next generation. The year to come will show whether the combined analysis of epigenomic and GWAS data will deepen our understanding of the underlying biological mechanisms.

  17. Unattended home-based polysomnography for sleep disordered breathing: current concepts and perspectives.

    Science.gov (United States)

    Bruyneel, Marie; Ninane, Vincent

    2014-08-01

    Recently, portable sleep recording devices became an accepted alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis in patients with a high pre-test probability of moderate to severe OSA but home polysomnography (H-PSG) was not recommended because there were insufficient data. The present review has analysed six prospective randomized crossover studies comparing H-PSG to in-lab PSG. These studies convincingly showed that H-PSG allows complete sleep evaluation. The quality of patients' sleep tends to be better at home. H-PSG is accurate for OSA diagnosis and the failure rate is low despite the absence of supervision. In addition, it could offer a final and comprehensive diagnosis for many other sleep disorders. It is also likely that H-PSG can reduce PSG-related costs but complete cost-effectiveness analyses are not yet available. Recently, remotely attended H-PSG via telemonitoring has been tested and may reduce H-PSG failure rate. In conclusion, H-PSG can be used to rule-in and rule out OSA in suspected patients, even in the presence of co-morbidities and is an alternative when simplified sleep testing is negative. Future developments should target simplification of technical aspects of H-PSG, together with remote monitoring, in order to obtain good quality H-PSG performed in adequate conditions.

  18. Interventions for posttraumatic stress disorder in psychiatric practice across Europe: a trainees’ perspective

    Directory of Open Access Journals (Sweden)

    Katja Koelkebeck

    2015-09-01

    Full Text Available Background: With an annual prevalence of 0.9–2.6%, posttraumatic stress disorder (PTSD is very common in clinical practice across Europe. Despite the fact that evidence-based interventions have been developed, there is no evidence on their implementation in clinical practice and in national psychiatric training programmes. Objective and method: The Early Career Psychiatrists Committee of the European Psychiatric Association conducted a survey in 23 European countries to explore implementation of evidence-based interventions for PTSD and training options. Results: The findings indicate that pharmacotherapy was available in the majority of the participating countries (n=19, 82.8%. However, psychological interventions were much less widespread. For example, psychoeducation was widely available in 52% of the countries (n=12, cognitive-behavioural therapy in 26.2% (n=6, and specific trauma-focused techniques were rarely available. Training on PTSD was part of the official training in 13 countries (56.5%, predominantly in the form of theoretical seminars. Conclusions: Overall, this survey indicates that the treatment for PTSD is largely focused on pharmacotherapy, with psychological evidence-based interventions poorly available, especially outside specialized centres. Poor implementation is linked to the lack of official training in evidence-based interventions for psychiatric trainees across Europe.

  19. Van Gogh and lithium. Creativity and bipolar disorder: perspective of an academic psychologist.

    Science.gov (United States)

    Smith, M

    1999-12-01

    Meg Smith experienced her first serious depressive episode during the final years of her Bachelor of Arts degree. The experience of depressive illness and good counselling interested her in counselling so she switched from a potential career as an English teacher to the study of psychology and counselling. After completing a master's degree in clinical psychology, she worked as a counsellor at a women's health centre until she experienced a manic episode in 1980. After recovering from the episode and the experience of being an involuntary patient, she began to explore the implications of the diagnosis of 'manic depressive illness'. Meg is currently a senior lecturer in social policy at the Bankstown campus of the University of Western Sydney Macarthur. She finds that her position as an academic has enabled her to speak out about social policy and legislation in the area of mental illness. She is currently president of the NSW Association for Mental Health and active in the development of support groups and information resources for people who experience mood disorder.

  20. Recovery in Borderline Personality Disorder (BPD: a qualitative study of service users' perspectives.

    Directory of Open Access Journals (Sweden)

    Christina Katsakou

    Full Text Available BACKGROUND: Symptom improvement in Borderline Personality Disorder (BPD is more common than previously hypothesised. However, it remains unclear whether it reflects service users' personal goals of recovery. The present study aimed to explore what service users with BPD view as recovery. METHODS: 48 service users were recruited from secondary mental health services and their views on their personal goals and the meaning of recovery were explored in in-depth semi-structured interviews. The study drew on grounded theory and thematic analysis. RESULTS: Service users believed that recovery involved developing self-acceptance and self-confidence, gaining control over emotions, improving relationships, employment, and making progress in symptoms like suicidality and self-harming. They felt that psychotherapies for BPD often had an extreme focus on specific areas, like self-harming or relationships, and that some of their goals were neglected. Although full recovery was seen as a distant goal, interviewees felt that they could learn how to deal with their problems in more effective ways and make meaningful progress in their lives. CONCLUSIONS: Specialist therapies for BPD explicitly address some of the recovery goals that are important to service users, whereas other goals are only indirectly or poorly addressed. Professionals might need to work with service users towards devising comprehensive individualised case formulations, including all treatment targets that are important to service users, their priorities, and long-term plans on how their targets might be met and which services might be involved.

  1. Transition for Adolescents with Autism Spectrum Disorder: South African Parent and Professional Perspectives

    Directory of Open Access Journals (Sweden)

    Meagan eMeiring

    2016-06-01

    Full Text Available Adolescents with autism and their families experience a significant increase in the number of challenges encountered when leaving the structure of the formal education system. The purpose of this study was to gain an understanding of the factors parents and professionals regard as important in preparing for transition of adolescents with autism spectrum disorder (ASD to adulthood, vocational and residential arrangements. Semi-structured interviews were conducted with 14 participants (i.e. 7 parents and 7 professionals who were involved with adolescents with ASD in Johannesburg, South Africa. The findings revealed that there was a need for advocacy on behalf of learners with ASD transitioning into adult working and living environments. The responses of the participants highlighted needs for curriculum transformation from basic literacy skills to development and teaching of functional self-help and daily living skills. The results also indicated lack of planning and the absence of service facilities for adolescents with Autism post-school. There was a general feeling of fear and uncertainty when the participants thought about transition of adolescents with Autism and their future. However, there was also a sense of hope and optimism. Transition of adolescents with Autism into adulthood is a challenging and stressful time for parents and professionals involved in trying to prepare them. With appropriate attention and support structures, individuals with Autism can attain a reasonable quality of life, including residential, employment and social opportunities.

  2. Stem Cell Therapy for Treatment of Ocular Disorders

    Directory of Open Access Journals (Sweden)

    Padma Priya Sivan

    2016-01-01

    Full Text Available Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

  3. Stem Cell Therapy for Treatment of Ocular Disorders.

    Science.gov (United States)

    Sivan, Padma Priya; Syed, Sakinah; Mok, Pooi-Ling; Higuchi, Akon; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Awang Hamat, Rukman; Umezawa, Akihiro; Kumar, Suresh

    2016-01-01

    Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

  4. The activation of monocyte and T cell networks in patients with bipolar disorder

    NARCIS (Netherlands)

    Drexhage, Roosmarijn C.; Hoogenboezem, Thomas H.; Versnel, Marjan A.; Berghout, Arie; Nolen, Willem A.; Drexhage, Hemmo A.

    2011-01-01

    Objectives: We recently described a monocyte pro-inflammatory state in patients with bipolar disorder (BD). We hypothesized that the CD4(+)T cell system is also activated and determined percentages of Th1, Th2, Th17 and CD4(+)CD25(high)FoxP3(+) regulatory T cells. Methods: We carried out a detailed

  5. Advances in unrelated and alternative donor hematopoietic cell transplantation for nonmalignant disorders

    NARCIS (Netherlands)

    Shenoy, Shalini; Boelens, Jaap J.

    2015-01-01

    PURPOSE OF REVIEW: The role of hematopoietic cell transplantation in non-malignant disorders has increased exponentially with the recognition that multiple diseases can be controlled or cured if engrafted with donor-derived cells. This review provides an overview of advances made in alternative dono

  6. Glia, mast cells and related: new therapeutic perspectives?

    Directory of Open Access Journals (Sweden)

    Guido Orlandini

    2011-09-01

    Full Text Available Glia exerts a pathogenic role in the development and maintenance of pain. In the past, glia was considered only support material; the glia is 70 to 90 percent of the CNS cells. Normally in a resting state, it is activated by substances released from central terminals of C fibers and releases cytokines that enhance excitatory synaptic transmission in the dorsal horn of the spinal cord (that is the basis of central sensitization, with allodynia-hyperalgesia. By analogy with the role of glia, it has been suggested the importance of the mast cell, a connective ubiquitous cell filled with granules that contain histamine, heparin, serotonin, and NGF as well as lipid droplets that contain hyaluronic acid and a cell membrane on which cannabinoid receptors 1 and 2 and vanilloid are located. Nociceptive stimuli cause mast cell degranulation and the release of substances contained in the granules. ___________________________________________________

  7. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders.

    Science.gov (United States)

    Ye, Zhaohui; Zhan, Huichun; Mali, Prashant; Dowey, Sarah; Williams, Donna M; Jang, Yoon-Young; Dang, Chi V; Spivak, Jerry L; Moliterno, Alison R; Cheng, Linzhao

    2009-12-24

    Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS cell lines were generated from previously frozen cord blood or adult CD34(+) cells of healthy donors, and could be redirected to hematopoietic differentiation. Multiple iPS cell lines were also generated from peripheral blood CD34(+) cells of 2 patients with myeloproliferative disorders (MPDs) who acquired the JAK2-V617F somatic mutation in their blood cells. The MPD-derived iPS cells containing the mutation appeared normal in phenotypes, karyotype, and pluripotency. After directed hematopoietic differentiation, the MPD-iPS cell-derived hematopoietic progenitor (CD34(+)CD45(+)) cells showed the increased erythropoiesis and gene expression of specific genes, recapitulating features of the primary CD34(+) cells of the corresponding patient from whom the iPS cells were derived. These iPS cells provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis.

  8. Changing Perspectives: Exploring a Pedagogy to Examine Other Perspectives about Stem Cell Research

    Science.gov (United States)

    France, Bev; Mora, Helen A.; Bay, Jacquie L.

    2012-01-01

    This study explores how teachers developed and critically evaluated a range of teaching strategies that could support the discussion of a socio-scientific issue (SSI) that had the potential to be controversial. The issue was stem cell research and six New Zealand teachers of senior biology students (grades 12/13) took part in an action research…

  9. [Early detection of developmental disorders: the need for a new perspective].

    Science.gov (United States)

    de Winter, M

    1988-02-01

    Early detection of abnormality in young children (aged 0-7) in the Netherlands is to be organized on two levels. First, regional cooperation between child-health professionals and institutions will be stimulated in order to form a nationwide network of 'multidisciplinary teams', with the task of coordinating early detection in a specific area. These teams are to advise parents and professionals in those cases where a child's development is suspected of being 'at risk'. The second part of the program is a campaign to promote the idea of early detection among the population. The aim is to develop the 'signalizing' and diagnostic abilities of parents, teachers and child-health professionals through education and training. The subject of early detection seemed and still seems to be a focus of different interests, and of conflicts of competence between different groups and schools of professionals and different institutions. In this article some of the main conflicting issues are discussed. One of the important problems concerning early detection is the question of defining normality and abnormality. It is concluded that in the case of early detection of both somatic and psychosomatic disorder there can be no such thing as an absolute scientific rationality, as is often suggested. Theoretical frameworks underlying methods of early detection are influenced by social, cultural and historical factors, and thus form a social construction. Finally a protocol-approach is being suggested, a method that might clear some of the problems concerning the content and organizational procedures of the Dutch system for early detection.

  10. CELL-SELEX: Novel Perspectives of Aptamer-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Hans P. Wendel

    2008-04-01

    Full Text Available Aptamers, single stranded DNA or RNA molecules, generated by a method called SELEX (systematic evolution of ligands by exponential enrichment have been widely used in various biomedical applications. The newly developed Cell-SELEX (cell based-SELEX targeting whole living cells has raised great expectations for cancer biology, -therapy and regenerative medicine. Combining nanobiotechnology with aptamers, this technology opens the way to more sophisticated applications in molecular diagnosis. This paper gives a review of recent developments in SELEX technologies and new applications of aptamers.

  11. Clinical perspectives for regulatory T cells in transplantation tolerance

    OpenAIRE

    Hippen, Keli L.; Riley, James L.; June, Carl H.; Blazar, Bruce R.

    2011-01-01

    Three main types of CD4+ regulatory T cells can be distinguished based upon whether they express Foxp3 and differentiate naturally in the thymus (natural Tregs) or are induced in the periphery (inducible Tregs); or whether they are FoxP3 negative but secrete IL-10 in response to antigen (Tregulatory type 1, Tr1 cells). Adoptive transfer of each cell type has proven highly effective in mouse models at preventing graft vs. host disease (GVHD) and autoimmunity. Although clinical application was ...

  12. Why Cells are Microscopic: A Transport-Time Perspective.

    Science.gov (United States)

    Soh, Siowling; Banaszak, Michal; Kandere-Grzybowska, Kristiana; Grzybowski, Bartosz A

    2013-03-21

    Physical-chemical reasoning is used to demonstrate that the sizes of both prokaryotic and eukaryotic cells are such that they minimize the times needed for the macromolecules to migrate throughout the cells and interact/react with one another. This conclusion does not depend on a particular form of the crowded-medium diffusion model, as thus points toward a potential optimization principle of cellular organisms. In eukaryotes, size optimality renders the diffusive transport as efficient as active transport - in this way, the cells can conserve energetic resources that would otherwise be expended in active transport.

  13. A disordered carbon as a novel anode material in lithium-ion cells

    Energy Technology Data Exchange (ETDEWEB)

    Bonino, F.; Brutti, S.; Reale, P.; Scrosati, B. [Dipartimento di Chimica, Universita ' ' La Sapienza' ' , I-00185 Rome (Italy); Gherghel, L.; Wu, J.; Muellen, K. [Max Planck Institute for Polymer Research, Ackermannweg 10, D-55124 Mainz (Germany)

    2005-03-22

    The electrochemical behavior of a disordered carbon used as the anode in a lithium battery has been tested. The characteristics of this carbon, especially its specific capacity and cycle life, are such that it is a potentially unique, high-performance anode material for new types of lithium-ion batteries. The Figure shows the specific capacity versus cycle number of the disordered carbon electrode in a lithium-ion cell. (Abstract Copyright [2005], Wiley Periodicals, Inc.)

  14. Innate immune pattern recognition: a cell biological perspective.

    Science.gov (United States)

    Brubaker, Sky W; Bonham, Kevin S; Zanoni, Ivan; Kagan, Jonathan C

    2015-01-01

    Receptors of the innate immune system detect conserved determinants of microbial and viral origin. Activation of these receptors initiates signaling events that culminate in an effective immune response. Recently, the view that innate immune signaling events rely on and operate within a complex cellular infrastructure has become an important framework for understanding the regulation of innate immunity. Compartmentalization within this infrastructure provides the cell with the ability to assign spatial information to microbial detection and regulate immune responses. Several cell biological processes play a role in the regulation of innate signaling responses; at the same time, innate signaling can engage cellular processes as a form of defense or to promote immunological memory. In this review, we highlight these aspects of cell biology in pattern-recognition receptor signaling by focusing on signals that originate from the cell surface, from endosomal compartments, and from within the cytosol.

  15. High-efficiency silicon heterojunction solar cells: Status and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    De Wolf, S.; Geissbuehler, J.; Loper, P.; Martin de Nicholas, S.; Seif, J.; Tomasi, A.; Ballif, C.

    2015-05-11

    Silicon heterojunction technology (HJT) uses silicon thin-film deposition techniques to fabricate photovoltaic devices from mono-crystalline silicon wafers (c-Si). This enables energy-conversion efficiencies above 21 %, also at industrial-production level. In this presentation we review the present status of this technology and point out recent trends. We first discuss how the properties of thin hydrogenated amorphous silicon (a-Si:H) films can be exploited to fabricate passivating contacts, which is the key to high- efficiency HJT solar cells. Such contacts enable very high operating voltages, approaching the theoretical limits, and yield small temperature coefficients. With this approach, an increasing number of groups are reporting devices with conversion efficiencies well over 20 % on both-sides contacted n-type cells, Panasonic leading the field with 24.7 %. Exciting results have also been obtained on p-type wafers. Despite these high voltages, important efficiency gains can still be made in fill factor and optical design. This requires improved understanding of carrier transport across device interfaces and reduced parasitic absorption in HJT solar cells. For the latter, several strategies can be followed: Short-wavelength losses can be reduced by replacing the front a-Si:H films with wider-bandgap window layers, such as silicon alloys or even metal oxides. Long- wavelength losses are mitigated by introducing new high-mobility TCO’s such as hydrogenated indium oxide, and also by designing new rear reflectors. Optical shadow losses caused by the front metallization grid are significantly reduced by replacing printed silver electrodes with fine-line plated copper contacts, leading also to possible cost advantages. The ultimate approach to minimize optical losses is the implementation of back-contacted architectures, which are completely devoid of grid shadow losses and parasitic absorption in the front layers can be minimized irrespective of electrical

  16. Drawings of Blood Cells Reveal People's Perception of Their Blood Disorder: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Steven Ramondt

    Full Text Available Sickle cell disease (SCD and thalassemia are rare but chronic blood disorders. Recent literature showed impaired quality of life (QOL in people with these blood disorders. Assessing one of the determinants of QOL (i.e. illness perceptions therefore, is an important next research area.We aimed to explore illness perceptions of people with a blood disorder with drawings in addition to the Brief Illness Perception Questionnaire (Brief IPQ. Drawings are a novel method to assess illness perceptions and the free-range answers drawings offer can add additional insight into how people perceive their illness.We conducted a cross-sectional study including 17 participants with a blood disorder. Participants' illness perceptions were assessed by the Brief IPQ and drawings. Brief IPQ scores were compared with reference groups from the literature (i.e. people with asthma or lupus erythematosus.Participants with SCD or thalassemia perceived their blood disorder as being more chronic and reported more severe symptoms than people with either asthma or lupus erythematosus. In the drawings of these participants with a blood disorder, a greater number of blood cells drawn was negatively correlated with perceived personal control (P<0.05, indicating that a greater quantity in the drawing is associated with more negative or distressing beliefs.Participants with a blood disorder perceive their disease as fairly threatening compared with people with other chronic illnesses. Drawings can add additional insight into how people perceive their illness by offering free-range answers.

  17. Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Baldur Kristjánsson

    2014-01-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease most commonly occurring in the ageing population. It is a slow progressive condition resulting in the destruction of hyaline cartilage followed by pain and reduced activity. Conventional treatments have little effects on the progression of the condition often leaving surgery as the last option. In the last 10 years tissue engineering utilising mesenchymal stem cells has been emerging as an alternative method for treating OA. Mesenchymal stem cells (MSCs are multipotent progenitor cells found in various tissues, most commonly bone marrow and adipose tissue. MSCs are capable of differentiating into osteocytes, adipocytes, and chondrocytes. Autologous MSCs can be easily harvested and applied in treatment, but allogenic cells can also be employed. The early uses of MSCs focused on the implantations of cell rich matrixes during open surgeries, resulting in the formation of hyaline-like durable cartilage. More recently, the focus has completely shifted towards direct intra-articular injections where a great number of cells are suspended and injected into affected joints. In this review the history and early uses of MSCs in cartilage regeneration are reviewed and different approaches in current trends are explained and evaluated.

  18. High-efficiency silicon heterojunction solar cells: Status and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    De Wolf, S.

    2015-04-27

    Silicon heterojunction technology (HJT) uses silicon thin-film deposition techniques to fabricate photovoltaic devices from mono-crystalline silicon wafers (c-Si). This enables energy-conversion efficiencies above 21 %, also at industrial-production level. In this presentation we review the present status of this technology and point out recent trends. We first discuss how the properties of thin hydrogenated amorphous silicon (a-Si:H) films can be exploited to fabricate passivating contacts, which is the key to high- efficiency HJT solar cells. Such contacts enable very high operating voltages, approaching the theoretical limits, and yield small temperature coefficients. With this approach, an increasing number of groups are reporting devices with conversion efficiencies well over 20 % on n-type wafers, Panasonic leading the field with 24.7 %. Exciting results have also been obtained on p-type wafers. Despite these high voltages, important efficiency gains can still be made in fill factor and optical design. This requires improved understanding of carrier transport across device interfaces and reduced parasitic absorption in HJT solar cells. For the latter, several strategies can be followed: Short- wavelength losses can be reduced by replacing the front a-Si:H films with wider-bandgap window layers, such as silicon alloys or even metal oxides. Long-wavelength losses are mitigated by introducing new high-mobility TCO’s such as hydrogenated indium oxide, and also by designing new rear reflectors. Optical shadow losses caused by the front metalisation grid are significantly reduced by replacing printed silver electrodes with fine-line plated copper contacts, leading also to possible cost advantages. The ultimate approach to minimize optical losses is the implementation of back-contacted architectures, which are completely devoid of grid shadow losses and parasitic absorption in the front layers can be minimized irrespective of electrical transport requirements. The

  19. Advances and perspectives of colorectal cancer stem cell vaccine.

    Science.gov (United States)

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  20. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

    Full Text Available The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs. In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  1. Clinical utility of flow cytometry in the study of erythropoiesis and nonclonal red cell disorders.

    Science.gov (United States)

    Chesney, Alden; Good, David; Reis, Marciano

    2011-01-01

    Erythropoiesis involves proliferation and differentiation of small population of hematopoietic stem cells resident in the bone marrow into mature red blood cells. The determination of the cellular composition of the blood is a valuable tool in the diagnosis of diseases and monitoring of therapy. Flow cytometric analysis is increasingly being used to characterize the heterogeneous cell populations present in the blood and the hematopoietic cell differentiation and maturation pathways of the bone marrow. Here we discuss the role of flow cytometry in the study of erythropoiesis and nonclonal red blood cell disorders. First, we discuss flow cytometric analysis of reticulocytes. Next, we review salient quantitative methods that can be used for detection of fetal-maternal hemorrhage (FMH). We also discuss flow cytometric analysis of high hemoglobin F (HbF) in Sickle Cell Disease (SCD), hereditary spherocytosis (HS), red cell survival and red cell volume. We conclude by discussing cell cycle of erythroid cells.

  2. Cancer stem cells: therapeutic implications and perspectives in cancer therapy

    Directory of Open Access Journals (Sweden)

    Lu Han

    2013-04-01

    Full Text Available The cancer stem cell (CSC theory is gaining increasing attention from researchers and has become an important focus of cancer research. According to the theory, a minority population of cancer cells is capable of self-renewal and generation of differentiated progeny, termed cancer stem cells (CSCs. Understanding the properties and characteristics of CSCs is key to future study on cancer research, such as the isolation and identification of CSCs, the cancer diagnosis, and the cancer therapy. Standard oncology treatments, such as chemotherapy, radiotherapy and surgical resection, can only shrink the bulk tumor and the tumor tends to relapse. Thus, therapeutic strategies that focus on targeting CSCs and their microenvironmental niche address the ineffectiveness of traditional cancer therapies to eradicate the CSCs that otherwise result in therapy resistance. The combined use of traditional therapies with targeted CSC-specific agents may target the whole cancer and offer a promising strategy for lasting treatment and even cure.

  3. A Review of Cell Formation from Perspective of Objective Function

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaoqing; TANG Jiafu

    2006-01-01

    The initial and significant step in the design of a cellular manufacturing system is cell formation (CF). CF problem is proposed in this paper as a decision problem that determines to manufacture specified types of part in a manufacturing plant which machines and their associated parts are grouped together to form cell in a way that a concerned objective is optimized. For describing CF problem clearly, this paper firstly presents a review of cell formation problem from the view points of objective function. The CF problems are classified into three categories, which are cost oriented, flexibility oriented and grouping efficiency oriented CF problems. Then, the paper presents a comprehensive conceptual mathematical formulation describing the general cost problem and a decision variable for comprehensive describing routing flexibility and two trade-off questions in grouping efficiency issues. Finally, based on the review and discussion, the paper proposes five directions for future research in the CF field.

  4. Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder in vascular endothelial cells and colon cancer cells.

    Science.gov (United States)

    Ribeiro-Varandas, Edna; Pereira, H Sofia; Viegas, Wanda; Delgado, Margarida

    2016-06-01

    Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans.

  5. Periodontal ligament stem cells: an update and perspectives.

    Science.gov (United States)

    Chamila Prageeth Pandula, P K; Samaranayake, L P; Jin, L J; Zhang, Chengfei

    2014-05-01

    Chronic periodontitis is a serious infectious and inflammatory oral disease of humans worldwide. Conventional treatment modalities are effective for controlling periodontal disease. However, the regeneration of damaged periodontal tissues remains a major challenge in clinical practice due to the complex structure of the periodontium. Stem cell-based regenerative approaches combined with the usage of emerging biomaterials are entering a new era in periodontal regeneration. The present review updates the current knowledge of periodontal ligament stem cell-based approaches for periodontal regeneration, and elaborates on the potentials for clinical application.

  6. Cancer stem cells: an insight and future perspective.

    Science.gov (United States)

    Kaur, Sandeep; Singh, Gurdeep; Kaur, Kirandeep

    2014-01-01

    The cancer stem cell (CSC) concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are typically rare. Rare CSCs have been isolated from a number of human tumors, including hematopoietic, brain, colon, and breast cancer. With the growing evidence that CSCs exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. Understanding the biology of CSCs will contribute to the identification of molecular targets important for future therapies.

  7. Disorder improves nanophotonic light trapping in thin-film solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Paetzold, U. W., E-mail: u.paetzold@fz-juelich.de; Smeets, M.; Meier, M.; Bittkau, K.; Merdzhanova, T.; Smirnov, V.; Carius, R.; Rau, U. [IEK5—Photovoltaik, Forschungszentrum Jülich GmbH, 52425 Jülich (Germany); Michaelis, D.; Waechter, C. [Fraunhofer Institut für Angewandte Optik und Feinmechanik, Albert Einstein Str. 7, D-07745 Jena (Germany)

    2014-03-31

    We present a systematic experimental study on the impact of disorder in advanced nanophotonic light-trapping concepts of thin-film solar cells. Thin-film solar cells made of hydrogenated amorphous silicon were prepared on imprint-textured glass superstrates. For periodically textured superstrates of periods below 500 nm, the nanophotonic light-trapping effect is already superior to state-of-the-art randomly textured front contacts. The nanophotonic light-trapping effect can be associated to light coupling to leaky waveguide modes causing resonances in the external quantum efficiency of only a few nanometer widths for wavelengths longer than 500 nm. With increasing disorder of the nanotextured front contact, these resonances broaden and their relative altitude decreases. Moreover, overall the external quantum efficiency, i.e., the light-trapping effect, increases incrementally with increasing disorder. Thereby, our study is a systematic experimental proof that disorder is conceptually an advantage for nanophotonic light-trapping concepts employing grating couplers in thin-film solar cells. The result is relevant for the large field of research on nanophotonic light trapping in thin-film solar cells which currently investigates and prototypes a number of new concepts including disordered periodic and quasi periodic textures.

  8. Metabolic shifts: a fitness perspective for microbial cell factories

    NARCIS (Netherlands)

    Goel, A.; Wortel, M.T.; Molenaar, D.; Teusink, B.

    2012-01-01

    Performance of industrial microorganisms as cell factories is limited by the capacity to channel nutrients to desired products, of which optimal production usually requires careful manipulation of process conditions, or strain improvement. The focus in process improvement is often on understanding a

  9. Corneal stem cells and tissue engineering: Current advances and future perspectives.

    Science.gov (United States)

    de Araujo, Aline Lütz; Gomes, José Álvaro Pereira

    2015-06-26

    Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there are many challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

  10. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  11. Reduced Neurite Density in Neuronal Cell Cultures Exposed to Serum of Patients with Bipolar Disorder

    Science.gov (United States)

    Wollenhaupt-Aguiar, Bianca; Pfaffenseller, Bianca; Chagas, Vinicius de Saraiva; Castro, Mauro A A; Passos, Ives Cavalcante; Kauer-Sant’Anna, Márcia; Kapczinski, Flavio

    2016-01-01

    Background: Increased inflammatory markers and oxidative stress have been reported in serum among patients with bipolar disorder (BD). The aim of this study is to assess whether biochemical changes in the serum of patients induces neurotoxicity in neuronal cell cultures. Methods: We challenged the retinoic acid-differentiated human neuroblastoma SH-SY5Y cells with the serum of BD patients at early and late stages of illness and assessed neurite density and cell viability as neurotoxic endpoints. Results: Decreased neurite density was found in neurons treated with the serum of patients, mostly patients at late stages of illness. Also, neurons challenged with the serum of late-stage patients showed a significant decrease in cell viability. Conclusions: Our findings showed that the serum of patients with bipolar disorder induced a decrease in neurite density and cell viability in neuronal cultures. PMID:27207915

  12. [Retinal regeneration with iPS cells ‒ Clinical trials for retinal degenerative disorders].

    Science.gov (United States)

    Sugita, Sunao

    2015-01-01

    Potential for re-programming cells has become widely accepted as a tool for obtaining transplantation materials. There has been great interest in cell-based therapies, including retinal transplants, because there is a reduced risk of immune rejection. Stem cells have the capacity for self-renewal plus the capacity to generate several differentiated cells. They are derived from many sources including human adult-derived induced pluripotent stem (iPS) cells and have found early application in the context of ocular disease. In results, our established iPS-retinal pigment epithelial (RPE) cells are high-quality RPE cells. iPS cells-derived RPE cells clearly showed polygonal morphology (mostly hexagonal) and contained melanin. Moreover, RPE cells derived from iPS cells had many characteristics of mature RPE cells in vivo, but no characteristics of pluripotent stem cells. Recently, we transplanted RPE cell sheets to treat a patient with wet age-related macular degeneration (September, 2014). In addition, we are now conducting experiments to determine whether allogeneic T cells can recognize iPS-RPE cells from HLA-A, B, DRB1 locus homozygote donors. iPS bank might be useful as allografts in retinal disorders, if the recipient T cells cannot respond to allogeneic RPE cells because of match to some of main HLA antigens.

  13. Integrating cell phones and mobile technologies into public health practice: a social marketing perspective.

    Science.gov (United States)

    Lefebvre, Craig

    2009-10-01

    Mobile communications are being used for many purposes, from instant messaging (IM), mobile or microblogging (Twitter), social networking sites (Facebook, MySpace), e-mail to basic voicemail. A brief background on cell phone and mobile technology use in public health is reviewed. The focus of the article is framing the use of mobile technologies in public health from a social marketer's perspective--using the 4 Ps marketing mix as a guide.

  14. Human cloning, stem cell research. An Islamic perspective.

    Science.gov (United States)

    Al-Aqeel, Aida I

    2009-12-01

    The rapidly changing technologies that involve human subjects raise complex ethical, legal, social, and religious issues. Recent advances in the field of cloning and stem cell research have introduced new hopes for the treatment of serious diseases. But this promise has raised many complex questions. This field causes debate and challenge, not only among scientists but also among ethicists, religious scholars, governments, and politicians. There is no consensus on the morality of human cloning, even within specific religious traditions. In countries in which religion has a strong influence on political decision making, the moral status of the human embryo is at the center of the debate. Because of the inevitable consequences of reproductive cloning, it is prohibited in Islam. However, stem cell research for therapeutic purposes is permissible with full consideration, and all possible precautions in the pre-ensoulment stages of early fetus development, if the source is legitimate.

  15. Roles Nrf2 Plays in Myeloid Cells and Related Disorders

    Directory of Open Access Journals (Sweden)

    Eri Kobayashi

    2013-01-01

    Full Text Available The Keap1-Nrf2 system protects animals from oxidative and electrophilic stresses. Nrf2 is a transcription factor that induces the expression of genes essential for detoxifying reactive oxygen species (ROS and cytotoxic electrophiles. Keap1 is a stress sensor protein that binds to and ubiquitinates Nrf2 under unstressed conditions, leading to the rapid proteasomal degradation of Nrf2. Upon exposure to stress, Keap1 is modified and inactivated, which allows Nrf2 to accumulate and activate the transcription of a battery of cytoprotective genes. Antioxidative and detoxification activities are important for many types of cells to avoid DNA damage and cell death. Accumulating lines of recent evidence suggest that Nrf2 is also required for the primary functions of myeloid cells, which include phagocytosis, inflammation regulation, and ROS generation for bactericidal activities. In fact, results from several mouse models have shown that Nrf2 expression in myeloid cells is required for the proper regulation of inflammation, antitumor immunity, and atherosclerosis. Moreover, several molecules generated upon inflammation activate Nrf2. Although ROS detoxification mediated by Nrf2 is assumed to be required for anti-inflammation, the entire picture of the Nrf2-mediated regulation of myeloid cell primary functions has yet to be elucidated. In this review, we describe the Nrf2 inducers characteristic of myeloid cells and the contributions of Nrf2 to diseases.

  16. Suppressor cell activity in a proliferative disorder of T lymphocytes.

    Science.gov (United States)

    Kupa, A; Thomas, M E; Moore, H; Bradley, J; Zola, H; Hooper, M; Harding, P

    1981-06-01

    We report details of the immunological profile of a patient with the candidiasis endocrinopathy syndrome who has developed T-type chronic lymphocytic leukaemia. The patient is anergic to a panel of delayed hypersensitivity skin tests, and has poor in vitro mitogenic responses, but B cell function in vivo is not impaired. Subsequent functional studies have revealed that cells from the patient have a significant suppressive effect in coculture (P less than 0.05) on the responses of healthy donor lymphocytes (NR) to the mitogen phytohaemagglutinin (PHA). A degree of selectivity for the suppressive effect is suggested by the lack of similar effects on coculture responses to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Mitomycin C treatment of the patient's cells reduced their suppressive activity but significant suppression was still observed in the majority of PHA cocultures. The suppressor activity required the presence of the patient's cells in cocultures, as no suppression was observed when the patient's serum or cell culture supernatant were included instead of the patient's cells in NR cultures.

  17. Non-Small Cell Carcinoma Biomarker Testing: The Pathologist's Perspective.

    Directory of Open Access Journals (Sweden)

    Elisa eBrega

    2014-07-01

    Full Text Available Biomarker testing has become standard of care for patients diagnosed with non-small cell lung cancer. Although it can be successfully performed in circulating tu-mor cells, at present, the vast majority of investigations are carried out using di-rect tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically signifi-cant, particularly in cases of lung adenocarcinomas (ADC, which in turn, has prompted a new proposal for the histologic classification of such pulmonary neo-plasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire pro-cess happens in a timely fashion. Therefore, it is part of the pathologist’s respon-sibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play NSCLC bi-omarker testing, as well as to provide a summarized review of the main NSCLC bi-omarkers of

  18. Mesenchymal stem cell therapy for osteoarthritis: current perspectives.

    Science.gov (United States)

    Wyles, Cody C; Houdek, Matthew T; Behfar, Atta; Sierra, Rafael J

    2015-01-01

    Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

  19. A CLINICAL STUDY OF LIMBAL STEM CELL TRANSPLANTATION IN VARIOUS OCULAR SURFACE DISORDERS

    Directory of Open Access Journals (Sweden)

    Rashmi

    2015-10-01

    Full Text Available AIMS: The purpose of this study is to evaluate the various causes of limbal stem cell deficiency, to assess signs and symptoms in ocular surface disorder and improvement following stem cell transplantation, to carry out limbal stem cell transplantation in various ocular surface disorders and to assess various intraoperative and postoperative complications following stem cell transplantation. METHODS: This study included 40 cases of ocular surface disorders treated with limbal autograft transplantation. Patients were recorded in a predesigned proforma, including the detailed history and complete ophthalmological examination. All cases of ocular surface disorders were treated with conjunctivo-limbal autograft transplantation under peribulbar and facial anaesthesia. RESULT: Maximum number of patients belong to age group 30-40 years. Males were more commonly affected by ocular surface disorders than females. (1.8:1. various causes of limbal stem cell deficiency were reviewed. The most common etiology associated with limbal stem cell deficiency was pterygia (60% followed by vascularised leucomatous corneal opacity (20%, chemical burns (15% and epitheliopathy (5%. Most common symptoms reported by patients were redness (100%, foreign body sensation (90%, watering (85% and photophobia (50%. Most common signs found were conjunctival congestion (90%, corneal vascularization (70%, conjunctivalisation (70% and epithelial defects (30%. 72.5% of patients reported increased ocular comfort. Postoperative incidence of redness was reduced from 90% to 20%, watering from 85% to 15% and photophobia from 50% to 25%. Improvement in signs was noted as decrease in conjunctival congestion from 90% to 22.2%, vascularisation from 70% to 35%, conjunctivalisation from 70% to 21.5% and epithelial defects from 30% to 16.6%. CONCLUSIONS: Use of autologous limbal transplantation with corneal and conjunctival tissue as a vehicle was useful for ocular surface reconstruction in

  20. Attention-Deficit/Hyperactivity Disorder (ADHD in Adulthood: Concordance and Differences between Self- and Informant Perspectives on Symptoms and Functional Impairment.

    Directory of Open Access Journals (Sweden)

    Beatrice Mörstedt

    Full Text Available Attention-deficit/hyperactivity disorder (ADHD is a severe mental illness, associated with major impairment and a high comorbidity rate. Particularly undiagnosed ADHD in adulthood has serious consequences. Thus, a valid diagnosis is important. In adulthood, the diagnostic process for ADHD is complicated: symptoms may overlap with comorbid disorders, and the onset and progression of the disorder must be reconstructed retrospectively. Guidelines for the diagnostic process recommend the inclusion of additional informant ratings. Research into the relation between self- and informant ratings shows extremely heterogeneous results. The levels of agreement range from low to high. The focus of this study is the concordance and differences between self- and informant ratings on ADHD symptoms and impairments. In this regard, two possible influencing factors (gender and relationship type are also examined. 114 people participated in this study, 77 with an ADHD diagnosis and 37 without a diagnosis. For all participants, either parents or partners also rated ADHD symptoms and impairments. Small to moderate concordance was found between self- and informant ratings, with females being slightly more concordant than males, particularly for ratings of problems with self-concept. Examination of the consistency within a particular perspective showed that people with ADHD seemed to be unaware of the causal relation between ADHD symptoms and their impairments. A close investigation found almost no influence of gender and relationship type on differences within perspectives. Based on these results, the implications for the diagnostic process are that additional informant information is clearly necessary and helpful.

  1. Attention-Deficit/Hyperactivity Disorder (ADHD) in Adulthood: Concordance and Differences between Self- and Informant Perspectives on Symptoms and Functional Impairment.

    Science.gov (United States)

    Mörstedt, Beatrice; Corbisiero, Salvatore; Bitto, Hannes; Stieglitz, Rolf-Dieter

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a severe mental illness, associated with major impairment and a high comorbidity rate. Particularly undiagnosed ADHD in adulthood has serious consequences. Thus, a valid diagnosis is important. In adulthood, the diagnostic process for ADHD is complicated: symptoms may overlap with comorbid disorders, and the onset and progression of the disorder must be reconstructed retrospectively. Guidelines for the diagnostic process recommend the inclusion of additional informant ratings. Research into the relation between self- and informant ratings shows extremely heterogeneous results. The levels of agreement range from low to high. The focus of this study is the concordance and differences between self- and informant ratings on ADHD symptoms and impairments. In this regard, two possible influencing factors (gender and relationship type) are also examined. 114 people participated in this study, 77 with an ADHD diagnosis and 37 without a diagnosis. For all participants, either parents or partners also rated ADHD symptoms and impairments. Small to moderate concordance was found between self- and informant ratings, with females being slightly more concordant than males, particularly for ratings of problems with self-concept. Examination of the consistency within a particular perspective showed that people with ADHD seemed to be unaware of the causal relation between ADHD symptoms and their impairments. A close investigation found almost no influence of gender and relationship type on differences within perspectives. Based on these results, the implications for the diagnostic process are that additional informant information is clearly necessary and helpful.

  2. Sourcing human embryos for embryonic stem cell lines: Problems & perspectives

    Directory of Open Access Journals (Sweden)

    Rajvi H Mehta

    2014-01-01

    Full Text Available The ability to successfully derive human embryonic stem cells (hESC lines from human embryos following in vitro fertilization (IVF opened up a plethora of potential applications of this technique. These cell lines could have been successfully used to increase our understanding of human developmental biology, transplantation medicine and the emerging science of regenerative medicine. The main source for human embryos has been ′discarded′ or ′spare′ fresh or frozen human embryos following IVF. It is a common practice to stimulate the ovaries of women undergoing any of the assisted reproductive technologies (ART and retrieve multiple oocytes which subsequently lead to multiple embryos. Of these, only two or maximum of three embryos are transferred while the rest are cryopreserved as per the decision of the couple. In case a couple does not desire to ′cryopreserve′ their embryos then all the embryos remaining following embryo transfer can be considered ′spare′ or if a couple is no longer in need of the ′cryopreserved′ embryos then these also can be considered as ′spare′. But, the question raised by the ethicists is, "what about ′slightly′ over-stimulating a woman to get a few extra eggs and embryos? The decision becomes more difficult when it comes to ′discarded′ embryos. As of today, the quality of the embryos is primarily assessed based on morphology and the rate of development mainly judged by single point assessment. Despite many criteria described in the literature, the quality assessment is purely subjective. The question that arises is on the decision of ′discarding′ embryos. What would be the criteria for discarding embryos and the potential ′use′ of ESC derived from the ′abnormal appearing′ embryos? This paper discusses some of the newer methods to procure embryos for the derivation of embryonic stem cell lines which will respect the ethical concerns but still provide the source material.

  3. Systemic Problems: A perspective on stem cell aging and rejuvenation

    Science.gov (United States)

    Conboy, Irina M.; Conboy, Michael J.; Rebo, Justin

    2015-01-01

    This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a “silver bullet” putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are “beyond parabiosis” for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging. PMID:26540176

  4. Sperm cell biology: current perspectives and future prospects

    Institute of Scientific and Technical Information of China (English)

    R John Aitken; Ralf R Henkel

    2011-01-01

    @@ Major advances in biomolecular techniques as well as in the sensitivity and accuracy of mass spectrometers are transform-ing the scientific landscape by fueling unprecedented advances in ana-lytical biochemistry-the 'omics revolution, which refers to the study of genes (genomics), transcripts (transcriptomics), proteins (proteo-mics) and the various metabolites (metabolomics). It is now possible to secure inventories of lipids, proteins, metabolites and RNA species in purified cell populations and to determine how these entities change in relation to cellular function.

  5. Disordered, strongly scattering porous materials as miniature multipass gas cells

    CERN Document Server

    Svensson, Tomas; Lewander, Märta; Xu, Can T; Svanberg, Sune

    2010-01-01

    Spectroscopic gas sensing is both a commercial success and a rapidly advancing scientific field. Throughout the years, massive efforts have been directed towards improving detection limits by achieving long interaction pathlengths. Prominent examples include the use of conventional multipass gas cells, sophisticated high-finesse cavities, gas-filled holey fibers, integrating spheres, and diffusive reflectors. Despite this rich flora of approaches, there is a continuous struggle to reduce size, gas volume, cost and alignment complexity. Here, we show that extreme light scattering in porous materials can be used to realise miniature gas cells. Near-infrared transmission through a 7 mm zirconia (ZrO2) sample with a 49% porosity and subwavelength pore structure (on the order of 100 nm) gives rise to an effective gas interaction pathlength above 5 meters, an enhancement corresponding to 750 passes through a conventional multipass cell. This essentially different approach to pathlength enhancement opens a new route...

  6. Bone marrow scan evaluation of arthropathy in sickle cell disorders

    Energy Technology Data Exchange (ETDEWEB)

    Alavi, A.; Schumacher, H.R.; Dorwart, B.; Kuhl, D.E.

    1976-04-01

    Twelve patients with sickle cell hemoglobinopathies and arthropathy were studied, using technetium Tc 99m sulfur colloid bone marrow scans. Eight of 12 had decreased marrow radionuclide activity adjacent to painful joints, suggesting obliteration of vessels supplying bone marrow. Four patients without marrow defects on scanning had causes other than infarction for their joint symptoms, viz, small fractures, postinfectious synovitis, degenerative arthritis, and osteochondromas. Roentgenograms never showed bony abnormalities in five patients with marrow infarctions, and, in three others, showed defects several months later than did the marrow scans. Bone marrow scans offer a sensitive and early diagnostic aid in sickle cell hemoglobinopathies with arthropathy.

  7. Modern perspectives on numerical modeling of cardiac pacemaker cell.

    Science.gov (United States)

    Maltsev, Victor A; Yaniv, Yael; Maltsev, Anna V; Stern, Michael D; Lakatta, Edward G

    2014-01-01

    Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent "coupled-clock" theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age.

  8. SnS Thin Film Solar Cells: Perspectives and Limitations

    Directory of Open Access Journals (Sweden)

    Simone Di Mare

    2017-02-01

    Full Text Available Thin film solar cells have reached commercial maturity and extraordinarily high efficiency that make them competitive even with the cheaper Chinese crystalline silicon modules. However, some issues (connected with presence of toxic and/or rare elements are still limiting their market diffusion. For this reason new thin film materials, such as Cu2ZnSnS4 or SnS, have been introduced so that expensive In and Te, and toxic elements Se and Cd, are substituted, respectively, in CuInGaSe2 and CdTe. To overcome the abundance limitation of Te and In, in recent times new thin film materials, such as Cu2ZnSnS4 or SnS, have been investigated. In this paper we analyze the limitations of SnS deposition in terms of reproducibility and reliability. SnS deposited by thermal evaporation is analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy, and atomic force microscopy. The raw material is also analyzed and a different composition is observed according to the different number of evaporation (runs. The sulfur loss represents one of the major challenges of SnS solar cell technology.

  9. [Helper T cell paradigm: Th17 and regulatory T cells involved in autoimmune inflammatory disorders, pathogen defense and allergic diseases].

    Science.gov (United States)

    Noma, Takeshi

    2010-01-01

    The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells. Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection. Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders. Th17 cells are required the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation, and produce IL-17, IL-22, IL-17F, IL-21 and CCL20. FOXP3+ regulatory T (Treg) cells produce TGF-β and IL-10, which regulate effector T cells, and thus maintain peripheral tolerance. Four functionally unique CD4+ T cells, including the regulatory T (Treg) cells are now involved in the regulation of immune responses to pathogens, self-antigens and allergens. Any defect in the entire CD4+T cell population might results in human diseases. In this review, the biology of Th17 cells and Treg cells and their role in immune diseases are presented.

  10. Treating hearing disorders with cell and gene therapy

    Science.gov (United States)

    Gillespie, Lisa N.; Richardson, Rachael T.; Nayagam, Bryony A.; Wise, Andrew K.

    2014-12-01

    Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.

  11. A transgenic mouse model of sickle cell disorder.

    NARCIS (Netherlands)

    D.R. Greaves (David); P.J. Fraser (Peter); M.A. Vidal; M.J. Hedges; D. Ropers; L. Luzzatto; F.G. Grosveld (Frank)

    1990-01-01

    textabstractA single base-pair mutation (beta s) in codon 6 of the human beta-globin gene, causing a single amino-acid substitution, is the cause of sickle cell anaemia. The mutant haemoglobin molecule, HbS, polymerizes when deoxygenated and causes deformation of the erythrocytes to a characteristic

  12. Hydrogel-Based Nanocomposites and Mesenchymal Stem Cells: A Promising Synergistic Strategy for Neurodegenerative Disorders Therapy

    Directory of Open Access Journals (Sweden)

    Diego Albani

    2013-01-01

    Full Text Available Hydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs, to improve and to tailor their viscoelastic properties upon injection and release profile. An intriguing application is hydrogel loading with mesenchymal stem cells (MSCs that are a very promising therapeutic tool for neurodegenerative or traumatic disorders of the CNS. This multidisciplinary review will focus on the basic concepts to design acellular and cell-loaded materials with specific and tunable rheological and functional properties. The use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic strategy for nervous tissue applications will be then discussed.

  13. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders

    Science.gov (United States)

    Gurwitz, David

    2016-01-01

    The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

  14. Autism Spectrum Disorders: Is Mesenchymal Stem Cell Personalized Therapy the Future?

    Directory of Open Access Journals (Sweden)

    Dario Siniscalco

    2012-01-01

    Full Text Available Autism and autism spectrum disorders (ASDs are heterogeneous neurodevelopmental disorders. They are enigmatic conditions that have their origins in the interaction of genes and environmental factors. ASDs are characterized by dysfunctions in social interaction and communication skills, in addition to repetitive and stereotypic verbal and nonverbal behaviours. Immune dysfunction has been confirmed with autistic children. There are no defined mechanisms of pathogenesis or curative therapy presently available. Indeed, ASDs are still untreatable. Available treatments for autism can be divided into behavioural, nutritional, and medical approaches, although no defined standard approach exists. Nowadays, stem cell therapy represents the great promise for the future of molecular medicine. Among the stem cell population, mesenchymal stem cells (MSCs show probably best potential good results in medical research. Due to the particular immune and neural dysregulation observed in ASDs, mesenchymal stem cell transplantation could offer a unique tool to provide better resolution for this disease.

  15. Advances in understanding the pathogenesis of the red cell volume disorders.

    Science.gov (United States)

    Badens, Catherine; Guizouarn, Hélène

    2016-09-01

    Genetic defects of erythrocyte transport proteins cause disorders of red blood cell volume that are characterized by abnormal permeability to the cations Na(+) and K(+) and, consequently, by changes in red cell hydration. Clinically, these disorders are associated with chronic haemolytic anaemia of variable severity and significant co-morbidities, such as iron overload. This review provides an overview of recent insights into the molecular basis of this group of rare anaemias involving cation channels and transporters dysfunction. To date, a total of 5 different membrane proteins have been reported to be responsible for volume homeostasis alteration when mutated, 3 of them leading to overhydrated cells (AE1 [also termed SLC4A1], RHAG and GLUT1 [also termed SCL2A1) and 2 others to dehydrated cells (PIEZO1 and the Gardos Channel). These findings are not only of basic scientific interest, but also of direct clinical significance for improving diagnostic procedures and identify potential approaches for novel therapeutic strategies.

  16. Predation and eukaryote cell origins: a coevolutionary perspective.

    Science.gov (United States)

    Cavalier-Smith, T

    2009-02-01

    Cells are of only two kinds: bacteria, with DNA segregated by surface membrane motors, dating back approximately 3.5Gy; and eukaryotes, which evolved from bacteria, possibly as recently as 800-850My ago. The last common ancestor of eukaryotes was a sexual phagotrophic protozoan with mitochondria, one or two centrioles and cilia. Conversion of bacteria (=prokaryotes) into a eukaryote involved approximately 60 major innovations. Numerous contradictory ideas about eukaryogenesis fail to explain fundamental features of eukaryotic cell biology or conflict with phylogeny. Data are best explained by the intracellular coevolutionary theory, with three basic tenets: (1) the eukaryotic cytoskeleton and endomembrane system originated through cooperatively enabling the evolution of phagotrophy; (2) phagocytosis internalised DNA-membrane attachments, unavoidably disrupting bacterial division; recovery entailed the evolution of the nucleus and mitotic cycle; (3) the symbiogenetic origin of mitochondria immediately followed the perfection of phagotrophy and intracellular digestion, contributing greater energy efficiency and group II introns as precursors of spliceosomal introns. Eukaryotes plus their archaebacterial sisters form the clade neomura, which evolved from a radically modified derivative of an actinobacterial posibacterium that had replaced the ancestral eubacterial murein peptidoglycan by N-linked glycoproteins, radically modified its DNA-handling enzymes, and evolved cotranslational protein secretion, but not the isoprenoid-ether lipids of archaebacteria. I focus on this phylogenetic background and on explaining how in response to novel phagotrophic selective pressures and ensuing genome internalisation this prekaryote evolved efficient digestion of prey proteins by retrotranslocation and 26S proteasomes, then internal digestion by phagocytosis, lysosomes, and peroxisomes, and eukaryotic vesicle trafficking and intracellular compartmentation.

  17. The risk factors of post-transplant lymphoproliferative disorders following haploidentical hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张春丽

    2014-01-01

    Objective Post-transplant lymphoproliferative disorder(PTLD)occurring after allogeneic hematopoietic stem cell transplantation(allo-HSCT)is rare but severe.Risk factors including pre-HSCT exposure variables,conditioning regimens,transplant-related complications,and post-HSCT immune reconstitution were investigated in the development of PTLD after allo-HSCT.Methods A

  18. Stem cells in neuroinjury and neurodegenerative disorders: challenges and future neurotherapeutic prospects.

    Science.gov (United States)

    Mouhieddine, Tarek H; Kobeissy, Firas H; Itani, Muhieddine; Nokkari, Amaly; Wang, Kevin K W

    2014-05-01

    The prevalence of neurodegenerative diseases and neural injury disorders is increasing worldwide. Research is now focusing on improving current neurogenesis techniques including neural stem cell therapy and other biochemical drug-based approaches to ameliorate these disorders. Unfortunately, we are still facing many obstacles that are rendering current neurotherapies ineffective in clinical trials for reasons that are yet to be discovered. That is why we should start by fully understanding the complex mechanisms of neurogenesis and the factors that affect it, or else, all our suggested therapies would fail since they would not be targeting the essence of the neurological disorder but rather the symptoms. One possible paradigm shift is to switch from neuroprotectant therapies towards neurodegeneration/neurorestorative approaches. In addition, other and our laboratories are increasingly focusing on combining the use of pharmacological agents (such as Rho-associated kinase (ROCK) inhibitors or other growth factors (such as brain-derived neurotrophic factor (BDNF)) and stem cell treatment to enhance the survivability and/or differentiation capacity of transplanted stem cells in neurotrauma or other neurodegeneration animal models. Ongoing stem cell research is surely on the verge of a breakthrough of multiple effective therapeutic options for neurodegenerative disorders. Once, we fully comprehend the process of neurogenesis and its components, we will fully be capable of manipulating and utilizing it. In this work, we discuss the current knowledge of neuroregenerative therapies and their associated challenges.

  19. Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes

    NARCIS (Netherlands)

    Franceschi, L. De; Bosman, G.J.C.G.M.; Mohandas, N.

    2014-01-01

    PURPOSE OF REVIEW: This review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known as acanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditary disorders that include chorea-acanthocytosis (ChAc) and McLeod syndro

  20. Sickle Cell Disease: quality of life in patients with hemoglobin SS and SC disorders

    OpenAIRE

    2013-01-01

    OBJECTIVE Sickle cell disease comprises chronic, genetically determined disorders, presenting significant morbidity and high prevalence in Brazil. The goal of this study was to evaluate the quality of life of sickle cell disease patients (hemoglobin SS and SC) and their sociodemographic and clinical characteristics. METHODS Data was collected from clinical records and semi-structured interviews consisting of clinical questionnaires and the World Health Organization Quality of Life-brief qu...

  1. Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

    OpenAIRE

    Phillips, Tycel; Devata, Sumana; Wilcox, Ryan A.

    2016-01-01

    The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin’s lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targetin...

  2. Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum.

    Science.gov (United States)

    Richardson, A J; Ross, M A

    2000-01-01

    There is increasing evidence that abnormalities of fatty acid and membrane phospholipid metabolism play a part in a wide range of neurodevelopmental and psychiatric disorders. This proposal is discussed here in relation to attention-deficit/hyperactivity disorder (ADHD), dyslexia, developmental coordination disorder (dyspraxia) and the autistic spectrum. These are among the most common neurodevelopmental disorders of childhood, with significant implications for society as well as for those directly affected. However, controversy still surrounds both the identification and management of these conditions, and while their aetiology is recognized as being complex and multifactorial, little progress has yet been made in elucidating predisposing factors at the biological level. An overview is provided here of the contents of this Special Issue, which contains a selection of reports from a unique multidisciplinary workshop involving both researchers and clinicians. Its purpose was to explore the possibility that ADHD, dyslexia, dyspraxia and autism fall within a phospholipid spectrum of disorders. This proposal could explain the high degree of co-morbidity between these conditions, their aggregation within families and relation to other psychiatric disorders, and a range of associated features that are already well known at a clinical level. The existing evidence for fatty acid abnormalities in these disorders is summarized, and new approaches are outlined that have the potential to improve both the identification and the management of these and related neurodevelopmental and psychiatric conditions.

  3. Perspectives for induced pluripotent stem cell technology: new insights into human physiology involved in somatic mosaicism.

    Science.gov (United States)

    Nagata, Naoki; Yamanaka, Shinya

    2014-01-31

    Induced pluripotent stem cell technology makes in vitro reprogramming of somatic cells from individuals with various genetic backgrounds possible. By applying this technology, it is possible to produce pluripotent stem cells from biopsy samples of arbitrarily selected individuals with various genetic backgrounds and to subsequently maintain, expand, and stock these cells. From these induced pluripotent stem cells, target cells and tissues can be generated after certain differentiation processes. These target cells/tissues are expected to be useful in regenerative medicine, disease modeling, drug screening, toxicology testing, and proof-of-concept studies in drug development. Therefore, the number of publications concerning induced pluripotent stem cells has recently been increasing rapidly, demonstrating that this technology has begun to infiltrate many aspects of stem cell biology and medical applications. In this review, we discuss the perspectives of induced pluripotent stem cell technology for modeling human diseases. In particular, we focus on the cloning event occurring through the reprogramming process and its ability to let us analyze the development of complex disease-harboring somatic mosaicism.

  4. Red blood cell transfusion in preterm neonates: current perspectives

    Directory of Open Access Journals (Sweden)

    Chirico G

    2014-06-01

    Full Text Available Gaetano ChiricoNeonatology and Neonatal Intensive Care Unit, Children Hospital, Spedali Civili, Brescia, ItalyAbstract: Preterm neonates, especially very low birth weight infants, remain a category of patients with high transfusion needs; about 90% of those with <1,000 g birth weight may be transfused several times during their hospital stay. However, neonatal red blood cells (RBC transfusion is not without risks. In addition to well-known adverse events, several severe side effects have been observed unique to preterm infants, such as transfusion-related acute gut injury, intraventricular hemorrhage, and increased mortality risk. It is therefore important to reduce the frequency of RBC transfusion in critically ill neonates, by delayed clamping or milking the umbilical cord, using residual cord blood for initial laboratory investigations, reducing phlebotomy losses, determining transfusion guidelines, and ensuring the most appropriate nutrition, with the optimal supplementation of iron, folic acid, and vitamins. Ideally, RBC transfusion should be tailored to the individual requirements of the single infant. However, many controversies still remain, and the decision on whether to transfuse or not is often made on an empirical basis. Recently, a few clinical trials have been performed with the aim to compare the risk/benefit ratio of restrictive versus liberal transfusion criteria. No significant differences in short-term outcomes were observed, suggesting that the restrictive criteria may reduce the need for transfusion and the related side effects. Neurodevelopmental long-term outcome seemed more favorable in the liberal group at first evaluation, especially for boys, and significantly better in the restrictive group at a later clinical investigation. Magnetic resonance imaging scans, performed at an average age of 12 years, showed that intracranial volume was substantially smaller in the liberal group compared with controls. When sex effects

  5. Diagnosis and epidemiology of red blood cell enzyme disorders

    Directory of Open Access Journals (Sweden)

    Richard Van Wijk

    2013-03-01

    Full Text Available The red blood cell possess an active metabolic machinery that provides the cell with energy to pump ions against electrochemical gradients, to maintain its shape, to keep hemoglobin iron in the reduced (ferrous form, and to maintain enzyme and hemoglobin sulfhydryl groups. The main source of metabolic energy comes from glucose. Glucose is metabolized through the glycolytic pathway and through the hexose monophosphate shunt. Glycolysis catabolizes glucose to pyruvate and lactate, which represent the end products of glucose metabolism in the erythrocyte. Adenosine diphosphate (ADP is phosphorylated to adenosine triphosphate (ATP, and nicotinamide adenine dinucleotide (NAD+ is reduced to NADH in glycolysis. 2,3- Bisphosphoglycerate, an important regulator of the oxygen affinity of hemoglobin, is generated during glycolysis by the Rapoport-Luebering shunt. The hexose monophosphate shunt oxidizes glucose-6-phosphate, reducing NADP+ to reduced nicotinamide adenine dinucleotide phosphate (NADPH. The red cell lacks the capacity for de novo purine synthesis but has a salvage pathway that permits synthesis of purine nucleotides from purine bases...

  6. Perspectives on the metallic interconnects for solid oxide fuel cells

    Institute of Scientific and Technical Information of China (English)

    ZHU Wei-zhong; YAN Mi

    2004-01-01

    The various stages and progress in the development of interconnect materials for solid oxide fuel cells (SOFCs) over the last two decades are reviewed. The criteria for the application of materials as interconnects are highlighted. Interconnects based on lanthanum chromite ceramics demonstrate many inherent drawbacks and therefore are only useful for SOFCs operating around 1000 ℃. The advance in the research of anode-supported flat SOFCs facilitates the replacement of ceramic interconnects with metallic ones due to their significantly lowered working temperature. Besides, interconnects made of metals or alloys offer many advantages as compared to their ceramic counterpart. The oxidation response and thermal expansion behaviors of various prospective metallic interconnects are examined and evaluated. The minimization of contact resistance to achieve desired and reliable stack performance during their projected lifetime still remains a highly challenging issue with metallic interconnects. Inexpensive coating materials and techniques may play a key role in pro moting the commercialization of SOFC stack whose interconnects are constructed of some current commercially available alloys. Alternatively, development of new metallic materials that are capable of forming stable oxide scales with sluggish growth rate and sufficient electrical conductivity is called for.

  7. How cells sense extracellular matrix stiffness: a material’s perspective

    Science.gov (United States)

    Trappmann, Britta; Chen, Christopher S.

    2014-01-01

    The mechanical properties of the extracellular matrix (ECM) in which cells reside have emerged as an important regulator of cell fate. While materials based on natural ECM have been used to implicate the role of substrate stiffness for cell fate decisions, it is difficult in these matrices to isolate mechanics from other structural parameters. In contrast, fully synthetic hydrogels offer independent control over physical and adhesive properties. New synthetic materials that also recreate the fibrous structural hierarchy of natural matrices are now being designed to study substrate mechanics in more complex ECMs. This perspective examines the ways in which new materials are being used to advance our understanding of how extracellular matrix stiffness impacts cell function. PMID:23611564

  8. Stem cells in human neurodegenerative disorders--time for clinical translation?

    Science.gov (United States)

    Lindvall, Olle; Kokaia, Zaal

    2010-01-01

    Stem cell-based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment.

  9. Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer.

    Science.gov (United States)

    Da Costa, Lydie; Suner, Ludovic; Galimand, Julie; Bonnel, Amandine; Pascreau, Tiffany; Couque, Nathalie; Fenneteau, Odile; Mohandas, Narla

    2016-01-01

    Inherited red blood cell (RBC) membrane disorders, such as hereditary spherocytosis, elliptocytosis and hereditary ovalocytosis, result from mutations in genes encoding various RBC membrane and skeletal proteins. The RBC membrane, a composite structure composed of a lipid bilayer linked to a spectrin/actin-based membrane skeleton, confers upon the RBC unique features of deformability and mechanical stability. The disease severity is primarily dependent on the extent of membrane surface area loss. RBC membrane disorders can be readily diagnosed by various laboratory approaches that include RBC cytology, flow cytometry, ektacytometry, electrophoresis of RBC membrane proteins and genetics. The reference technique for diagnosis of RBC membrane disorders is the osmotic gradient ektacytometry. However, in spite of its recognition as the reference technique, this technique is rarely used as a routine diagnosis tool for RBC membrane disorders due to its limited availability. This may soon change as a new generation of ektacytometer has been recently engineered. In this review, we describe the workflow of the samples shipped to our Hematology laboratory for RBC membrane disorder analysis and the data obtained for a large cohort of French patients presenting with RBC membrane disorders using a newly available version of the ektacytomer.

  10. [Microchips based on three dimensional gel cells: history and perspective].

    Science.gov (United States)

    Kolchinskiĭ, A M; Griadunov, D A; Lysov, Iu P; Mikhaĭlovich, V M; Nasedkina, T V; Turygin, A Iu; Rubina, A Iu; Barskiĭ, V E; Zasedatelev, A S

    2004-01-01

    The review describes the history of creation and development of the microchip technology and its role in the human genome project in Russia. The emphasis is placed on the three-dimensional gel-based microchips developed at the Center of Biological Microchips headed by A.D. Mirzabekov since 1988. The gel-based chips of the last generation, IMAGE chips (Immobilized Micro Array of Gel Elements), have a number of advantages over the previous versions. The microchips are manufactured by photo-initiated copolymerization of gel components and immobilized molecules (DNA, proteins, and ligands). This ensures an even distribution of the immobilized probe throughout the microchip gel element with a high yield (about 50% for oligonucleotides). The use of methacrylamide as a main component of the polymerization mixture resulted in a substantial increase of gel porosity without affecting its mechanical strength and stability, which allowed one to work with the DNA fragments of up to 500 nt in length, as well as with rather large protein molecules. At present, the gel-based microchips are widely applied to address different problems. The generic microchips containing a complete set of possible hexanucleotides are used to reveal the DNA motifs binding with different proteins and to study the DNA-protein interactions. The oligonucleotide microchips are a cheap and reliable tool of diagnostics designed for mass application. Biochips have been developed for identification of the tuberculosis pathogen and its antibiotic-resistant forms; for diagnostics of orthopoxviruses, including the smallpox virus; for diagnostics of the anthrax pathogen; and for identification of chromosomal rearrangements in leukemia patients. The protein microchips can be adapted for further use in proteomics. Bacterial and yeast cells were also immobilized in the gel, maintaining their viability, which open a wide potential for creation biosensors on the basis of microchips.

  11. Nicotinic receptors and functional regulation of GABA cell microcircuitry in bipolar disorder and schizophrenia.

    Science.gov (United States)

    Benes, Francine M

    2012-01-01

    Studies of the hippocampus in postmortem brains from patients with schizophrenia and bipolar disorder have provided evidence for a defect of GABAergic interneurons. Significant decreases in the expression of GAD67, a marker for GABA cell function, have been found repeatedly in several different brain regions that include the hippocampus. In this region, nicotinic receptors are thought to play an important role in modulating the activity of GABAergic interneurons by influences of excitatory cholinergic afferents on their activity. In bipolar disorder, this influence appears to be particularly prominent in the stratum oriens of sectors CA3/2 and CA1, two sites where these cells constitute the exclusive neuronal cell type. In sector CA3/2, this layer receives a robust excitatory projection from the basolateral amygdala (BLA) and this is thought to play a central role in regulating GABA cells at this locus. Using laser microdissection, recent studies have focused selectively on these two layers and their associated GABA cells using microarray technology. The results have provided support for the idea that nicotinic cholinergic receptors play a particularly important role in regulating the activity of GABA neurons at these loci by regulating the progression of cell cycle and the repair of damaged DNA. In bipolar disorder, there is a prominent reduction in the expression of mRNAs for several different nicotinic subunit isoforms. These decreases could reflect a diminished influence of this receptor system on these GABA cells, particularly in sector CA3/2 where a preponderance of abnormalities have been observed in postmortem studies. In patients with bipolar disorder, excitatory nicotinic cholinergic fibers from the medial septum may converge with glutamatergic fibers from the BLA on GABAergic interneurons in the stratum oriens of CA3/2 and result in disturbances of their genomic and functional integrity, ones that may induce disruptions of the integration of

  12. Perspectives on stem cell-based elastic matrix regenerative therapies for abdominal aortic aneurysms.

    Science.gov (United States)

    Bashur, Chris A; Rao, Raj R; Ramamurthi, Anand

    2013-06-01

    Abdominal aortic aneurysms (AAAs) are potentially fatal conditions that are characterized by decreased flexibility of the aortic wall due to proteolytic loss of the structural matrix. This leads to their gradual weakening and ultimate rupture. Drug-based inhibition of proteolytic enzymes may provide a nonsurgical treatment alternative for growing AAAs, although it might at best be sufficient to slow their growth. Regenerative repair of disrupted elastic matrix is required if regression of AAAs to a healthy state is to be achieved. Terminally differentiated adult and diseased vascular cells are poorly capable of affecting such regenerative repair. In this context, stem cells and their smooth muscle cell-like derivatives may represent alternate cell sources for regenerative AAA cell therapies. This article examines the pros and cons of using different autologous stem cell sources for AAA therapy, the requirements they must fulfill to provide therapeutic benefit, and the current progress toward characterizing the cells' ability to synthesize elastin, assemble elastic matrix structures, and influence the regenerative potential of diseased vascular cell types. The article also provides a detailed perspective on the limitations, uncertainties, and challenges that will need to be overcome or circumvented to translate current strategies for stem cell use into clinically viable AAA therapies. These therapies will provide a much needed nonsurgical treatment option for the rapidly growing, high-risk, and vulnerable elderly demographic.

  13. Plasmoacanthoma of oral cavity and plasma cell cheilitis: two sides of same disorder “oral plasma cell mucositis” ?

    Directory of Open Access Journals (Sweden)

    Gayatri Khatri

    2014-04-01

    Full Text Available Plasmoacanthoma and plasma cell cheilitis are rare disorders of obscure etiology characterized by a plasma cell infiltrate an 80-year-old woman presented with a verrucous, fleshy, skin colored plaque over lips, gingiva, and the palate and painful swallowing for over a period of 6 months. Histopathology of the lesion showed dense infiltrate of plasma cells. The lesions resolved completely after intralesional triamcinolone acetonide. Another 52-year-old male had progressively enlarging, erosive lesion over vermilion border of lower lip for 6months resembling actinic cheilitis. Histology was diagnostic of plasma cell cheilitis. Treatment with topical clobetasol propionate was effective. Plasma cell cheilitis and plasmoacanthoma perhaps represent a spectrum of oral ”plasma cell mucositis” with plasmoacanthoma being an advanced version of the former.

  14. A bidirectional relationship between depression and the autoimmune disorders – New perspectives from the National Child Development Study

    Science.gov (United States)

    Danese, Andrea; Lewis, Cathryn M.; Maughan, Barbara

    2017-01-01

    Background Depression and the autoimmune disorders are comorbid—the two classes of disorders overlap in the same individuals at a higher frequency than chance. The immune system may influence the pathological processes underlying depression; understanding the origins of this comorbidity may contribute to dissecting the mechanisms underlying these disorders. Method We used population cohort data from the 1958 British birth cohort study (the National Child Development Study) to investigate the ages at onset of depression and 23 autoimmune disorders. We used self-report data to ascertain life-time history of depression, autoimmune disorders and their ages at onset. We modelled the effect of depression onset on subsequent autoimmune disorder onset, and vice versa, and incorporated polygenic risk scores for depression and autoimmune disorder risk. Results In our analytic sample of 8174 individuals, 315 reported ever being diagnosed with an autoimmune disorder (3.9%), 1499 reported ever experiencing depression (18.3%). There was significant comorbidity between depression and the autoimmune disorders (OR = 1.66, 95% CI = 1.27–2.15). Autoimmune disorder onset associated with increased subsequent hazard of depression onset (HR = 1.39, 95% CI = 1.11–1.74, P = 0.0037), independently of depression genetic risk. Finally, depression increased subsequent hazard of autoimmune disorder onset (HR = 1.40, 95% CI = 1.09–1.80, P = 0.0095), independently of autoimmune disorder genetic risk. Discussion Our results point to a bidirectional relationship between depression and the autoimmune disorders. This suggests that shared risk factors may contribute to this relationship, including both common environmental exposures that increase baseline inflammation levels, and shared genetic factors. PMID:28264010

  15. Perspectives on research and development of microbial fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ortega-Martinez, A.; Vazquez Larios, A.L.; Solorza-Feria, O.; Poggi Varaldo, H.M. [Centro de Investigacion y de Estudios Avanzados del IPN, Mexico D.F. (Mexico)]. E-mail: hectorpoggi2001@gmail.com; rareli@hotmail.com

    2009-09-15

    Microbial fuel cells (MFC), is an anoxic electrochemical bioreactor where bacteria grow in the absence of oxygen in a chamber containing an anode which it may be covered by a biofilm. Microorganisms anoxically oxidize the organic substrate and electrons generated are released to the anode. Released protons are transferred to the cathode. Natural or forced aeration of the cathode supplies the oxygen for the final reaction 2H{sup +} + 2e{sup -} + (1/2) O{sub 2} = H{sub 2}O. In this work, we present a critical review on MFC focused on subjects that are receiving a growing interest from the research and technological communities: (i) types of MFC, their relative advantages and disadvantages and ranges of application; (ii) development of biocathodes; (iii) enrichment procedures of microbial communities in MFC. Recent research shows that one-chamber fitted with cathode aerated by natural aeration, and other special types of high performance MFC, have displaced the historical two-chamber MFC. Recent studies showed that electrochemically active bacteria (EAB) can be successfully enriched in MFC. The cost and eventual poisoning of the platinum catalyst used at the cathode is a major limitation to MFC application and economic viability. Researchers have started working on the concept of biocathodes that would use bacteria instead of platinum as a biocatalyst. Microbial enrichment of inocula seeded to MFC may provide a way to enrich the consortium with EAB, thus substantially increasing the transfer of electrons to the anode. Bioaugmentation of consortia in MFC with strains EAB, could contribute to the same goal. [Spanish] Las celdas de combustible microbianas (CCM) son un biorrector anoxico donde las bacterias crecen en ausencia de oxigeno en una camara que contiene un anodo que puede cubrirse con una biopelicula. Los microorganismos oxidan onoxicamente el sustrato organico y los electrones generados se liberan al anodo. Los protones liberados se transfieren al catodo. La

  16. Giant cell interstitial pneumonia: unusual lung disorder and an update

    Institute of Scientific and Technical Information of China (English)

    Dai Jinghong; Huang Mei; Cao Min; Miao Liyun; Xiao Yonglong; Shi Yi; Meng Fanqing

    2014-01-01

    Background Giant cell interstitial pneumonia (GIP) was a rare form of pneumoconiosis,associated with exposure to hard metals,which had been reported mostly as isolated case reports.We described eight cases of GIP diagnosed in our hospital during the past seven years,with particular reference to new findings.Methods Eight patients with GIP confirmed by biopsy in the Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University from 2005 to 2011 were retrospectively analyzed.For each patient,the occupy histories and medical records were thoroughly reviewed and clinic data were extracted.Two radiologists,without knowledge of any of the clinical and functional findings,independently reviewed the HRCT scans of all patients.Follow-up data were collected.Results Among the eight patients,seven had a history of exposure to hard metal dusts,one denied an exposure history.The most common manifestations were cough and dyspnea.One patient initiated with pneumothorax and another pleural effusion,both of which were uncommon to GIP.The main pathologic appearances were the presence of macrophages and multinucleated giant cells in the alveolar space.The clinical symptoms and radiographic abnormalities were obviously improved after cessation of exposure and receiving corticosteroid treatments,recurrences were observed in two patients when they resumed work.In spite of exposure cessation and corticosteroid treatment,one patient developed pulmonary fibrosis at seven years follow-up.Conclusions Awareness of the patients' occupational history often provided clues to the diagnosis of GIP.Histopathologic examinations were necessary to establish the right diagnosis.Exposure cessation was of benefit to most patients; however,pulmonary fibrosis was possible in spite of exposure cessation and corticosteroid treatment.Better ways should be found out to improve the outcome and quality of life.

  17. Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

    Directory of Open Access Journals (Sweden)

    Hohlfeld Reinhard

    2011-10-01

    Full Text Available Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS and neuromyelitis optica (NMO generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg and cytokine production of CD11b+ antigen presenting cells (APC were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM. Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and

  18. Nanoscale bio-platforms for living cell interrogation: current status and future perspectives

    Science.gov (United States)

    Chang, Lingqian; Hu, Jiaming; Chen, Feng; Chen, Zhou; Shi, Junfeng; Yang, Zhaogang; Li, Yiwen; Lee, Ly James

    2016-02-01

    The living cell is a complex entity that dynamically responds to both intracellular and extracellular environments. Extensive efforts have been devoted to the understanding intracellular functions orchestrated with mRNAs and proteins in investigation of the fate of a single-cell, including proliferation, apoptosis, motility, differentiation and mutations. The rapid development of modern cellular analysis techniques (e.g. PCR, western blotting, immunochemistry, etc.) offers new opportunities in quantitative analysis of RNA/protein expression up to a single cell level. The recent entries of nanoscale platforms that include kinds of methodologies with high spatial and temporal resolution have been widely employed to probe the living cells. In this tutorial review paper, we give insight into background introduction and technical innovation of currently reported nanoscale platforms for living cell interrogation. These highlighted technologies are documented in details within four categories, including nano-biosensors for label-free detection of living cells, nanodevices for living cell probing by intracellular marker delivery, high-throughput platforms towards clinical current, and the progress of microscopic imaging platforms for cell/tissue tracking in vitro and in vivo. Perspectives for system improvement were also discussed to solve the limitations remains in current techniques, for the purpose of clinical use in future.

  19. Nanoscale bio-platforms for living cell interrogation: current status and future perspectives.

    Science.gov (United States)

    Chang, Lingqian; Hu, Jiaming; Chen, Feng; Chen, Zhou; Shi, Junfeng; Yang, Zhaogang; Li, Yiwen; Lee, Ly James

    2016-02-14

    The living cell is a complex entity that dynamically responds to both intracellular and extracellular environments. Extensive efforts have been devoted to the understanding intracellular functions orchestrated with mRNAs and proteins in investigation of the fate of a single-cell, including proliferation, apoptosis, motility, differentiation and mutations. The rapid development of modern cellular analysis techniques (e.g. PCR, western blotting, immunochemistry, etc.) offers new opportunities in quantitative analysis of RNA/protein expression up to a single cell level. The recent entries of nanoscale platforms that include kinds of methodologies with high spatial and temporal resolution have been widely employed to probe the living cells. In this tutorial review paper, we give insight into background introduction and technical innovation of currently reported nanoscale platforms for living cell interrogation. These highlighted technologies are documented in details within four categories, including nano-biosensors for label-free detection of living cells, nanodevices for living cell probing by intracellular marker delivery, high-throughput platforms towards clinical current, and the progress of microscopic imaging platforms for cell/tissue tracking in vitro and in vivo. Perspectives for system improvement were also discussed to solve the limitations remains in current techniques, for the purpose of clinical use in future.

  20. Borderline Personality Disorder and Narcissistic Personality Disorder Diagnoses From the Perspective of the DSM-5 Personality Traits: A Study on Italian Clinical Participants.

    Science.gov (United States)

    Fossati, Andrea; Somma, Antonella; Borroni, Serena; Maffei, Cesare; Markon, Kristian E; Krueger, Robert F

    2016-12-01

    To evaluate the associations between Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Alternative Model of Personality Disorder traits and domains and categorically diagnosed narcissistic personality disorder (NPD) and borderline personality disorder (BPD), respectively, 238 inpatient and outpatient participants who were consecutively admitted to the Clinical Psychology and Psychotherapy Unit of San Raffaele Hospital in Milan, Italy, were administered the Personality Inventory for DSM-5 (PID-5) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Based on SCID-II, the participants were assigned to the following groups: a) NPD (n = 49), b) BPD (n = 32), c) any other PD (n = 91), and d) no PD (n = 63). Emotional lability, separation insecurity, depressivity, impulsivity, risk taking, and hostility were significantly associated with BPD diagnosis. Attention seeking significantly discriminated participants who received an SCID-II categorical NPD diagnosis. Separation insecurity, impulsivity, distractibility, and perceptual dysregulation were the DSM-5 traits that significantly discriminated BPD participants. Domain-level analyses confirmed and extended trait-level findings.

  1. Potential primary roles of glial cells in the mechanisms of psychiatric disorders.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Kimoto, Sohei; Rosen, Kenneth M; Kishimoto, Toshifumi; Makinodan, Manabu

    2015-01-01

    While neurons have long been considered the major player in multiple brain functions such as perception, emotion, and memory, glial cells have been relegated to a far lesser position, acting as merely a "glue" to support neurons. Multiple lines of recent evidence, however, have revealed that glial cells such as oligodendrocytes, astrocytes, and microglia, substantially impact on neuronal function and activities and are significantly involved in the underlying pathobiology of psychiatric disorders. Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g., through neurotransmitters, neurotrophic factors, and cytokines) and physically (e.g., through gap junctions), supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia.

  2. Intermediate-filaments: from disordered building blocks to well-ordered cells

    Science.gov (United States)

    Kornreich, Micha; Malka-Gibor, Eti; Laser-Azogui, Adi; Doron, Ofer; Avinery, Ram; Herrmann, Harald; Beck, Roy

    In the past decade it was found that ~50% of human proteins contain long disordered regions, which play significant functional roles. As these regions lack a defined 3D folded structure, their ensemble conformations can be studied using polymer physics statistical-mechanics arguments. We measure the structure and mechanical response of hydrogels composed of neuronal intermediate filaments proteins. In the nervous system, these proteins provide cells with their mechanical support and shape, via interactions of their long, highly charged and disordered protein chains. We employ synchrotron small-angle X-ray scattering and various microscopy techniques to investigate such hydrogels from the nano- to the macro-scale. In contrast to previous polymer physics theories and experiments, we find that shorter and less charged chains can promote network expansion. The results are explained by intricate interactions between specific domains on the interacting chains, and also suggest a novel structural justification for the changing protein compositions observed during neuronal development. We address the following questions: Can protein disorder have an important role in cellular architecture? Can structural disorder in the micro-scale induce orientational and translational order on the macro-scale? How do the physical properties of disordered protein regions, such as charge, length, and hydrophobicity, modulate the cellular super-structure?

  3. ESCRT-III mediated cell division in Sulfolobus acidocaldarius - a reconstitution perspective.

    Science.gov (United States)

    Härtel, Tobias; Schwille, Petra

    2014-01-01

    In the framework of synthetic biology, it has become an intriguing question what would be the minimal representation of cell division machinery. Thus, it seems appropriate to compare how cell division is realized in different microorganisms. In particular, the cell division system of Crenarchaeota lacks certain proteins found in most bacteria and Euryarchaeota, such as FtsZ, MreB or the Min system. The Sulfolobaceae family encodes functional homologs of the eukaryotic proteins vacuolar protein sorting 4 (Vps4) and endosomal sorting complex required for transport-III (ESCRT-III). ESCRT-III is essential for several eukaryotic pathways, e.g., budding of intraluminal vesicles, or cytokinesis, whereas Vps4 dissociates the ESCRT-III complex from the membrane. Cell Division A (CdvA) is required for the recruitment of crenarchaeal ESCRT-III proteins to the membrane at mid-cell. The proteins polymerize and form a smaller structure during constriction. Thus, ESCRT-III mediated cell division in Sulfolobus acidocaldarius shows functional analogies to the Z ring observed in prokaryotes like Escherichia coli, which has recently begun to be reconstituted in vitro. In this short perspective, we discuss the possibility of building such an in vitro cell division system on basis of archaeal ESCRT-III.

  4. ESCRT-III mediated cell division in Sulfolobus acidocaldarius –A reconstitution perspective

    Directory of Open Access Journals (Sweden)

    Tobias eHärtel

    2014-06-01

    Full Text Available In the framework of Synthetic Biology, it has become an intriguing question what would be the minimal representation of cell division machinery. Thus, it seems appropriate to compare how cell division is realized in different microorganisms. In particular, the cell division system of Crenarchaeota lacks certain proteins found in most bacteria and Euryarchaeota, such as FtsZ, MreB or the Min system. The Sulfolobaceae family encodes functional homologs of the eukaryotic proteins Vps4 and ESCRT-III. ESCRT-III is essential for several eukaryotic pathways, e.g. budding of intralumenal vesicles (ILVs, or cytokinesis, whereas Vps4 dissociates the ESCRT-III complex from the membrane. CdvA (Cell Division A is required for the recruitment of crenarchaeal ESCRT-III proteins to the membrane at mid-cell. The proteins polymerize and form a smaller structure during constriction. Thus, ESCRT-III mediated cell division in S. acidocaldarius shows functional analogies to the Z ring observed in prokaryotes like E. coli, which has recently begun to be reconstituted in vitro. In this short perspective, we discuss the possibility of building such an in vitro cell division system on basis of archaeal ESCRT-III.

  5. Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics.

    Science.gov (United States)

    Kim, Mi-Gyeong; Kim, Dongyoon; Suh, Soo-Kyung; Park, Zewon; Choi, Min Joung; Oh, Yu-Kyoung

    2016-04-01

    Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody-drug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR-T therapy.

  6. Special issue for stem cells: a multi-perspective look at stem cells

    Institute of Scientific and Technical Information of China (English)

    Qi ZHOU

    2010-01-01

    The past few years may have been a golden time in the history of stem cell research. The unique properties stem cells possess, to proliferate indefinitely and to differentiate into multiple kinds of cells, make these cells wonderful platforms for studying organism development and valuable sources for regenerative medicine.

  7. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    Science.gov (United States)

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

  8. Effects of disorder in location and size of fence barriers on molecular motion in cell membranes

    CERN Document Server

    Kalay, Z; Kenkre, V M

    2008-01-01

    The effect of disorder in the energetic heights and in the physical locations of fence barriers encountered by transmembrane molecules such as proteins and lipids in their motion in cell membranes is studied theoretically. The investigation takes as its starting point a recent analysis of a periodic system with constant distances between barriers and constant values of barrier heights, and employs effective medium theory to treat the disorder. The calculations make possible, in principle, the extraction of confinement parameters such as mean compartment sizes and mean intercompartmental transition rates from experimentally reported published observations. The analysis should be helpful both as an unusual application of effective medium theory and as an investigation of observed molecular movements in cell membranes.

  9. The immunophenotypic characteristics of 260 patients with CD5~+ B cell lymphoproliferative disorders

    Institute of Scientific and Technical Information of China (English)

    易树华

    2014-01-01

    Objective To explore the immunophenotypic characteristics of CD5+B cell lymphoproliferative disorders(BLPD)of Chinese patients.Methods Immunophenotyping of bone marrow and(or)of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodes,and the patients clinical data were retrospectively analyzed.The difference in immunophenotypes and

  10. Human embryonic stem cell cultivation: historical perspective and evolution of xeno-free culture systems.

    Science.gov (United States)

    Desai, Nina; Rambhia, Pooja; Gishto, Arsela

    2015-02-22

    Human embryonic stem cells (hESC) have emerged as attractive candidates for cell-based therapies that are capable of restoring lost cell and tissue function. These unique cells are able to self-renew indefinitely and have the capacity to differentiate in to all three germ layers (ectoderm, endoderm and mesoderm). Harnessing the power of these pluripotent stem cells could potentially offer new therapeutic treatment options for a variety of medical conditions. Since the initial derivation of hESC lines in 1998, tremendous headway has been made in better understanding stem cell biology and culture requirements for maintenance of pluripotency. The approval of the first clinical trials of hESC cells for treatment of spinal cord injury and macular degeneration in 2010 marked the beginning of a new era in regenerative medicine. Yet it was clearly recognized that the clinical utility of hESC transplantation was still limited by several challenges. One of the most immediate issues has been the exposure of stem cells to animal pathogens, during hESC derivation and during in vitro propagation. Initial culture protocols used co-culture with inactivated mouse fibroblast feeder (MEF) or human feeder layers with fetal bovine serum or alternatively serum replacement proteins to support stem cell proliferation. Most hESC lines currently in use have been exposed to animal products, thus carrying the risk of xeno-transmitted infections and immune reaction. This mini review provides a historic perspective on human embryonic stem cell culture and the evolution of new culture models. We highlight the challenges and advances being made towards the development of xeno-free culture systems suitable for therapeutic applications.

  11. The split personality of NKT cells in malignancy, autoimmune and allergic disorders.

    Science.gov (United States)

    Subleski, Jeff J; Jiang, Qun; Weiss, Jonathan M; Wiltrout, Robert H

    2011-10-01

    NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy.

  12. Genome engineering of isogenic human ES cells to model autism disorders.

    Science.gov (United States)

    Martinez, Refugio A; Stein, Jason L; Krostag, Anne-Rachel F; Nelson, Angelique M; Marken, John S; Menon, Vilas; May, Ryan C; Yao, Zizhen; Kaykas, Ajamete; Geschwind, Daniel H; Grimley, Joshua S

    2015-05-26

    Isogenic pluripotent stem cells are critical tools for studying human neurological diseases by allowing one to study the effects of a mutation in a fixed genetic background. Of particular interest are the spectrum of autism disorders, some of which are monogenic such as Timothy syndrome (TS); others are multigenic such as the microdeletion and microduplication syndromes of the 16p11.2 chromosomal locus. Here, we report engineered human embryonic stem cell (hESC) lines for modeling these two disorders using locus-specific endonucleases to increase the efficiency of homology-directed repair (HDR). We developed a system to: (1) computationally identify unique transcription activator-like effector nuclease (TALEN) binding sites in the genome using a new software program, TALENSeek, (2) assemble the TALEN genes by combining golden gate cloning with modified constructs from the FLASH protocol, and (3) test the TALEN pairs in an amplification-based HDR assay that is more sensitive than the typical non-homologous end joining assay. We applied these methods to identify, construct, and test TALENs that were used with HDR donors in hESCs to generate an isogenic TS cell line in a scarless manner and to model the 16p11.2 copy number disorder without modifying genomic loci with high sequence similarity.

  13. A unifying perspective on personality pathology across the life span: developmental considerations for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders.

    Science.gov (United States)

    Tackett, Jennifer L; Balsis, Steve; Oltmanns, Thomas F; Krueger, Robert F

    2009-01-01

    Proposed changes in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) include replacing current personality disorder (PD) categories on Axis II with a taxonomy of dimensional maladaptive personality traits. Most of the work on dimensional models of personality pathology, and on personality disorders per se, has been conducted on young and middle-aged adult populations. Numerous questions remain regarding the applicability and limitations of applying various PD models to early and later life. In the present paper, we provide an overview of such dimensional models and review current proposals for conceptualizing PDs in DSM-V. Next, we extensively review existing evidence on the development, measurement, and manifestation of personality pathology in early and later life focusing on those issues deemed most relevant for informing DSM-V. Finally, we present overall conclusions regarding the need to incorporate developmental issues in conceptualizing PDs in DSM-V and highlight the advantages of a dimensional model in unifying PD perspectives across the life span.

  14. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality.

    Science.gov (United States)

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W; Böttcher, Sebastian; van Dongen, Jacques J M; Orfao, Alberto; Almeida, Julia

    2015-12-15

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.

  15. Liver cell transplantation for Crigler-Najjar syndrome type I: Update a and perspectives

    Institute of Scientific and Technical Information of China (English)

    Philippe A Lysy; Mustapha Najimi; Xavier Stephenne; Annick Bourgois; Francoise Smets; Etienne M Sokal

    2008-01-01

    Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. CriglerNajjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.

  16. [The application of stem cells for research and treatment of neurological disorders].

    Science.gov (United States)

    Sveinsson, Olafur A; Gudjonsson, Thorarinn; Petersen, Petur Henry

    2008-02-01

    It has long been a common view that neurons in the human central nervous system were not capable of self renewal. But in the mid-1990s scientists discovered that certain areas of the human brain do have the ability generate new neurons, at least under certain circumstances. It was subsecuently confirmed that the human central nervous system contains stem cells similar to the cells which originally give rise to the central nervous sysem during fetal development. The possible use of stem cells in the treatment of various neurological disorders, holds great promise. However, much research needs to be carried out before stem cell therapy can be moved from the bench to the bedside. Now researchers are pursuing two fundamental strategies to exploit the possible application of stem cells. One is to cultivate stem cells in vitro and to design the right differentiation profile of cells suitable for implantation. The other strategy relies on studying endogenous signals that could stimulate the patient s own stem cells and repair mechanisms. Here we give an overview of neural stem cells and their possible future use in the treatment of neural diseases such as Parkinson s disease, motor neuron disease and spinal cord injury.

  17. Being a case manager for persons with borderline personality disorder: perspectives of community mental health center clinicians.

    Science.gov (United States)

    Nehls, N

    2000-02-01

    The scope of case management has expanded to include persons with chronic, nonpsychotic disorders, in particular, persons diagnosed with borderline personality disorder. Despite more widespread use, literature about case management for persons with this disorder is limited. To address this gap in knowledge, a study of the day-to-day experiences of case managers who care for persons with borderline personality disorder was conducted. Seventeen community mental health center case managers gave their informed consent to participate in individual, in-depth interviews. The interviews were analyzed using an interpretive phenomenological research approach. The analysis showed a pattern of monitoring self-involvement. The case managers monitored themselves in terms of expressing concern and setting boundaries. These shared practices highlight a central and unique component of being a case manager for persons with borderline personality disorder, that is, the case manager's focus of attention is on self. By focusing on the self, case managers seek to retain control of the nature of the relationship. The author asserts that the matter to be resolved is not to determine whether retaining or relinquishing control is better, but rather, how best to help practitioners maintain a helpful relationship over time with persons who have borderline personality disorder. In an effort to accomplish this goal, questions about current helping practices and suggestions for working collaboratively with persons who have this diagnosis are provided.

  18. Teaching a changing paradigm in physiology: a historical perspective on gut interstitial cells.

    Science.gov (United States)

    Drumm, Bernard T; Baker, Salah A

    2017-03-01

    The study and teaching of gastrointestinal (GI) physiology necessitates an understanding of the cellular basis of contractile and electrical coupling behaviors in the muscle layers that comprise the gut wall. Our knowledge of the cellular origin of GI motility has drastically changed over the last 100 yr. While the pacing and coordination of GI contraction was once thought to be solely attributable to smooth muscle cells, it is now widely accepted that the motility patterns observed in the GI tract exist as a result of a multicellular system, consisting of not only smooth muscle cells but also enteric neurons and distinct populations of specialized interstitial cells that all work in concert to ensure proper GI functions. In this historical perspective, we focus on the emerging role of interstitial cells in GI motility and examine the key discoveries and experiments that led to a major shift in a paradigm of GI physiology regarding the role of interstitial cells in modulating GI contractile patterns. A review of these now classic experiments and papers will enable students and educators to fully appreciate the complex, multicellular nature of GI muscles as well as impart lessons on how shifting paradigms in physiology are fueled by new technologies that lead to new emerging discoveries.

  19. Reasons for rarity of Th17 cells in inflammatory sites of human disorders.

    Science.gov (United States)

    Annunziato, Francesco; Santarlasci, Veronica; Maggi, Laura; Cosmi, Lorenzo; Liotta, Francesco; Romagnani, Sergio

    2013-11-15

    T helper 17 (Th17) cells have been reported to be responsible for several chronic inflammatory diseases. However, a peculiar feature of human Th17 cells is that they are very rare in the inflammatory sites in comparison with Th1 cells. The first reason for this rarity is the existence of some self-regulatory mechanisms that limit their expansion. The limited expansion of human Th17 cells is related to the retinoic acid orphan (ROR)C-dependent up-regulation of the interleukin (IL)-4 induced gene 1 (IL4I1), which encodes for a l-phenylalanine oxidase, that has been shown to down-regulate CD3ζ expression in T cells. This results in abnormalities of the molecular pathway which is responsible for the impairment of IL-2 production and therefore for the lack of cell proliferation in response to T-cell receptor (TCR) signalling. IL4I1 up-regulation also associates with the increased expression of Tob1, a member of the Tob/BTG anti-proliferative protein family, which is involved in cell cycle arrest. A second reason for the rarity of human Th17 cells in the inflammatory sites is their rapid shifting into the Th1 phenotype, which is mainly related to the activity of IL-12 and TNF-α. We have named these Th17-derived Th1 cells as non-classic because they differ from classic Th1 cells for the expression of molecules specific for Th17 cells, such as RORC, CD161, CCR6, IL4I1, and IL-17 receptor E. This distinction may be important for defining the respective pathogenic role of Th17, non-classic Th1 and classic Th1 cells in many human inflammatory disorders.

  20. Promise(s of using mesenchymal stem cells in reproductive disorders

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Venkatesan

    2014-01-01

    Full Text Available In recent times, infertility among both man and woman has become a major concern affecting about 20 per cent of the population worldwide and has been attributed in part to several aetiological factors such as changes in lifestyle, which includes sedentary life, dietary habits, sleep anomalies, environmental pollution, etc. Assisted reproductive technologies (ART have come to the rescue of many such couples, but presence of metabolic disorders such as obesity, diabetes with insulin resistance (IR and its secondary complications (micro- and macro-vascular complications, become confounders to the outcome of ART. Cell therapies are arising as a new hope in the management of reproductive disorders and currently, the efficacy of mesenchymal stem cells (MSCs harvested from the adult sources finds wide application in the management of diseases like stroke, neuropathy, nephropathy, myopathy, wounds in diabetes, etc. Given the capacity of MSCs to preferentially home to damaged tissue and modulate the cellular niche/microenvironment to augment tissue repairs and regeneration, the present review outlines the applications of MSCs in the management of infertility/reproductive disorders.

  1. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

    Directory of Open Access Journals (Sweden)

    Mami eNoda

    2015-06-01

    Full Text Available It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS. Among hormones closely related to the nervous system, thyroid hormones (THs are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of human brain, leading to various neurological dysfunctions. In adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Though hypothyroidism impairs synaptic transmission and plasticity, its effect on glial cells and cellular mechanisms are unknown. This mini-review article summarizes how THs are transported to the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, showing an example of glioendocrine system. It may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders.

  2. [Hereditary red cell membrane disorders in Japan: comparison with other countries].

    Science.gov (United States)

    Nakanishi, Hidekazu; Wada, Hideho; Suemori, Shinichiro; Sugihara, Takashi

    2015-07-01

    Red cell membrane disorders are the most common type of inherited hemolytic disorders in the Japanese population. In hereditary spherocytosis (HS), the primary presentation is a loss of membrane surface area, leading to reduced deformability because of defects in the membrane proteins ankyrin, band 3, β-spectrin, α spectrin, or protein 4.2 (P4.2). Complete P4.2 deficiencies, which are inherited in an autosomal recessive manner, comprise a unique HS subgroup and are common in Japanese, but rare in other populations. In contrast, the principle presentation in hereditary elliptocytosis (HE) is mechanical weakness of the erythrocyte membrane skeleton due to defects in α-spectrin, β-spectrin, or protein 4.1. Although α-spectrin mutations are the most frequent cause of HE in Caucasian, African, and Mediterranean populations, these mutations are rare in the Japanese population, in which P4.1 deficiencies are instead most common. Furthermore, hereditary stomatocytoses (HSt) are disorders of monovalent cation permeability in the red cell membrane.

  3. Pharmacological perspectives from Brazilian Salvia officinalis (Lamiaceae): antioxidant, and antitumor in mammalian cells.

    Science.gov (United States)

    Garcia, Charlene S C; Menti, Caroline; Lambert, Ana Paula F; Barcellos, Thiago; Moura, Sidnei; Calloni, Caroline; Branco, Cátia S; Salvador, Mirian; Roesch-Ely, Mariana; Henriques, João A P

    2016-03-01

    Salvia officinalis (Lamiaceae) has been used in south of Brazil as a diary homemade, in food condiment and tea-beverage used for the treatment of several disorders. The objective of this study was to characterize chemical compounds in the hydroalcoholic (ExtHS) and aqueous (ExtAS) extract from Salvia officinalis (L.) by gas chromatography-mass spectrometry (GC-MS) and by high-resolution electrospray ionization mass spectrometry (ESI-QTOF MS/MS), evaluate in vitro ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), catalase (CAT-like) and superoxide dismutase (SOD-like) activity, moreover cytotoxic by MTT assay, alterations on cell morphology by giemsa and apoptotic-induced mechanism for annexin V/propidium iodide. Chemical identification sage extracts revealed the presence of acids and phenolic compounds. In vitro antioxidant analysis for both extracts indicated promising activities. The cytotoxic assays using tumor (Hep-2, HeLa, A-549, HT-29 and A-375) and in non-tumor (HEK-293 and MRC-5), showed selectivity for tumor cell lines. Immunocytochemistry presenting a majority of tumor cells at late stages of the apoptotic process and necrosis. Given the results presented here, Brazilian Salvia officinalis (L.) used as condiment and tea, may protect the body against some disease, in particularly those where oxidative stress is involved, like neurodegenerative disorders, inflammation and cancer.

  4. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Giordani Rodrigues Dos Passos

    2016-01-01

    Full Text Available Several animal and human studies have implicated CD4+ T helper 17 (Th17 cells and their downstream pathways in the pathogenesis of central nervous system (CNS autoimmunity in multiple sclerosis (MS and neuromyelitis optica spectrum disorders (NMOSD, challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.

  5. Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications.

    Science.gov (United States)

    Dos Passos, Giordani Rodrigues; Sato, Douglas Kazutoshi; Becker, Jefferson; Fujihara, Kazuo

    2016-01-01

    Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.

  6. Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective

    Institute of Scientific and Technical Information of China (English)

    Gaoyang Liang; Yi Zhang

    2013-01-01

    Pluripotent stem cells,like embryonic stem cells (ESCs),have specialized epigenetic landscapes,which are important for pluripotency maintenance.Transcription factor-mediated generation of induced pluripotent stem cells (iPSCs)requires global change of somatic cell epigenetic status into an ESC-like state.Accumulating evidence indicates that epigenetic mechanisms not only play important roles in the iPSC generation process,but also affect the properties of reprogrammed iPSCs.Understanding the roles of various epigenetic factors in iPSC generation contributes to our knowledge of the reprogramming mechanisms.

  7. Embryonic stem cells or induced pluripotent stem cells? A DNA integrity perspective.

    Science.gov (United States)

    Bai, Qiang; Desprat, Romain; Klein, Bernard; Lemaître, Jean-Marc; De Vos, John

    2013-04-01

    Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical research and medical applications. iPSCs were initially favorably compared to ESCs. This view was first based on ethical arguments (the generation of iPSCs does not require the destruction of an embryo) and on immunological reasons (it is easier to derive patient HLA-matched iPSCs than ESCs). However, several reports suggest that iPSCs might be characterized by higher occurrence of epigenetic and genetic aberrations than ESCs as a consequence of the reprogramming process. We focus here on the DNA integrity of pluripotent stem cells and examine the three main sources of genomic abnormalities in iPSCs: (1) genomic variety of the parental cells, (2) cell reprogramming, and (3) in vitro cell culture. Recent reports claim that it is possible to generate mouse or human iPSC lines with a mutation level similar to that of the parental cells, suggesting that "genome-friendly" reprogramming techniques can be developed. The issue of iPSC DNA integrity clearly highlights the crucial need of guidelines to define the acceptable level of genomic integrity of pluripotent stem cells for biomedical applications. We discuss here the main issues that such guidelines should address.

  8. Infrared Harvesting Colloidal Quantum Dot Solar Cell Based on Multi-scale Disordered Electrodes

    KAUST Repository

    Tian, Yi

    2015-06-23

    Colloidal quantum dot photovoltaics (CQDPV) offer a big potential to be a renewable energy source due to low cost and tunable band-gap. Currently, the certified power conversion efficiency of CQDPV has reached 9.2%. Compared to the 31% theoretical efficiency limit of single junction solar cells, device performances have still have a large potential to be improved. For photovoltaic devices, a classical way to enhance absorption is to increase the thickness of the active layers. Although this approach can improve absorption, it reduces the charge carriers extraction efficiency. Photo-generated carriers, in fact, are prone to recombine within the defects inside CQD active layers. In an effort to solve this problem, we proposed to increase light absorption from a given thickness of colloidal quantum dot layers with the assistance of disorder. Our approach is to develop new types of electrodes with multi-scale disordered features, which localize energy into the active layer through plasmonic effects. We fabricated nanostructured gold substrates by electrochemical methods, which allow to control surface disorder as a function of deposition conditions. We demonstrated that the light absorption from 600 nm to 800 nm is impressively enhanced, when the disorder of the nanostructured surface increases. Compared to the planar case, the most disorder case increased 65% light absorption at the wavelength of λ = 700nm in the 100 nm PbS film. The average absorption enhancement across visible and infrared region in 100 nm PbS film is 49.94%. By developing a photovoltaic module, we measured a dramatic 34% improvement in the short-circuit current density of the device. The power conversion efficiency of the tested device in top-illumination configuration showed 25% enhancement.

  9. Evaluation of Chromosomal Disorders in Tissue and Blood Samples in Patients with Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Parvaneroo

    2004-12-01

    Full Text Available Statement of Problem: Many studies have indicated that genetic disturbances are common findings in patients with Oral Squamous Cell Carcinoma (OSCC. Identification of these changes can be helpful in diagnostic procedures of these tumors.Purpose: The aim of this study was to appraise the chromosomal disorders in blood and tissue patients with OSCC.Methods and Materials: In this descriptive study, the study group consisted of all OSCC patients who were referred to the Faculty of Dentistry, Tehran University of Medical Sciences, Maxillofacial Surgery Clinic of Shariati Hospital, and Amir Aalam Hospital fromSeptember 2000 to November 2002. In order to study chromosomal disorders in the peripheral blood lymphocytes, 5 mL of blood was obtained from each patient In patients with the large lesion, a piece of involved tissue were obtained and cultured for 24 hours.This led to 29 blood samples and 16 tissue specimens and any relation between OSCC and age, sex, smoking and alcohol use were evaluated.Results: In this study, OSCC was more common in males than in females (3 to 5. 31% of our patients were smokers, and one had a history of alcoholic consumption. There was an increase in incidence of OSCC with age. In this study, all patients had numerical(aneuploidy, polyploidy and structural chromosomal disorders (double minute, fragment,breakage and dicentric. There was significant difference between blood and tissue chromosomal disorders (aneuploidy, polyploidy,breakage in OSCC patients.Conclusion: It can be concluded that chromosomes in patients with OSCC might show some genetic aberration and evaluation of involved tissue might be better way for determining this disorders.

  10. CRISPR/Cas9-mediated genome engineering of CHO cell factories: Application and perspectives.

    Science.gov (United States)

    Lee, Jae Seong; Grav, Lise Marie; Lewis, Nathan E; Faustrup Kildegaard, Helene

    2015-07-01

    Chinese hamster ovary (CHO) cells are the most widely used production host for therapeutic proteins. With the recent emergence of CHO genome sequences, CHO cell line engineering has taken on a new aspect through targeted genome editing. The bacterial clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system enables rapid, easy and efficient engineering of mammalian genomes. It has a wide range of applications from modification of individual genes to genome-wide screening or regulation of genes. Facile genome editing using CRISPR/Cas9 empowers researchers in the CHO community to elucidate the mechanistic basis behind high level production of proteins and product quality attributes of interest. In this review, we describe the basis of CRISPR/Cas9-mediated genome editing and its application for development of next generation CHO cell factories while highlighting both future perspectives and challenges. As one of the main drivers for the CHO systems biology era, genome engineering with CRISPR/Cas9 will pave the way for rational design of CHO cell factories.

  11. Emotional Abilities in Children with Oppositional Defiant Disorder (ODD): Impairments in Perspective-Taking and Understanding Mixed Emotions are Associated with High Callous-Unemotional Traits.

    Science.gov (United States)

    O'Kearney, Richard; Salmon, Karen; Liwag, Maria; Fortune, Clare-Ann; Dawel, Amy

    2017-04-01

    Most studies of emotion abilities in disruptive children focus on emotion expression recognition. This study compared 74 children aged 4-8 years with ODD to 45 comparison children (33 healthy; 12 with an anxiety disorder) on behaviourally assessed measures of emotion perception, emotion perspective-taking, knowledge of emotions causes and understanding ambivalent emotions and on parent-reported cognitive and affective empathy. Adjusting for child's sex, age and expressive language ODD children showed a paucity in attributing causes to emotions but no other deficits relative to the comparison groups. ODD boys with high levels of callous-unemotional traits (CU) (n = 22) showed deficits relative to low CU ODD boys (n = 25) in emotion perspective-taking and in understanding ambivalent emotions. Low CU ODD boys did not differ from the healthy typically developing boys (n = 12). Impairments in emotion perceptive-taking and understanding mixed emotions in ODD boys are associated with the presence of a high level of CU.

  12. Addressing access barriers to services for mothers at risk for perinatal mood disorders: A social work perspective.

    Science.gov (United States)

    Keefe, Robert H; Brownstein-Evans, Carol; Rouland Polmanteer, Rebecca S

    2016-01-01

    This article identifies variables at the micro/individual, mezzo/partner/spouse and family, and macro/health care-system levels that inhibit mothers at risk for perinatal mood disorders from accessing health and mental health care services. Specific recommendations are made for conducting thorough biopsychosocial assessments that address the mothers' micro-, mezzo-, and macro-level contexts. Finally, the authors provide suggestions for how to intervene at the various levels to remove access barriers for mothers living with perinatal mood disorders as well as their families.

  13. Stiffening of Red Blood Cells Induced by Disordered Cytoskeleton Structures: A Joint Theory-experiment Study

    CERN Document Server

    Lai, Lipeng; Lim, Chwee Teck; Cao, Jianshu

    2015-01-01

    The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bi-layer. Among various cell types, the Red Blood Cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria infected RBCs (iRBCs) showed that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the worm-like chain (WLC) model for single spectrins and the Effective Medium Theory (EMT) for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with ...

  14. Attributes of Oct4 in stem cell biology: perspectives on cancer stem cells of the ovary

    Directory of Open Access Journals (Sweden)

    Samardzija Chantel

    2012-11-01

    Full Text Available Abstract Epithelial ovarian cancer (EOC remains the most lethal of all the gynaecological malignancies with drug resistance and recurrence remaining the major therapeutic barrier in the management of the disease. Although several studies have been undertaken to understand the mechanisms responsible for chemoresistance and subsequent recurrence in EOC, the exact mechanisms associated with chemoresistance/recurrence continue to remain elusive. Recent studies have shown that the parallel characteristics commonly seen between embryonic stem cells (ESCs and induced pluripotent stem cells (iPSC are also shared by a relatively rare population of cells within tumors that display stem cell-like features. These cells, termed ‘cancer initiating cells’ or ‘cancer stem cells (CSCs’ have been shown not only to display increased self renewal and pluripotent abilities as seen in ESCs and iPSCs, but are also highly tumorigenic in in vivo mouse models. Additionally, these CSCs have been implicated in tumor recurrence and chemoresistance, and when isolated have consistently shown to express the master pluripotency and embryonic stem cell regulating gene Oct4. This article reviews the involvement of Oct4 in cancer progression and chemoresistance, with emphasis on ovarian cancer. Overall, we highlight why ovarian cancer patients, who initially respond to conventional chemotherapy subsequently relapse with recurrent chemoresistant disease that is essentially incurable.

  15. Cost-effectiveness of targeted therapeutics in metastatic renal cell cancer seen from two different economic perspectives

    NARCIS (Netherlands)

    Mihajlović, J.; Postma, M.J.

    2014-01-01

    Objectives: To assess the cost-effectiveness of first line metastatic renal cell cancer (mRCC) drugs from the perspective of two different economic and clinical settings, The Netherlands (NL) and Serbia (SRB). Methods: The research included all first line mRCC therapeutics recommended by the Europea

  16. E-Mental Health Self-Management for Psychotic Disorders : State of the Art and Future Perspectives

    NARCIS (Netherlands)

    van der Krieke, Lian; Wunderink, Lex; Emerencia, Ando; de Jonge, Peter; Sytema, Sjoerd

    2014-01-01

    The aim of this review was to investigate to what extent information technology may support self-management among service users with psychotic disorders. The investigation aimed to answer the following questions: What types of e mental health self-management interventions have been developed and eva

  17. Variation in Socio-Economic Burden for Caring of Children with Autism Spectrum Disorder in Oman: Caregiver Perspectives

    Science.gov (United States)

    Al-Farsi, Yahya M.; Waly, Mostafa I.; Al-Sharbati, Marwan M.; Al-Shafaee, Mohamed; Al-Farsi, Omar; Al-Fahdi, Samiya; Ouhtit, Allal; Al-Khaduri, Maha; Al-Adawi, Samir

    2013-01-01

    A cross-sectional study was conducted to investigate whether caregiver's variations in socioeconomic status (SES) has direct bearing on challenges of nurturing children with autism spectrum disorder (ASD) in Oman. A cadre of caregivers (n = 150) from two types of SES (low-income and middle-high income) were compared based on four domains: (1)…

  18. Definition and structure of body-relatedness from the perspective of patients with severe somatoform disorder and their therapists.

    NARCIS (Netherlands)

    Kalisvaart, H.; Broeckhuysen, S. van; Bühring, M.; Kool, M.B.; Dulmen, S. van; Geenen, R.

    2012-01-01

    Background: How a patient is connected with one's body is core to rehabilitation of somatoform disorder but a common model to describe body-relatedness is missing. The aim of our study was to investigate the components and hierarchical structure of body-relatedness as perceived by patients with seve

  19. Role of Communication in the Context of Educating Children with Attention-Deficit/Hyperactivity Disorder: Parents' and Teachers' Perspectives

    Science.gov (United States)

    Koro-Ljungberg, Mirka; Bussing, Regina; Wilder, JeffriAnne; Gary, Faye

    2011-01-01

    Recent school policies increasingly support "parent-integrated" school environments, which benefit from effective parent-school collaborations and strong communication skills to ensure optimal educational outcomes. However, invisible disabilities, such as attention-deficit/hyperactivity disorder, provide unique sociopolitical contexts that shape…

  20. Involvement in Bullying among Children with Autism Spectrum Disorders: Parents' Perspectives on the Influence of School Factors

    Science.gov (United States)

    Zablotsky, Benjamin; Bradshaw, Catherine P.; Anderson, Connie; Law, Paul

    2012-01-01

    Children with developmental disabilities are at an increased risk for involvement in bullying, and children with autism spectrum disorders (ASDs) may be at particular risk because of challenges with social skills and difficulty maintaining friendships, yet there has been little empirical research on involvement in bullying among children with ASD.…

  1. Issues in Bilingualism and Heritage Language Maintenance: Perspectives of Minority-Language Mothers of Children with Autism Spectrum Disorders

    Science.gov (United States)

    Yu, Betty

    2013-01-01

    Purpose: The author investigated the language practices of 10 bilingual, Chinese/English-speaking, immigrant mothers with their children with autism spectrum disorders. The aim was to understand (a) the nature of the language practices, (b) their constraints, and (c) their impact. Method: The author employed in-depth phenomenological interviews…

  2. Counseling a Biracial Female College Student with an Eating Disorder: A Case Study Applying an Integrative Biopsychosocialcultural Perspective

    Science.gov (United States)

    Smart, Rebekah

    2010-01-01

    This case study describes short-term counseling with a young biracial woman experiencing an eating disorder. A biopsychosocialcultural conceptualization of the problem is described. The counseling approach is informed by feminist and multicultural theory and uses both interpersonal and cognitive behavior therapy. (Contains 1 figure.)

  3. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

    Science.gov (United States)

    Gill, Saar

    2016-08-01

    Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

  4. Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Israel Henig

    2014-10-01

    Full Text Available Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.

  5. Stress, Glucocorticoid Hormones and Hippocampal Neural Progenitor Cells: Implications to Mood Disorders

    Directory of Open Access Journals (Sweden)

    Tomoshige eKino

    2015-08-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis and its end-effectors glucocorticoid hormones play central roles in the adaptive response to numerous stressors that can be either internal or external. Thus, this system has a strong impact on the brain hippocampus and its major functions, such as cognition, memory as well as behavior and mood. The hippocampal area of the adult brain contains neural stem cells or more committed neural progenitor cells, which retain throughout the human life the ability of self-renewal and to differentiate into multiple neural cell lineages, such as neurons, astrocytes and oligodendrocytes. Importantly, these characteristic cells contribute significantly to the above-indicated functions of the hippocampus, while various stressors and glucocorticoids influence proliferation, differentiation and fate of these cells. This review offers an overview of the current understanding on the interactions between the HPA axis/glucocorticoid stress-responsive system and hippocampal neural progenitor cells by focusing on the actions of glucocorticoids. Also addressed is a further discussion on the implications of such interactions to the pathophysiology of mood disorders.

  6. Sickle Cell Disease: quality of life in patients with hemoglobin SS and SC disorders

    Directory of Open Access Journals (Sweden)

    Sonia Aparecida dos Santos Pereira

    2013-01-01

    Full Text Available OBJECTIVE Sickle cell disease comprises chronic, genetically determined disorders, presenting significant morbidity and high prevalence in Brazil. The goal of this study was to evaluate the quality of life of sickle cell disease patients (hemoglobin SS and SC and their sociodemographic and clinical characteristics. METHODS Data was collected from clinical records and semi-structured interviews consisting of clinical questionnaires and the World Health Organization Quality of Life-brief questionnaire. RESULTS Interviews were conducted with 400 patients, aged between 18 and 72, treated in the Fundação HEMOMINAS in Belo Horizonte. The participants predominantly had sickle cell disease hemoglobin SS variant (65.5%, were female (61.8%, single (55.3, with up to 8 years of schooling (49.6%, and self-defined as mulattos (50%. Pain crises, hospitalizations, blood transfusions, and other morbidities of sickle cell disease had a significant impact on the quality of life of these patients. CONCLUSION Within this group, the social profile was that of low income and unemployed with sickle cell disease considered to be a significant impediment to finding a job. Evaluating quality of life as a determining factor of health is essential for the creation of specific policies and measures, appropriate for the specific characteristics and social context of sickle cell disease.

  7. Current approaches to treatments for schizophrenia spectrum disorders, part II: psychosocial interventions and patient-focused perspectives in psychiatric care

    Directory of Open Access Journals (Sweden)

    Chien WT

    2013-09-01

    Full Text Available Wai Tong Chien, Sau Fong Leung, Frederick KK Yeung, Wai Kit Wong School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Abstract: Schizophrenia is a disabling psychiatric illness associated with disruptions in cognition, emotion, and psychosocial and occupational functioning. Increasing evidence shows that psychosocial interventions for people with schizophrenia, as an adjunct to medications or usual psychiatric care, can reduce psychotic symptoms and relapse and improve patients' long-term outcomes such as recovery, remission, and illness progression. This critical review of the literature was conducted to identify the common approaches to psychosocial interventions for people with schizophrenia. Treatment planning and outcomes were also explored and discussed to better understand the effects of these interventions in terms of person-focused perspectives such as their perceived quality of life and satisfaction and their acceptability and adherence to treatments or services received. We searched major healthcare databases such as EMBASE, MEDLINE, and PsycLIT and identified relevant literature in English from these databases. Their reference lists were screened, and studies were selected if they met the criteria of using a randomized controlled trial or systematic review design, giving a clear description of the interventions used, and having a study sample of people primarily diagnosed with schizophrenia. Five main approaches to psychosocial intervention had been used for the treatment of schizophrenia: cognitive therapy (cognitive behavioral and cognitive remediation therapy, psychoeducation, family intervention, social skills training, and assertive community treatment. Most of these five approaches applied to people with schizophrenia have demonstrated satisfactory levels of short- to medium-term clinical efficacy in terms of symptom control or reduction, level of

  8. The maturation of narcissism: commentary for the special series "Narcissistic personality disorder--new perspectives on diagnosis and treatment".

    Science.gov (United States)

    Hopwood, Christopher J

    2014-10-01

    Comments on the articles by A. E. Skodol et al. (see record 2013-24395-001), E. Ronningstam (see record 2014-42878-005), D. Diamond et al. (see record 2014-42878-004), and A. L. Pincus et al. (see record 2014-01439-001). This series of articles raises an interesting meta-issue worthy of further consideration: How specific is vulnerability to narcissism? Is this a "Criterion A" feature of most personality disorders, with variants (e.g., paranoid, histrionic, etc.) defined by how one reacts to an inner sense of fragility, vulnerability, or immaturity? Or should vulnerability be more meaningfully incorporated into the specific criteria for narcissistic personality disorder, which have tended to overemphasize grandiosity? These are important questions that can only be worked out meaningfully with further research.

  9. The use of dried blood spot samples in the diagnosis of lysosomal storage disorders--current status and perspectives.

    Science.gov (United States)

    Reuser, Arnold J; Verheijen, Frans W; Bali, Deeksha; van Diggelen, Otto P; Germain, Dominique P; Hwu, Wuh-Liang; Lukacs, Zoltan; Mühl, Adolf; Olivova, Petra; Piraud, Monique; Wuyts, Birgit; Zhang, Kate; Keutzer, Joan

    2011-01-01

    Dried blood spot (DBS) methods are currently available for identification of a range of lysosomal storage disorders (LSDs). These disorders are generally characterized by a deficiency of activity of a lysosomal enzyme and by a broad spectrum of phenotypes. Diagnosis of LSD patients is often delayed, which is of particular concern as therapeutic outcomes (e.g. enzyme replacement therapy) are generally more favorable in early disease stages. Experts in the field of LSDs diagnostics and screening programs convened and reviewed experiences with the use of DBS methods, and discuss the diagnostic challenges, possible applications and quality programs in this paper. Given the easy sampling and shipping and stability of samples, DBS has evident advantages over other laboratory methods and can be particularly helpful in the early identification of affected LSD patients through neonatal screening, high-risk population screening or family screening.

  10. Discussion of "Eating disorders and attachment: a contemporary psychodynamic perspective:" does the attachment model of eating disorders indicate the need for psychodynamic treatment?

    Science.gov (United States)

    Thompson-Brenner, Heather

    2014-06-01

    Tasca and Balfour have done admirable work highlighting the importance of attachment security in the psychopathology of eating disorders (EDs), and their contributions are extremely valuable. For their points to be fully appreciated by the research and treatment-research communities, additional data are needed in key areas. Research is needed to help clarify the relative roles and cause-and-effect relationships between attachment insecurity, reflective functioning, and emotion regulation in the development and maintenance of EDs. Tasca and Balfour furthermore call their model "psychodynamic," and call for psychodynamically informed treatment for patients with attachment insecurity. For this call to be heeded, additional research is needed to examine whether the unique elements of psychodynamic psychotherapy have particular benefit for patients with insecure attachment styles. The unique psychodynamic elements considered in this comment include a therapeutic focus on reflective functioning, the patient's developmental history, the "unconscious," and the transference and countertransference. The utility of a non-directive (or patient-directed) therapeutic process is also considered. Investigation of these treatment issues could be extremely useful to practitioners and patients alike.

  11. Parents' perspectives on the value of assistance dogs for children with autism spectrum disorder: a cross-sectional study

    OpenAIRE

    Burgoyne, Louise N.; Dowling, Lisa; Fitzgerald, Anthony P.; Connolly, Micaela; Browne, John P; Ivan J Perry

    2014-01-01

    Objective While there is an emerging literature on the usefulness of assistance dogs for children with autism spectrum disorder (ASD), there is a dearth of quantitative data on the value of assistance dog interventions for the family unit and family functioning. Using previously validated scales and scales developed specifically for this study, we measured parents’/guardians’ perceptions of how having an assistance dog affects: (1) child safety from environmental dangers, (2) public reception...

  12. Definition and structure of body-relatedness from the perspective of patients with severe somatoform disorder and their therapists.

    Directory of Open Access Journals (Sweden)

    Hanneke Kalisvaart

    Full Text Available BACKGROUND: How a patient is connected with one's body is core to rehabilitation of somatoform disorder but a common model to describe body-relatedness is missing. The aim of our study was to investigate the components and hierarchical structure of body-relatedness as perceived by patients with severe somatoform disorder and their therapists. METHODS: Interviews with patients and therapists yielded statements about components of body-relatedness. Patients and therapists individually sorted these statements according to similarity. Hierarchical cluster analysis was applied to these sortings. Analysis of variance was used to compare the perceived importance of the statements between patients and therapists. RESULTS: The hierarchical structure included 71 characteristics of body-relatedness. It consisted of three levels with eight clusters at the lowest level: 1 understanding, 2 acceptance, 3 adjustment, 4 respect for the body, 5 regulation, 6 confidence, 7 self-esteem, and 8 autonomy. The cluster 'understanding' was considered most important by patients and therapists. Patients valued 'regulating the body' more than therapists. CONCLUSION: According to patients with somatoform disorders and their therapists, body-relatedness includes awareness of the body and self by understanding, accepting and adjusting to bodily signals, by respecting and regulating the body, by confiding and esteeming oneself and by being autonomous. This definition and structure of body-relatedness may help professionals to improve interdisciplinary communication, assessment, and treatment, and it may help patients to better understand their symptoms and treatment. (German language abstract, Abstract S1; Spanish language abstract, Abstract S2.

  13. Endocrine Disorders in Childhood Cancer Survivors Treated with Haemopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Christina Wei

    2014-06-01

    Full Text Available The increasing number of haemopoietic stem cell transplantations (HSCT taking place worldwide has offered a cure to many high risk childhood malignancies with an otherwise very poor prognosis. However, HSCT is associated with an increased risk of morbidity and premature death, and patients who have survived the acute complications continue to face lifelong health sequelae as a result of the treatment. Endocrine dysfunction is well described in childhood HSCT survivors treated for malignancies. The endocrine system is highly susceptible to damage from the conditioning therapy, such as, alkylating agents and total body irradiation, which is given prior stem cell infusion. Although not immediately life-threatening, the impact of these abnormalities on the long term health and quality of life in these patients may be considerable. The prevalence, risk factors, clinical approaches to investigations and treatments, as well as the implications of ongoing surveillance of endocrine disorders in childhood HSCT survivors, are discussed in this review.

  14. Calcium Alternans is Due to an Order-Disorder Phase Transition in Cardiac Cells

    Science.gov (United States)

    Alvarez-Lacalle, Enrique; Echebarria, Blas; Spalding, Jon; Shiferaw, Yohannes

    2015-03-01

    Electromechanical alternans is a beat-to-beat alternation in the strength of contraction of a cardiac cell, which can be caused by an instability of calcium cycling. Using a distributed model of subcellular calcium we show that alternans occurs via an order-disorder phase transition which exhibits critical slowing down and a diverging correlation length. We apply finite size scaling along with a mapping to a stochastic coupled map model, to show that this transition in two dimensions is characterized by critical exponents consistent with the Ising universality class. These findings highlight the important role of cooperativity in biological cells, and suggest novel approaches to investigate the onset of the alternans instability in the heart.

  15. Reduced number of peripheral natural killer cells in schizophrenia but not in bipolar disorder.

    Science.gov (United States)

    Karpiński, Paweł; Frydecka, Dorota; Sąsiadek, Maria M; Misiak, Błażej

    2016-05-01

    Overwhelming evidence indicates that subthreshold inflammatory state might be implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BPD). It has been reported that both groups of patients might be characterized by abnormal lymphocyte counts. However, little is known about alterations in lymphocyte proportions that may differentiate SCZ and BPD patients. Therefore, in this study we investigated blood cell proportions quantified by means of microarray expression deconvolution using publicly available data from SCZ and BPD patients. We found significantly lower counts of natural killer (NK) cells in drug-naïve and medicated SCZ patients compared to healthy controls across all datasets. In one dataset from SCZ patients, there were no significant differences in the number of NK cells between acutely relapsed and remitted SCZ patients. No significant difference in the number of NK cells between BPD patients and healthy controls was observed in all datasets. Our results indicate that SCZ patients, but not BPD patients, might be characterized by reduced counts of NK cells. Future studies looking at lymphocyte counts in SCZ should combine the analysis of data obtained using computational deconvolution and flow cytometry techniques.

  16. Evaluation of Red Cell Membrane Cytoskeletal Disorders Using a Flow Cytometric Method in South Iran

    Directory of Open Access Journals (Sweden)

    Habib Alah Golafshan

    2014-03-01

    Full Text Available OBJECTIVE: The diagnosis of hereditary red blood cell (RBC membrane disorders, and in particular hereditary spherocytosis (HS and Southeast Asian ovalocytosis (SAO, is based on clinical history, RBC morphology, and other conventional tests such as osmotic fragility. However, there are some milder cases of these disorders that are difficult to diagnose. The application of eosin-5’-maleimide (EMA was evaluated for screening of RBC membrane defects along with some other anemias. We used EMA dye, which binds mostly to band 3 protein and to a lesser extent some other membrane proteins, for screening of some membrane defects such as HS. METHODS: Fresh RBCs from hematologically normal controls and patients with HS, SAO, hereditary elliptocytosis, hereditary spherocytosis with pincered cells, severe iron deficiency, thalassemia minor, and autoimmune hemolytic anemia were stained with EMA dye and analyzed for mean fluorescent intensity (MFI using a flow cytometer. RESULTS: RBCs from patients with HS and iron deficiency showed a significant reduction in MFI compared to those from normal controls (p<0.0001 and p<0.001, respectively, while macrocytic RBCs showed a significant increase in MFI (p<0.01. A significant correlation was shown between mean corpuscular volume and MFI, with the exceptions of HS and thalassemia minor. CONCLUSION: Our results showed that the flow cytometric method could be a reliable diagnostic method for screening and confirmation, with higher sensitivity and specificity (95% and 93%, respectively than conventional routine tests for HS patients prior to further specific membrane protein molecular tests.

  17. Current approaches to treatments for schizophrenia spectrum disorders, part II: psychosocial interventions and patient-focused perspectives in psychiatric care.

    Science.gov (United States)

    Chien, Wai Tong; Leung, Sau Fong; Yeung, Frederick Kk; Wong, Wai Kit

    2013-01-01

    Schizophrenia is a disabling psychiatric illness associated with disruptions in cognition, emotion, and psychosocial and occupational functioning. Increasing evidence shows that psychosocial interventions for people with schizophrenia, as an adjunct to medications or usual psychiatric care, can reduce psychotic symptoms and relapse and improve patients' long-term outcomes such as recovery, remission, and illness progression. This critical review of the literature was conducted to identify the common approaches to psychosocial interventions for people with schizophrenia. Treatment planning and outcomes were also explored and discussed to better understand the effects of these interventions in terms of person-focused perspectives such as their perceived quality of life and satisfaction and their acceptability and adherence to treatments or services received. We searched major health care databases such as EMBASE, MEDLINE, and PsycLIT and identified relevant literature in English from these databases. Their reference lists were screened, and studies were selected if they met the criteria of using a randomized controlled trial or systematic review design, giving a clear description of the interventions used, and having a study sample of people primarily diagnosed with schizophrenia. Five main approaches to psychosocial intervention had been used for the treatment of schizophrenia: cognitive therapy (cognitive behavioral and cognitive remediation therapy), psychoeducation, family intervention, social skills training, and assertive community treatment. Most of these five approaches applied to people with schizophrenia have demonstrated satisfactory levels of short- to medium-term clinical efficacy in terms of symptom control or reduction, level of functioning, and/or relapse rate. However, the comparative effects between these five approaches have not been well studied; thus, we are not able to clearly understand the superiority of any of these interventions. With the

  18. Emotional disorders and their interventions:A perspective of mental imagery%情绪障碍及其干预:心理表象的视角

    Institute of Scientific and Technical Information of China (English)

    王铭; 江光荣

    2016-01-01

    心理表象在多种情绪障碍中均表现出病理性特点。研究者基于心理表象主要对创伤后应激障碍、抑郁心境、双相障碍情绪和社交焦虑进行了心理病理学解释,尤其关注闪回和过度概化记忆等两种典型症状,并且重视心理表象在情绪症状维持中的作用。概括而言,研究者强调记忆形成与提取过程的异常、认知与行为的保护性策略的负强化、对事件及自我的认知偏差等三类因素对情绪障碍的致病作用。目前,针对或运用心理表象的干预与训练方法包括减少消极表象、改变消极表象内容、提高积极表象能力、提高记忆的具体性等四类。未来应注重侵入性表象的功能分析以及相关的心理病理学模型研究,并拓展干预与训练研究。%Abnormal mental imagery is a common phenomenon across many emotional disorders. From a perspective of mental imagery, many researchers tried to understand the psychopathology of posttraumatic stress disorder (PTSD), depressive mood, emotions of bipolar disorder, and social anxiety. Empirical research mainly focused on two typical symptoms, which were flashbacks in PTSD and overgeneral memory, and emphasized on the functions of mental imagery in maintenance of emotional symptoms. Overall, three types of pathogenic factors of emotional disorders were underlined, including abnormal processing in memory formation and retrieval, negative reinforcement of cognitive and behavioral protective strategies, and cognitive biases toward events and self. Existing interventions and trainings targeting or using mental imagery can be divided into four categories: reducing negative images, changing contents of negative images, enhancing ability of positive images, and increasing concreteness of memory. Future directions include further analysis on the functions of intrusive imagery, exploration of the relevant psychopathology models, and expanding studies on

  19. Mean platelet volume and red cell distribution width levels in initial evaluation of panic disorder

    Directory of Open Access Journals (Sweden)

    Asoglu M

    2016-09-01

    Full Text Available Mehmet Asoglu,1 Mehmet Aslan,2 Okan Imre,1 Yuksel Kivrak,3 Oznur Akil,1 Emin Savik,4 Hasan Buyukaslan,5 Ulker Fedai,1 Abdurrahman Altındag6 1Department of Psychiatry, Faculty of Medicine, Harran University, Sanliurfa, 2Department of Internal Medicine, Faculty of Medicine, Yuzuncu Yil University, Van, 3Department of Psychiatry, Faculty of Medicine, Kafkas University, Kars, 4Department of Clinical Biochemistry, Faculty of Medicine, Harran University, 5Department of Emergency Medicine, Faculty of Medicine, Harran University, Sanliurfa, 6Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey Background: As the relationship between psychological stress and platelet activation has been widely studied in recent years, activated platelets lead to certain biochemical changes, which occur in the brain in patients with mental disorders. However, data relating to the mean platelet volume (MPV in patients with panic disorder (PD are both limited and controversial. Herein, we aimed to evaluate, for the first time, the red cell distribution width (RDW levels combined with MPV levels in patients with PD.Patients and methods: Between January 2012 and June 2015, data of 30 treatment-naïve patients (16 females, 14 males; mean age: 37±10 years; range: 18–59 years who were diagnosed with PD and 25 age- and sex-matched healthy volunteers (10 females, 15 males; mean age: 36±13 years; range: 18–59 years (control group were retrospectively analyzed. The white blood cell count (WBC, MPV, and RDW levels were measured in both groups.Results: The mean WBC, MPV, and RDW levels were 9,173.03±2,400.31/mm3, 8.19±1.13 fl, and 12.47±1.14%, respectively, in the PD group. These values were found to be 7,090.24±1,032.61, 6.85±0.67, and 11.63±0.85, respectively, in the healthy controls. The WBC, MPV, and RDW levels were significantly higher in the patients with PD compared to the healthy controls (P=0.001, P=0.001, and P=0

  20. The psychological perspective on mental health and mental disorder research: introduction to the ROAMER work package 5 consensus document.

    Science.gov (United States)

    Wittchen, Hans-Ulrich; Knappe, Susanne; Schumann, Gunter

    2014-01-01

    This paper provides an overview of the theoretical framework of the Psychological Sciences' reviews and describes how improved psychological research can foster our understanding of mental health and mental disorders in a complementary way to biomedical research. Core definitions of the field and of psychological interventions and treatment in particular are provided. The work group's consensus regarding strength and weaknesses of European Union (EU) research in critical areas is summarized, highlighting the potential of a broader comprehensive "Behaviour Science programme" in forthcoming programmatic EU funding programmes.

  1. Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders

    Directory of Open Access Journals (Sweden)

    GABRIELA D. COLPO

    2015-08-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and anti-inflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

  2. Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders.

    Science.gov (United States)

    Colpo, Gabriela D; Ascoli, Bruna M; Wollenhaupt-Aguiar, Bianca; Pfaffenseller, Bianca; Silva, Emily G; Cirne-Lima, Elizabeth O; Quevedo, João; Kapczinski, Flávio; Rosa, Adriane R

    2015-08-01

    Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and anti-inflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

  3. Pluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery.

    Science.gov (United States)

    Lo Cicero, Alessandra; Nissan, Xavier

    2015-11-01

    Progeria, or Hutchinson-Gilford progeria syndrome (HGPS), is a rare, fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (p.G608G) of the LMNA, leading to the production of a mutated form of lamin A precursor called progerin. In HGPS, progerin accumulates in cells causing progressive molecular defects, including nuclear shape abnormalities, chromatin disorganization, damage to DNA and delays in cell proliferation. Here we report how, over the past five years, pluripotent stem cells have provided new insights into the study of HGPS and opened new original therapeutic perspectives to treat the disease.

  4. Evolving towards a human-cell based and multiscale approach to drug discovery for CNS disorders

    Directory of Open Access Journals (Sweden)

    Eric eSchadt

    2014-12-01

    Full Text Available A disruptive approach to therapeutic discovery and development is required in order to significantly improve the success rate of drug discovery for central nervous system (CNS disorders. In this review, we first assess the key factors contributing to the frequent clinical failures for novel drugs. Second, we discuss cancer translational research paradigms that addressed key issues in drug discovery and development and have resulted in delivering drugs with significantly improved outcomes for patients. Finally, we discuss two emerging technologies that could improve the success rate of CNS therapies: human induced pluripotent stem cell (hiPSC-based studies and multiscale biology models. Coincident with advances in cellular technologies that enable the generation of hiPSCs directly from patient blood or skin cells, together with methods to differentiate these hiPSC lines into specific neural cell types relevant to neurological disease, it is also now possible to combine data from large-scale forward genetics and post-mortem global epigenetic and expression studies in order to generate novel predictive models. The application of systems biology approaches to account for the multiscale nature of different data types, from genetic to molecular and cellular to clinical, can lead to new insights into human diseases that are emergent properties of biological networks, not the result of changes to single genes. Such studies have demonstrated the heterogeneity in etiological pathways and the need for studies on model systems that are patient-derived and thereby recapitulate neurological disease pathways with higher fidelity. In the context of two common and presumably representative neurological diseases, the neurodegenerative disease Alzheimer’s Disease (AD, and the psychiatric disorder schizophrenia (SZ, we propose the need for, and exemplify the impact of, a multiscale biology approach that can integrate panomic, clinical, imaging, and literature

  5. Bringing fuel cells to reality and reality to fuel cells: A systems perspective on the use of fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Saxe, Maria

    2008-10-15

    The hopes and expectations on fuel cells are high and sometimes unrealistically positive. However, as an emerging technology, much remains to be proven and the proper use of the technology in terms of suitable applications, integration with society and extent of use is still under debate. This thesis is a contribution to the debate, presenting results from two fuel cell demonstration projects, looking into the introduction of fuel cells on the market, discussing the prospects and concerns for the near-term future and commenting on the potential use in a future sustainable energy system. Bringing fuel cells to reality implies finding near-term niche applications and markets where fuel cell systems may be competitive. In a sense fuel cells are already a reality as they have been demonstrated in various applications world-wide. However, in many of the envisioned applications fuel cells are far from being competitive and sometimes also the environmental benefit of using fuel cells in a given application may be questioned. Bringing reality to fuel cells implies emphasising the need for realistic expectations and pointing out that the first markets have to be based on the currently available technology and not the visions of what fuel cells could be in the future. The results from the demonstration projects show that further development and research on especially the durability for fuel cell systems is crucial and a general recommendation is to design the systems for high reliability and durability rather than striving towards higher energy efficiencies. When sufficient reliability and durability are achieved, fuel cell systems may be introduced in niche markets where the added values presented by the technology compensate for the initial high cost

  6. Induction of the GABA cell phenotype: an in vitro model for studying neurodevelopmental disorders.

    Directory of Open Access Journals (Sweden)

    Sivan Subburaju

    Full Text Available Recent studies of the hippocampus have suggested that a network of genes is associated with the regulation of the GAD₆₇ (GAD1 expression and may play a role in γ-amino butyric acid (GABA dysfunction in schizophrenia (SZ and bipolar disorder (BD. To obtain a more detailed understanding of how GAD₆₇ regulation may result in GABAergic dysfunction, we have developed an in vitro model in which GABA cells are differentiated from the hippocampal precursor cell line, HiB5. Growth factors, such as PDGF, and BDNF, regulate the GABA phenotype by inducing the expression of GAD₆₇ and stimulating the growth of cellular processes, many with growth cones that form appositions with the cell bodies and processes of other GAD₆₇-positive cells. These changes are associated with increased expression of acetylated tubulin, microtubule-associated protein 2 (MAP2 and the post-synaptic density protein 95 (PSD95. The addition of BDNF, together with PDGF, increases the levels of mRNA and protein for GAD₆₇, as well as the high affinity GABA uptake protein, GAT1. These changes are associated with increased concentrations of GABA in the cytoplasm of "differentiated" HiB5 neurons. In the presence of Ca²⁺ and K⁺, newly synthesized GABA is released extracellularly. When the HiB5 cells appear to be fully differentiated, they also express GAD₆₅, parvalbumin and calbindin, and GluR subtypes as well as HDAC1, DAXX, PAX5, Runx2, associated with GAD₆₇ regulation. Overall, these results suggest that the HiB5 cells can differentiate into functionally mature GABA neurons in the presence of gene products that are associated with GAD₆₇ regulation in the adult hippocampus.

  7. Mast Cell Activation Syndrome: Proposed Diagnostic Criteria: Towards a global classification for mast cell disorders

    OpenAIRE

    2010-01-01

    The term “mast cell activation syndrome (MCAS)” is finding increasing use as a diagnosis for individuals who present with signs and symptoms involving the dermis, gastrointestinal track and cardiovascular system; frequently accompanied by neurologic complaints. Such patients often have undergone multiple extensive medical evaluations by different physicians in varied disciplines without a definitive medical diagnosis until the diagnosis of “MCAS” is applied. However, “MCAS” as a distinct clin...

  8. Stem cell therapy in animal models of central nervous system (CNS diseases: therapeutic role, challenges and perspectives

    Directory of Open Access Journals (Sweden)

    Swapan Kumar Maiti

    2014-09-01

    Full Text Available Many human diseases relating to central nervous system (CNS are mimicked in animal models to evaluate the efficacy of stem cell therapy. The therapeutic role of stem cells in animal models of CNS diseases include replacement of diseased or degenerated neuron, oligodendrocytes or astrocytes with healthy ones, secretion of neurotrophic factors and delivery of therapeutics/genes. Scaffolds can be utilized for delivering stem cells in brain. Sustained delivery of stem cells, lineage specific differentiation, and enhanced neuronal network integration are the hallmarks of scaffold mediated stem cell delivery in CNS diseases. This review discusses the therapeutic role, challenges and future perspectives of stem cell therapy in animal models of CNS diseases.

  9. Phenomenology in need of treatment: commentary for the special series "Narcissistic personality disorder--new perspectives on diagnosis and treatment".

    Science.gov (United States)

    Perry, J Christopher

    2014-10-01

    Comments on the articles by A. E. Skodol et al. (see record 2013-24395-001), E. Ronningstam (see record 2014-42878-005), D. Diamond et al. (see record 2014-42878-004), and A. L. Pincus et al. (see record 2014-01439-001). Good delineation of the phenomenology of narcissistic personality disorder (NPD) is necessary but insufficient for informing us on what to do clinically. Perry suspects that we will see reams of publications comparing Section III and II diagnoses with various external measures and possibly experimental procedures. We will learn some important things, along with many facts without actionable consequences. However, because NPD does not show many differential relationships to particular functional measures, I believe that treatment studies will likely be the most informative.

  10. Parenting styles and parents' perspectives on how their own emotions affect the functioning of children with autism spectrum disorders.

    Science.gov (United States)

    Zhou, Ting; Yi, Chunli

    2014-03-01

    The grounded theory method was used to analyze the parenting styles used by caregivers to rear children with autism spectrum disorders (ASD) and to investigate parents' experiences regarding how to help their child overcome the symptoms. Thirty-two parents from 28 families of children with ASD in mainland China were interviewed. Analysis of interview transcripts revealed four patterns of parenting styles which varied in affiliation to the roles of caretaker and coach. Based on their experience, a sizable group of parents perceived that their own emotions influence the child's emotions and his/her symptoms. The results suggest the value of developing intervention programs on emotion regulation and positive parenting for the parents of children with ASD.

  11. [Timely diagnosis and efficient early-rehabilitation for schizophrenic disorders in the community -- perspectives of a new standard].

    Science.gov (United States)

    Amering, Michaela

    2006-02-01

    Schizophrenia and schizophrenia spectrum disorders are severe mental illnesses with diverse courses of illness and often severe long-term disabilities. The sooner therapeutic and rehabilitative measures are taken the better the prognostic outlook is. Wrong but persistent stereotypes of incurability and dangerousness associated with schizophrenia pose severe obstacles to timely diagnosis and interventions and must be overcome. Today various efficient methods in therapy and rehabilitation are available. Evidence-based interventions are best delivered by multi-professional teams in the community. A person-centred approach combines biological, psychological, and social treatments in an integrated model including the social network and the individual goals of patients and their families. Concepts and results of international research efforts regarding state-of-the-art management of schizophrenia are presented and discussed.

  12. An evidenced-based perspective on the validity of attention-deficit/hyperactivity disorder in the context of high intelligence.

    Science.gov (United States)

    Rommelse, Nanda; van der Kruijs, Marieke; Damhuis, Jochem; Hoek, Ineke; Smeets, Stijn; Antshel, Kevin M; Hoogeveen, Lianne; Faraone, Stephen V

    2016-12-01

    The validity of Attention-Deficit/Hyperactivity Disorder (ADHD) in individuals with high intelligence is disputed, since high intelligence may 'mimic' the symptoms of ADHD in the absence of the specific pathophysiological pathways for ADHD. Conversely, increased risk of a missed ADHD diagnosis may occur due to compensatory strategies in the highly intelligent individual. A systematic literature review was performed including cognitive and behavioral studies, addressing a specific set of criteria for validating ADHD in the context of high intelligence. Albeit limited in number, available results suggest that ADHD is a valid construct in the context of high intelligence, showing characteristic clinical features (except possibly for hyperactivity being a less specific pathology marker), course and outcome and a characteristic response to treatment. Importantly, ADHD and IQ are negatively correlated on nearly all phenotypic and cognitive constructs, underlining the need for taking IQ into account as potential moderator in ADHD studies and more systematically studying ADHD in the high intelligent population.

  13. Allo-hematopoietic stem cell transplantation is a potential treatment for a patient with a combined disorder of hereditary spherocytosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-hui; WANG Yu; ZHAO Ting; LIU Kai-yan; HUANG Xiao-jun; FU Hai-xia; XU Lan-ping; LIU Dai-hong; CHEN Huan; HAN Wei; CHEN Yu-hong; WANG Feng-rong; WANG Jing-zhi

    2012-01-01

    Both human hereditary spherocytosis (HS) and chronic myelogenous leukemia (CML) are life threatening.Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation.The complete donor erythroid cells were obtained.The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation (HSCT).Reticulocyte counts normalized,and BCR-ABL was cleared away.The total bilirubin level was also corrected in this recipient.Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation.HS was not a contraindication for patient in the matched sibling transplant setting.

  14. Technological advances for deciphering the complexity of psychiatric disorders: merging proteomics with cell biology.

    Science.gov (United States)

    Wesseling, Hendrik; Guest, Paul C; Lago, Santiago G; Bahn, Sabine

    2014-08-01

    Proteomic studies have increased our understanding of the molecular pathways affected in psychiatric disorders. Mass spectrometry and two-dimensional gel electrophoresis analyses of post-mortem brain samples from psychiatric patients have revealed effects on synaptic, cytoskeletal, antioxidant and mitochondrial protein networks. Multiplex immunoassay profiling studies have found alterations in hormones, growth factors, transport and inflammation-related proteins in serum and plasma from living first-onset patients. Despite these advances, there are still difficulties in translating these findings into platforms for improved treatment of patients and for discovery of new drugs with better efficacy and side effect profiles. This review describes how the next phase of proteomic investigations in psychiatry should include stringent replication studies for validation of biomarker candidates and functional follow-up studies which can be used to test the impact on physiological function. All biomarker candidates should now be tested in series with traditional and emerging cell biological approaches. This should include investigations of the effects of post-translational modifications, protein dynamics and network analyses using targeted proteomic approaches. Most importantly, there is still an urgent need for development of disease-relevant cellular models for improved translation of proteomic findings into a means of developing novel drug treatments for patients with these life-altering disorders.

  15. [Disorders of carbohydrate metabolism, dyslipidemia, and bone metabolic disease after hematopoietic stem cell transplantation].

    Science.gov (United States)

    Wędrychowicz, Anna; Starzykk, Jerzy

    2013-01-01

    Among long-term survivors after hematopoietic stem cell transplantation (HSCT) late endocrine complications are observed in 20-50%. Very often these complications influence significantly the patient´s life and have to be treated till the end of life. Their proper prevention and monitoring are extremely important in patients who underwent HSCT during childhood. Since the 90s of the last millennium/century, thyroid dysfunction, disorders of somatic and sexual development, and disturbances of fertility have been presented in several publications. In the paper, less known endocrine complications after HSCT published in the last years are discussed. Disorders of carbohydrate metabolism, post-transplant diabetes and insulin resistance are presented. Moreover, dyslipidemia, hypertension, and post-transplant bone metabolic disease are demonstrated/shown. The paper describes the etiopathogenesis, methods of prevention as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover, actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

  16. Stiffening of Red Blood Cells Induced by Cytoskeleton Disorders: A Joint Theory-Experiment Study.

    Science.gov (United States)

    Lai, Lipeng; Xu, Xiaofeng; Lim, Chwee Teck; Cao, Jianshu

    2015-12-01

    The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bilayer. Among various cell types, the red blood cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two-dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria-infected RBCs (iRBCs) show that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the wormlike chain model for single spectrins and the effective medium theory for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with increasing end-to-end distances of spectrins, but has a nonmonotonic dependence on the variance of the end-to-end distance distributions. These predictions are verified quantitatively by our atomic force microscopy and micropipette aspiration measurements of iRBCs. The model may, from a molecular level, provide guidelines for future identification of new treatment methods for RBC-related diseases, such as malaria infection.

  17. Wnt/β-catenin and its diverse physiological cell signaling pathways in neurodegenerative and neuropsychiatric disorders.

    Science.gov (United States)

    Al-Harthi, Lena

    2012-12-01

    Wnt signaling is a fundamental pathway in embryogenesis which is evolutionary conserved from metazoans to humans. Much of our understanding of Wnt signaling events emerged from key developmental studies in drosophila, zebra fish, xenopus, and mice. Considerable data now exists on the role of Wnt signaling beyond these developmental processes and in particular its role in health and disease. The focus of this special issue is on Wnt/β-catenin and its diverse physiological cell signaling pathways in neurodegenerative and neuropsychiatric disorders. This special issue is composed of six reviews and two original articles selected to highlight recent advances in the role of Wnt signaling in CNS embryonic development, in adult brain function, in neurodegenerative conditions such as Alzheimer's disease, schizophrenia, NeuroAIDS, and in gliomas. The finding that β-catenin can translocate to the nucleus where it binds to TCF/LEF transcription factors to regulate target gene expression was a seminal observation that linked β-catenin/LEF to T cell development and differentiation. We also provide a nostalgic look on recent advances in role of Wnts in T cell development and maturation. These reviews highlight the extensive body of work in these thematic areas as well as identify knowledge gaps, where appropriate. Understanding Wnt function under healthy and diseased conditions may provide a therapeutic resource, albeit it a challenging one, in diseases where dysfunctional and/or diminished Wnt signaling is a prominent player in the disease process.

  18. Stiffening of Red Blood Cells Induced by Cytoskeleton Disorders: A Joint Theory-Experiment Study

    Science.gov (United States)

    Lai, Lipeng; Xu, Xiaofeng; Lim, Chwee Teck; Cao, Jianshu

    2015-12-01

    The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bi-layer. Among various cell types, the Red Blood Cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria infected RBCs (iRBCs) showed that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the worm-like chain (WLC) model for single spectrins and the Effective Medium Theory (EMT) for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with increasing end-to-end distances of spectrins, but has a non-monotonic dependence on the variance of the end-to-end distance distributions. These predictions are verified quantitively by our AFM and micropipette aspiration measurements of iRBCs. The model may, from a molecular level, provide guidelines for future identification of new treatment methods for RBC related diseases, such as malaria infection.

  19. Challenges and perspectives to enhance cattle production via in vitro techniques: focus on epigenetics and cell-secreted vesicles

    Directory of Open Access Journals (Sweden)

    Fabiana Fernandes Bressan

    2015-10-01

    Full Text Available This review aim to present some clinical problems found in IVP-derived animals focusing on NT procedures and to discuss the possible role of epigenetics in such process. Also, as cell-secreted vesicles have been reported as possible regulators of important physiological reproductive processes such as folliculogenesis and fertilization, it is also presented herein a new perspective of manipulating the pre-implantation period trough effector molecules contained in such vesicles.

  20. T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model.

    Science.gov (United States)

    Slyepchenko, Anastasiya; Maes, Michael; Köhler, Cristiano A; Anderson, George; Quevedo, João; Alves, Gilberto S; Berk, Michael; Fernandes, Brisa S; Carvalho, André F

    2016-05-01

    The exact pathophysiology of major depressive disorder (MDD) remains elusive. The monoamine theory, which hypothesizes that MDD emerges as a result of dysfunctional serotonergic, dopaminergic and noradrenergic pathways, has guided the therapy of this illness for several decades. More recently, the involvement of activated immune, oxidative and nitrosative stress pathways and of decreased levels of neurotrophic factors has provided emerging insights regarding the pathophysiology of MDD, leading to integrated theories emphasizing the complex interplay of these mechanisms that could lead to neuroprogression. In this review, we propose an integrative model suggesting that T helper 17 (Th17) cells play a pivotal role in the pathophysiology of MDD through (i) microglial activation, (ii) interactions with oxidative and nitrosative stress, (iii) increases of autoantibody production and the propensity for autoimmunity, (iv) disruption of the blood-brain barrier, and (v) dysregulation of the gut mucosa and microbiota. The clinical and research implications of this model are discussed.

  1. Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.

    Science.gov (United States)

    Hoban, Megan D; Orkin, Stuart H; Bauer, Daniel E

    2016-02-18

    Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development.

  2. Organic sensitizers for dye-sensitized solar cell (DSSC): Properties from computation, progress and future perspectives

    Science.gov (United States)

    Obotowo, I. N.; Obot, I. B.; Ekpe, U. J.

    2016-10-01

    The advent of the dye-sensitized solar cells (DSSCs) came at a time when the quest for alternative energy was high, replacing p-n junction photovoltaic devices. Its uniqueness arises from the fact that unlike the conventional systems where the semiconductor assumes the task of light absorption and charge transport, the two functions are separated in DSSC. Organic sensitizers have been used to harvest a large fraction of sunlight ranging from the UV region to the near infrared region of the spectrum leading to power conversion efficiencies of up to ∼ 10.65 % for metal-free organic sensitizers. Currently, experimental analysis of photo sensitizers utilized in DSSCs is often a trial and error process, often laborious and require extensive and expensive chemical synthesis. In most cases, disappointing results from late-stage of the dye synthesis indicate an urgent need to understand the properties of the dyes at a molecular level, before experiments take place. Fortunately, the use of quantum chemical calculations especially Density Functional Theory (DFT) to screen potential dyes has helped in developing efficient sensitizers and to reduce cost. In the present review article, we discuss the current state of the field, new concepts, design strategies, challenges facing the theoretical design and development of organic sensitizers for DSSCs and future perspectives.

  3. Adjuvant chemotherapy for resected non-small-cell lung cancer: future perspectives for clinical research

    Directory of Open Access Journals (Sweden)

    Bonomi Maria

    2011-12-01

    Full Text Available Abstract Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB disease has shown so far a limited (if sizable efficacy, the role of modern radiotherapies requires to be evaluated in large prospective randomized trials and the relative impact of age and comorbidities should be weighted to assess the reliability of the trials' evidences in the context of the everyday-practice. In addition, a conclusive evidence of the best partner for cisplatin is currently awaited as well as a deeper investigation of the fading effect of chemotherapy over time. The limited survival benefit since first studies were published and the lack of reliable prognostic and predictive factors beyond pathological stage, strongly call for the identification of bio-molecular markers and classifiers to identify which patients should be treated and which drugs should be used. Given the disappointing results of targeted therapy in this setting have obscured the initial promising perspectives, a biomarker-selection approach may represent the basis of future trials exploring adjuvant treatment for resected NSCLC.

  4. Thin film solar cells based on layered chalcogenides: Fundamentals and perspectives of van der Waals epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Jaegermann, W.; Pettenkofer, C.; Lang, O.; Schlaf, R.; Tiefenbacher, S.; Tomm, Y. [Hahn-Meitner-Inst., Berlin (Germany)

    1994-12-31

    The preparation of thin films of layered chalcogenide semiconductors as MX and MX{sub 2} (X = S, Se) based on the concept of van der Waals epitaxy (VDWE) is presented for different substrate/overlayer combinations as GaSe, InSe, SnSe{sub 2}, WS{sub 2} on WSe{sub 2}, GaSe, MoTe{sub 2}, graphite and mica. In all cases stoichiometric films are formed either as epitaxial layers or strongly textured films with the c-axis aligned in spite of strong lattice mismatch. The interfaces are non-reactive and atomically abrupt. The electronic properties of the interfaces are mostly ideal showing band offsets according to the electron affinity rule and no operative interface states. However, doping of the films is still a problem which limits the band bending and the attainable surface photovoltage. The perspectives and preconditions for the further development of layered semiconductor VDWE films for solar cells will be critically discussed.

  5. [Gender identity disorder and related sexual behavior problems in children and adolescents: from the perspective of development and child psychiatry].

    Science.gov (United States)

    Yamashita, Hiroshi

    2013-01-01

    The present paper reviews the theoretical and empirical literature on children and adolescents with gender identity disorder. The organizational framework underlying this review is one that presents gender behavior in children and adolescents as a continuum rather than as a dichotomy of normal versus abnormal categories. Theories of normative gender development, prevalence, assessment, developmental trajectories, and comorbidity were investigated. There is a greater fluidity and likelihood of change in the pre-pubertal period. It was reported that the majority of affected children had been eventually developing a homosexual orientation. As an approach to determine the prevalence of GID in clinical samples in our child psychiatry clinic, screening instruments that include items on cross-gender or cross-sex identification were used. We applied the Child Behavior Checklist (CBCL). Of the 113 items in the Japanese version of the CBCL, there are two measures of cross-gender identification: "behaves like opposite sex" and "wishes to be opposite sex." Like the other items, they are scored on a 3-point scale of: 0-not true, 1- somewhat true, and 2-very true. Our study of 323 clinically-referred children aged 4-15 years reported that, among the boys, 9.6% assigned a score of 1 (somewhat true) or a score of 2 (very true) to the two items. The corresponding rates for the clinically-referred girls were 24.5%. The item of diagnosis of GID in our clinical sample was significantly higher than in non-referred children, reported as 2-5% using the same method. Two clinical case histories of screened children are also presented. Both of them were diagnosed with PDDNOS. Together with the literature review, most of the gender-related symptoms in autistic spectrum disorders (ASD) could be related to the behavioral and psychological characteristics of autism as shown in case histories. ASD subjects in adolescence can sometimes develop a unique confusion of identity that occasionally

  6. T-cell receptor gene rearrangement analysis: cutaneous T cell lymphoma, peripheral T cell lymphoma, and premalignant and benign cutaneous lymphoproliferative disorders.

    Science.gov (United States)

    Zelickson, B D; Peters, M S; Muller, S A; Thibodeau, S N; Lust, J A; Quam, L M; Pittelkow, M R

    1991-11-01

    T-cell receptor gene rearrangement analysis is a useful technique to detect clonality and determine lineage of lymphoid neoplasms. We examined 103 patients with mycosis fungoides, Sézary syndrome, peripheral T cell lymphoma, potentially malignant lymphoproliferative disorders including pre-Sézary syndrome, large plaque parapsoriasis, lymphomatoid papulosis and follicular mucinosis, and various benign inflammatory infiltrates. A clonal rearrangement was detected in skin samples in 20 of 24 patients with mycosis fungoides and in peripheral blood samples in 19 of 21 patients with Sézary syndrome. A clonal population was also detected in seven of eight cases classified as peripheral T cell lymphoma. The potentially malignant dermatoses tended to have clonal rearrangement, with the exception of large plaque parapsoriasis, and further follow-up is needed to correlate clonality with the disease course. These studies demonstrate the value of molecular genetics as an adjunct to morphology in the examination of patients with cutaneous lymphoproliferative disease.

  7. Immigrant Children with Autism Spectrum Disorder: The Relationship between the Perspective of the Professionals and the Parents’ Point of View

    Science.gov (United States)

    Pondé, Milena Pereira; Rousseau, Cécile

    2013-01-01

    Background: The purpose of this study was to compare a medical diagnosis of autism spectrum disorder (ASD) with the perceptions of immigrant parents regarding their child’s difficulties. Methods: Semistructured interviews were conducted with parents. The children were assessed using the ADOS, and a multiaxial diagnosis was reached using the DSM-IV. Results: The majority of parents recognized symptoms in their child that were related to autism. Less often, however, parents believed their children had a developmental delay or communication problem rather than an ASD. There were also parents who failed to see any problem at all in their child although the child was, nonetheless, diagnosed as having an ASD. Conclusions: The failure of immigrant mothers to acknowledge a diagnosis of ASD in their younger children may represent an attempt to preserve hope for their child’s future. Mothers of older children may not, however, agree with the psychiatric diagnosis. Community services need to balance the need to convey accurate medical information with the need to protect parents’ investment in their children. This may be particularly true for immigrant parents who are living outside their cultural framework. PMID:23667359

  8. Parents' perspectives on care of children with autistic spectrum disorder in South Asia - Views from Pakistan and India.

    Science.gov (United States)

    Minhas, Ayesha; Vajaratkar, Vivek; Divan, Gauri; Hamdani, Syed Usman; Leadbitter, Kathy; Taylor, Carol; Aldred, Catherine; Tariq, Ahmareen; Tariq, Mahjabeen; Cardoza, Percy; Green, Jonathan; Patel, Vikram; Rahman, Atif

    2015-01-01

    Autism spectrum disorder (ASD) affects about 1.4% of the population in South Asia but very few have access to any form of health care service. The objective of this study was to explore the beliefs and practices related to the care of children with ASD to inform strategies for intervention. In Pakistan, primary data were collected through in-depth interviews of parents (N = 15), while in India a narrative review of existing studies was conducted. The results show that the burden of care is almost entirely on the mother, leading to high levels of stress. Poor awareness of the condition in both family members and front-line health-providers leads to delay in recognition and appropriate management. There is considerable stigma and discrimination affecting children with autism and their families. Specialist services are rare, concentrated in urban areas, and inaccessible to the majority. Strategies for intervention should include building community and family support networks to provide respite to the main carer. In the absence of specialists, community members such as community health workers, traditional practitioners and even motivated family members could be trained in recognizing and providing evidence-based interventions. Such task-shifting strategies should be accompanied by campaigns to raise awareness so greater inclusivity can be achieved.

  9. Psychologists’ perspectives on the diagnostic classification of mental disorders: Results from the WHO-IUPsyS Global Survey

    Science.gov (United States)

    Evans, Spencer C.; Reed, Geoffrey M.; Roberts, Michael C.; Esparza, Patricia; Watts, Ann D.; Correia, João Mendonça; Ritchie, Pierre; Maj, Mario; Saxena, Shekhar

    2013-01-01

    This study examined psychologists’ views and practices regarding diagnostic classification systems for mental and behavioral disorders so as to inform the development of the ICD-11 by the World Health Organization (WHO). WHO and the International Union of Psychological Science (IUPsyS) conducted a multilingual survey of 2155 psychologists from 23 countries, recruited through their national psychological associations. Sixty percent of global psychologists routinely used a formal classification system, with ICD-10 used most frequently by 51% and DSM-IV by 44%. Psychologists viewed informing treatment decisions and facilitating communication as the most important purposes of classification, and preferred flexible diagnostic guidelines to strict criteria. Clinicians favorably evaluated most diagnostic categories, but identified a number of problematic diagnoses. Substantial percentages reported problems with crosscultural applicability and cultural bias, especially among psychologists outside the USA and Europe. Findings underscore the priority of clinical utility and professional and cultural differences in international psychology. Implications for ICD-11 development and dissemination are discussed. PMID:23750927

  10. Chromatographic analysis of Hb S for the diagnosis of various sickle cell disorders in Pakistan.

    Science.gov (United States)

    Hashmi, Nazish Khalid; Moiz, Bushra; Nusrat, Maliha; Hashmi, Mashhooda Rasool

    2008-08-01

    Sickle cell disease remains a relatively obscure theme in research on haemoglobinopathies in Pakistan. Limited data is available regarding its prevalence in the country. The objective of our study was not only to estimate the frequency of different sickle cell diseases but also to provide quantitative estimation of haemoglobin S and other haemoglobin variants using an automated high-performance liquid chromatography (HPLC) system. For this purpose, we retrospectively evaluated the results of HPLC performed on all patients with suspected haemoglobinopathies during the years 2005 and 2006. Information derived from various sources was used to identify a particular genotype by analysing each sample containing Hb S with respect to haemoglobin, red cell indices and levels of various associated haemoglobin variants. Analysis of 15,699 samples identified 302 patients with Hb S (1.92%). The genotypes identified included Sbeta(0) (46.7%), SS (19.2%), SA (11.6%), Sbeta(+) (8.6%) and SD (2.3%). Thirty-five cases could not be categorised and were labelled 'unclassified'. Majority of the patients (62.3%) were below the age of 18 years. Balochistan, which is the largest province based on the area, yielded the highest number of patients (n = 140). In the Sbeta(0) group, the mean haemoglobin and Hb S were lower in children compared to adults (p value of 0.001 and 0.016, respectively). We conclude that sickle cell disorders are prevalent in Pakistan to a significant extent, being concentrated in certain areas of the country. We present the first report of various haemoglobin S genotypes from our population. It is hoped that it will act as a database to characterise the same for our population.

  11. Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies.

    Science.gov (United States)

    Nestor, Michael W; Phillips, Andre W; Artimovich, Elena; Nestor, Jonathan E; Hussman, John P; Blatt, Gene J

    2016-05-01

    Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental condition. Symptoms of ASD cover the spectrum from mild qualitative differences in social interaction to severe communication and social and behavioral challenges that require lifelong support. Attempts at understanding the pathophysiology of ASD have been hampered by a multifactorial etiology that stretches the limits of current behavioral and cell based models. Recent progress has implicated numerous autism-risk genes but efforts to gain a better understanding of the underlying biological mechanisms have seen slow progress. This is in part due to lack of appropriate models for complete molecular and pharmacological studies. The advent of induced pluripotent stem cells (iPSC) has reinvigorated efforts to establish more complete model systems that more reliably identify molecular pathways and predict effective drug targets and candidates in ASD. iPSCs are particularly appealing because they can be derived from human patients and controls for research purposes and provide a technology for the development of a personalized treatment regimen for ASD patients. The pluripotency of iPSCs allow them to be reprogrammed into a number of CNS cell types and phenotypically screened across many patients. This quality is already being exploited in protocols to generate 2-dimensional (2-D) and three-dimensional (3-D) models of neurons and developing brain structures. iPSC models make powerful platforms that can be interrogated using electrophysiology, gene expression studies, and other cell-based quantitative assays. iPSC technology has limitations but when combined with other model systems has great potential for helping define the underlying pathophysiology of ASD. Autism Res 2016, 9: 513-535. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  12. A high throughput screen identifies Nefopam as targeting cell proliferation in β-catenin driven neoplastic and reactive fibroproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Raymond Poon

    Full Text Available Fibroproliferative disorders include neoplastic and reactive processes (e.g. desmoid tumor and hypertrophic scars. They are characterized by activation of β-catenin signaling, and effective pharmacologic approaches are lacking. Here we undertook a high throughput screen using human desmoid tumor cell cultures to identify agents that would inhibit cell viability in tumor cells but not normal fibroblasts. Agents were then tested in additional cell cultures for an effect on cell proliferation, apoptosis, and β-catenin protein level. Ultimately they were tested in Apc1638N mice, which develop desmoid tumors, as well as in wild type mice subjected to full thickness skin wounds. The screen identified Neofopam, as an agent that inhibited cell numbers to 42% of baseline in cell cultures from β-catenin driven fibroproliferative disorders. Nefopam decreased cell proliferation and β-catenin protein level to 50% of baseline in these same cell cultures. The half maximal effective concentration in-vitro was 0.5 uM and there was a plateau in the effect after 48 hours of treatment. Nefopam caused a 45% decline in tumor number, 33% decline in tumor volume, and a 40% decline in scar size when tested in mice. There was also a 50% decline in β-catenin level in-vivo. Nefopam targets β-catenin protein level in mesenchymal cells in-vitro and in-vivo, and may be an effective therapy for neoplastic and reactive processes driven by β-catenin mediated signaling.

  13. The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder

    Directory of Open Access Journals (Sweden)

    Oliveira J.R.M.

    1999-01-01

    Full Text Available Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD, the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the e4 allele of the apolipoprotein E (APOE gene (on chromosome 19 is the major susceptibility locus for the most common late onset AD (LOAD. Serotonin (5-hydroxytryptamine or 5-HT is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s of this 5-HTT gene-linked polymorphic region (5-HTTLPR is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.

  14. Relationship between symptom impairment and treatment outcome in children and adolescents with attention-deficit/hyperactivity disorder: a physician perspective.

    Science.gov (United States)

    Setyawan, Juliana; Fridman, Moshe; Hodgkins, Paul; Quintero, Javier; Erder, M Haim; Katić, Božena J; Harpin, Valerie

    2015-03-01

    We evaluated the association between those symptoms/behaviours of attention-deficit/hyperactivity disorder (ADHD) that were present at diagnosis and outcomes of treatment in children and adolescents in six European countries. Physicians abstracted clinical records from patients (6-17 years) diagnosed with ADHD between 2004 and 2007 and treated for ≥2 years. Physicians scored the severity of impairment for core ADHD symptoms and additional (non-core) ADHD symptoms/behaviours at diagnosis and estimated treatment adherence (defined as an estimated >80 % adherence on weekdays and >50 % adherence on weekends). Treatment modalities included pharmacological treatment, behavioural therapy, or both. Pharmacological treatment was further subclassified by medication class. The outcome, optimal treatment success (OTS), was defined as complete symptom control with high satisfaction with treatment. Multivariate logistic regression modelling examined the relationship between OTS and symptom impairment. Of 730 patients, 200 (27 %) achieved OTS. These patients were more likely to demonstrate lower impairment in non-core ADHD symptoms/behaviours and have fewer pre-existing comorbidities. They were also more likely to be adherent and engaged with treatment, with an explicit treatment goal to improve inattention/school performance. Neither core symptoms' severity nor treatment types were associated with OTS. OTS rates were low, with patients having less impairment of non-core ADHD symptoms/behaviours and fewer comorbidities more likely to achieve OTS. Potentially modifiable factors affecting OTS were as follows: treatment adherence, treatment engagement, and a treatment goal to improve inattention/school performance. These data suggest that there may be opportunities to optimize current treatment use, and develop new treatment strategies to improve core and non-core ADHD symptoms/behaviours.

  15. Perspectives on neurocognitive rehabilitation as an adjunct treatment for addictive disorders: From cognitive improvement to relapse prevention.

    Science.gov (United States)

    Rezapour, Tara; DeVito, Elise E; Sofuoglu, Mehmet; Ekhtiari, Hamed

    2016-01-01

    Addiction, as a brain disorder, can be defined with two distinct but interacting components: drug dependency and neurocognitive deficits. Most of the therapeutic interventions in addiction medicine, including pharmacological or psychosocial therapies, that are in clinical use have been mainly focused on directly addressing addictive behaviors, especially drug use and urges to use drugs. In the field of addiction treatment, it is often presumed that drug users' neurocognitive deficits will reverse following abstinence. However, in many cases, neurocognitive deficits are not fully ameliorated following sustained abstinence, and neurocognitive function may further deteriorate in early abstinence. It can be argued that many cognitive functions, such as sustained attention and executive control, are essential for full recovery and long-term abstinence from addiction. Recent advances in cognitive neuroscience have provided scientific foundations for neurocognitive rehabilitation as a means of facilitating recovery from drug addiction. Neurocognitive rehabilitation for drug addicted individuals could be implemented as part of addiction treatment, with highly flexible delivery methods including traditional "paper and pencil" testing, or computer-based technology via laptops, web-based, or smartphones in inpatient and outpatient settings. Despite this promise, there has been limited research into the potential efficacy of neurocognitive rehabilitation as a treatment for drug addiction. Further, many questions including the optimum treatment length, session duration, and necessary treatment adherence for treatment efficacy remain to be addressed. In this chapter, we first introduce cognitive rehabilitation as one of the potential areas to bridge the gap between cognitive neuroscience and addiction medicine, followed by an overview of current challenges and future directions.

  16. The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder.

    Science.gov (United States)

    Oliveira, J R; Zatz, M

    1999-04-01

    Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD), the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the epsilon 4 allele of the apolipoprotein E (APOE) gene (on chromosome 19) is the major susceptibility locus for the most common late onset AD (LOAD). Serotonin (5-hydroxytryptamine or 5-HT) is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT) gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s) of this 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.

  17. Blood Disorders

    Science.gov (United States)

    ... people with blood disorders. Magnitude of the Problem Complications from deep vein thrombosis (DVT) kill more people each year than breast cancer, motor vehicle accidents, and HIV combined. Sickle cell trait ...

  18. Metal Disorder in Cu2ZnSnS4 (CZTS) Solar Cells from Multi-Scale Simulations

    Science.gov (United States)

    Wallace, Suzanne; Frost, Jarvist; Walsh, Aron

    Kesterite-structured Cu2ZnSnS4 (CZTS) is a promising earth-abundant and non-toxic material for the active layer of thin-film solar cells due to its high optical absorption coefficient of >104 cm-1 and sunlight matched band gap of 1.5 eV. Device efficiencies are hampered by low open circuit voltage (VOC) compared to the optical band gap. One possible origin of this is disorder amongst the Cu and Zn ions. Such disorder could lead to sub band-gap recombination centres due to fluctuations in electrostatic potential from the presence of charged defects. Understanding the origin of these sub-gap states, and the resulting impediment on device performance, is essential to discover design and processing rules for high efficiency kesterite, and other multi-component semiconductor, devices. We investigate this by writing custom Monte-Carlo codes to simulate the on-lattice disorder. A generalised Ising Hamiltonian is parameterised with hybrid density functional theory (DFT) total-energy calculations on defect pairs. The resulting disorder is simulated as a function of temperature, and the order-disorder behaviour and resulting local and long-range electrostatic potential variation due to Cu-Zn disorder is quantified.

  19. Cytoskeleton disorder and cell cycle arrest may be associated with the alteration of protein CEP135 by microgravity

    Science.gov (United States)

    Hang, Xiaoming; Sun, Yeqing; Wu, Di; Li, Yixiao; Liu, Zhiyuan

    In the past decades, alterations in the morphology, cytoskeleton and cell cycle have been observed in cells in vitro under microgravity conditions. But the underlying mechanisms are not absolutely identified yet. Our previous study on proteomic and microRNA expression profiles of zebrafish embryos exposed to simulated-microgravity has demonstrated a serial of microgravity-sensitive molecules. Centrosomal protein of 135 kDa (CEP135) was found down-regulated, but the mRNA expression level of it was up-regulated in zebrafish embryos after simulated-microgravity. However, the functional study on CEP135 is very limited and it has not been cloned in zebrafish till now. In this study, we try to determine whether the cytoskeleton disorder and cell cycle arrest is associated with the alteration of CEP135 by microgravity. Full-length cDNA of cep135 gene was firstly cloned from mitosis phase of ZF4. The sequence was analyzed and the phylogenetic tree was constructed based on the similarity to other species. Zebrafish embryonic cell line ZF4 were exposed to simulated microgravity for 24 and 48 hours, using a rotary cell culture system (RCCS) designed by NASA. Quantitative analysis by western blot showed that CEP135 expression level was significantly decreased two times after 24 hour simulated microgravity. Cell cycle detection by flow cytometer indicated ZF4 cells were blocked in G1 phase after 24 and 48 hour simulated microgravity. Moreover, double immunostained ZF4 cells with anti-tubulin and anti-CEP135antibodies demonstrated simulated microgravity could lead to cytoskeleton disorder and CEP135 abnormality. Further investigations are currently being carried out to determine whether knockdown and over-expression of CEP135 will modulate cytoskeleton and cell cycle. In vitro data in combination within vivo results might, at least in part, explain the dramatic effects of microgravity. Key Words: microgravity; CEP135; Cytoskeleton disorder; G1 arrest; ZF4 cell line

  20. Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain.

    Science.gov (United States)

    Barker, Roger A; de Beaufort, Inez

    2013-11-01

    Should patients with Parkinson's disease participate in research involving stem cell treatments? Are induced pluripotent stem cells (iPSC) the ethical solution to the moral issues regarding embryonic stem cells? How can we adapt trial designs to best assess small numbers of patients in receipt of invasive experimental therapies? Over the last 20 years there has been a revolution in our ability to make stem cells from different sources and use them for therapeutic gain in disorders of the brain. These cells, which are defined by their capacity to proliferate indefinitely as well as differentiate into selective phenotypic cell types, are viewed as being especially attractive for studying disease processes and for grafting in patients with chronic incurable neurodegenerative disorders of the CNS such as Parkinson's disease (PD). In this review we briefly discuss and summarise where our understanding of stem cell biology has taken us relative to the clinic and patients, before dealing with some of the major ethical issues that work of this nature generates. This includes issues to do with the source of the cells, their ownership and exploitation along with questions about patient recruitment, consent and trial design when they translate to the clinic for therapeutic use.

  1. Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

    Science.gov (United States)

    Nagy, K; Marschalkó, Márta; Kemény, B; Horváth, A

    2005-01-01

    The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

  2. Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases: Focus on Childhood Neurological Disorders.

    Science.gov (United States)

    Barral, Serena; Kurian, Manju A

    2016-01-01

    The study of neurological disorders often presents with significant challenges due to the inaccessibility of human neuronal cells for further investigation. Advances in cellular reprogramming techniques, have however provided a new source of human cells for laboratory-based research. Patient-derived induced pluripotent stem cells (iPSCs) can now be robustly differentiated into specific neural subtypes, including dopaminergic, inhibitory GABAergic, motorneurons and cortical neurons. These neurons can then be utilized for in vitro studies to elucidate molecular causes underpinning neurological disease. Although human iPSC-derived neuronal models are increasingly regarded as a useful tool in cell biology, there are a number of limitations, including the relatively early, fetal stage of differentiated cells and the mainly two dimensional, simple nature of the in vitro system. Furthermore, clonal variation is a well-described phenomenon in iPSC lines. In order to account for this, robust baseline data from multiple control lines is necessary to determine whether a particular gene defect leads to a specific cellular phenotype. Over the last few years patient-derived neural cells have proven very useful in addressing several mechanistic questions related to central nervous system diseases, including early-onset neurological disorders of childhood. Many studies report the clinical utility of human-derived neural cells for testing known drugs with repurposing potential, novel compounds and gene therapies, which then can be translated to clinical reality. iPSCs derived neural cells, therefore provide great promise and potential to gain insight into, and treat early-onset neurological disorders.

  3. Pinning-depinning transition in a stochastic growth model for the evolution of cell colony fronts in a disordered medium

    Science.gov (United States)

    Moglia, Belén; Albano, Ezequiel V.; Guisoni, Nara

    2016-11-01

    We study a stochastic lattice model for cell colony growth, which takes into account proliferation, diffusion, and rotation of cells, in a culture medium with quenched disorder. The medium is composed of sites that inhibit any possible change in the internal state of the cells, representing the disorder, as well as by active medium sites that do not interfere with the cell dynamics. By means of Monte Carlo simulations we find that the velocity of the growing interface, which is taken as the order parameter of the model, strongly depends on the density of active medium sites (ρA). In fact, the model presents a (continuous) second-order pinning-depinning transition at a certain critical value of ρAcrit, such as, for ρA>ρAcrit , the interface moves freely across the disordered medium, but for ρArelevant critical exponents, our study reveals that within the depinned phase the interface can be rationalized in terms of the Kardar-Parisi-Zhang universality class, but when approaching the critical threshold, the nonlinear term of the Kardar-Parisi-Zhang equation tends to vanish and then the pinned interface belongs to the quenched Edwards-Wilkinson universality class.

  4. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

    Science.gov (United States)

    O'Dushlaine, C; Kenny, E; Heron, E; Donohoe, G; Gill, M; Morris, D; Corvin, A

    2011-03-01

    Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (PSchizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

  5. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

    LENUS (Irish Health Repository)

    O'Dushlaine, C

    2011-03-01

    Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the \\'enrichment\\' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

  6. Red blood cell folate levels in pregnant women with a history of mood disorders: a case series

    Science.gov (United States)

    Yaremco, Elyse; Inglis, Angela; Innis, Sheila M.; Hippman, Catriona; Carrion, Prescilla; Lamers, Yvonne; Honer, William G.; Austin, Jehannine

    2014-01-01

    Objective Maternal folate supplementation reduces offspring risk for neural tube defects (NTDs) and other congenital abnormalities. Maternal red blood cell (RBC) folate concentrations of >906nmol/L have been associated with the lowest risk of having an NTD affected pregnancy. Mood disorders (e.g. depression, bipolar disorder) are common among women and can be associated with folate deficiency. Thus, pregnant women with histories of mood disorders may be prone to RBC folate levels insufficient to provide optimal protection against NTDs. While previous studies have assessed RBC folate concentrations in pregnant women from the general population, none have looked specifically at a group of pregnant women who have a history of a mood disorder. Methods We collected data about RBC folate concentrations and folic acid supplement intake during early pregnancy (906nmol/L, despite all participants reporting current daily use of folic acid supplements. Data regarding offspring were available for 22 women: birthweights ranged from 2296g to 4819g, and congenital abnormalities were identified in two (hypoplastic left heart, annular pancreas). Conclusion Data from this exploratory case series suggest a need for future larger scale controlled studies investigating RBC folate concentrations in early pregnancy and offspring outcomes among women with and without histories of mood disorders. PMID:23760977

  7. Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

    Directory of Open Access Journals (Sweden)

    Hidenori Kawashima

    2015-03-01

    Full Text Available Metastatic lesions of renal cell carcinoma (RCC occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets. 

  8. Adult stem cells in neural repair: Current options, limitations and perspectives

    OpenAIRE

    Mariano,Eric Domingos; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi; Lepski, Guilherme

    2015-01-01

    Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseases that defy doctors and researchers around the world. Stem cells can be divided into three main groups: (1) embryonic stem cells; (2) fetal stem cells; and (3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, plur...

  9. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders

    OpenAIRE

    2009-01-01

    Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS ...

  10. Annual Research Review: The Promise of Stem Cell Research for Neuropsychiatric Disorders

    Science.gov (United States)

    Vaccarino, Flora M.; Urban, Alexander Eckehart; Stevens, Hanna E.; Szekely, Anna; Abyzov, Alexej; Grigorenko, Elena L.; Gerstein, Mark; Weissman, Sherman

    2011-01-01

    The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders,…

  11. Effect of Batroxobin on Expression of Neural Cell Adhesion Molecule in Temporal Infarction Rats and Spatial Learning and Memory Disorder

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats and at the same time NCAM expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of NCAM immune reactive cells of Batroxobin-treated rats was more than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats and the regulation of the expression of NCAM is probably related to the neuroprotective mechanism.

  12. Parent and Child Perspectives on the Nature of Anxiety in Children and Young People with Autism Spectrum Disorders: A Focus Group Study

    Science.gov (United States)

    Ozsivadjian, Ann; Knott, Fiona; Magiati, Iliana

    2012-01-01

    Anxiety disorders are common among children and young people with autism spectrum disorders (ASD). Despite growing knowledge about the prevalence, phenomenology and treatment of anxiety disorders, relatively little is understood about the nature and impact of anxiety in this group and little is known about autism-specific factors that may have a…

  13. Stochastic anomaly of methylome but persistent SRY hypermethylation in disorder of sex development in canine somatic cell nuclear transfer

    OpenAIRE

    Young-Hee Jeong; Hanlin Lu; Chi-Hun Park; Meiyan Li; Huijuan Luo; Joung Joo Kim; Siyang Liu; Kyeong Hee Ko; Shujia Huang; In Sung Hwang; Mi Na Kang; Desheng Gong; Kang Bae Park; Eun Ji Choi; Jung Hyun Park

    2016-01-01

    Somatic cell nuclear transfer (SCNT) provides an excellent model for studying epigenomic reprogramming during mammalian development. We mapped the whole genome and whole methylome for potential anomalies of mutations or epimutations in SCNT-generated dogs with XY chromosomal sex but complete gonadal dysgenesis, which is classified as 78, XY disorder of sex development (DSD). Whole genome sequencing revealed no potential genomic variations that could explain the pathogenesis of DSD. However, e...

  14. Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Long-term consequences of traumatic brain injury (TBI are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD, yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long

  15. Polyclonal Immunoglobulin G N-Glycosylation in the Pathogenesis of Plasma Cell Disorders.

    Science.gov (United States)

    Mittermayr, Stefan; Lê, Giao N; Clarke, Colin; Millán Martín, Silvia; Larkin, Anne-Marie; O'Gorman, Peter; Bones, Jonathan

    2017-02-03

    The pathological progression from benign monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) and finally to active myeloma (MM) is poorly understood. Abnormal immunoglobulin G (IgG) glycosylation in myeloma has been reported. Using a glycomic platform composed of hydrophilic interaction UPLC, exoglycosidase digestions, weak anion-exchange chromatography, and mass spectrometry, polyclonal IgG N-glycosylation profiles from 35 patients [MGUS (n = 8), SMM (n = 5), MM (n = 8), complete-response (CR) post-treatment (n = 5), relapse (n = 4), healthy age-matched control (n = 5)] were characterized to map glycan structures in distinct disease phases of multiple myeloma. N-Glycan profiles from MGUS resembled normal control. The abundance of neutral glycans containing terminal galactose was highest in SMM, while agalactosylated glycans and fucosylated glycans were lowest in MM. Three afucosyl-biantennary-digalactosylated-sialylated species (A2G2S1, A2BG2S1, and A2BG2S2) decreased 2.38-, 2.4-, and 4.25-fold, respectively, from benign to active myeloma. Increased light chain sialylation was observed in a longitudinal case of transformation from MGUS to MM. Bisecting N-acetylglucosamine was lowest in the CR group, while highest in relapsed disease. Gene expression levels of FUT 8, ST6GAL1, B4GALT1, RECK, and BACH2 identified from publicly available GEP data supported the glycomic changes seen in MM compared to control. The observed differential glycosylation underlined the heterogeneity of the myeloma spectrum. This study demonstrates the feasibility of mapping glycan modifications on the IgG molecule and provides proof of principle that differential IgG glycosylation patterns can be successfully identified in plasma cell disorders.

  16. The challenges of translating stem cells for spinal cord injury and related disorders: what are the barriers and opportunities?

    Science.gov (United States)

    Hewson, Stephanie M; Fehlings, Lauren N; Messih, Mark; Fehlings, Michael G

    2013-02-01

    Stem cell therapies have significant potential to treat spinal cord injury (SCI), but it remains difficult to translate these therapies from 'bench to bedside'. Identifying barriers to translation and understanding how these barriers are viewed by stakeholders in the field of stem cell research are key steps to clinical translation. The Stem Cell Global Blueprint Conference, held in Toronto (ON, Canada) presented a unique opportunity to analyze the perspectives of multiple stakeholders on the future of stem cell therapies for SCI treatment. This article is an analysis of data collected at the conference, including a consensus-building process and pre- and in-conference questionnaires. The authors used these data to assess current perceptions of stem cell research and compared the findings with the literature. The authors identified the major barriers according to a wide range of stakeholders and what strategies they suggested to overcome these obstacles, with the aim of forwarding discussion on stem cell research. It is not a systematic review of the area, but rather a presentation of expert opinion with literature citations to give context and support to their arguments and suggestions. The authors believe that the international SCI community is ready for larger-scale clinical translation, which will require the continued cooperation of all stakeholders in the stem cell and SCI communities.

  17. Understanding the role of P2X7 in affective disorders – are glial cells the major players?

    Directory of Open Access Journals (Sweden)

    Leanne eStokes

    2015-07-01

    Full Text Available The pathophysiology of several psychiatric disorders has been linked to biomarkers of inflammation generating a theory of major depressive disorder as an inflammatory disease and infection and autoimmunity as major risk factors for schizophrenia. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7-/- mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, dopamine and inflammatory changes have been observed in the brains of P2X7-/- mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain.

  18. Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease.

    Science.gov (United States)

    Golpanian, Samuel; Schulman, Ivonne H; Ebert, Ray F; Heldman, Alan W; DiFede, Darcy L; Yang, Phillip C; Wu, Joseph C; Bolli, Roberto; Perin, Emerson C; Moyé, Lem; Simari, Robert D; Wolf, Ariel; Hare, Joshua M

    2016-02-01

    An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical and clinical studies have shown paradoxical results, with inconsistent findings regarding the relationship between the cell dose and clinical benefit. Such phenomena can, at least in part, be attributed to variations in cell dosing or concentration and the route of administration (ROA). Although clinical trials of cell-based therapy for cardiovascular disease began more than a decade ago, specification of the optimal dosage and ROA has not been established. The present review summarizes what has been learned regarding the optimal cell dosage and ROA from preclinical and clinical studies of stem cell therapy for heart disease and offers a perspective on future directions. Significance: Preclinical and clinical studies on cell-based therapy for cardiovascular disease have shown inconsistent results, in part because of variations in study-specific dosages and/or routes of administration (ROA). Future preclinical studies and smaller clinical trials implementing cell-dose and ROA comparisons are warranted before proceeding to pivotal trials.

  19. Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders.

    Science.gov (United States)

    Montagne, Axel; Gauberti, Maxime; Macrez, Richard; Jullienne, Amandine; Briens, Aurélien; Raynaud, Jean-Sébastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit; Docagne, Fabian; Defer, Gilles; Vivien, Denis; Maubert, Eric

    2012-11-01

    Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuroinflammation.

  20. Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Lu Zeng

    2016-11-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs induced NAFLD cell model. Methods: This study was divided into four groups including Control group, Model group (FFA group, Alisol A 24-acetate (FFA+A group, Fenofibrate (FFA+F group. Preventive role of Alisol A 24-acetate was evaluated using 10µM Alisol A 24-acetate plus 1 mM FFA (oleate:palmitate=2:1 incubated with HepG2 cells for 24 h, which was determined by Oil Red O Staining, Oil Red O based colorimetric assay and intracellular triglyceride (TG content. Besides, the inflammatory cytokines tumor necrosis factor (TNF- α, interleukin (IL-6 levels as well as the protein and mRNA expressions that were involved in fatty acid synthesis and oxidation including Adiponectin, AMP-activated protein kinase (AMPK α, peroxisome proliferator-activated receptor (PPAR α, sterol regulatory element binding protein 1c (SREBP-1c, acetyl-CoA carboxylase (ACC, fatty acid synthase (FAS, carnitine palmitoyltransferase 1 (CPT1 and acyl coenzyme A oxidase 1 (ACOX1 were detected. Results: Alisol A 24-acetate significantly decreased the numbers of lipid droplets, Oil Red O lipid content, and intracellular TG content. Besides, inflammatory cytokines TNF-α, IL-6 levels were markedly inhibited by Alisol A 24-acetate. Furthermore, Alisol A 24-acetate effectively increased the protein and mRNA expressions of Adiponectin, the phosphorylation of AMPKα, CPT1 and ACOX1, whereas decreased SREBP-1c, the phosphorylation of ACC and

  1. CD8-positive T-cell lymphoproliferative disorder associated with Epstein-Barr virus-infected B-cells in a rheumatoid arthritis patient under methotrexate treatment.

    Science.gov (United States)

    Koji, Hitoshi; Yazawa, Takuya; Nakabayashi, Kimimasa; Fujioka, Yasunori; Kamma, Hiroshi; Yamada, Akira

    2016-01-01

    We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells.

  2. Composite Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorder and Tubular Adenoma in a Rectal Polyp.

    Science.gov (United States)

    Lo, Amy A; Gao, Juehua; Rao, M Sambasivia; Yang, Guang-Yu

    2016-02-01

    Composite tumors are formed when there is intermingling between two components of separate tumors seen histologically. Cases demonstrating composite tubular adenoma with other types of tumors in the colon are rare. Composite tubular adenomas with nonlymphoid tumors including carcinoids, microcarcinoids, and small cell undifferentiated carcinoma have been reported in the literature. The occurrence of composite lymphoma and tubular adenoma within the colorectal tract is extremely rare. Only three cases have been reported and include one case of mantle cell lymphoma and two cases of diffuse large B-cell lymphoma arising in composite tubular adenomas. We present the first case of composite Epstein-Barr virus-associated B-cell lymphoproliferative disorder and tubular adenoma in a rectal polyp with a benign endoscopic appearance.

  3. The mirror has two faces: dissociative identity disorder and the defence of pathological criminal incapacity--a South African criminal law perspective.

    Science.gov (United States)

    Stevens, Philip

    2013-03-01

    Dissociative identity disorder poses numerous medico legal issues whenever the insanity defence emerges. Within the context of the South African criminal law, the impact of dissociative identity disorder on criminal responsibility has only been addressed very briefly in one decided case. Various questions arise as to the impact that the distinctive diagnostic features of dissociative identity disorder could possibly have on the defence of pathological criminal incapacity, or better known as the insanity defence, within the ambit of the South African criminal law. In this contribution the author reflects on the mental disorder known as dissociative identity disorder or multiple personality disorder, against the backdrop of the defence of pathological criminal incapacity. Reflections are also provided pertaining to the various medico legal issues at stake whenever this defence has to be adjudicated upon.

  4. A label-free proteome analysis strategy for identifying quantitative changes in erythrocyte membranes induced by red cell disorders.

    Science.gov (United States)

    Pesciotta, Esther N; Sriswasdi, Sira; Tang, Hsin-Yao; Mason, Philip J; Bessler, Monica; Speicher, David W

    2012-12-05

    Red blood cells have been extensively studied but many questions regarding membrane properties and pathophysiology remain unanswered. Proteome analysis of red cell membranes is complicated by a very wide dynamic range of protein concentrations as well as the presence of proteins that are very large, very hydrophobic, or heterogeneously glycosylated. This study investigated the removal of other blood cell types, red cell membrane extraction, differing degrees of fractionation using 1-D SDS gels, and label-free quantitative methods to determine optimized conditions for proteomic comparisons of clinical blood samples. The results showed that fractionation of red cell membranes on 1-D SDS gels was more efficient than low-ionic-strength extractions followed by 1-D gel fractionation. When gel lanes were sliced into 30 uniform slices, a good depth of analysis that included the identification of most well-characterized, low-abundance red cell membrane proteins including those present at 500 to 10,000 copies per cell was obtained. Furthermore, the size separation enabled detection of changes due to proteolysis or in vivo protein crosslinking. A combination of Rosetta Elucidator quantitation and subsequent statistical analysis enabled the robust detection of protein differences that could be used to address unresolved questions in red cell disorders. This article is part of a Special Issue entitled: Integrated omics.

  5. Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors.

    Science.gov (United States)

    Breece, Elizabeth; Paciotti, Brian; Nordahl, Christine Wu; Ozonoff, Sally; Van de Water, Judy A; Rogers, Sally J; Amaral, David; Ashwood, Paul

    2013-07-01

    The pathophysiology of autism spectrum disorder (ASD) is not yet known; however, studies suggest that dysfunction of the immune system affects many children with ASD. Increasing evidence points to dysfunction of the innate immune system including activation of microglia and perivascular macrophages, increases in inflammatory cytokines/chemokines in brain tissue and CSF, and abnormal peripheral monocyte cell function. Dendritic cells are major players in innate immunity and have important functions in the phagocytosis of pathogens or debris, antigen presentation, activation of naïve T cells, induction of tolerance and cytokine/chemokine production. In this study, we assessed circulating frequencies of myeloid dendritic cells (defined as Lin-1(-)BDCA1(+)CD11c(+) and Lin-1(-)BDCA3(+)CD123(-)) and plasmacytoid dendritic cells (Lin-1(-)BDCA2(+)CD123(+) or Lin-1(-)BDCA4(+) CD11c(-)) in 57 children with ASD, and 29 typically developing controls of the same age, all of who were enrolled as part of the Autism Phenome Project (APP). The frequencies of dendritic cells and associations with behavioral assessment and MRI measurements of amygdala volume were compared in the same participants. The frequencies of myeloid dendritic cells were significantly increased in children with ASD compared to typically developing controls (pfrequencies of myeloid dendritic cells were positively associated with abnormal right and left amygdala enlargement, severity of gastrointestinal symptoms and increased repetitive behaviors. The frequencies of plasmacytoid dendritic cells were also associated with amygdala volumes as well as developmental regression in children with ASD. Dendritic cells play key roles in modulating immune responses and differences in frequencies or functions of these cells may result in immune dysfunction in children with ASD. These data further implicate innate immune cells in the complex pathophysiology of ASD.

  6. Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective from a New Mouse Model

    Directory of Open Access Journals (Sweden)

    Konstantina Alexandropoulos

    2015-01-01

    Full Text Available Autoimmune hepatitis (AIH is an immune-mediated disorder that affects the liver parenchyma. Diagnosis usually occurs at the later stages of the disease, complicating efforts towards understanding the causes of disease development. While animal models are useful for studying the etiology of autoimmune disorders, most of the existing animal models of AIH do not recapitulate the chronic course of the human condition. In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the high tolerogenic capacity of the liver. Recently, we described a new mouse model that exhibited spontaneous and chronic liver inflammation that recapitulated the known histopathological and immunological parameters of AIH. The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus, the very process thought to inhibit AIH induction by liver-specific expression of exogenous antigens. The mutation led to depletion of specialized thymic epithelial cells that present self-antigens and eliminate autoreactive T-cells before they exit the thymus. Based on our findings, which are summarized below, we believe that this mouse model represents a relevant experimental tool towards elucidating the cellular and molecular aspects of AIH development and developing novel therapeutic strategies for treating this disease.

  7. Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration.

    Science.gov (United States)

    Estrela, Carlos; Alencar, Ana Helena Gonçalves de; Kitten, Gregory Thomas; Vencio, Eneida Franco; Gava, Elisandra

    2011-01-01

    In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer's disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.

  8. [Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

    Science.gov (United States)

    Griesser, D H

    1995-01-01

    Rearrangements are developmentally regulated genetic recombinations in T and B cells which generate functional T cell receptor (TcR) and immunoglobulin genes, respectively. Different variable, sometimes diversity, and joining gene segments which are discontinuously spread out within their chromosomal location in germline configuration, are randomly assembled in individual lymphocytes. These rearrangements can be detected by Southern Blot analysis if more than 5% of a total lymphocyte population in a biopsy specimen carries the same clonal rearrangement. We analyzed DNA from 324 snap-frozen biopsy specimens from lympho-proliferative disorders. None of the 20 reactive lesions and four malignant myelomonocytic tumors had a clonal antigen receptor gene rearrangement. All 117 malignant B cell lymphomas of different subtypes and 95 of 97 malignant T cell lymphomas showed a clonal gene rearrangement. Only two angioimmunoblastic lymphadenopathy(AILD)-type T cell lymphomas did not have immune receptor gene rearrangements. They were morphologically indistinguishable from the other 47 T/AILD lymphomas with clonal rearrangement patterns. In most cases TcR beta and immunoglobulin heavy chain (IgH) gene probes were sufficient for lineage assignment of the clonal T or B lymphocyte population. In 18% of B lymphomas, however, a cross-lineage rearrangement of TcR beta genes, and in 20% of the T cell lymphomas a clonal IgH gene rearrangement was detected. After exclusion of centrocytic, large cell anaplastic lymphomas (LCAL) of B-type, and T/AILD lymphomas which are overrepresented in our study, only 10% of the remaining 147 T and B cell lymphomas had aberrant rearrangements. TcR rearrangements other than those of the beta chain genes were extremely rare in B cell lymphomas, as were Ig kappa rearrangements in T lymphomas. Only two T/AILD lymphomas had IgH and Ig kappa rearrangement in addition to their clonal T cell receptor gene rearrangements. Both samples likely contain a clonal B

  9. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

    Directory of Open Access Journals (Sweden)

    Chan Koon H

    2010-09-01

    Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

  10. [Current status and perspective on regenerative medicine for spinal cord injury using iPS cell].

    Science.gov (United States)

    Nakamura, Masaya; Toyama, Yoshiaki; Okano, Hideyuki

    2013-01-01

    Stimulated by the 2012 Nobel Prize in Physiology or Medicine awarded for Shinya Yamanaka and Sir John Gurdon, there is an increasing interest in the iPS cells and reprogramming technologies in medical science. While iPS cells are expected to open new era providing enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine, safety-related concerns for iPS cell-based cell therapy should be resolved prior to the clinical application of iPS cells. In this symposium, the pre-clinical investigations of cell therapy for SCI using neural stem/progenitor cells derived from iPS cells, and their safety issues in vivo are outlined.

  11. RNA-binding proteins in mouse male germline stem cells: a mammalian perspective.

    Science.gov (United States)

    Qi, Huayu

    2016-01-01

    Adult stem cells that reside in particular types of tissues are responsible for tissue homeostasis and regeneration. Cellular functions of adult stem cells are intricately related to the gene expression programs in those cells. Past research has demonstrated that regulation of gene expression at the transcriptional level can decisively alter cell fate of stem cells. However, cellular contents of mRNAs are sometimes not equivalent to proteins, the functional units of cells. It is increasingly realized that post-transcriptional and translational regulation of gene expression are also fundamental for stem cell functions. Compared to differentiated somatic cells, effects on cellular status manifested by varied expression of RNA-binding proteins and global protein synthesis have been demonstrated in several stem cell systems. Through the cooperation of both cis-elements of mRNAs and trans-acting RNA-binding proteins that are intimately associated with them, regulation of localization, stability, and translational status of mRNAs directly influences the self-renewal and differentiation of stem cells. Previous studies have uncovered some of the molecular mechanisms that underlie the functions of RNA-binding proteins in stem cells in invertebrate species. However, their roles in adult stem cells in mammals are just beginning to be unveiled. This review highlights some of the RNA-binding proteins that play important functions during the maintenance and differentiation of mouse male germline stem cells, the adult stem cells in the male reproductive organ.

  12. Adult stem cells in neural repair: Current options, limitations and perspectives.

    Science.gov (United States)

    Mariano, Eric Domingos; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi; Lepski, Guilherme

    2015-03-26

    Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseases that defy doctors and researchers around the world. Stem cells can be divided into three main groups: (1) embryonic stem cells; (2) fetal stem cells; and (3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

  13. The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders.

    Science.gov (United States)

    Slavin, Shimon; Kurkalli, Basan G S; Karussis, Dimitrios

    2008-11-01

    No specific treatment exists for patients with multiple sclerosis (MS) who fail to respond to conventional immunosuppressive and immunomodulating modalities. Furthermore, no method is available for regeneration of existing defect in the central nervous system (CNS). The ultimate goals of MS treatment, similarly to other autoimmune diseases, are twofold: first, to eliminate self-reactive lymphocytes and to prevent de novo development of self-reactivity by induction of self-tolerance. Second, attempting regeneration and repair of existing damage. In the case of MS, there is a need to stop the ongoing process of inflammation against the CNS by self-reactive lymphocytes thus facilitating spontaneous re-myelinization while in parallel attempt to recover existing neurological deficits caused by the autoimmune process resulting in demyelinization. Cell therapy stands out as the most rationale approach for neurological regeneration. In the absence of clinically applicable approaches involving the use of embryonic stem cells, we are investigating the feasibility and efficacy of enriched autologous mesenchymal stromal cells (MSC) injected intrathecally and intravenously to induce in situ immunomodulation and neuroprotection and possibly facilitate repair of the CNS in patients with MS and other neurodegenerative disorders. Our preclinical results suggest that bone marrow cells may provide a source of stem cells with a potential for migration into inflamed CNS and differentiate into cells expressing neuronal and glial cell markers. Based on the preclinical data, we are currently evaluating the safety of a similar therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.

  14. Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy

    OpenAIRE

    Simerman, Ariel A; Dumesic, Daniel A; Chazenbalk, Gregorio D.

    2014-01-01

    In 2010, Multilineage Differentiating Stress Enduring (Muse) cells were introduced to the scientific community, offering potential resolution to the issue of teratoma formation that plagues both embryonic stem (ES) and induced pluripotent (iPS) stem cells. Isolated from human bone marrow, dermal fibroblasts, adipose tissue and commercially available adipose stem cells (ASCs) under severe cellular stress conditions, Muse cells self-renew in a controlled manner and do not form teratomas when in...

  15. Nanophotonic Light Management for Silicon Heterojunction Solar Cells with Planar Passivation Layers - Implementation and Material Perspective

    OpenAIRE

    Smeets, Michael; Ermes, Markus; Pomaska, Manuel; Ding, Kaining; Paetzold, Ulrich W.; Bittkau, Karsten

    2016-01-01

    The successful implementation of light management concepts processed after the planar passivation of SHJ solar cells is demonstrated. We present prototype solar cells, improved performance and discuss promising approaches for future development.

  16. Cell Fusion in the War on Cancer: A Perspective on the Inception of Malignancy

    Directory of Open Access Journals (Sweden)

    Jeffrey L. Platt

    2016-07-01

    Full Text Available Cell fusion occurs in development and in physiology and rarely in those settings is it associated with malignancy. However, deliberate fusion of cells and possibly untoward fusion of cells not suitably poised can eventuate in aneuploidy, DNA damage and malignant transformation. How often cell fusion may initiate malignancy is unknown. However, cell fusion could explain the high frequency of cancers in tissues with low underlying rates of cell proliferation and mutation. On the other hand, cell fusion might also engage innate and adaptive immune surveillance, thus helping to eliminate or retard malignancies. Here we consider whether and how cell fusion might weigh on the overall burden of cancer in modern societies.

  17. Epithelial cell polarity and tumorigenesis: new perspectives for cancer detection and treatment

    Institute of Scientific and Technical Information of China (English)

    Danila CORADINI; Claudia CASARSA; Saro ORIANA

    2011-01-01

    Loss of cell-cell adhesion and cell polarity is commonly observed in tumors of epithelial origin and correlates with their invasion into adjacent tissues and formation of metastases. Growing evidence indicates that loss of cell polarity and cell-cell adhesion may also be important in early stage of cancer. In first part of this review, we delineate the current understanding of the mechanisms that establish and maintain the polarity of epithelial tissues and discuss the involvement of cell polarity and apical junctional complex components in tumor pathogenesis. In the second part we address the clinical significance of cell polarity and junctional complex components in can- cer diagnosis and prognosis. Finally, we explore their potential use as therapeutic targets in the treatment of cancer.

  18. Current progress and future perspectives for organic/inorganic perovskite solar cells

    OpenAIRE

    Boix, Pablo P.; Kazuteru Nonomura; Nripan Mathews; Subodh G. Mhaisalkar

    2014-01-01

    The recent emergence of efficient solar cells based on organic/inorganic lead halide perovskite absorbers promises to transform the fields of dye-sensitized, organic, and thin film solar cells. Solution processed photovoltaics incorporating perovskite absorbers have achieved efficiencies of 15% [1] in solid-state device configurations, superseding liquid dye sensitized solar cell (DSC), evaporated and tandem organic solar cells, as well as various thin film photovoltaics; thus establishing pe...

  19. Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jie, E-mail: jie.wang2@osumc.edu [Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH (United States); Osei, Kwame [Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH (United States)

    2011-07-22

    Highlights: {yields} Primary proinsulin maturation disorder is inherent in Ins2{sup +/Akita} islets/{beta}-cells. {yields} A consequence is the inefficient conversion of proinsulin to insulin. {yields} Post-translational defects occur as well in the involved PC1/3 and PC2 convertases. {yields} Proinsulin maturation chaos results in defects in the following conversion process. {yields} A link of the proinsulin maturation disorder and hyperproinsulinemia is suggested. -- Abstract: Disproportionate hyperproinsulinemia is an indicator of {beta}-cell dysfunction in diabetes and the basis underlying this abnormality remains obscure. Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) in normal {beta}-cells as a result of the integration of maturation and disposal processes. PIHO is susceptible to environmental and genetic influences. Perturbation of PIHO produces a number of toxic consequences with known association to {beta}-cell failure in diabetes. To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2{sup +/Akita} islets/{beta}-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene. Our metabolic-labeling studies found an increased ratio of proinsulin to insulin in the cellular or released proteins of Ins2{sup +/Akita} islets. Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the {beta}-cells of Ins2{sup +/Akita} islets in spite of no declines of these two convertases at the transcriptional and translational levels. Immunoblot analyses in cloned Ins2{sup +/Akita} {beta}-cells further confirmed the increased ratio of proinsulin

  20. Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy.

    Science.gov (United States)

    Simerman, Ariel A; Dumesic, Daniel A; Chazenbalk, Gregorio D

    2014-01-01

    In 2010, Multilineage Differentiating Stress Enduring (Muse) cells were introduced to the scientific community, offering potential resolution to the issue of teratoma formation that plagues both embryonic stem (ES) and induced pluripotent (iPS) stem cells. Isolated from human bone marrow, dermal fibroblasts, adipose tissue and commercially available adipose stem cells (ASCs) under severe cellular stress conditions, Muse cells self-renew in a controlled manner and do not form teratomas when injected into immune-deficient mice. Furthermore, Muse cells express classic pluripotency markers and differentiate into cells from the three embryonic germ layers both spontaneously and under media-specific induction. When transplanted in vivo, Muse cells contribute to tissue generation and repair. This review delves into the aspects of Muse cells that set them apart from ES, iPS, and various reported adult pluripotent stem cell lines, with specific emphasis on Muse cells derived from adipose tissue (Muse-AT), and their potential to revolutionize the field of regenerative medicine and stem cell therapy.

  1. Adult stem cells in neural repair: Current options,limitations and perspectives

    Institute of Scientific and Technical Information of China (English)

    Eric Domingos Mariano; Manoel Jacobsen Teixeira; Suely Kazue Nagahashi Marie; Guilherme Lepski

    2015-01-01

    Stem cells represent a promising step for the future ofregenerative medicine. As they are able to differentiateinto any cell type, tissue or organ, these cells are greatcandidates for treatments against the worst diseasesthat defy doctors and researchers around the world.Stem cells can be divided into three main groups (1)embryonic stem cells; (2) fetal stem cells; and (3) adultstem cells. In terms of their capacity for proliferation,stem cells are also classified as totipotent, pluripotentor multipotent. Adult stem cells, also known as somaticcells, are found in various regions of the adult organism,such as bone marrow, skin, eyes, viscera and brain.They can differentiate into unipotent cells of theresiding tissue, generally for the purpose of repair.These cells represent an excellent choice in regenerativemedicine, every patient can be a donor of adult stemcells to provide a more customized and efficient therapyagainst various diseases, in other words, they allow theopportunity of autologous transplantation. But in orderto start clinical trials and achieve great results, we needto understand how these cells interact with the hosttissue, how they can manipulate or be manipulated bythe microenvironment where they will be transplantedand for how long they can maintain their multipotentstate to provide a full regeneration.

  2. Cell Phones in the Classroom: Teachers' Perspectives of Inclusion, Benefits, and Barriers

    Science.gov (United States)

    Thomas, Kevin M.; O'Bannon, Blanche W.; Bolton, Natalie

    2013-01-01

    Historically viewed as a disruption by teachers, cell phones have been banned from 69% of classrooms (Common Sense Media, 2009). The increased ubiquity and instructional features of cell phones have prompted some teachers to re-evaluate the ban and consider the benefits associated with allowing cell phones in the classroom. This study surveyed 79…

  3. Current perspectives on natural killer cell education and tolerance: emerging roles for inhibitory receptors

    Directory of Open Access Journals (Sweden)

    Thomas LM

    2015-03-01

    Full Text Available L Michael Thomas Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA Abstract: Natural killer (NK cells are regulated through the coordinated functions of activating and inhibitory receptors. These receptors can act during the initial engagement of an NK cell with a target cell, or in subsequent NK cell engagements to maintain tolerance. Notably, each individual possesses a sizable minority-population of NK cells that are devoid of inhibitory receptors that recognize the surrounding MHC class I (ie, self-MHC. Since these NK cells cannot perform conventional inhibition, they are rendered less responsive through the process of NK cell education (also known as licensing in order to reduce the likelihood of auto-reactivity. This review will delineate current views on NK cell education, clarify various misconceptions about NK cell education, and, lastly, discuss the relevance of NK cell education in anti-cancer therapies. Keywords: natural killer cell education, natural killer cell inhibitory receptors, immunotherapy, cancer

  4. Cell Phones in the Classroom: Teachers' Perspectives of Inclusion, Benefits, and Barriers

    Science.gov (United States)

    Thomas, Kevin M.; O'Bannon, Blanche W.; Bolton, Natalie

    2013-01-01

    Historically viewed as a disruption by teachers, cell phones have been banned from 69% of classrooms (Common Sense Media, 2009). The increased ubiquity and instructional features of cell phones have prompted some teachers to re-evaluate the ban and consider the benefits associated with allowing cell phones in the classroom. This study surveyed 79…

  5. Emotional well-being in children and adolescents treated with atomoxetine for attention-deficit/hyperactivity disorder: Findings from a patient, parent and physician perspective using items from the pediatric adverse event rating scale (PAERS

    Directory of Open Access Journals (Sweden)

    Dittmann Ralf W

    2008-05-01

    Full Text Available Abstract Background The objective of this analysis was to measure changes in items on the Pediatric Adverse Event Rating Scale (PAERS that relate to emotional well-being of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD during treatment with atomoxetine for up to 24 weeks from the perspective of the patient, the parent, and the physician. Methods Patients aged 6–17 years with ADHD were treated with atomoxetine (target dose 1.2 mg/kg/day. In the two studies on which this secondary analysis is based the PAERS was used to assess the tolerability of atomoxetine in children and adolescents. This scale has a total of 48 items. The ten items that reflect emotional well-being were selected to measure changes over time from a patient, parent, and physician perspective. Results 421 patients were treated with atomoxetine. 355 patients completed the 8-week treatment period, and 260 patients completed the 24-week treatment period. The ten items that reflect emotional well-being were grouped in five dimensions: depressed mood, self-harm, irritability/agitation, drowsiness, and euphoria. The scores of these dimensions decreased over time, both from a patient as well as from a parent and physician perspective. Only the dimension self-harm was extremely low at baseline and stayed low over time. The mean scores for the ten items depended on the rater perspective. Conclusion The emotional well-being of children and adolescents with ADHD improved in terms of depressed mood, irritability/agitation, drowsiness, and euphoria during treatment with atomoxetine for up to 24 weeks.

  6. Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Akin, C; Gilfillan, A M

    2008-01-01

    KIT is a member of the tyrosine kinase family of growth factor receptors which is expressed on a variety of haematopoietic cells including mast cells. Stem cell factor (SCF)-dependent activation of KIT is critical for mast cell homeostasis and function. However, when KIT is inappropriately activa...

  7. Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?

    Science.gov (United States)

    Castorina, Alessandro; Szychlinska, Marta Anna; Marzagalli, Rubina; Musumeci, Giuseppe

    2015-06-01

    Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration. Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during long-term culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-related transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.

  8. Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?

    Directory of Open Access Journals (Sweden)

    Alessandro Castorina

    2015-01-01

    Full Text Available Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration.Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during long-term culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-related transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.

  9. Transplantation of autologous bone marrow stromal cells (BMSC for CNS disorders – Strategy and tactics for clinical application

    Directory of Open Access Journals (Sweden)

    Satoshi Kuroda

    2010-01-01

    Full Text Available Background – There is increasing evidence that the transplanted bone marrow stromal cells (BMSC significantly promote functional recovery after central nervous system (CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, brain contusion and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with neurological disorders. In this paper, therefore, we discuss what we should clarify to establish cell transplantation therapy in clinical situation and describe our recent works for this purpose.Methods and Results – The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. Using optical imaging and MRI techniques, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. Functional imaging such as PET scan may have the potential to assess the beneficial effects of BMSC transplantation. The BMSC can be expanded using the animal protein-free culture medium, which would maintain their potential of proliferation, migration, and neural differentiation.Conclusion – It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future

  10. Stem cells for clinical use in cardiovascular medicine: current limitations and future perspectives.

    Science.gov (United States)

    Menasché, Philippe

    2005-10-01

    Cell transplantation is currently gaining a growing interest as a potential new means of improving the prognosis of patients with cardiac failure. The basic assumption is that left ventricular dysfunction is largely due to the loss of a critical number of cardiomyocytes and that it can be partly reversed by implantation of new contractile cells into the postinfarction scars. Primarily for practical reasons, autologous skeletal myoblasts have been the first to undergo clinical trials and now that the feasibility of the procedure is well established, efficacy data are expected from the ongoing randomized studies. Bone marrow stem cells are also generating a great deal of interest, particularly in patients with acute myocardial infarction, and are currently undergoing extensive clinical testing although recent data have raised a cautionary note about the transdifferentiation potential of these cells. While experimental studies and early-phase clinical trials tend to support the concept that cell therapy may enhance cardiac repair, several key issues still need to be addressed including (1) the optimal type of donor cells in relation to the clinical profile of the patients, (2) the mechanism by which cell engraftment improves cardiac function, (3) the optimization of cell survival, (4) the development of less invasive cell delivery techniques and (5) the potential benefits of cell transplantation in nonischemic heart failure. Current evidence suggests, however, that adult stem cells (myogenic or marrow-derived) fail to electromechanically integrate within the recipient heart, thereby mandating the search for second generation cell types able to achieve this goal which is the prerequisite for an effective enhancement of contractile function. Preliminary data suggest that cells that feature a true cardiomyogenic phenotype such as cardiac stem cells and cardiac-precommitted embryonic stem cells may fall in this category and carry the potential for ensuring a true

  11. Pluripotent cells in farm animals: state of the art and future perspectives.

    Science.gov (United States)

    Nowak-Imialek, Monika; Niemann, Heiner

    2012-01-01

    Pluripotent cells, such as embryonic stem (ES) cells, embryonic germ cells and embryonic carcinoma cells are a unique type of cell because they remain undifferentiated indefinitely in in vitro culture, show self-renewal and possess the ability to differentiate into derivatives of the three germ layers. These capabilities make them a unique in vitro model for studying development, differentiation and for targeted modification of the genome. True pluripotent ESCs have only been described in the laboratory mouse and rat. However, rodent physiology and anatomy differ substantially from that of humans, detracting from the value of the rodent model for studies of human diseases and the development of cellular therapies in regenerative medicine. Recently, progress in the isolation of pluripotent cells in farm animals has been made and new technologies for reprogramming of somatic cells into a pluripotent state have been developed. Prior to clinical application of therapeutic cells differentiated from pluripotent stem cells in human patients, their survival and the absence of tumourigenic potential must be assessed in suitable preclinical large animal models. The establishment of pluripotent cell lines in farm animals may provide new opportunities for the production of transgenic animals, would facilitate development and validation of large animal models for evaluating ESC-based therapies and would thus contribute to the improvement of human and animal health. This review summarises the recent progress in the derivation of pluripotent and reprogrammed cells from farm animals. We refer to our recent review on this area, to which this article is complementary.

  12. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Directory of Open Access Journals (Sweden)

    Esther Reina-Romo

    2011-11-01

    Full Text Available Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

  13. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Science.gov (United States)

    Sanz-Herrera, Jose A.; Reina-Romo, Esther

    2011-01-01

    Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

  14. Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

    Science.gov (United States)

    Jasmin; de Souza, Gustavo Torres; Louzada, Ruy Andrade; Rosado-de-Castro, Paulo Henrique; Mendez-Otero, Rosalia; Campos de Carvalho, Antonio Carlos

    2017-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have been used for diagnoses in biomedical applications, due to their unique properties and their apparent safety for humans. In general, SPIONs do not seem to produce cell damage, although their long-term in vivo effects continue to be investigated. The possibility of efficiently labeling cells with these magnetic nanoparticles has stimulated their use to noninvasively track cells by magnetic resonance imaging after transplantation. SPIONs are attracting increasing attention and are one of the preferred methods for cell labeling and tracking in preclinical and clinical studies. For clinical protocol approval of magnetic-labeled cell tracking, it is essential to expand our knowledge of the time course of SPIONs after cell incorporation and transplantation. This review focuses on the recent advances in tracking SPION-labeled stem cells, analyzing the possibilities and limitations of their use, not only focusing on myocardial infarction but also discussing other models. PMID:28182122

  15. Tongue Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  16. Mental Disorders

    Science.gov (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

  17. Skeletal muscle perfusion and stem cell delivery in muscle disorders using intra-femoral artery canulation in mice.

    Science.gov (United States)

    Matthias, Nadine; Hunt, Samuel D; Wu, Jianbo; Darabi, Radbod

    2015-11-15

    Muscular dystrophies are among major inherited muscle disorders characterized by progressive muscle damage and fibrosis with no definitive cure. Recently, gene or cell based therapies have been developed to restore the missing gene expression or replace the damaged tissues. In order to test the efficiency of these therapies in mice models of muscular dystrophies, the arterial route of delivery is very advantageous as it provides uniform muscle exposure to the therapeutic agents or cells. Although there are few reports of arterial delivery of the therapeutic agents or cells in mice, there is no in-depth description and evaluation of its efficacy in perfusion of downstream muscles. This study is aimed to develop a practical method for intra-femoral artery perfusion in mice and to evaluate perfusion efficiency using near-infrared-fluorescence (NIRF) imaging as well as histology following stem cell delivery. Our results provide a practical guide to perform this delicate method in mice. By using a sensitive fluorescent dye, different muscle groups of the hindlimb have been evaluated for proper perfusion. As the final step, we have validated the efficiency of arterial cell delivery into muscles using human iPS-derived myogenic cells in an immunodeficient mouse model for Duchenne muscular dystrophy (NSG-mdx(4cv)).

  18. Nanoparticle-based CT imaging technique for longitudinal and quantitative stem cell tracking within the brain: application in neuropsychiatric disorders.

    Science.gov (United States)

    Betzer, Oshra; Shwartz, Amit; Motiei, Menachem; Kazimirsky, Gila; Gispan, Iris; Damti, Efrat; Brodie, Chaya; Yadid, Gal; Popovtzer, Rachela

    2014-09-23

    A critical problem in the development and implementation of stem cell-based therapy is the lack of reliable, noninvasive means to image and trace the cells post-transplantation and evaluate their biodistribution, final fate, and functionality. In this study, we developed a gold nanoparticle-based CT imaging technique for longitudinal mesenchymal stem cell (MSC) tracking within the brain. We applied this technique for noninvasive monitoring of MSCs transplanted in a rat model for depression. Our research reveals that cell therapy is a potential approach for treating neuropsychiatric disorders. Our results, which demonstrate that cell migration could be detected as early as 24 h and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression-related brain regions. We further developed a noninvasive quantitative CT ruler, which can be used to determine the number of cells residing in a specific brain region, without tissue destruction or animal scarification. This technique may have a transformative effect on cellular therapy, both for basic research and clinical applications.

  19. Psychiatric Disorders in a Sample of Saudi Arabian Adolescents with Sickle Cell Disease

    Science.gov (United States)

    Amr, Mostafa Abdel-Monhem; Amin, Tarek Tawfik; Hablas, Hatem Refaat

    2010-01-01

    The objectives of this study were to determine the magnitude of psychiatric disorders and to define socio-demographic and disease-related risk factors in a sample of adolescents with SCD in Al-Hassa, Saudi Arabia. The sample consisted of 110 adolescents with SCD and a convenient sample of 202 adolescents without SCD as controls. Psychiatric…

  20. Clearance of p16(Ink4a)-positive senescent cells delays ageing-associated disorders

    NARCIS (Netherlands)

    Baker, Darren J.; Wijshake, Tobias; Tchkonia, Tamar; LeBrasseur, Nathan K.; Childs, Bennett G.; van de Sluis, Bart; Kirkland, James L.; van Deursen, Jan M.

    2011-01-01

    Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellul