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. Psychosocial impact of sickle cell disorder: perspectives from a Nigerian setting

    OpenAIRE

    Egunjobi Feyijimi E; Anie Kofi A; Akinyanju Olu O

    2010-01-01

    Abstract Sickle Cell Disorder is a global health problem with psychosocial implications. Nigeria has the largest population of people with sickle cell disorder, with about 150,000 births annually. This study explored the psychosocial impact of sickle cell disorder in 408 adolescents and adults attending three hospitals in Lagos, Nigeria. A questionnaire was designed for the study, with some of commonly described areas of psychosocial impact including general public perceptions and attitudes, ...

  3. 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.

  4. Bipolar spectrum disorders. New perspectives.

    OpenAIRE

    Piver, Andre; Yatham, Lakshmi N.; Raymond W. Lam

    2002-01-01

    OBJECTIVE: To review new perspectives on diagnosis, clinical features, epidemiology, and treatment of bipolar II and related disorders. QUALITY OF EVIDENCE: Articles were identified by searching MEDLINE and ClinPSYCH from January 1994 to August 2001 using the key words bipolar disorder, type II or 2; hypomania; spectrum; or variants. Reference lists from articles were reviewed. Overall, the quality of evidence was not high; we found no randomized controlled trials that specifically addressed ...

  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

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    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. 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…

  8. 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.

  9. Neuronal generation from somatic stem cells: current knowledge and perspectives on the treatment of acquired and degenerative central nervous system disorders.

    Science.gov (United States)

    Corti, S; Locatelli, F; Strazzer, S; Guglieri, M; Comi, G P

    2003-06-01

    Stem cell transplantation through cell replacement or as vector for gene delivery is a potential strategy for the treatment of neurodegenerative diseases. Several studies have reported the transdifferentiation of different somatic stem cells into neurons in vitro or after transplantation into animal models. This observation has pointed out the perspective of using an ethical and accessible cell source to "replace" damaged neurons or provide support to brain tissue. However, recent findings such as the cell fusion phenomenon have raised some doubts about the real existence of somatic stem cell plasticity. In this review, we will discuss current evidence and controversial issues about the neuroneogenesis from various sources of somatic cells focusing on the techniques of isolation, expansion in vitro as well as the inductive factors that lead to transdifferentiation in order to identify the factors peculiar to this process. The morphological, immunochemical, and physiological criteria to correctly judge whether the neuronal transdifferentation occurred are critically presented. We will also discuss the transplantation experiments that were done in view of a possible clinical therapeutic application. Animal models of stroke, spinal cord and brain trauma have improved with Mesenchymal Stem Cells or Bone Marrow transplantation. This improvement does not seem to depend on the replacement of the lost neurons but may be due to increased expression levels of neurotrophic factors, thus suggesting a beneficial effect of somatic cells regardless of transdifferentiation. Critical understanding of available data on the mechanisms governing the cell fate reprogramming is a necessary achievement toward an effective cell therapy. PMID:12762483

  10. Eating Disorders and Treatment from Different Perspectives

    NARCIS (Netherlands)

    S.M. de la Rie (Simone)

    2009-01-01

    textabstractEating disorders (EDs) are rare, but very serious psychiatric disorders, with a low recovery rate (1,2). This warrants studies on treatment quality to improve the course and consequences of EDs and enhance recovery rates. Despite the increasing recognition of the value of patient input,

  11. 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...... 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...... 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....

  12. 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…

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

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    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,…

  14. Alexithymia in Eating Disorders: a transcultural perspective

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    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.

  15. Autism Spectrum Disorder: the Present Perspective

    OpenAIRE

    Chaudhuri, S.; Chatterjee, N

    2015-01-01

    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 ea...

  16. A Global Workspace perspective on mental disorders

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    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.

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

    OpenAIRE

    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 repo...

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

    OpenAIRE

    Manuela eGander; Kathrin eSevecke; Anna eBuchheim

    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. 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 attac...

  19. 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

  20. Vitiligo as an inflammatory skin disorder: a therapeutic perspective.

    Science.gov (United States)

    Taïeb, Alain

    2012-01-01

    From a therapeutic standpoint, vitiligo is still regarded by many physicians as a simple problem of regenerative medicine, with the main aim to repopulate the depigmented skin with functional melanocytes from the margins of the lesions or from intact progenitors in hair follicles. However, recent research in vitiligo suggests that various local triggers alert the skin immune innate system and may precede adaptive immune responses targeting melanocytes. This scenario is close to that of other common skin inflammatory disorders like psoriasis and atopic, and suggests to target as a priority this clinically silent inflammatory component of he disease. This perspective highlights possible targets for intervention. PMID:22099450

  1. 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

  2. First- and Third-Person Perspectives in Psychotic Disorders and Mood Disorders with Psychotic Features

    Directory of Open Access Journals (Sweden)

    Lucrezia Islam

    2011-01-01

    Full Text Available Lack of insight, very frequent in schizophrenia, can be considered a deficit in Theory of Mind (ToM performances, and is also found in other psychiatric disorders. In this study, we used the first- to third-person shift to examine subjects with psychotic and psychotic mood disorders. 92 patients were evaluated with SANS and SAPS scales and asked to talk about their delusions. They were asked to state whether they thought what they said was believable for them and for the interviewer. Two weeks later, 79 patients listened to a tape where their delusion was reenacted by two actors and were asked the same two questions. Some patients gained insight when using third-person perspective. These patients had lower SAPS scores, a lower score on SAPS item on delusions, and significant improvement in their SAPS delusion score at the second interview. Better insight was not related to a specific diagnostic group.

  3. Stem Cell Therapy in Pediatric Neurological Disorders

    OpenAIRE

    Farnaz Torabian; Arvin Aghayi Nejad; Arash Akhavan Rezayat; Mehran Beiraghi Toosi; Ali Reza Attaei Nakhaie; Hamid Reza Rahimi

    2015-01-01

    Pediatric neurological disorders including muscular dystrophy, cerebral palsy, and spinal cord injury are defined as a heterogenous group of diseases, of which some are known to be genetic. The two significant features represented for stem cells, leading to distinguish them from other cell types are addressed as below: they can renew themselves besides the ability to differentiate into cells with special function as their potency. Researches about the role of stem cells in repair of damaged t...

  4. 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.

  5. 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. PMID:26321974

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

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    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.

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

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    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

  8. Problems attract problems: a network perspective on mental disorders

    NARCIS (Netherlands)

    A.O.J. Cramer; D. Borsboom

    2015-01-01

    What is the nature of mental disorders such as major depression and panic disorder? Are mental disorders analogous to tumors, in that they exist as separate entities somewhere in people's minds? Do mental disorders cause symptoms such as insomnia and fatigue? Until very recently, it was exactly this

  9. Lived Experiences from the Perspective of Individuals with Autism Spectrum Disorder: A Qualitative Meta-Synthesis

    Science.gov (United States)

    DePape, Anne-Marie; Lindsay, Sally

    2016-01-01

    Autism spectrum disorder (ASD) includes deficits in social communication and repetitive behavior. Secondhand accounts from parents suggest that ASD affects many aspects of life. However, little is known about this disorder from first-person perspective. This meta-synthesis examines children, adolescents, and adults with ASD to understand their…

  10. Sex Differences in Stress-Related Psychiatric Disorders: Neurobiological Perspectives

    OpenAIRE

    Bangasser, Debra A.; Valentino, Rita J.

    2014-01-01

    Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease ...

  11. Nanotechnology Based Treatments for Neurological Disorders from Genetics Perspective

    OpenAIRE

    Kurek, Nicholas S.; Sathees B. Chandra

    2013-01-01

    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 nanoparti...

  12. The treatment of conduct disorder: Perspectives from across Canada

    OpenAIRE

    Moretti, M. M.; Emmrys, C.; Grizenko, N.; Holland, R.; Moore, K; Shamsie, J.; Hamilton, H

    1997-01-01

    Provides a synopsis of treatment programs for conduct-disordered children in Canada. Five groups of authors from British Columbia, Ontario, Quebec, and New Brunswick describe their approaches to the treatment of children with conduct disorder. All programs emphasize the need to use multimodal treatment schemes, including day and short-term residential care, as well as the need to base programs on identified factors associated with the development of conduct disorder.

  13. Peroxisome Biogenesis Disorders: Biological, Clinical and Pathophysiological Perspectives

    Science.gov (United States)

    Braverman, Nancy E.; D'Agostino, Maria Daniela; MacLean, Gillian E.

    2013-01-01

    The peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to multiple peroxisome enzyme deficiencies, complex developmental sequelae and progressive disabilities. Mammalian peroxisome assembly involves the protein products of 16 "PEX" genes;…

  14. 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…

  15. 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…

  16. 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…

  17. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W;

    2015-01-01

    Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency...... serum 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...

  18. [Cognitive behavioral treatments of bipolar disorder: current knowledge and perspectives].

    Science.gov (United States)

    Khazaal, Y; Pomini, V

    2006-09-20

    A significant proportion of patients with bipolar disorder experience relapse, psychosocial impairment and persistent symptoms despite available pharmacotherapy. Prognosis is frequently worsened by poor adhesion to mood stabilizing agents. Cognitive and behavioural therapy (CBT) tends to diminish depressive symptoms, improve treatment adherence and reduce the risk of depressive and manic relapses. CBT effect appears to diminish in patients with a history of over twelve episodes. Most studies exclude patients with comorbid psychiatric disorder, rapid cycling, schizoaffective disorder or patients lacking adherence to mood stabilizing agents. Patients would benefit from development of CBT techniques focusing on the mentioned problems. PMID:17073177

  19. 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

  20. 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.

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

    OpenAIRE

    Yoshie eYamaguchi; Young-A eLee; Yukiori eGoto

    2015-01-01

    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 f...

  2. Dopamine in socioecological and evolutionary perspectives: implications for psychiatric disorders

    OpenAIRE

    Yamaguchi, Yoshie; Lee, Young-A; Goto, Yukiori

    2015-01-01

    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 fun...

  3. Visual Perspective Taking Impairment in Children with Autistic Spectrum Disorder

    Science.gov (United States)

    Hamilton, Antonia F. de C.; Brindley, Rachel; Frith, Uta

    2009-01-01

    Evidence from typical development and neuroimaging studies suggests that level 2 visual perspective taking--the knowledge that different people may see the same thing differently at the same time--is a mentalising task. Thus, we would expect children with autism, who fail typical mentalising tasks like false belief, to perform poorly on level 2…

  4. 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…

  5. 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…

  6. 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.

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

    OpenAIRE

    Søren Ventegodt; Niels Jørgen Andersen; Shimshon Neikrug; Isack Kandel; Joav Merrick

    2005-01-01

    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 emo...

  8. 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

  9. 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.

  10. 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

  11. Outdoor Adventure & Eating Disorders: A Personal Perspective to Research.

    Science.gov (United States)

    Richards, Kaye

    1999-01-01

    A female outdoor educator who had recovered from anorexia nervosa reflects on the boundaries between her personal and professional identity as she anticipates taking on a research role in adventure-therapy programs. Gender issues in outdoor education are discussed in relation to women's body image and eating disorders. (SV)

  12. An eating disorder is more than just disordered eating Bio-psycho-social perspectives

    OpenAIRE

    Ahrén-Moonga, Jennie

    2009-01-01

    Several reports show that stress and psychiatric ill health are increasing in adolescents. Eating disorders (ED) and related conditions such as depression, self-injurious behaviour and suicide attempts are becoming more common, especially among young women. Eating disorders include two main categories: anorexia nervosa (self-starvation) and bulimia nervosa (binge eating and compensatory actions). These disorders do not only involve deviations in eating behaviour, but also in...

  13. Potential Hormonal Mechanisms of Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder: A New Perspective

    OpenAIRE

    Martel, Michelle M.; Klump, Kelly; Nigg, Joel T.; Breedlove, S. Marc; Sisk, Cheryl L.

    2009-01-01

    Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This ...

  14. A statistical perspective on association studies of psychiatric disorders

    DEFF Research Database (Denmark)

    Foldager, Leslie

    2014-01-01

    ), dichotomous trait (disease status) as well as genetic markers including GxG interactions. We use Tobit regression to handle data below the detection limit of MBL. The involvement of the immune system may also be less direct as seen by the findings how infections impact disorders, e.g. via interaction between......Gene-gene (GxG) and gene-environment (GxE) interactions likely play an important role in the aetiology of complex diseases like psychiatric disorders. Thus, we aim at investigating methodological aspects of and apply methods from statistical genetics taking interactions into account. In addition we...... from the X chromosome and discuss how to analyse with and without the assumption of inactivation of one of the female X chromosomes early in development. In addition this paper includes analysis of the interaction between genetic markers and age and sex. Haplotype analysis and other multilocus...

  15. 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.

  16. Thyroid disorders and radio iodine therapy: dental perspectives

    International Nuclear Information System (INIS)

    Thyroid disorders; hyper/hypothyroidism/thyroiditis/neoplasms are widely prevalent endocrine disorders. Oral manifestations of hyperthyroidism are increased susceptibility to caries, periodontal disease, maxillary/mandibular osteoporosis, premature shedding of deciduous teeth and early eruption of permanent teeth, sjogren and burning mouth syndromes. Undiagnosed/untreated hyperthyroidism often precipitates as 'Thyroid storm' during a stressful episode of surgical intervention/trauma. Hypothyroidism shows macroglossia, micrognathia, dysgeusia, thick lips, delayed eruption of teeth, poor periodontal health, enamel hypoplasia, anterior open bite, delayed wound healing and subnormal growth of jaws. Its congenital variant has underdeveloped mandible/overdeveloped maxilla, shortening of skull base and flaring of nostrils. Stomatodynia predominates in subacute thyroiditis. Radioactive iodine (131I) is a common mode of therapy for thyrotoxicosis and carcinomas; where its beta radiations cause destruction of thyroid follicles. Since all forms of iodine are actively taken up by the salivary glands, salivary dysfunction is a consequent of 131I therapy. It usually presents as xerostomia, mucositis, stomatitis, glossitis and dysguesia. Though reversible and dose-dependent to some extent, damage to bone marrow and gonads are also reported. It follows that thyroid disorders and its therapy with radio iodine show wide ranging side effects: both dental and general. In this context, this paper explains a novel method to evaluate these changes through salivary biochemistry, dental indices and periodontal markers. (author)

  17. 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

  18. Obsessive-Compulsive Disorder: Its What And How From An Islamic Perspective

    Directory of Open Access Journals (Sweden)

    Abdul Latif Abdul Razak

    2014-06-01

    Full Text Available Obsessive–Compulsive Disorder (OCD is a type of anxiety in which a person suffers from obsessions i.e. unwanted intrusive ideas which recur to the person persistently; and compulsions i.e. behaviours that a person feels compelled to perform epeatedly in a ritualistic manner with the aim of relieving the anxiety from the unpleasant obsessive thoughts. Although compulsion and obsession are common, once the individual experiences xcessive discomfort, then he or she would be diagnosed as a patient of this disorder. Most of the research outputs on this disorder are based on secular and irreligious perspectives. Thus, this research aims at religiously diagnosing its root causes and exploring its remedies based the Qur’an and Sunnah and the works of early Muslim scholars. The finding shows that this disorder, its etiology and treatment, has been extensively discussed in many works of early Muslim scholars that can be benefited by modern psychotherapists.

  19. Working memory genetics in schizophrenia and related disorders: An RDoC perspective.

    Science.gov (United States)

    Schwarz, Emanuel; Tost, Heike; Meyer-Lindenberg, Andreas

    2016-01-01

    Improved classification of mental disorders through neurobiological measures will require a set of traits that map to transdiagnostic subgroups of patients and align with heritable, core psychopathological processes at the center of the disorders of interest. A promising candidate is working memory (WM) function, for which deficits have been reported across multiple diagnostic entities including schizophrenia, bipolar disorder, ADHD, autism, and major depressive disorder. Here we review genetic working memory associations and their brain functional correlates from the perspective of identifying patient subgroups across conventional diagnostic boundaries, explore the utility of multimodal investigations integrating functional information at the neural systems level and explore potential limitations as well as future directions for research. PMID:26365198

  20. 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.

  1. Progenitor cells in the kidney: biology and therapeutic perspectives

    NARCIS (Netherlands)

    Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.

    2004-01-01

    Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of

  2. [Chronic B-cell lymphoproliferative disorders with hairy cells].

    Science.gov (United States)

    Troussard, Xavier; Cornet, Édouard

    2015-01-01

    The standardized blood smear examination is the first step in the diagnosis of a B-cell chronic lymphoproliferative disorder and can guide further investigations. In the laboratory, the identification of hairy cells on blood smear is a matter of daily practice. Hairy cell proliferations represent heterogeneous entities and their respective diagnoses can be difficult. If hairy cell leukemia (HCL) and splenic marginal zone lymphoma (SMZL) represent separate entities, the variant form of HCL (HCLv) and splenic diffuse red pulp small B-cell lymphoma (SDRPL) remain provisional entities in the 2008 WHO classification. We discuss the main clinical and biological characteristics of these four entities and appropriate means to characterize, identify and distinguish from each other; standardized blood smear examination, multiparameter flow cytometry analysis, analysis of the repertoire of immunoglobulins heavy chains genes and their mutational status (mutated or unmutated profile), molecular analyses: BRAF gene V600E mutation in HCL and MAP2K1 gene mutations in HCLv. We also discuss the main therapeutic aspects with emphasis on the new targeted drugs that enter into force in the therapeutic arsenal. PMID:25858127

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. Real space Dynamical Super Cell Approximation for interacting disordered systems

    OpenAIRE

    Moradian, Rostam

    2004-01-01

    Effective medium super-cell approximation method which is introduced for disordered systems is extended to a general case of interacting disordered systems. We found that the dynamical cluster approximation (DCA) and also the non local coherent potential approximation (NLCPA) are two simple case of this technique. Whole equations of this formalism derived by using the effective medium theory in real space.

  12. 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

  13. 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.

  14. An evolutionary perspective on the co-occurrence of social anxiety disorder and alcohol use disorder.

    Science.gov (United States)

    Bulley, Adam; Miloyan, Beyon; Brilot, Ben; Gullo, Matthew J; Suddendorf, Thomas

    2016-05-15

    Social Anxiety Disorder (SAD) commonly co-occurs with, and often precedes, Alcohol Use Disorder (AUD). In this paper, we address the relationship between SAD and AUD by considering how natural selection left socially anxious individuals vulnerable to alcohol use, and by addressing the underlying mechanisms. We review research suggesting that social anxiety has evolved for the regulation of behaviors involved in reducing the likelihood or consequences of threats to social status. The management of potential threats to social standing is important considering that these threats can result in reduced cooperation or ostracism - and therefore to reduced access to coalitional partners, resources or mates. Alcohol exerts effects upon evolutionarily conserved emotion circuits, and can down-regulate or block anxiety (or may be expected to do so). As such, the ingestion of alcohol can artificially signal the absence or successful management of social threats. In turn, alcohol use may be reinforced in socially anxious people because of this reduction in subjective malaise, and because it facilitates social behaviors - particularly in individuals for whom the persistent avoidance of social situations poses its own threat (i.e., difficulty finding mates). Although the frequent co-occurrence of SAD and AUD is associated with poorer treatment outcomes than either condition alone, a richer understanding of the biological and psychosocial drives underlying susceptibility to alcohol use among socially anxious individuals may improve the efficacy of therapeutic interventions aimed at preventing or treating this comorbidity. PMID:26914963

  15. B-cell survival factors in autoimmune rheumatic disorders

    Science.gov (United States)

    Morais, Sandra A.; Vilas-Boas, Andreia

    2015-01-01

    Autoimmune rheumatic disorders have complex etiopathogenetic mechanisms in which B cells play a central role. The importance of factors stimulating B cells, notably the B-cell activating factor (BAFF) and A proliferation inducing ligand (APRIL) axis is now recognized. BAFF and APRIL are cytokines essential for B-cell proliferation and survival from the immature stages to the development of plasma cells. Their levels are increased in some subsets of patients with autoimmune disorders. Several recent biologic drugs have been developed to block this axis, namely belimumab [already licensed for systemic lupus erythematosus (SLE) treatment], tabalumab, atacicept and blisibimod. Many clinical trials to evaluate the safety and efficacy of these drugs in several autoimmune disorders are ongoing, or have been completed recently. This review updates the information on the use of biologic agents blocking BAFF/APRIL for patients with SLE, rheumatoid arthritis, Sjögren’s syndrome and myositis. PMID:26288664

  16. Quality of care in psychosis and bipolar disorder from the service user perspective.

    Science.gov (United States)

    Skelly, Niamh; Schnittger, Rebecca I; Butterly, Lisa; Frorath, Charlotte; Morgan, Craig; McLoughlin, Declan M; Fearon, Paul

    2013-12-01

    According to the recovery model of mental health care, service development should incorporate the expert knowledge of service users. To date, there has been limited research into conceptualizations of mental health care quality among services users diagnosed with bipolar disorder or psychosis. To investigate service user perspectives on quality of care, we conducted six focus groups (N = 29) with inpatients and outpatients of an independent Irish mental health service. We undertook an inductive thematic analysis of the data. Participants identified proactive staff, meaningful and warm staff-patient interactions, and safety and sociability in the inpatient environment as components of good quality mental health care. Participants also discussed how the implementation of best practice guidelines does not necessarily improve quality of care from the service user perspective. This and similar qualitative research should be used to inform service development and the creation of evaluation instruments compatible with the recovery model. PMID:24163347

  17. Ethical perspectives on the management of disorders of sex development in children

    OpenAIRE

    Lathrop, Breanna

    2015-01-01

    Breanna Lathrop,1,2 Teresa B Cheney3 1Good Samaritan Health Center, Atlanta, GA, USA; 2South University, Savannah, GA, USA; 3AppleCare Immediate Care, LLC, Statesboro, GA, USA Abstract: The management of a child with disorders of sex development is complex from both a medical and sociocultural perspective. Decisions impacting the future sexual function and sex identity of the child are made on behalf of the child by their parents and health care providers. Such decisions are rarely straightf...

  18. 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.

  19. 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.

  20. 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...

  1. 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

  2. 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.

  3. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

    Directory of Open Access Journals (Sweden)

    Tim eKroon

    2013-10-01

    Full Text Available Brain function and behaviour undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability neurodevelopmental disorders (NDDs and their corresponding genetic mouse models, impairments in many neuronal and behavioural phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioural development (referred to also as ‘neurotypical’ development and timing of NDD impairments are not fully investigated.This perspective highlights temporal patterns of synaptic and neuronal impairment, with a restricted focus on autism and intellectual disability types of NDDs. Given the varying known genetic and environmental causes for NDDs, this perspective proposes two strategies for investigation: (1 a focus on neurobiological mechanisms underlying known critical periods in the (typically normal-developing brain (2 investigation of spatio-temporal expression profiles of genes implicated in monogenic syndromes throughout affected brain regions.This approach may help explain why many NDDs with differing genetic causes can result in overlapping phenotypes at similar developmental stages and better predict vulnerable periods within these disorders, with implications for both therapeutic rescue and ultimately, prevention.

  4. 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.

  5. 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.

  6. A perspective on microfluidic biofuel cells.

    Science.gov (United States)

    Lee, Jin Wook; Kjeang, Erik

    2010-01-01

    This review article presents how microfluidic technologies and biological materials are paired to assist in the development of low cost, green energy fuel cell systems. Miniaturized biological fuel cells, employing enzymes or microorganisms as biocatalysts in an environmentally benign configuration, can become an attractive candidate for small-scale power source applications such as biological sensors, implantable medical devices, and portable electronics. State-of-the-art biofuel cell technologies are reviewed with emphasis on microfabrication compatibility and microfluidic fuel cell designs. Integrated microfluidic biofuel cell prototypes are examined with comparisons of their performance achievements and fabrication methods. The technical challenges for further developments and the potential research opportunities for practical cell designs are discussed.

  7. 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.

  8. Optogenetic cell control in experimental models of neurological disorders.

    Science.gov (United States)

    Tønnesen, Jan

    2013-10-15

    The complexity of the brain, in which different neuronal cell types are interspersed and complexly interconnected, has posed a major obstacle in identifying pathophysiological mechanisms underlying prevalent neurological disorders. This is largely based in the inability of classical experimental approaches to target defined neural populations at sufficient temporal and spatial resolution. As a consequence, effective clinical therapies for prevalent neurological disorders are largely lacking. Recently developed optogenetic probes are genetically expressed photosensitive ion channels and pumps that in principal overcome these limitations. Optogenetic probes allow millisecond resolution functional control over selected optogenetically transduced neuronal populations targeted based on promoter activity. This optical cell control scheme has already been applied to answer fundamental questions pertaining to neurological disorders by allowing researchers to experimentally intercept, or induce, pathophysiological neuronal signaling activity in a highly controlled manner. Offering high temporal resolution control over neural activity at high cellular specificity, optogenetic tools constitute a game changer in research aiming at understanding pathophysiological signaling mechanisms in neurological disorders and in developing therapeutic strategies to correct these. In this regard, recent experimental work has provided new insights in underlying mechanisms, as well as preliminary proof-of-principle for optogenetic therapies, of several neurological disorders, including Parkinson's disease, epilepsy and progressive blindness. This review synthesizes experimental work where optogenetic tools have been applied to explore pathologic neural network activity in models of neurological disorders. PMID:23871610

  9. 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.

  10. 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.

  11. Treatment, deterrence or labelling: mentally disordered offenders' perspectives on social control.

    Science.gov (United States)

    Dixon, Jeremy

    2015-11-01

    Mentally disordered offenders are a group of service users who experience substantial amounts of control and supervision. This article uses theories of social control to analyse the way in which mechanisms of control are understood by this group. Semi-structured interviews with mentally disordered offenders in England who were subject to a restriction order under the Mental Health Act 1983 (as amended by the Mental Health Act 2007) provided the empirical basis for this study. The offenders had a number of perspectives on the restriction order. Firstly, it was seen as a mechanism for identifying those suffering from a mental disorder and for providing appropriate treatment. Secondly, the restriction order was viewed as a form of disciplinary control through which societal norms might be internalised. Thirdly, it was seen as labelling offenders in a manner that was experienced as limiting and oppressive. A number of research participants were aware that the order acted to limit staff actions. These participants saw the order as a means by which they might shape the support that they received in order to further their own aims.A video abstract of this article can be found at: https://www.youtube.com/watch?v=qwIwDI2sOTY&feature=youtu.be. PMID:26235431

  12. 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.

  13. Clinical perspectives of cancer stem cell research in radiation oncology

    International Nuclear Information System (INIS)

    Radiotherapy has a proven potential to eradicate cancer stem cells which is reflected by its curative potential in many cancer types. Considerable progress has been made in identification and biological characterisation of cancer stem cells during the past years. Recent biological findings indicate significant inter- and intratumoural and functional heterogeneity of cancer stem cells and lead to more complex models which have potential implications for radiobiology and radiotherapy. Clinical evidence is emerging that biomarkers of cancer stem cells may be prognostic for the outcome of radiotherapy in some tumour entities. Perspectives of cancer stem cell based research for radiotherapy reviewed here include their radioresistance compared to the mass of non-cancer stem cells which form the bulk of all tumour cells, implications for image- and non-image based predictive bio-assays of the outcome of radiotherapy and a combination of novel systemic treatments with radiotherapy

  14. Induced pluripotent stem cells for modeling neurological disorders.

    Science.gov (United States)

    Russo, Fabiele B; Cugola, Fernanda R; Fernandes, Isabella R; Pignatari, Graciela C; Beltrão-Braga, Patricia C B

    2015-12-24

    Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism. PMID:26722648

  15. 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.

  16. [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.

  17. 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...

  18. Single cell genomics: advances and future perspectives.

    OpenAIRE

    Macaulay, Iain C.; Thierry Voet

    2014-01-01

    Advances in whole-genome and whole-transcriptome amplification have permitted the sequencing of the minute amounts of DNA and RNA present in a single cell, offering a window into the extent and nature of genomic and transcriptomic heterogeneity which occurs in both normal development and disease. Single-cell approaches stand poised to revolutionise our capacity to understand the scale of genomic, epigenomic, and transcriptomic diversity that occurs during the lifetime of an individual organis...

  19. 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.

  20. 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

  1. 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…

  2. 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 (

  3. 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…

  4. 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.

  5. Experimental modification of perspective on thoughts and metacognitive beliefs in alcohol use disorder.

    Science.gov (United States)

    Caselli, Gabriele; Gemelli, Antonella; Spada, Marcantonio M; Wells, Adrian

    2016-10-30

    Metacognitive therapy is designed to impact directly on cognitive monitoring and control processes such that individuals can develop alternative ways of experiencing and regulating thoughts. One technique used for this purpose is 'detached mindfulness' which promotes a decentred perspective to thoughts and decouples repetitive thinking and coping from their occurrence. This study set out to test the effects of detached mindfulness against a control condition, a brief exposure to alcohol-related thoughts. Eight patients diagnosed with alcohol use disorder in an abstinence regime were exposed to detached mindfulness versus brief exposure in a counterbalanced repeated-measures design. Results showed that detached mindfulness led to significantly greater decreases in meta-appraisal and metacognitive beliefs about alcohol-related thoughts compared to a brief exposure. Significantly greater decreases in distress and urge to use alcohol were also observed in detached mindfulness. The clinical implications are discussed. PMID:27467702

  6. 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.

  7. New generation solar cells: Concepts, trends and perspectives

    OpenAIRE

    Ragoussi, Maria Eleni; Torres, Tomás

    2015-01-01

    Organic, dye-sensitized and perovskite solar cell technologies have triggered widespread interest in recent years due to their very promising potential towards a high solar electricity future. A number of important milestones have marked the roadmap of each sector on the way to today's outstanding performances, but there still remains plenty of scope for further improvement. The most influential landmarks, together with basic concepts and future perspectives, are unraveled in this review

  8. An update on stem cell transplantation in autoimmune rheumatologic disorders.

    Science.gov (United States)

    Mascarenhas, Sheryl; Avalos, Belinda; Ardoin, Stacy P

    2012-12-01

    Stem cell transplant (SCT) has long been the standard of care for several hematologic, immunodeficient, and oncologic disorders. Recently, SCT has become an increasingly utilized therapy for refractory autoimmune rheumatologic disorders (ARDs). The efficacy of SCT in ARDs has been attributed to resetting an aberrant immune system either through direct immune replacement with hematopoietic stem cells or through immunomodulation with mesenchymal stem cells. Among ARDs, refractory systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are the most common indications for SCT. SCT has also been used in refractory rheumatoid arthritis, inflammatory myopathies, antiphospholipid syndrome, granulomatosis with polyangiitis, and pediatric ARDs. Complete responses have been reported in approximately 30 % of patients in all disease categories. Transplant-related mortality, however, remains a concern. Future large multi-center prospective randomized clinical trials will help to better define the specific role of SCT in the treatment of patients with ARDs. PMID:22956390

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Marina Kukla, PhD

    2015-08-01

    Full Text Available 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.

  11. 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.

  12. An historical perspective on cell mechanics.

    Science.gov (United States)

    Pelling, Andrew E; Horton, Michael A

    2008-04-01

    The physical properties of the protoplasm have long been of interest, and today, several intricate methods, including atomic force microscopy, have been employed in studies of cellular mechanics. However, many current concepts and experimental approaches actually have their beginnings over 300 years ago. Unfortunately, these pioneering studies have been all but forgotten. In this paper, we have reviewed some of the early literature on cellular mechanics to place modern work within an historical framework. It is clear that with current nanoscience approaches, modern experiments employing cell indentation, manipulation, particle rheology and micro- or nano-needle poking are now quantifying mechanical properties which were only qualitatively described 100 years ago. Aside from the variety of approaches our predecessors have employed to understand cellular mechanics, we feel an understanding of the past will help to propel nanoscience into the future. As nanophysiology and nanomedicine are developing, we as a community should take time to consider the early roots of these fields. PMID:18064487

  13. 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.

  14. 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.

  15. 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.

  16. Role of Corticotropin Releasing Factor in Anxiety Disorders: A Translational Research Perspective

    OpenAIRE

    Risbrough, Victoria B.; Stein, Murray B.

    2006-01-01

    Anxiety disorders are a group of mental disorders that include generalized anxiety disorder (GAD), panic disorder, phobic disorders (e.g., specific phobias, agoraphobia, social phobia) and posttraumatic stress disorder (PTSD). Anxiety disorders are among the most common of all mental disorders and, when coupled with an awareness of the disability and reduced quality of life they convey, they must be recognized as a serious public health problem. Over 20 years of preclinical studies point to a...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. New perspectives in human stem cell therapeutic research

    Directory of Open Access Journals (Sweden)

    Trounson Alan

    2009-06-01

    Full Text Available Abstract Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action of many of these cells are unknown and this raises the concern of unpredictable results in the future. Nevertheless there is considerable optimism that immune suppression and anti-inflammatory properties of mesenchymal stem cells will be of benefit for many conditions such as graft versus host disease, solid organ transplants and pulmonary fibrosis. Where bone marrow and mesenchymal stem cells are being studied for heart disease, stroke and other neurodegenerative disorders, again progress is mixed and mostly without significant benefit. However, correction of multiple sclerosis, at least in the short term is encouraging. Clinical trials on the use of embryonic stem cell derivatives for spinal injury and macular degeneration are beginning and a raft of other clinical trials can be expected soon, for example, the use of neural stem cells for killing inoperable glioma and embryonic stem cells for regenerating β islet cells for diabetes. The change in attitude to embryonic stem cell research with the incoming Obama administration heralds a new co-operative environment for study and evaluation of stem cell therapies. The Californian stem cell initiative (California Institute for Regenerative Medicine has engendered global collaboration for this new medicine that will now also be supported by the US Federal Government. The active participation of governments, academia, biotechnology, pharmaceutical companies, and private investment is a powerful consortium for

  2. 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.

  3. 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.

  4. Candidaemia in patients with haematological disorders and stem cell transplant

    Directory of Open Access Journals (Sweden)

    AM Al-Jasser

    2006-11-01

    Full Text Available The incidence of non-albicans species of Candida has recently increased, especially in patients with malignant haematological disorders receiving fluconazole prophylaxis. A retrospective study of patients who developed candidaemia at Riyadh Armed Forces Hospital between January 1992 and December 2002 was carried out. Thirty one episodes of candidaemia occurred in 27 patients with a variety of haematological disorders. Twenty-four episodes were caused by non-albicans species of Candida and only 7 episodes were caused by C.albicans. The most frequent underlying haematological disorders were acute myeloid leukaemia (AML followed by acute lymphoblastic leukaemia (ALL. The main predisposing factors for the development of candidaemia were: broad spectrum antibiotics, central venous catheters, neutropenia, cytotoxic chemotherapy, coexisting bacterial infections, steroid therapy, relapsing or untreated primary disease and fluconazole prophylaxis.Eight episodes were complicated by chronic disseminated candidiasis. Amphotericin-B and amBisome were used in the treatment of Candida infections. The treatment was successful in 86% of the episodes of C. albicans and 50% of the episodes due to non-albicans species of Candida. The highest mortality rate was encountered with C.tropicalis infections.Candidaemia is an important cause of mortality and morbidity in patients with malignant haematological disorders and stem cell transplant. The predominance of non-albicans species of Candida especially C.krusei and C.tropicalis is alarming. The early administration of appropriate antifungal therapy and the removal of infected intravascular catheters improve the outcome considerably.

  5. 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.

  6. A perspective on the proposal for neurocognitive disorder criteria in DSM-5 as applied to HIV-associated neurocognitive disorders

    OpenAIRE

    Goodkin, Karl; Fernandez, Francisco; Forstein, Marshall; Miller, Eric N.; Becker, James T; Douaihy, Antoine; Cubano, Luis; Santos, Flavia H; Filho, Nelson Silva; Zirulnik, Jorge; Singh, Dinesh

    2011-01-01

    HIV-associated neurocognitive disorders remain common in the current era of effective antiretroviral therapy. However, the severity at presentation of these disorders has been reduced, and the typical manifestations have changed. A revision of the American Academy of Neurology (AAN) criteria has been made on this basis, and a revision of the analogous criteria by the American Psychiatric Association will be forthcoming in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5. This...

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

    OpenAIRE

    Hees, Hiske L.; Karen Nieuwenhuijsen; Koeter, Maarten W.J.; Ute Bültmann; 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 (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 quant...

  8. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling.

    Science.gov (United States)

    Rock, Jason R; Randell, Scott H; Hogan, Brigid L M

    2010-01-01

    The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling', affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease. PMID:20699479

  9. Veterans' Perspectives on Benefits and Drawbacks of Peer Support for Posttraumatic Stress Disorder.

    Science.gov (United States)

    Hundt, Natalie E; Robinson, Andrew; Arney, Jennifer; Stanley, Melinda A; Cully, Jeffrey A

    2015-08-01

    Peer support has been increasingly utilized within the Department of Veterans Affairs and offers an opportunity to augment existing care for posttraumatic stress disorder (PTSD). The current study sought to examine Veterans' perspectives on the potential benefits and drawbacks of peer support for PTSD. A sample of 23 Veterans with substantial treatment experience completed one-time qualitative interviews that were transcribed and coded for thematic content using grounded theory methodology. Results indicated that Veterans identified numerous potential benefits to a peer support program, including social support, purpose and meaning, normalization of symptoms and hope, and therapeutic benefits. Veterans also identified ways that peer support could complement psychotherapy for PTSD by increasing initiation and adherence to treatment and supporting continued use of skills after termination. Results also indicated that Veterans may prefer peer support groups that are separated according to trauma type, gender, and era of service. Other findings highlighted the importance of the leadership and interpersonal skills of a peer support group leader. Overall, Veterans found peer support to be a highly acceptable complement to existing PTSD treatments with few drawbacks. PMID:26226526

  10. 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.

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

    Science.gov (United States)

    Vogl, Julia; Heine, Astrid M; Steinhoff, Nikolaus; Weiss, Konrad; Tucek, Gerhard

    2015-01-01

    A growing understanding of music therapy with patients with disorders of consciousness (DOC) 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. PMID:26300720

  12. 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.

  13. The Use of Pluripotent Stem Cell for Personalized Cell Therapies against Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Hye-Yeong Ha

    2011-01-01

    Full Text Available Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.

  14. The role of mast cells in functional GI disorders.

    Science.gov (United States)

    Wouters, Mira M; Vicario, Maria; Santos, Javier

    2016-01-01

    Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia. PMID:26194403

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Neural Stem Cell Regulation, Fibroblast Growth Factors, and the Developmental Origins of Neuropsychiatric Disorders

    OpenAIRE

    Hanna E Stevens; Smith, Karen M.; Brian Rash; Vaccarino, Flora M.

    2010-01-01

    There is increasing appreciation for the neurodevelopmental underpinnings of many psychiatric disorders. Disorders that begin in childhood such as autism, language disorders or mental retardation as well as adult-onset mental disorders may have origins early in neurodevelopment. Neural stem cells (NSCs) can be defined as self-renewing, multipotent cells that are present in both the embryonic and adult brain. Several recent research findings demonstrate that psychiatric illness may begin with ...

  20. 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

  1. 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.

  2. 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

  3. Modeling Neurological Disorders by Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Tanut Kunkanjanawan

    2011-01-01

    Full Text Available Studies of human brain development are critical as research on neurological disorders have been progressively advanced. However, understanding the process of neurogenesis through analysis of the early embryo is complicated and limited by a number of factors, including the complexity of the embryos, availability, and ethical constrains. The emerging of human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs has shed light of a new approach to study both early development and disease pathology. The cells behave as precursors of all embryonic lineages; thus, they allow tracing the history from the root to individual branches of the cell lineage tree. Systems for neural differentiation of hESCs and iPSCs have provided an experimental model that can be used to augment in vitro studies of in vivo brain development. Interestingly, iPSCs derived from patients, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. This paper summarizes the recent reports of the development of iPSCs from patients who suffer from neurological diseases and evaluates the feasibility of iPSCs as a disease model. The benefits and obstacles of iPSC technology are highlighted in order to raising the cautions of misinterpretation prior to further clinical translations.

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

    OpenAIRE

    Lee, Young-A; Yamaguchi, Yoshie; Goto, Yukiori

    2015-01-01

    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 generati...

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

    OpenAIRE

    Young-A Lee; Yoshie Yamaguchi; Yukiori Goto

    2015-01-01

    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 gener...

  6. Caregiver Perspectives about Assistive Technology Use with Their Young Children with Autism Spectrum Disorders

    Science.gov (United States)

    Cardon, Teresa A.; Wilcox, M. Jeanne; Campbell, Philippa H.

    2011-01-01

    The purpose was to examine how caregivers of infants and toddlers with autism spectrum disorder view their daily activities/routines and in what way, if any, assistive technology (AT) acts as a support. A total of 134 families who reported their child's disability as autism spectrum disorder/pervasive developmental disorder completed a survey…

  7. 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.

  8. 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.

  9. The promise of stem cell research for neuropsychiatric disorders

    OpenAIRE

    Vaccarino, Flora M.; Urban, Alexander Eckehart; Stevens, Hanna; Szekely, Anna; Abyzov, Alexej; Grigorenko, Elena; 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, attention deficit hyperactivity disorder, obsessive compulsive disorder and many other neurodevelopmental conditions. However, precisely how genes may f...

  10. Human DNA repair disorders in dermatology: A historical perspective, current concepts and new insight.

    Science.gov (United States)

    Moriwaki, Shinichi

    2016-02-01

    Products of DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4 PPs), are continually formed in genomes after exposure to UV radiation. When these DNA damages remain unrepaired in essential DNA sites for prolonged periods, DNA replication and transcription are hampered or mutation is induced, which may cause cell death, cellular senescence, and carcinogenesis of the skin. To protect against such UV-induced DNA damage, living organisms nicely retain "DNA repair systems", which can efficiently repair "harmful" DNA damage through precise mechanisms by the integrated functions of many proteins. In humans, the failure of DNA repair systems causes a variety of disorders. Dermatological conditions such as hereditary photodermatoses, xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are caused by congenital functional defects in the nucleotide excision repair (NER) system or the translesion synthesis (TLS) system. In this review, we describe the historical progress, recent findings, and future prospects of studies of human diseases associated with DNA-repair defects. PMID:26493104

  11. 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.

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

    OpenAIRE

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

    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...

  13. 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.

  14. Pulmonary Langerhans Cell Histiocytosis: An Update From the Pathologists' Perspective.

    Science.gov (United States)

    Roden, Anja C; Yi, Eunhee S

    2016-03-01

    Context .- Pulmonary Langerhans cell histiocytosis (PLCH) is a rare histiocytic disorder that almost exclusively affects the lungs of smokers. PLCH is characterized by bronchiolocentric nodules and/or cysts in an upper and mid lung distribution with sparing of the costophrenic angles. The diagnosis can be challenging and often requires transbronchial biopsy or surgical lung biopsy. Pulmonary hypertension is a relatively common and sometimes severe complication of PLCH. The pathogenesis of PLCH is still debated. Recently, BRAF V600E mutation and BRAF expression have been identified in some patients with PLCH, suggesting that at least a subset of PLCH has a clonal proliferation. While smoking cessation is the first-line treatment of PLCH, some patients might require additional treatment and eventually transplant. Given that the lesional cells of PLCH express BRAF in some patients, MAPKinase pathway-targeted treatment might be useful for therapy-resistant patients. Objective . -To present the more recently recognized clinical and pathologic aspects of PLCH, including pulmonary hypertension in PLCH, pathogenesis, and treatment, as well as the basic diagnostic approach to PLCH. Data Sources .- Authors' own research, and search of literature database (PubMed) and UpToDate. Conclusions . -Despite the recent progress, more studies are needed to elucidate the biology of PLCH for identification of prognostic factors and appropriate treatment options, especially for therapy-refractory PLCH cases. PMID:26927717

  15. 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…

  16. 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…

  17. 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

  18. A modal perspective on the transverse Anderson localization of light in disordered optical lattices

    CERN Document Server

    Karbasi, Salman; Mafi, Arash

    2013-01-01

    We frame the transverse Anderson localization of light in a one-dimensional disordered optical lattice in the language of localized propagating eigenmodes. The modal analysis allows us to explore localization behavior of a disordered lattice independent of the properties of the external excitation. Various localization-related phenomena, such as the periodic revival of a propagating Anderson-localized beam are easily explained in modal language. We characterize the localization strength by the average width of the guided modes and carry out a detailed analysis of localization behavior as a function of the optical and geometrical parameters of the disordered lattice. We also show that in order to obtain a minimum average mode width, the average width of the individual random sites in the disordered lattice must be larger than the wavelength of the light by approximately a factor of two or more, and the optimum site width for the maximum localization depends on the design parameters of the disordered lattice.

  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...... 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...... or a schizophrenia spectrum disorder had lower RTT scores, controlling for verbal IQ and age, compared to those who did not develop any mental illness. Although in the expected direction, RTT scores for those with schizophrenia spectrum disorders were not significantly different from those who developed a non...

  20. 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.

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

    OpenAIRE

    Sabine Wislet-Gendebien; Emerence Laudet; Virginie Neirinckx; Bernard Rogister

    2012-01-01

    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 th...

  2. 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

  3. 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.

  4. Reconsideration of animal models of schizophrenia and other psychiatric disorders with evolutionary perspective.

    OpenAIRE

    Lee, Young-A; Goto, Yukiori

    2013-01-01

    Studies utilizing animal models for understanding biological mechanisms of such psychiatric disorders as schizophrenia have been now flourishing. Animal models are a essential part of translational research, and without them, it is not possible to develop therapeutic strategies to treat psychiatric disorders. Accordingly, importance of animal models has been increasingly emphasized. However, on the other side, limitations of such an animal model approach have been growingly deceptive. The aim...

  5. RDoC and Translational Perspectives on the Genetics of Trauma-Related Psychiatric Disorders

    OpenAIRE

    Montalvo-Ortiz, Janitza L; Gelernter, Joel; Hudziak, James; Kaufman, Joan

    2015-01-01

    Individuals with a history of child abuse are at high risk for depression, anxiety disorders, aggressive behavior, and substance use problems. The goal of this paper is to review studies of the genetics of these stress-related psychiatric disorders. An informative subset of studies that examined candidate gene by environment (GxE) predictors of these psychiatric problems in individuals maltreated as children is reviewed, together with extant genome wide association studies (GWAS). Emerging fi...

  6. How do women under the care of eating disorder services experience sibling relationships: a phenomenological perspective

    OpenAIRE

    Smith, Jennifer Anne

    2011-01-01

    Eating disorders are increasing in our society and prior research has considered the role of families, carers, partners and children in the development of these difficulties. Siblings, however, have been largely overlooked. The role of sibling relationships is not well understood, despite siblings being a long term, significant feature of many individuals with eating disorders’ lives. This study aims to investigate the experiences of women with eating disorders and their sib...

  7. "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.

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

    OpenAIRE

    Lopes, R; Fernandes, L

    2012-01-01

    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 “de...

  9. 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…

  10. 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…

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

    OpenAIRE

    Bernsen, Roos; Jongste, Johan; 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 of 700 families were collected in this retrospective study. A minority of these 700 families refused vaccinations for religious reasons. The relation between pertussis-vaccination status and atopic disorders was an...

  12. 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.

  13. 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…

  14. 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…

  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. Experiences of emergency department care from the perspective of families in which a child has autism spectrum disorder.

    Science.gov (United States)

    Nicholas, David B; Zwaigenbaum, Lonnie; Muskat, Barbara; Craig, William R; Newton, Amanda S; Kilmer, Christopher; Greenblatt, Andrea; Roberts, Wendy; Cohen-Silver, Justine

    2016-07-01

    Care for children with autism spectrum disorder (ASD) in the emergency department (ED) is increasingly recognized as difficult. Communication, sensory and behavioral challenges in a high intensity environment pose risks for negative experiences and outcomes. Through semi-structured interviews, parents (n = 31) and their children (n = 4) with ASD shared their perspectives on ED care. Participants identified issues that negatively affected care experiences, including care processes, communication issues, insufficient staff knowledge about ASD, and inadequate partnership with parents. Elements contributing to an improved ED experience were also cited, including staff knowledge about ASD, child- and family-centered care, and clarity of communication. Findings inform an emerging model of ED care. Recommendations for capacity building and practice development are offered. PMID:27315287

  17. 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.

  18. 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…

  19. 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

  20. Eating disorders and equine therapy: a nurse's perspective on connecting through the recovery process.

    Science.gov (United States)

    Dezutti, Joyce E

    2013-09-01

    Patients with eating disorders may have the most complex interdisciplinary treatment plans of any mental illness. Nurses need innovative evidence-based treatment interventions to assist their patients with eating disorders on their road to recovery. Although much has been written about equine-assisted psychotherapy (EAP) and equine-facilitated psychotherapy, the literature has not described a detailed session that can help nurses understand how this experiential treatment works and the impact it can have on the patient. A review of the literature on eating disorders and on the use of equine therapy in its treatment is presented in this article. In addition, the role of the nurse during equine therapy will be highlighted, and an individual example will provide a detailed review of an EAP session. PMID:23786240

  1. Eating disorders among adolescents in South African public schools – a biblical perspective

    Directory of Open Access Journals (Sweden)

    S. Schoeman

    2005-07-01

    Full Text Available Society’s obsession with thinness and body image is part of every school’s hidden curriculum. The ideal to be skinny and thin resulted in an escalation in eating disorders among adolescents in South Africa. Some of the learners are only in the senior phase (Grades 7 to 9 of the general education and training band. It is therefore timely to review the problem of eating disorders, especially among adolescents in South African public schools. The purpose of this article is firstly to provide policy-makers, curriculum developers, educational ad-ministrators and educators with knowledge of the biblical view of health and to illustrate the pedagogical potential of such a view. Secondly the purpose is to assist Christian educators in teaching learners in public schools the necessary knowledge, skills, values and attitudes to counteract eating disorders by using, among other things, biblical truths.

  2. Delayed sleep phase disorder: clinical perspective with a focus on light therapy

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2016-04-01

    Full Text Available Mariana G Figueiro Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USAAbstract: Delayed sleep phase disorder (DSPD is common among adolescents and further increases their susceptibility to chronic sleep restriction and associated detrimental outcomes, including increased risk of depression, drug and alcohol use, behavioral problems, and poor scholastic performance. DSPD is characterized by sleep onset that occurs significantly later than desired bedtimes and societal norms. Individuals with DSPD exhibit long sleep latencies when attempting to sleep at conventional bedtimes. Circadian sleep disorders such as DSPD can occur when there is misalignment between sleep timing and societal norms. This review discusses studies using light therapy to advance the timing of sleep in adolescents and college students, in particular on those suffering from DSPD. A discussion on how to increase effectiveness of light therapy in the field will also be provided.Keywords: circadian, melatonin, light, sleep, sleep phase disorder, adolescents

  3. [Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder].

    Science.gov (United States)

    Tanaka, Teruaki; Inoue, Takeshi; Suzuki, Katsuji; Kitaichi, Yuji; Masui, Takuya; Denda, Kenzo; Koyama, Tsukasa

    2007-01-01

    Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to

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

    Science.gov (United States)

    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 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 these young persons' problems. PMID:24875238

  5. 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.

  6. 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…

  7. Strengthening the Status of Psychotherapy for Personality Disorders: An Integrated Perspective on Effects and Costs

    NARCIS (Netherlands)

    A. Bartak (Anna); D.I. Soeteman (Djora); R. Verheul (Roel); J.J. van Busschbach (Jan)

    2007-01-01

    textabstractObjective: Despite scientific evidence of effectiveness, psychotherapy for personality disorders is not yet fully deployed, nor is its reimbursement self-evident. Both clinicians and health care policy-makers increasingly rely on evidence-based medicine and health economics when determin

  8. 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…

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

    NARCIS (Netherlands)

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

  10. A longitudinal perspective on childhood adversities and onset risk of various psychiatric disorders

    NARCIS (Netherlands)

    Oldehinkel, Albertine J; Ormel, Johan

    2015-01-01

    It is well-known that childhood adversities can have long-term effects on mental health, but a lot remains to be learned about the risk they bring about for a first onset of various psychiatric disorders, and how this risk develops over time. In the present study, which was based on a Dutch longitud

  11. 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…

  12. 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…

  13. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

    OpenAIRE

    Tim eKroon; Martijn eSierksma; Rhiannon Mair Meredith

    2013-01-01

    Brain function and behaviour undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability neurodevelopmental disorders (NDDs) and their corresponding genetic mouse models, impairments in many neuronal and behavioural phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioural development (referred to...

  14. Living with a Brother Who Has an Autism Spectrum Disorder: A Sister's Perspective

    Science.gov (United States)

    Connell, Zara O.; Halloran, Maeve O.; Doody, Owen

    2016-01-01

    People with Autism Spectrum Disorder (ASD) are born into families and influence family functioning both positively and negatively. One of the most enduring relationships a person with ASD will have is their relationship with a brother or sister. Services for people with ASD should provide effective support to families, which include brothers,…

  15. 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…

  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. 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. T follicular helper (Tfh ) cells in normal immune responses and in allergic disorders.

    Science.gov (United States)

    Varricchi, G; Harker, J; Borriello, F; Marone, G; Durham, S R; Shamji, M H

    2016-08-01

    Follicular helper T cells (Tfh ) are located within germinal centers of lymph nodes. Cognate interaction between Tfh , B cells, and IL-21 drives B cells to proliferate and differentiate into plasma cells thereby leading to antibody production. Tfh cells and IL-21 are involved in infectious and autoimmune diseases, immunodeficiencies, vaccination, and cancer. Human peripheral blood CXCR5(+) CD4(+) T cells comprise different subsets of Tfh -like cells. Despite the importance of the IgE response in the pathogenesis of allergic disorders, little is known about the role of follicular and blood Tfh cells and IL-21 in human and experimental allergic disease. Here, we review recent advances regarding the phenotypic and functional characteristics of both follicular and blood Tfh cells and of the IL-21/IL-21R system in the context of allergic disorders. PMID:26970097

  19. Role of Stem Cells in Treatment of Neurological Disorder

    OpenAIRE

    Ul Hassan, Ashfaq; Hassan, Ghulam; Rasool, Zahida

    2009-01-01

    Stem cells or mother or queen of all cells are pleuropotent and have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood c...

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

    OpenAIRE

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

    2013-01-01

    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 in...

  1. 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

    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...... 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...

  2. 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.

  3. 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.

  4. The comorbidity of bipolar disorder and cardiovascular diseases from pharmacotherapy perspective.

    Science.gov (United States)

    Vuksan-Cusa, Bjanka; Marcinko, Darko; Sagud, Marina; Jakovljević, Miro

    2009-09-01

    The heart and mind are intimately linked. Patients with severe mental disorders have increased mortality rates compared with the general population and the leading cause of premature death is cardiovascular disease (CVD). Despite their high prevalence and substantial medical impact, comorbidity between cardiac conditions and psychiatric illnesses frequently go undiagnosed and untreated. It is very interesting to investigate the impact of mental health on cardiac disease and what is the complex underlying mechanism that links these two conditions. PMID:19794361

  5. THE COMORBIDITY OF BIPOLAR DISORDER AND CARDIOVASCULAR DISEASES FROM PHARMACOTHERAPY PERSPECTIVE

    OpenAIRE

    Vuksan–Ćusa, Bjanka; Marčinko, Darko; Šagud, Marina; Jakovljević, Miro

    2009-01-01

    The heart and mind are intimately linked. Patients with severe mental disorders have increased mortality rates compared with the general population and the leading cause of premature death is cardiovascular disease (CVD). Despite their high prevalence and substantial medical impact, comorbidity between cardiac conditions and psychiatric illnesses frequently go undiagnosed and untreated. It is very interesting to investigate the impact of mental health on cardiac disease and what is the com...

  6. Psychiatric disorders and aggression in the printed media: is there a link? a central European perspective

    OpenAIRE

    Nawka Alexander; Rukavina Tea; Nawková Lucie; Jovanović Nikolina; Brborović Ognjen; Raboch Jiří

    2012-01-01

    Abstract Background A content analysis was used to describe the association between psychiatric disorders and aggression in the printed media in the Czech Republic and Slovakia. Methods Articles were chosen from the most widely read daily newspapers and magazines in both countries during five one-week periods in 2007. A coding manual was developed and a content analysis was performed. Aggressive behavior was assessed by two separate categories - the role of the mentally ill person in the viol...

  7. Obsessive-Compulsive Disorder: Its What And How From An Islamic Perspective

    OpenAIRE

    Abdul Latif Abdul Razak

    2014-01-01

    Obsessive–Compulsive Disorder (OCD) is a type of anxiety in which a person suffers from obsessions i.e. unwanted intrusive ideas which recur to the person persistently; and compulsions i.e. behaviours that a person feels compelled to perform epeatedly in a ritualistic manner with the aim of relieving the anxiety from the unpleasant obsessive thoughts. Although compulsion and obsession are common, once the individual experiences xcessive discomfort, then he or she would be diagnosed as a pa...

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

    OpenAIRE

    Julia eVogl; Astrid Maria Heine; Nikolaus eSteinhoff; Konrad eWeiss; Gerhard eTucek

    2015-01-01

    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...

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

    OpenAIRE

    Vogl, Julia; Heine, Astrid M.; Steinhoff, Nikolaus; Weiss, Konrad; Tucek, Gerhard

    2015-01-01

    A growing understanding of music therapy with patients with disorders of consciousness (DOC) 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 resear...

  10. 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.

  11. Values as determinant of meaning among patients with psychiatric disorders in the perspective of recovery.

    Science.gov (United States)

    Huguelet, Philippe; Guillaume, Sébastien; Vidal, Sonia; Mohr, Sylvia; Courtet, Philippe; Villain, Lucile; Girod, Chloé; Hasler, Roland; Prada, Paco; Olié, Emilie; Perroud, Nader

    2016-01-01

    Recovery is a personal process of growth that involves hope, self-identity, meaning in life and responsibility. Determinants of meaning have not been explored among populations of patients with persistent psychiatric conditions. However, an evidence-based approach aiming at assessing such determinants should provide some insight into the psychotherapeutic aspects of recovery. We tested a model hypothesizing that some symptoms and social parameters of patients are related to values, and secondarily to meaning in life, and in turn that meaning is associated with various parameters, such as depressiveness and self-esteem. We assessed 176 patients with schizophrenia, anorexia, borderline personality disorder and bipolar disorder. Overall, our hypotheses proved correct: firstly, characteristics such as depression, hopelessness, self-esteem and the number of relationships influenced values; secondly, the presence and an enactment of values were associated with meaning, and thirdly, meaning was associated with some symptoms and social characteristics. This model was confirmed in the four psychiatric populations under study. These results support the relevance of addressing values and meaning in the recovery-oriented care of patients with persistent psychiatric disorders, in addition to other psychosocial interventions which are more systematically considered in this area. PMID:27272094

  12. 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.

  13. 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.

  14. 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.

  15. Undifferentiated negative affect and impulsivity in borderline personality and depressive disorders: A momentary perspective.

    Science.gov (United States)

    Tomko, Rachel L; Lane, Sean P; Pronove, Lisa M; Treloar, Hayley R; Brown, Whitney C; Solhan, Marika B; Wood, Phillip K; Trull, Timothy J

    2015-08-01

    Individuals with borderline personality disorder (BPD) often report experiencing several negative emotions simultaneously, an indicator of "undifferentiated" negative affect. The current study examined the relationship between undifferentiated negative affect and impulsivity. Participants with a current BPD (n = 67) or depressive disorder (DD; n = 38) diagnosis carried an electronic diary for 28 days, reporting on emotions and impulsivity when randomly prompted (up to 6 times per day). Undifferentiated negative affect was quantified using momentary intraclass correlation coefficients, which indicated how consistently negative emotion items were rated across fear, hostility, and sadness subscales. Undifferentiated negative affect at the occasion-level, day-level, and across 28 days was used to predict occasion-level impulsivity. Multilevel modeling was used to test the hypothesis that undifferentiated negative emotion would be a significant predictor of momentary impulsivity above and beyond levels of overall negative affect. Undifferentiated negative affect at the occasion and day levels were significant predictors of occasion-level impulsivity, but undifferentiated negative affect across the 28-day study period was only marginally significant. Results did not differ depending on BPD or DD status, though individuals with BPD did report significantly greater momentary impulsivity and undifferentiated negative affect. Undifferentiated negative affect may increase risk for impulsivity among individuals with BPD and depressive disorders, and the current data suggest that this process can be relatively immediate as well as cumulative over the course of a day. This research supports the consideration of undifferentiated negative affect as a transdiagnostic construct, but one that may be particularly relevant for those with BPD. PMID:26147324

  16. Cognitive and Neural Aspects of Information Processing in Major Depressive Disorder: An Integrative Perspective

    Directory of Open Access Journals (Sweden)

    Lara Catherine Foland-Ross

    2012-11-01

    Full Text Available Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder.

  17. 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 in...... order to promote a fuller understanding of the implications of comorbidity and to exploit its potential value with regard to etiopathogenic and therapeutic issues. This position paper makes recommendations of improved methodological standards and procedures and discusses a range of options that can...

  18. Fetal Alcohol Spectrum Disorders and Challenges Faced by Caregivers: Clinicians' Perspectives.

    Science.gov (United States)

    Baskin, Jonathan; Delja, Jolie R; Mogil, Catherine; Gorospe, Clarissa M; Paley, Blair

    2016-01-01

    BackgroundThere is a notable absence of evidence based early interventions for young children with FASD.  ObjectiveThis study examines clinicians' perspectives regarding the needs of caregivers of children with FASD and how such perspectives informed the development of a family-centered early intervention for young children with prenatal alcohol exposure.  Method19 professionals who work with children with prenatal alcohol exposure and / or in out-of-home care were recruited to participate in focus groups. The facilitator used a semi-structured topic guide to elicit feedback from participants. These data were transcribed, coded, and categorized to reflect themes in a manner informed by a grounded theory approach. A second investigator repeated the process. Codes were chosen and assigned to data by consensus.   ResultsThe coded data yielded five distinct perceived challenges faced by caregivers: (1) seeking and possibly receiving a diagnosis; (2) processing emotions and coming to terms with the child's difficulties; (3) seeking support and belonging within a knowledgeable community; (4) developing a new understanding of the child's behavior; and (5) becoming an educator, advocate, and expert on the child and FASD.   ConclusionProfessionals believe specific capacities are essential insofar as the human service systems that caregivers engage are perceived to be under-equipped to respond to the distinct set of challenges faced by children with FASD and their families. Findings are discussed in terms of how the proposed intervention was designed to address such challenges and to cultivate those key capacities in order for families to meet their children's needs. PMID:27462878

  19. 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

  20. 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.

  1. Neural stem cell regulation, fibroblast growth factors, and the developmental origins of neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Hanna E Stevens

    2010-09-01

    Full Text Available There is increasing appreciation for the neurodevelopmental underpinnings of many psychiatric disorders. Disorders that begin in childhood such as autism, language disorders or mental retardation as well as adult-onset mental disorders may have origins early in neurodevelopment. Neural stem cells (NSCs can be defined as self-renewing, multipotent cells that are present in both the embryonic and adult brain. Several recent research findings demonstrate that psychiatric illness may begin with abnormal specification, growth, expansion and differentiation of embryonic NSCs. For example, candidate susceptibility genes for schizophrenia, autism and major depression include the signaling molecule Disrupted In Schizophrenia-1 (DISC-1, the homeodomain gene engrailed-2 (EN-2, and several receptor tyrosine kinases (RTKs, including MET, brain-derived growth factor (BDNF and fibroblast growth factors (FGF, all of which have been shown to play important roles in NSCs or neuronal precursors. We will discuss here stem cell biology, signaling factors that affect these cells, and the potential contribution of these processes to the etiology of neuropsychiatric disorders. Hypotheses about how some of these factors relate to psychiatric disorders will be reviewed.

  2. New perspectives in human stem cell therapeutic research

    OpenAIRE

    Trounson Alan

    2009-01-01

    Abstract Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action o...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Stem Cell Therapy for Cardiovascular Disorders - Our Clinical Experience

    Directory of Open Access Journals (Sweden)

    Jayakrishnan AG

    2011-01-01

    Full Text Available Background: Autologous Bone Marrow stem Cell transplantation is a viable therapeutic option for patients with end stage heart failure due to cardiomyopathy of varied etiology as there are only limited treatment options other than cardiac transplantation. The rationale behind the application of stem cells in these patients include • Stem cells directly replace the affected cells by differentiation into the damaged cell type • Stem cells also exert Paracrine effects by secre tion of growth factors (VGEF,FGF-1to stimu late local cell growth•In addition to the above, stem cells release signaling factors which recruit stem cells from elsewhere by modulating the immune system.Materials and Methods: In this presentation we describe our study on a series of 13 patients who received isolated and expanded CD 34 cells from the bone marrow. Seven had ischemic dysfunction, three had dilated cardiomyopathy and three had primary pulmonary hypertension. Five patients received the stem cells via intracoronary injection, three directly into the myocardium and three intrapulmonary. Results: All patients showed functional improvement of the myocardium recorded by non-invasive investigations and improvement in the quality of life. Follow up period ranged from 6 months to 2 years. Conclusion: Our experience with bone marrow derived stem cells in patients with cardiomyopathy has been encouraging. More studies are planned in the future.

  12. Use and Needs in Contexts : An Ethnographic Study on Cell Phone Use from a Contextual Usability Perspective

    OpenAIRE

    Friberg, Hanna

    2003-01-01

    The focus of this thesis is usability of an everyday used product; the cell phone seen from a Human – Computer Interaction perspective. The purpose with the thesis is to create an understanding of how cell phones are used by persons in natural /public settings and in everyday activities. Further the purpose is to describe users’ experiences of using cell phones. In this study, ethnography was used as method. The theoretical framework is the contextual usability perspective. The cell phone is ...

  13. The role of mast cells in functional GI disorders

    OpenAIRE

    Wouters, Mira; Vicario, Maria; Santos, Javier

    2016-01-01

    Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrie...

  14. 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.

  15. Dilemmas, diagnosis and de-stigmatization: parental perspectives on the diagnosis of autism spectrum disorders.

    Science.gov (United States)

    Russell, Ginny; Norwich, Brahm

    2012-04-01

    Many children who display autistic behaviours at clinical levels do not receive a formal diagnosis. This study used qualitative methods to examine parental influence in pursuing or avoiding a diagnosis of autism spectrum disorder (ASD). The aim was to explore the function of ASD diagnosis for parents, and examine whether a diagnosis affected how parents perceived ASD. Seventeen parents participated in in-depth semi-structured interviews, which were analyzed using thematic and grounded theory approaches. Data analysis revealed dilemmas faced by parents: whether to act to retain the 'normal' status of the child or to 'normalize' the child through diagnosis and subsequent remediation. Parents who had received an ASD diagnosis for their children became proactive in trying to reduce stigmatization of ASD more widely, and in some cases actively advocating ASD diagnosis to other parents. Thus their actions may make it more likely that others will opt for diagnosis in the future. PMID:22219019

  16. 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.

  17. Microglial Cells as a Link between Cannabinoids and the Immune Hypothesis of Psychiatric Disorders

    OpenAIRE

    Lisboa, Sabrina F.; Gomes, Felipe V; Guimaraes, Francisco S.; Campos, Alline C

    2016-01-01

    Psychiatric disorders are one of the leading causes of disability worldwide. Although several therapeutic options are available, the exact mechanisms responsible for the genesis of these disorders remain to be fully elucidated. In the last decade, a body of evidence has supported the involvement of the immune system in the pathophysiology of these conditions. Microglial cells play a significant role in maintaining brain homeostasis and surveillance. Dysregulation of microglial functions has b...

  18. 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.)

  19. The utility of patient specific induced pluripotent stem cells for the modelling of Autistic Spectrum Disorders

    OpenAIRE

    Cocks, Graham; Curran, Sarah; Gami, Priya; Uwanogho, Dafe; Jeffries, Aaron R.; Kathuria, Annie; Lucchesi, Walter; Wood, Victoria; Dixon, Rosemary; Ogilvie, Caroline; Steckler, Thomas; Price, Jack

    2013-01-01

    Until now, models of psychiatric diseases have typically been animal models. Whether they were to be used to further understand the pathophysiology of the disorder, or as drug discovery tools, animal models have been the choice of preference in mimicking psychiatric disorders in an experimental setting. While there have been cellular models, they have generally been lacking in validity. This situation is changing with the advent of patient-specific induced pluripotent stem cells (iPSCs). In t...

  20. Vitamin A status and hematological values in sickle cell disorder cases

    Directory of Open Access Journals (Sweden)

    Shuchismita Behera

    2012-01-01

    Full Text Available Background: Sickle cell anemia (SCA, which is an inherited blood disorder characterized primarily by chronic anemia and oxidative stress plays a major role in pathophysiology. Objective: This study aims to evaluate vitamin A (serum retinol status and hematological parameters in children with homozygous and heterozygous sickle cell disorders and compared with age- and sex-matched healthy controls. Materials and Methods:A sample of 80 referred cases (37 sickle cell disorders and 43 normal cases aged 2-40 years were included in the study. Hematological parameters were measured in cell counter and serum retinol by high-performance liquid chromatography. Results: The mean hemoglobin (Hb and serum retinol were significantly lower among cases with sickle cell disease than in sickle cell trait and normal. Vitamin A deficiency (retinol < 20 μg/dl reported to be higher in homozygous cases (46.2% as compared to either heterozygous (29.2% or control (23.2% groups. Serum retinol was correlated directly with Hb, RBC count, and hematocrit levels, and inversely with percentage of sickling among sickle cell disorder cases. Conclusion: The results indicate that deprived vitamin A status with inductive oxidative stress is mainly due to sickling and hemolysis in SCA cases.

  1. 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.

  2. 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.

  3. 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.

  4. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    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. PMID:22319243

  5. Temporal integration of multisensory stimuli in autism spectrum disorder: a predictive coding perspective.

    Science.gov (United States)

    Chan, Jason S; Langer, Anne; Kaiser, Jochen

    2016-08-01

    Recently, a growing number of studies have examined the role of multisensory temporal integration in people with autism spectrum disorder (ASD). Some studies have used temporal order judgments or simultaneity judgments to examine the temporal binding window, while others have employed multisensory illusions, such as the sound-induced flash illusion (SiFi). The SiFi is an illusion created by presenting two beeps along with one flash. Participants perceive two flashes if the stimulus-onset asynchrony (SOA) between the two flashes is brief. The temporal binding window can be measured by modulating the SOA between the beeps. Each of these tasks has been used to compare the temporal binding window in people with ASD and typically developing individuals; however, the results have been mixed. While temporal order and simultaneity judgment tasks have shown little temporal binding window differences between groups, studies using the SiFi have found a wider temporal binding window in ASD compared to controls. In this paper, we discuss these seemingly contradictory findings and suggest that predictive coding may be able to explain the differences between these tasks. PMID:27324803

  6. 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.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Meiring, Meagan; Seabi, Joseph; Amod, Zaytoon; Vorster, Adri; Kern, Anwynne

    2016-01-01

    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. Semistructured 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. PMID:27375502

  10. Idiopathic restrictive cardiomyopathy - perspectives from genetics studies. Is it time to redefine these disorders?

    Directory of Open Access Journals (Sweden)

    Ajay Bahl

    2012-05-01

    Full Text Available Idiopathic restrictive cardiomyopathy (IRC is a rare form of heart muscle disease. Genetic studies have revealed that in about half the cases, IRC forms part of the hereditary sarcomeric contractile protein disease spectrum. Mutations in several sarcomere protein encoding genes are detected in 33-66% of cases. Among these, the mutations most commonly involve TNNI3 and MYH7. There is a disproportionately high incidence of TNNI3 mutations in patients with restrictive physiology. De novo mutations are also frequently seen in this group of patients. IRC and hypertrophic cardiomyopathy (HCM with restrictive phenotype reflect the same or very similar disorders with different names due to arbitrary cut offs in the left ventricular wall thickness rather than two separate distinct diseases. HCM with restrictive physiology should be considered part of a continuous spectrum with IRC. This is because patients with HCM with restrictive phenotype bear far greater clinical and genetic resemblance to IRC than to rest of the HCM cohort.

  11. 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.

  12. 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.

  13. 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

  14. 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. ___________________________________________________

  15. 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

  16. 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.

  17. 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…

  18. 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.

  19. 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

  20. Cell cycle control in Plasmodium falciparum: a genomics perspective

    OpenAIRE

    Waters, A.P.; Janse, C.J.; Doerig, Christian; Chakrabarti, Debopam

    2004-01-01

    The molecular mechanisms regulating cell proliferation and development in malaria parasites are still largely unknown. Phenomenological observations, pertaining to the organisation of the cell cycle during schizogony or to the signal transduction pathways whose activation is responsible for the developmental stage transitions, can now be complemented with information gathered from genomic databases. The PlasmoDB database has been used extensively to identify putative homologues of a number of...

  1. 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...

  2. Fuel cells and air quality: A California perspective

    Science.gov (United States)

    Lloyd, Alan C.; Leonard, Jonathan H.; George, Ranji

    1994-04-01

    The continuing challenge to improve the quality of urban air, worldwide, provides many opportunities to introduce cleaner technologies into the industrial energy base. The fuel cell is particularly attractive from an environmental viewpoint because of its inherent efficiency, zero or near-zero emissions, and quiet operation. Since 1991, fuel cells have made major institutional strides in being recognized as part of the solution to the major air-pollution problem in Southern California. Fuel cells and hydrogen are now receiving greater attention in the regulatory planning process. This process seeks to identify lower-emitting technologies and fuels that can assist the region in meeting health-based air-quality standards by the year 2010, and provide for a sustainable, health-grounded regional economy as well. Current demonstration projects involving fuel cells and hydrogen are discussed, as well as necessary plans and incentives for infrastructure development - a critical component of fuel-cell commercialization. Finally, an overview is presented of regulatory efforts that are being considered to support early markets for fuel cells.

  3. 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

  4. [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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. A transgenic mouse model of sickle cell disorder.

    NARCIS (Netherlands)

    D.R. Greaves; 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

  10. Motivations, experiences, and perspectives of bone marrow and peripheral blood stem cell donors: thematic synthesis of qualitative studies.

    Science.gov (United States)

    Garcia, Maria C; Chapman, Jeremy R; Shaw, Peter J; Gottlieb, David J; Ralph, Angelique; Craig, Jonathan C; Tong, Allison

    2013-07-01

    Hematopoietic stem cell (HSC) transplantation using bone marrow and peripheral blood stem cells is a lifesaving treatment for patients with leukemia or other blood disorders. However, donors face the risk of physical and psychosocial complications. We aimed to synthesize qualitative studies on the experiences and perspectives of HSC donors. We searched MEDLINE, Embase, PsycINFO, CINAHL, Google Scholar, and reference lists of relevant articles to November 13, 2012. Thematic synthesis was used to analyze the findings. Thirty studies involving 1552 donors were included. The decision to donate included themes of saving life, family loyalty, building a positive identity, religious conviction, fear of invasive procedures, and social pressure and obligation. Five themes about the donation experience were identified: mental preparedness (pervasive pain, intense disappointment over recipient death, exceeding expectations, and valuing positive recipient gains), burden of responsibility (striving to be a quality donor, unresolved guilt, and exacerbated grief), feeling neglected (medical dismissiveness and family inattention), strengthened relationships (stronger family ties, establishing blood bonds), and personal sense of achievement (satisfaction and pride, personal development, hero status, and social recognition). Although HSC donation was appreciated as an opportunity to save life, some donors felt anxious and unduly compelled to donate. HSC donors became emotionally invested and felt responsible for their recipient's outcomes and were profoundly grieved and disappointed if the transplantation was unsuccessful. To maximize donor satisfaction and mitigate the psychosocial risks for HSC donors, strategies to address the emotional challenges of anxiety, sense of coercion, guilt, and grief in donors are warranted. PMID:23603456

  11. 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.

  12. Turning Perspective in Photoelectrocatalytic Cells for Solar Fuels.

    Science.gov (United States)

    Perathoner, Siglinda; Centi, Gabriele; Su, Dangsheng

    2016-02-19

    The development of new devices for the use and storage of solar energy is a key step to enable a new sustainable energy scenario. The route for direct solar-to-chemical energy transformation, especially to produce liquid fuels, represents a necessary element to realize transition from the actual energy infrastructure. Photoelectrocatalytic (PECa) devices for the production of solar fuels are a key element to enable this sustainable scenario. The development of PECa devices and related materials is of increasing scientific and applied interest. This concept paper introduces the need to turn the viewpoint of research in terms of PECa cell design and related materials with respect to mainstream activities in the field of artificial photosynthesis and leaves. As an example of a new possible direction, the concept of electrolyte-less cell design for PECa cells to produce solar fuels by reduction of CO2 is presented. The fundamental and applied development of new materials and electrodes for these cells should proceed fully integrated with PECa cell design and systematic analysis. A new possible approach to develop semiconductors with improved performances by using visible light is also shortly presented. PMID:26663767

  13. 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.

  14. 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

  15. 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

  16. Drug hypersensitivity in clonal mast cell disorders : ENDA/EAACI position paper

    NARCIS (Netherlands)

    Bonadonna, P.; Pagani, M.; Aberer, W.; Bilo, M. B.; Brockow, K.; Elberink, H. Oude; Garvey, L.; Mosbech, H.; Romano, A.; Zanotti, R.; Torres, M. J.

    2015-01-01

    Mastocytosis is a clonal disorder characterized by the proliferation and accumulation of mast cells (MC) in different tissues, with a preferential localization in skin and bone marrow (BM). The excess of MC in mastocytosis as well as the increased releasability of MC may lead to a higher frequency a

  17. 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.

  18. The Pancreatic β-Cell: A Bioenergetic Perspective.

    Science.gov (United States)

    Nicholls, David G

    2016-10-01

    The pancreatic β-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasma membrane ion channels. The control mechanisms responsible for the unique responsiveness of the cell to glucose availability are discussed from bioenergetic and metabolic control standpoints. The concept of coupling factor facilitation of secretion is critiqued, and an attempt is made to unravel the bioenergetic basis of the oscillatory mechanisms controlling secretion. The need to consider the physiological constraints operating in the intact cell is emphasized throughout. The aim is to provide a coherent pathway through an extensive, complex, and sometimes bewildering literature, particularly for those unfamiliar with the field. PMID:27582250

  19. 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.

  20. Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.

    Science.gov (United States)

    Roh, Kyung-Ho; Nerem, Robert M; Roy, Krishnendu

    2016-06-01

    Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules. This paradigm shift in modern medicine of using cells as novel therapeutics can be realized only if suitable manufacturing technologies for large-scale, cost-effective, reproducible production of high-quality cells can be developed. Here we review the state of the art in therapeutic cell manufacturing, including cell purification and isolation, activation and differentiation, genetic modification, expansion, packaging, and preservation. We identify current challenges and discuss opportunities to overcome them such that cell therapies become highly effective, safe, and predictively reproducible while at the same time becoming affordable and widely available. PMID:27276552

  1. 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. PMID:24610628

  2. 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.

  3. IDIOPATHIC PULMONARY FIBROSIS: A DISORDER OF EPITHELIAL CELL DYSFUNCTION

    OpenAIRE

    Zoz, Donald F.; Lawson, William E.; Blackwell, Timothy S.

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, interstitial infiltrates in lung parenchyma, and restriction on pulmonary function testing. IPF is the most common and severe of the idiopathic interstitial pneumonias (IIPs), with most individuals progressing to respiratory failure. Multiple lines of evidence reveal prominent roles for alveolar epithelial cells (AECs) in disease. Our current disease paradigm is that ongoing or repetitive injurious stimuli in the pre...

  4. 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.

  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. Stem cell therapy in the management of shoulder rotatorcuff disorders

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Rotator cuff tears are frequent shoulder problems thatare usually dealt with surgical repair. Despite improvedsurgical techniques, the tendon-to-bone healing rateis unsatisfactory due to difficulties in restoring thedelicate transitional tissue between bone and tendon.It is essential to understand the molecular mechanismsthat determine this failure. The study of the molecularenvironment during embryogenesis and during normalhealing after injury is key in devising strategies to geta successful repair. Mesenchymal stem cells (MSC) candifferentiate into different mesodermal tissues and havea strong paracrine, anti-inflammatory, immunoregulatoryand angiogenic potential. Stem cell therapy is thus apotentially effective therapy to enhance rotator cuffhealing. Promising results have been reported with theuse of autologous MSC of different origins in animalstudies they have shown to have better healing properties,increasing the amount of fibrocartilage formationand improving the orientation of fibrocartilage fibers withless immunologic response and reduced lymphocyteinfiltration. All these changes lead to an increase inbiomechanical strength. However, animal research is stillinconclusive and more experimental studies are neededbefore human application. Future directions includeexpanded stem cell therapy in combination with growthfactors or different scaffolds as well as new stem celltypes and gene therapy.

  7. 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

  8. 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. PMID:26603718

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives

    Directory of Open Access Journals (Sweden)

    Zomer HD

    2015-09-01

    Full Text Available Helena D Zomer,1 Atanásio S Vidane,1 Natalia N Gonçalves,1 Carlos E Ambrósio2 1Department of Surgery, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil; 2Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil Abstract: Mesenchymal stem cells have awakened a great deal of interest in regenerative medicine due to their plasticity, and immunomodulatory and anti-inflammatory properties. They are high-yield and can be acquired through noninvasive methods from adult tissues. Moreover, they are nontumorigenic and are the most widely studied. On the other hand, induced pluripotent stem (iPS cells can be derived directly from adult cells through gene reprogramming. The new iPS technology avoids the embryo destruction or manipulation to generate pluripotent cells, therefore, are exempt from ethical implication surrounding embryonic stem cell use. The pre-differentiation of iPS cells ensures the safety of future approaches. Both mesenchymal stem cells and iPS cells can be used for autologous cell transplantations without the risk of immune rejection and represent a great opportunity for future alternative therapies. In this review we discussed the therapeutic perspectives using mesenchymal and iPS cells. Keywords: cell transplantation, cell therapy, iPS, MSC

  14. 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. PMID:19809002

  15. Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy

    OpenAIRE

    Sayres, Lauren C.; Allyse, Megan; Cho, Mildred K.

    2012-01-01

    Background The translation of novel genomic technologies from bench to bedside enjoins the comprehensive consideration of the perspectives of all stakeholders who stand to influence, or be influenced by, the translational course. Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it w...

  16. 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.

  17. Mast cell mediated and associated disorders in pregnancy: a risky game with an uncertain outcome?

    Directory of Open Access Journals (Sweden)

    Katja eWoidacki

    2014-05-01

    Full Text Available During pregnancy the maternal organism is under the influence of tremendous endocrine as well as immunological changes as an adaption to the implanted and developing fetus. In most cases, the maternal adaptations to pregnancy ensure both, the protection against harmful pathogens and the tolerance towards the growing semi-allogeneic fetus. However, under certain circumstances the unique hormonal milieu during pregnancy is causative of a shift into an unfavorable direction. Of particular importance are cellular disorders previous to pregnancy that involve cell types known for their susceptibility to hormones. One interesting cell type is the mast cell (MC, one of the key figures in allergic disorders. While physiological numbers of MCs were shown to positively influence pregnancy outcome, at least in mouse models, uncontrolled augmentations in quantity and/or activation can lead to pregnancy complications. Women that have the desire of getting pregnant and been diagnosed with MC mediated disorders such as urticaria and mastocytosis or chronic inflammatory diseases in which MCs are involved, including atopic dermatitis, asthma or psoriasis, may benefit from specialized medical assistance to ensure a positive pregnancy outcome. In the present review we address the course of pregnancy in women affected by MC mediated or associated disorders.

  18. 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.

  19. 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. PMID:10970706

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Assessing Relational Learning Deficits in Perspective-Taking in Children with High-Functioning Autism Spectrum Disorder

    Science.gov (United States)

    Rehfeldt, Ruth Anne; Dillen, Jeffrey E.; Ziomek, Megan M.; Kowalchuk, Rhonda K.

    2007-01-01

    Perspective-taking, or the ability to demonstrate awareness of informational states in oneself and in others, has been of recent interest in behavioral psychology. This is, in part, a result of a modern behavioral approach to human language and cognition known as Relational Frame Theory, which views perspective-taking as generalized operant…

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

    Directory of Open Access Journals (Sweden)

    Kazuhiko eYamamuro

    2015-05-01

    Full Text Available 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.

  6. 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. PMID:26029044

  7. 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

  8. 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.

  9. Critical realism, agency and sickle cell:case studies of young people with sickle cell disorder at school

    OpenAIRE

    Dyson, Simon; Atkin, Karl; Culley, Lorraine; Dyson, Sue

    2014-01-01

    Critical realism suggests that historical structures may operate as underlying generative mechanisms but not always be activated. This explains the near-absence of references to racism by black students with sickle cell disorder (SCD). Through case studies we show how latent mechanisms are not activated, and how social actors come to develop corporate agency. Themes discussed include: wider/historical racisms (carers' own experiences of overt racism at school); conscious actions (moving away ...

  10. Critical realism, agency and sickle cell: case studies of young people with sickle cell disorder at school

    OpenAIRE

    Dyson, Simon Martin; Atkin, Karl; Culley, Lorraine; Dyson, Sue E

    2014-01-01

    Critical realism suggests that historical structures may operate as underlying generative mechanisms but not always be activated. This explains the near-absence of references to racism by black students with sickle cell disorder (SCD). Through case studies we show how latent mechanisms are not activated, and how social actors come to develop corporate agency. Themes discussed include: wider/historical racisms (carers' own experiences of overt racism at school); conscious actions (moving away ...

  11. 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

  12. Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders;

    2015-01-01

    reproductive problems within the testicular dysgenesis syndrome (TDS), with large overlap between the syndromes. These disorders carry an increased but variable risk of germ cell neoplasia. In this review, we discuss the pathogenesis of germ cell neoplasia associated with gonadal dysgenesis, especially...... in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which...... are essentially the same precursor lesion but with different morphological structure dependent upon the masculinisation of the somatic niche. To assess the risk of germ cell neoplasia in different types of DSD, we have performed a PubMed search and provide here a synthesis of the evidence from studies published...

  13. [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.

  14. [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.

  15. Genetic red cell disorders and severity of falciparum malaria in Myanmar.

    OpenAIRE

    Oo, M.; Tin-Shwe; Marlar-Than; O'Sullivan, W. J.

    1995-01-01

    A hospital-based survey was undertaken to investigate the relationship between the incidence and severity of malaria infection and various red cell disorders in Myanmar. The mean parasitaemia levels of patients with alpha- or beta-thalassaemia trait or with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency were lower than those of individuals with normal haemoglobin AA or with heterozygous haemoglobin E. The double genetic defect of thalassaemia trait and severe G6PD deficiency appea...

  16. Pediatric T-Cell Post-Transplant Lymphoproliferative Disorder After Solid Organ Transplantation

    OpenAIRE

    Yang, Fan; Ying LI; Braylan, Raul; Hunger, Stephen P.; Yang, Li-Jun

    2008-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is the most after SOT (liver and lungs) and review cases reported in the literature. common treatment related malignancy that occurs after solid organ Both patients had a bimodal response to therapy with initial transplantation (SOT). PTLD has extended from its initial description eradication of bulky nodal disease with regimens typically used to as an Epstein–Barr virus (EBV)-driven B-cell proliferation to include treat leukemia, but persis...

  17. Stem cell therapy for white matter disorders: don't forget the microenvironment!

    Science.gov (United States)

    Dooves, Stephanie; van der Knaap, Marjo S; Heine, Vivi M

    2016-07-01

    White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in rodent disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial. PMID:27000179

  18. 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.

  19. 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

  20. 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.

  1. Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders

    Science.gov (United States)

    Muraro, Paolo A.; Wandinger, Klaus-Peter; Bielekova, Bibiana; Gran, Bruno; Marques, Adriana; Utz, Ursula; McFarland, Henry F.; Jacobson, Steve; Martin, Roland

    2016-01-01

    Summary T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/ TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4+ and CD8+ T cell clones through the detection and quantification of T cell receptor (TCR) α or β chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clono-type tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/ TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders. PMID:12477694

  2. 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.

  3. 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.

  4. Knr4: a disordered hub protein at the heart of fungal cell wall signalling.

    Science.gov (United States)

    Martin-Yken, Hélène; François, Jean Marie; Zerbib, Didier

    2016-09-01

    The most highly connected proteins in protein-protein interactions networks are called hubs; they generally connect signalling pathways. In Saccharomyces cerevisiae, Knr4 constitutes a connecting node between the two main signal transmission pathways involved in cell wall maintenance upon stress: the cell wall integrity and the calcium-calcineurin pathway. Knr4 is required to enable the cells to resist many cell wall-affecting stresses, and KNR4 gene deletion is synthetic lethal with the simultaneous deletion of numerous other genes involved in morphogenesis and cell wall biogenesis. Knr4 has been shown to engage in multiple physical interactions, an ability conferred by the intrinsic structural adaptability of major disordered regions present in the N-terminal and C-terminal parts of the protein. Taking all together, Knr4 is an intrinsically disordered hub protein. Available data from other fungi indicate the conservation of Knr4 homologs cellular function and localization at sites of polarized growth among fungal species, including pathogenic species. Because of their particular role in morphogenesis control and of their fungal specificity, these proteins could constitute interesting new pharmaceutical drug targets for antifungal combination therapy. PMID:27199081

  5. Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Nopporn Jongkamonwiwat

    2013-01-01

    Full Text Available Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders.

  6. The stimulated brain: A psychological perspective on deep brain stimulation for treatment-refractory obsessive-compulsive disorder

    NARCIS (Netherlands)

    M.H.M. Mantione

    2015-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with an estimated life-time prevalence of 2%. Severe OCD leads to pronounced suffering and has a major impact on family relationships, social life and the capacity to function at work. At present, clinical management of OCD consists

  7. [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.

  8. Influence of Weight on Shared Core Symptoms in Eating Disorders: Support or Challenge for a Transdiagnostic Perspective?

    Science.gov (United States)

    Schmitz, Catalina; Schnicker, Katja; Legenbauer, Tanja

    2016-09-01

    In terms of the transdiagnostic model of eating disorders, Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) share the same distinctive psychopathology. However, empirical evidence showing similarities between these eating disorder diagnoses for core symptoms is scarce, and the role of weight status is unclear. Data from a total of 168 female participants were collected between April 2004 and April 2008, at an outpatient unit specialized in eating disorder treatment. Core symptoms of eating disorders were measured via self-report questionnaires. In particular, women with BED and BN showed similar patterns of core symptomatology compared with AN. However, when body mass index (BMI) was considered in the analyses, there were no differences between the three diagnostic groups in relation to body image. Differences in eating behavior are not solely triggered by weight differences, whereas body image disturbances are a transdiagnostic phenomenon among EDs and should also be considered in the treatment of BED. PMID:27118052

  9. Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

    Science.gov (United States)

    Haggarty, Stephen J; Silva, M Catarina; Cross, Alan; Brandon, Nicholas J; Perlis, Roy H

    2016-06-01

    Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient-specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent

  10. 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.

  11. Illuminating vitamin D effects on B cells--the multiple sclerosis perspective.

    Science.gov (United States)

    Rolf, Linda; Muris, Anne-Hilde; Hupperts, Raymond; Damoiseaux, Jan

    2016-03-01

    Vitamin D is associated with many immune-mediated disorders. In multiple sclerosis (MS) a poor vitamin D status is a major environmental factor associated with disease incidence and severity. The inflammation in MS is primarily T-cell-mediated, but increasing evidence points to an important role for B cells. This has paved the way for investigating vitamin D effects on B cells. In this review we elaborate on vitamin D interactions with antibody production, T-cell-stimulating capacity and regulatory B cells. Although in vitro plasma cell generation and expression of co-stimulatory molecules are inhibited and the function of regulatory B cells is promoted, this is not supported by in vivo data. We speculate that differences might be explained by the B-cell-Epstein-Barr virus interaction in MS, the exquisite role of germinal centres in B-cell biology, and/or in vivo interactions with other hormones and vitamins that interfere with the vitamin D pathways. Further research is warranted to illuminate this tube-versus-body paradox. PMID:26714674

  12. 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. PMID:26895243

  13. Age-old wisdom concerning cell-based therapies with added knowledge in the stem cell era: our perspectives

    Directory of Open Access Journals (Sweden)

    Preethy S

    2013-04-01

    Full Text Available Senthilkumar Preethy,1,2 Sudhakar John,1 Jegatheesan Saravana Ganesh,1 Thangavelu Srinivasan,1 Hiroshi Terunuma,3 Masaru Iwasaki,4 Samuel J Abraham1,4 1Nichi-In Centre for Regenerative Medicine, 2Hope Foundation Trust, Chennai, India; 3Biotherapy Institute of Japan, Tokyo, 4Yamanashi University School of Medicine, Chuo, Japan Abstract: Among the various strategies providing a cure for illness, cell-based therapies have caught the attention of the world with the advent of the "stem cell" era. Our inherent understanding indicates that stem cells have been in existence since the birth of multicellular organisms. However, the formal discovery of stem cells in the last century, followed by their intricate and extensive analysis, has led to clinical and translational efforts with the aim of using them in the treatment of conditions which don't have a definitive therapeutic strategy, has fueled our interest and expectations. Technological advances in our ability to study their cellular components in depth, along with surface markers and other finer constituents, that were unknown until last century, have improved our understanding, leading to several novel applications. This has created a need to establish guidelines, and in that process, there are expressed understandings and views which describe cell therapy along lines similar to that of biologic products, drugs, and devices. However, the age-old wisdom of using cells as tools for curing illness should not be misled by recent knowledge, to make cell therapy using highly complex stem cells equal to factory-synthesized and reproducible chemical compounds, drugs, or devices. This article analyses the differences between these two entities from various perspectives. Keywords: cell transplantation, drugs, regenerative medicine, stem cells

  14. 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.

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

    Science.gov (United States)

    Noda, Mami

    2015-01-01

    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 the human brain, leading to various neurological dysfunctions. In the adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Although impact of hypothyroidism on synaptic transmission and plasticity is known, its effect on glial cells and related cellular mechanisms remain enigmatic. This mini-review article summarizes how THs are transported into the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, demonstrating an example of glioendocrine system. Neuroglial effects may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders. PMID:26089777

  16. 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.

  17. 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. PMID:27353637

  18. 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.

  19. 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.

  20. The stimulated brain: A psychological perspective on deep brain stimulation for treatment-refractory obsessive-compulsive disorder

    OpenAIRE

    Denys, D.A.J.P.; Nieman, D.H.; Mantione, M.H.M.

    2015-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with an estimated life-time prevalence of 2%. Severe OCD leads to pronounced suffering and has a major impact on family relationships, social life and the capacity to function at work. At present, clinical management of OCD consists of pharmacological treatment and cognitive behavioural therapy (CBT). Although both treatments are often effective, approximately 10% of patients remain severely affected and suffer from treatment-...

  1. 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 ...

  2. Qualitative Study of the Therapeutic Relationship in Speech and Language Therapy: Perspectives of Adults with Acquired Communication and Swallowing Disorders

    Science.gov (United States)

    Fourie, Robert J.

    2009-01-01

    Background: Considerations of the negotiated therapeutic relationship in speech and language therapy are somewhat scarce, with specific therapeutic factors generally framed from psycholinguistic, behavioural, or neurological perspectives. Aims: To explore the therapeutic relationship in speech and language therapy, focusing on the personal…

  3. 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.

  4. Compound polycrystalline solar cells. Recent progress and Y2K perspective

    Energy Technology Data Exchange (ETDEWEB)

    Birkmire, R.W. [Institute of Energy Conversion, University of Delaware, DE 19716 Newark (United States)

    2001-01-01

    A historical perspective on the development of polycrystalline thin-film solar cells based on CdTe and CuInSe{sub 2} is presented, and recent progress of these thin-film technologies is discussed. Impressive improvements in the efficiency of laboratory scale devices has not been easy to translate to the manufacturing environment, principally due to our lack of understanding of the basic science and engineering of these materials and devices. 'Next-generation' high-performance thin-film solar cells utilizing multijunction device configurations should achieve efficiencies of more than 25% within ten years. However, our cost-effective manufacturing of these more complex devices will be problematic unless the science and engineering issues associated with processing of thin-film PV devices are addressed.

  5. Red cell adhesion molecules, foetal haemoglobin and endothelial factors in sickle cell disorders

    OpenAIRE

    Mundee, Y.

    2001-01-01

    Sickle cell anaemia (SS) is a haemoglobinopathy involving production of sickle haemoglobin (HbS, β⁶Glu-->Val), which is able to polymerise leading to vaso-occlusion. Hydroxyurea (HU) treatment increases foetal haemoglobin (HbF) levels but decreases vaso-occlusion and red cell adhesion molecule (AM) expression, and therefore improves clinical symptoms. In this thesis, the contribution of AMs, HbF and endothelial factors to the severity of sickle cell disease has been studied....

  6. Cephalic Disorders

    Science.gov (United States)

    ... may be caused by a disturbance in the proliferation of nerve cells. Micrencephaly may also be associated with maternal problems ... as cephalic disorders. Understanding how genes control brain cell migration, proliferation, differentiation, and death, and how radiation, drugs, toxins, ...

  7. 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.

  8. Turning the fate of reprogramming cells from retinal disorder to regeneration by Pax6 in newts.

    Science.gov (United States)

    Casco-Robles, Martin Miguel; Islam, Md Rafiqul; Inami, Wataru; Tanaka, Hibiki Vincent; Kunahong, Ailidana; Yasumuro, Hirofumi; Hanzawa, Shiori; Casco-Robles, Roman Martin; Toyama, Fubito; Maruo, Fumiaki; Chiba, Chikafumi

    2016-01-01

    The newt, a urodele amphibian, has an outstanding ability- even as an adult -to regenerate a functional retina through reprogramming and proliferation of the retinal pigment epithelium (RPE) cells, even though the neural retina is completely removed from the eye by surgery. It remains unknown how the newt invented such a superior mechanism. Here we show that disability of RPE cells to regenerate the retina brings about a symptom of proliferative vitreoretinopathy (PVR), even in the newt. When Pax6, a transcription factor that is re-expressed in reprogramming RPE cells, is knocked down in transgenic juvenile newts, these cells proliferate but eventually give rise to cell aggregates that uniformly express alpha smooth muscle actin, Vimentin and N-cadherin, the markers of myofibroblasts which are a major component of the sub-/epi-retinal membranes in PVR. Our current study demonstrates that Pax6 is an essential factor that directs the fate of reprogramming RPE cells toward the retinal regeneration. The newt may have evolved the ability of retinal regeneration by modifying a mechanism that underlies the RPE-mediated retinal disorders. PMID:27640672

  9. Microgravity environment and compensatory: Decompensatory phases for intracranial hypertension form new perspectives to explain mechanism underlying communicating hydrocephalus and its related disorders.

    Science.gov (United States)

    Idris, Zamzuri; Mustapha, Muzaimi; Abdullah, Jafri M

    2014-01-01

    The pathogenesis underlying communicating hydrocephalus has been centered on impaired cerebrospinal fluid (CSF) outflow secondary to abnormal CSF pulsation and venous hypertension. Hydrodynamic theory of hydrocephalus fares better than traditional theory in explaining the possible mechanisms underlying communicating hydrocephalus. Nonetheless, hydrodynamic theory alone could not fully explain some conditions that have ventriculomegaly but without hydrocephalus. By revisiting brain buoyancy from a fresher perspective, called microgravity environment of the brain, introducing wider concepts of anatomical and physiological compensatory-decompensatory phases for a persistent raise in intracranial pressure, and along with combining these two concepts with the previously well-accepted concepts of Monro-Kellie doctrine, intracranial hypertension, cerebral blood flow, cerebral perfusion pressure, brain compliance and elasticity, cerebral autoregulation, blood-brain and blood-CSF barriers, venous and cardiopulmonary hypertension, Windkessel phenomenon, and cerebral pulsation, we provide plausible explanations to the pathogenesis for communicating hydrocephalus and its related disorders. PMID:24891884

  10. 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.

  11. 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. PMID:26839997

  12. 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.

  13. 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.

  14. Genetic Correction of Sickle Cell Anemia and β-Thalassemia: Progress and New Perspective

    OpenAIRE

    Ajay Perumbeti; Punam Malik

    2010-01-01

    Gene therapy for β-globinopathies, particularly β-thalassemia and sickle cell anemia, holds promise for the future as a definitive corrective approach for these common and debilitating disorders. Correction of the β-globinopathies using lentivirus vectors carrying the β- or γ-globin genes and elements of the locus control region has now been well established in murine models, and an understanding of "what is required to cure these diseases" has been developed in the first decade of the 21st c...

  15. Therapist and patient perspectives on cognitive-behavioral therapy for older adults with hoarding disorder: A collective case study

    OpenAIRE

    Ayers, Catherine R.; Bratiotis, Christiana; Saxena, Sanjaya; Wetherell, Julie Loebach

    2012-01-01

    Utilizing a qualitative approach, the current study explored therapist and patient perspectives on a specialized cognitive-behavioral therapy (CBT) protocol for clinically significant hoarding in older adult patients. Data were derived from the following sources: (1) therapist observation; (2) CBT consultant observation; (3) clinical treatment notes; (4) participant feedback, including a focus group; and (5) participant in-session notes and completed homework assignments. Our findings showed ...

  16. Natural killer (NK cells for cancer immunotherapy: pluripotent stem cells-derived NK cells as an immunotherapeutic perspective

    Directory of Open Access Journals (Sweden)

    Cristina eEguizabal

    2014-09-01

    Full Text Available Natural killer (NK cells play an essential role in the fight against tumor development. Over the last years, the progress made in the NK cell biology field and in deciphering how NK cell function is regulated, is driving efforts to utilize NK cell-based immunotherapy as a promising approach for the treatment of malignant diseases. Therapies involving NK cells may be accomplished by activating and expanding endogenous NK cells by means of cytokine treatment or by transferring exogenous cells by adoptive cell therapy and/or by hematopoietic stem cell transplantation (HSCT. NK cells that are suitable for adoptive cell therapy can be derived from different sources, including ex vivo expansion of autologous NK cells, unstimulated or expanded allogeneic NK cells from peripheral blood, derived from CD34+ hematopoietic progenitors from peripheral blood and umbilical cord blood, and NK cell lines. Besides, genetically modified NK cells expressing chimeric antigen receptors (CARs or cytokines genes may also have a relevant future as therapeutic tools. Recently, it has been described the derivation of large numbers of functional and mature NK cells from pluripotent stem cells (PSCs, both embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs, which adds another tool to the expanding NK cell-based cancer immunotherapy arsenal.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.)

  2. Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly.

    Science.gov (United States)

    Fadda, Elisa

    2016-01-01

    Lack of structure is often an essential functional feature of protein domains. The coordination of macromolecular assemblies in DNA repair pathways is yet another task disordered protein regions are highly implicated in. Here I review the available experimental and computational data and within this context discuss the functional role of structure and disorder in one of the essential scaffolding proteins in the nucleotide excision repair (NER) pathway, namely Xeroderma pigmentosum complementation group A (XPA). From the analysis of the current knowledge, in addition to protein-protein docking and secondary structure prediction results presented for the first time herein, a mechanistic framework emerges, where XPA builds the NER pre-incision complex in a modular fashion, as "beads on a string", where the protein-protein interaction "beads", or modules, are interconnected by disordered link regions. This architecture is ideal to avoid the expected steric hindrance constraints of the DNA expanded bubble. Finally, the role of the XPA structural disorder in binding affinity modulation and in the sequential binding of NER core factors in the pre-incision complex is also discussed. PMID:26865925

  3. 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.…

  4. Epidemiological and pathophysiological aspects of abdominal pain predominant functional gastrointestinal disorders in children and adolescents: a Sri Lankan perspective

    NARCIS (Netherlands)

    N.M. Devanarayana

    2015-01-01

    Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are a worldwide pediatric problem with uncertain pathology. Main objectives of this thesis were to assess epidemiology, risk factors and underlying pathophysiological mechanisms of AP-FGIDs. A systematic review and meta-anal

  5. 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)…

  6. 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

  7. 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

  8. 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.

  9. Cell Culture Models and Pharmacological Perspective for the Study of Breast Cancer Markers

    Science.gov (United States)

    Tovar, Cristian Layton

    2013-01-01

    Among the most prevalent neoplasias, breast cancer shows an astonishing tendency. Unfortunately this cancer has a high mortality worldwide, requiring sustained management of all actors involved in public health in order to get an early diagnosis and treatment. The methods associated with conventional cytogenetics and molecular cell culture, besides early detection of gene expression patterns associated with cancer susceptibility, have contributed to identify inherited genes and metabolic disorders related to obesity, which are also involved in breast cancer. In any case, a broad study of the above mentioned factors can give a predictive value to support the design of public health models to determine cancer risk in order to decrease the mortality from this disease. (1) Cell cultures offers a wide range of scientific approach for the study of breast cancer, including the analysis of biological function of several compounds in search of increasingly effective treatments with fewer side effects against this malignancy. (2)

  10. 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

  11. Nanostructured Ion-Exchange Membranes for Fuel Cells: Recent Advances and Perspectives.

    Science.gov (United States)

    He, Guangwei; Li, Zhen; Zhao, Jing; Wang, Shaofei; Wu, Hong; Guiver, Michael D; Jiang, Zhongyi

    2015-09-23

    Polymer-based materials with tunable nanoscale structures and associated microenvironments hold great promise as next-generation ion-exchange membranes (IEMs) for acid or alkaline fuel cells. Understanding the relationships between nanostructure, physical and chemical microenvironment, and ion-transport properties are critical to the rational design and development of IEMs. These matters are addressed here by discussing representative and important advances since 2011, with particular emphasis on aromatic-polymer-based nanostructured IEMs, which are broadly divided into nanostructured polymer membranes and nanostructured polymer-filler composite membranes. For each category of membrane, the core factors that influence the physical and chemical microenvironments of the ion nanochannels are summarized. In addition, a brief perspective on the possible future directions of nanostructured IEMs is presented. PMID:26270555

  12. 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.

  13. 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. PMID:27136938

  14. 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.

  15. 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.

  16. 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.

  17. Perspectives on Creating Clinically Relevant Blast Models for Mild Traumatic Brain Injury and Post Traumatic Stress Disorder Symptoms

    OpenAIRE

    Lisa eBrenner; Nazanin eBahraini; Hernández, Theresa D.

    2012-01-01

    Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full character...

  18. Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective.

    Science.gov (United States)

    Ding, Y; Lawrence, N; Olié, E; Cyprien, F; le Bars, E; Bonafé, A; Phillips, M L; Courtet, P; Jollant, F

    2015-01-01

    The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research. PMID:25710122

  19. The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM)

    OpenAIRE

    Zheng, Guoan; Lee, Seung Ah; Antebi, Yaron; Elowitz, Michael B.; Yang, Changhuei

    2011-01-01

    We report a chip-scale lensless wide-field-of-view microscopy imaging technique, subpixel perspective sweeping microscopy, which can render microscopy images of growing or confluent cell cultures autonomously. We demonstrate that this technology can be used to build smart Petri dish platforms, termed ePetri, for cell culture experiments. This technique leverages the recent broad and cheap availability of high performance image sensor chips to provide a low-cost and automated microscopy soluti...

  20. 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.

  1. Perspective of harnessing energy from landfill leachate via microbial fuel cells: novel biofuels and electrogenic physiologies.

    Science.gov (United States)

    Wu, Dong; Wang, Ting; Huang, Xinghua; Dolfing, Jan; Xie, Bing

    2015-10-01

    Organic carbon, nitrogen, and sulfur are highly concentrated in municipal solid waste (MSW) landfill leachate, which usually frustrates conventional leachate treatment technologies from the perspective of energy costs. Therefore, the possibility of converting leachate to a new energy source via microbial fuel cell (MFC) technology has been examined recently. This paper summarizes the power output and energy recovery efficiency of the leachate-fed MFCs according to different feeding patterns, cell structures, and loading rates. Also, we assess potential energy-generating chemicals in leachate like nitrogen and sulfur compounds and propose alternative pathways, which may lift strict ratios between organic carbon and nitrogen content in conventional denitrification of leachate and are expected to achieve a higher voltage than traditional organic-oxygen based cells. Although currently power output of leachate-fed MFCs is limited, it seems well possible that dynamic characteristics of MSW leachates and microbial physiologies underlying some bio-electrochemically efficient activities (e.g., direct interspecies electron transfer) could be stimulated in MFC systems to improve the present status. PMID:26239072

  2. Unusual Indolent Course of a Chronic Active Epstein-Barr Virus-Associated Natural Killer Cell Lymphoproliferative Disorder

    Science.gov (United States)

    Al-Riyami, Arwa Z.; Al-Farsi, Khalil; Al-Khabori, Murtadha; Al-Huneini, Mohammed; Al-Hadabbi, Ibrahim

    2016-01-01

    Natural killer (NK) cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus (EBV) plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement. A polymerase chain reaction (PCR) test revealed a high EBV viral load in the peripheral blood cells. The patient received a course of piperacillin-tazobactam for Klebsiella pneumoniae, but no active treatment for the lymphoproliferative disorder. However, his lymphocyte count, serum lactate dehydrogenase and liver enzymes dropped spontaneously. In addition, EBV PCR copies fluctuated and then decreased significantly. He remained clinically asymptomatic over the following four years. PMID:27226916

  3. A five-factor model perspective on psychopathy and comorbid Axis-II disorders in a forensic-psychiatric sample.

    Science.gov (United States)

    Decuyper, Mieke; De Fruyt, Filip; Buschman, Jos

    2008-01-01

    The validity of DSM-IV predictions [Widiger, T. A., Trull, T. J., Clarkin, J. F., Sanderson, C. J., & Costa, P. T., (2002). A description of the DSM-IV personality disorders with the five-factor model of personality. In Costa, P. T. & Widiger, T. A. (Eds.), Personality disorders and the five-factor model of personality (2nd ed.). Washington DC: American Psychological Association] concerning Antisocial Personality Disorder and the validity of the hypothesized associations between the Five-Factor Model and psychopathy were examined in 48 male forensic-psychiatric patients. Prevalence of psychopathy and comorbid personality pathology was also investigated, as well as the convergent validity of two Dutch personality disorder inventories. Patients provided self-descriptions on the NEO-PI-R [Costa, P. T., & McCrae, R. R., (1992b). Professional Manual: Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor-Inventory (NEO-FFI). Odessa, FL: Psychological Assessment Resources], and were administered the VKP [Duijsens, I. J., Haringsma, R., & EurelingsBontekoe, E. H. M., (1999). Handleiding VKP (Vragenlijst voor kenmerken van de persoonlijkheid). Gebaseerd op DSM-IV en ICD-10. Leiderdorp: Datec] and the ADP-IV [Schotte, C. K. W., & De Doncker, D. A. M., (1994). ADP-IV Questionnaire. Antwerp Belgium: University Hospital Antwerp] to assess personality pathology. Psychopathy was assessed using Hare's Psychopathy Checklist-Revised (PCL-R; [Hare, R. D., (1990). The Hare Psychopathy Checklist Revised Manual. Toronto: Multi-Health Systems]) based on a semi-structured interview and file records of psychiatric and psychological evaluations and criminal history. Results underscored the validity of the FFM Antisocial PD associations, but the hypothesized correlations between the FFM and Psychopathy were less supported. Results supported the convergent validity of the ADP-IV and the VKP, both at the dimensional and categorical level. Around 55% met the diagnostic threshold of

  4. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell.

    Science.gov (United States)

    Inamdar, Ajinkya C; Inamdar, Arati A

    2013-10-01

    Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung. The intravenous infusion of MSCs, the common mode of delivery, is followed by their entrapment in lung vasculature before MSCs reach to other organ systems thus indicating the feasible and promising approach of MSCs therapy for lung diseases. In this review, we discuss the mechanistic basis for MSCs therapy for asthma, ARDS, COPD, and ILD. PMID:23992090

  5. Human T-cell Lymphotropic Virus Type-1 (HTLV-1)-associated Bronchioloalveolar Disorder Presenting with Mosaic Perfusion.

    Science.gov (United States)

    Yamakawa, Hideaki; Yoshida, Masahiro; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Tanoue, Susumu; Sano, Koji; Nishiwaki, Kaichi; Sato, Shun; Shimizu, Yoshihiko; Kuwano, Kazuyoshi

    2015-01-01

    Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a specific state with chronic and progressive respiratory symptoms caused by bronchiolar or alveolar disorder characterized by smoldering adult T-cell leukemia or the HTLV-I carrier state. We herein report a rare case of HABA with an initial presentation of mosaic perfusion in the lung. The diagnosis was made according to the results of a flow cytometry analysis of the bronchoalveolar lavage fluid and pathological findings. Clinicians must be careful to recognize that mosaic perfusion may be a radiological finding of HABA. PMID:26631889

  6. 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.

  7. 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.

  8. 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

  9. Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders.

    Science.gov (United States)

    Millan, Mark J; Goodwin, Guy M; Meyer-Lindenberg, Andreas; Ove Ögren, Sven

    2015-05-01

    Modern neuropsychopharmacology commenced in the 1950s with the serendipitous discovery of first-generation antipsychotics and antidepressants which were therapeutically effective yet had marked adverse effects. Today, a broader palette of safer and better-tolerated agents is available for helping people that suffer from schizophrenia, depression and other psychiatric disorders, while complementary approaches like psychotherapy also have important roles to play in their treatment, both alone and in association with medication. Nonetheless, despite considerable efforts, current management is still only partially effective, and highly-prevalent psychiatric disorders of the brain continue to represent a huge personal and socio-economic burden. The lack of success in discovering more effective pharmacotherapy has contributed, together with many other factors, to a relative disengagement by pharmaceutical firms from neuropsychiatry. Nonetheless, interest remains high, and partnerships are proliferating with academic centres which are increasingly integrating drug discovery and translational research into their traditional activities. This is, then, a time of transition and an opportune moment to thoroughly survey the field. Accordingly, the present paper, first, chronicles the discovery and development of psychotropic agents, focusing in particular on their mechanisms of action and therapeutic utility, and how problems faced were eventually overcome. Second, it discusses the lessons learned from past successes and failures, and how they are being applied to promote future progress. Third, it comprehensively surveys emerging strategies that are (1), improving our understanding of the diagnosis and classification of psychiatric disorders; (2), deepening knowledge of their underlying risk factors and pathophysiological substrates; (3), refining cellular and animal models for discovery and validation of novel therapeutic agents; (4), improving the design and outcome of

  10. 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.

  11. 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. PMID:26636940

  12. 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. PMID:26898639

  13. 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.

  14. 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

  15. P15: The expression of Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders

    Science.gov (United States)

    Zhang, Peng

    2015-01-01

    Background Thymoma is thymic epithelial cell tumor. Studies have shown that thymoma associated with autoimmune disorders and possible mechanisms of autoimmune diseases is the central immune tolerance and peripheral tolerance obstacles have resulted in the breaking of the autoimmune response activation and immune tolerance. Tc17 cells and Th17 cells have been shown play an important role in tumor and autoimmune diseases’ development process. This study test the distribution of Tc17cells in thymoma and the expression of RORγt in thymus of thymoma patients with myasthenia gravis (MG) or other autoimmune diseases, the frequency of Th17/Tc17 in PBMCs, to explore the expression of Th17/Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders. Methods In this study, grouped as follows: (I) thymoma non gravis group (Tm groups); (II) thymoma with MG group thymoma with MG (MG group); (III) thymoma with MG associated with other autoimmune diseases group or anti- nuclear antibodies abnormal elevation of the group (AD group), to analyze the basic differences between the groups. In this study, we examined the RT-PCR to detect RORγt in the thymoma tissue, immunohistochemical double staining method to detect Tc17 cells expression and localization in the thymoma tissue distribution expression Th17/Tc17 in PBMCs by flow cytometry [Interleukin (IL)-17-producing CD8+ cells as Thl7 cells and IL-17-producing CD4+ cells as Tcl7 cells], analysis of differential expression of three in each group thymoma; and explore of Th17/Tc17 expression. Results (I) Tm groups and AD group serum CD8+ cells was statistically significant (PTc17 cells in MG/AD group was significantly higher than that in Tm, was statistically significant (PTc17 cells have risen trend in Tm groups and MG/AD group. Conclusions (I) CD8+ cells, CD4+/CD8+ T ratio, immunoglobulin, CRP and complement C3 levels can be used as indicators of evaluation of the role of the immune status of patients with

  16. 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.

  17. [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.

  18. 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. PMID:24400727

  19. 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.

  20. Perspectives on creating clinically relevant blast models for mild traumatic brain injury and post traumatic stress disorder symptoms

    Directory of Open Access Journals (Sweden)

    Lisa eBrenner

    2012-03-01

    Full Text Available Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic, behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI and/or post traumatic stress disorder (PTSD. Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast TBI can be used to facilitate the development of clinically relevant blast models.

  1. Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders.

    Science.gov (United States)

    Xu, Jie; Sun, Heather H; Fletcher, Christopher D M; Hornick, Jason L; Morgan, Elizabeth A; Freeman, Gordon J; Hodi, F Stephen; Pinkus, Geraldine S; Rodig, Scott J

    2016-04-01

    Programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2) are cell surface proteins expressed by activated antigen-presenting cells and by select malignancies that bind PD-1 on T cells to inhibit immune responses. Antibodies targeting PD-1 or PD-L1 elicit antitumor immunity in a subset of patients, and clinical response correlates with PD-1 ligand expression by malignant or immune cells within the tumor microenvironment. We examined the expression of PD-1 ligands on subsets of antigen-presenting cells and 87 histiocytic and dendritic cell disorders including those that are benign, borderline, and malignant. Within reactive lymphoid tissue, strong PD-L1 is detected on most macrophages, subsets of interdigitating dendritic cells, and plasmacytoid dendritic cells, but not on follicular dendritic cells or Langerhans cells. Macrophage/dendritic cell subsets do not express discernible PD-L2. Seven of 7 cases of sarcoidosis (100%), 6 of 6 cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) (100%), 2 of 11 cases of Rosai-Dorfman disease (18%), and 3 of 15 cases of Langerhans cell histiocytosis (20%) exhibited positivity for PD-L1. All cases of sarcoidosis were also positive for PD-L2. Seven of 14 histiocytic sarcomas (50%), 2 of 5 interdigitating dendritic cell sarcomas (40%), 10 of 20 follicular dendritic cell sarcomas (50%), and none of 9 blastic plasmacytoid dendritic cell neoplasms were positive for PD-L1. Eleven of 20 (55%) follicular dendritic cell sarcomas were also positive for PD-L2. PD-L1 and PD-L2 are useful new markers for identifying select histiocyte and dendritic cell disorders and reveal novel patient populations as rational candidates for immunotherapy. PMID:26752545

  2. Bleeding Disorders

    Science.gov (United States)

    ... times I'd miss work and skip the gym because I felt so lousy. So I decided ... cell called platelets. Your body also needs blood proteins called clotting factors. In people with bleeding disorders, ...

  3. UNEMPLOYMENT AND SOCIAL EXCLUSION OF YOUNG PEOPLE IN CROATIA: PERSPECTIVE OF UNEMPLOYED YOUTH AT RISK OR WITH BEHAVIOUR DISORDERS

    Directory of Open Access Journals (Sweden)

    Nivex Koller-Trbović

    2009-12-01

    Full Text Available Main goal of this paper is to provide insight into perspective of unemployed youth at risk or with potential risks in enviroment, aboutstatus and experiance of being unemployed. Krounauer model of social excluasion was taken as the base for interpretation of riskfactors related to unemployment. Mentioned model is defi ned with six dimesions: exclusion from labour market, economic exclusion,social isolation, institutional exclusion, spatial and cultural exclusion. Five focus groups with 19 unemployed youth (age from 18 to27 years from 4 cities in Croatia and from two types of institutions (croatian employment service and center for social welfare havebeen conducted. Results implicate that unemployment represents important factor for integration and independence of youth, andrelevant risk factor especially for economical exclusion. However, result shows that unemployment does not lead to social isolation asthird key dimesion in social exclusion model. These results are, to some extant, similar to results in other countries in EU, especiallyin south-east European countries (Italy, Spain, Greecee where research results show that unemployment do not neccessarily leads tosocial exclusion due to the strong family and friends support. Results can be used for the creation of public strategies in coping withrisk of (longterm youth unemployment and also with risk of their social exclusion.

  4. Clinical potential of phycocyanobilin for induction of T regulatory cells in the management of inflammatory disorders.

    Science.gov (United States)

    McCarty, Mark F

    2011-12-01

    Exposure of human mononuclear cells to phycocyanin in vitro is reported to promote generation of Treg cells. Induction of heme oxygenase-1 (HO-1) in lymphocytes has a similar effect, and it is not likely to be accidental that a key product of HO-1 activity, biliverdin, is homologous to the structure of phycocyanin's chromophore phycocyanobilin (PhyCB). Moreover, Treg induction is observed in mice injected with bilirubin, biliverdin's chief metabolite. These considerations suggest that bilirubin, generated within lymphocytes by HO-1 activation, may play a physiological role in the promotion of Treg immunomodulation. This effect of bilirubin is likely to be independent of NADPH oxidase inhibition, since the NAPDH oxidase activity of macrophages is necessary for Treg induction, possibly because it contributes to HO-1 induction in lymphocytes. In light of numerous reports that oral phycocyanin is beneficial in various rodent models of autoimmune disorders, it is reasonable to suspect that PhyCB-enriched spirulina extracts may have clinical potential for boosting Treg activity in human autoimmune or allergic syndromes, mimicking the physiological role of HO-1 induction in this regard. PMID:21917385

  5. 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.

  6. The effect of rat bone marrow derived mesenchymal stem cells transplantation for restoration of olfactory disorder.

    Science.gov (United States)

    Jo, Hyogyeong; Jung, Minyoung; Seo, Dong Jin; Park, Dong Joon

    2015-11-13

    The purpose of the study was to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on olfactory epithelium (OE) of morphologic and functional restoration following neural Sensorineural Disorder in rats. Except the Normal group, twenty-one rats underwent Triton X-100 (TX-100) irrigation to induce degeneration of OE, and then BMSCs and PBS were treated from the both medial canthus to the rear part of the both nasal cavity into the experimental group and then were observed for restoration according to time point. At two and four weeks after transplantation with BMSCs, restoration of OE was observed with olfactory marker protein (OMP) and behavioral test. And we observed the expression of OMP, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). After TX-100 irrigation, the OE almost disappeared in 3 days. At four weeks after transplantation with BMSCs, the thickness and cellular composition of OE was considerably restored to normal group and expression of OMP was markedly increased when compared with PBS group and reduced the searching time in the behavioral test. Furthermore at two weeks after treatment with BMSCs, expression of NGF and BDNF was greatly increased when compared with PBS group. However at four weeks after treatment with BMSCs, expression of NGF and BDNF was slightly decreased. Our results suggest the BMSCs transplantation affect restoration of OE and olfaction, most likely via regulation of the neurotrophic factor expression, especially the expression of NGF and BDNF and has a possibility of a new therapeutic strategy for the treatment of olfactory disorder caused by the degeneration of OE. PMID:26427869

  7. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells.

    Science.gov (United States)

    Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A; Fink, Kyle D

    2016-05-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.

  8. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells.

    Science.gov (United States)

    Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A; Fink, Kyle D

    2016-05-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. THERAPEUTIC MANAGEMENT OF PEDIATRIC ALLERGIC DISORDERS BY INDIAN MEDICINAL PLANTS WITH MAST CELL STABILIZING POTENTIAL: A REVIEW

    Directory of Open Access Journals (Sweden)

    Mahapatra Arun Kumar

    2013-04-01

    Full Text Available Every fifth child develops an allergic disorder sometime during childhood and these conditions gravely trouble the health status and quality of life of children. Conventional agents are being used to control allergic disorders. However, these are not entirely affordable and effective. Numerous medicinal plants have been used successfully for the prevention and management of pediatric allergic disorders in Indian traditional systems of medicine, Ayurveda. Medicinal plants with mast-cell stabilizing activity are being more desired, owing to lesser side-effects and low cost. This review focuses on the various plants with mast cell stabilizing activity that has been reported to be effective in various allergic disorders. These include Abrus precatorius (Gunja, Albizzia lebbeck (Shirish, Allium cepa (Palandu, Aristolochia bracteolate (ishwari moola, Bacopa monnieri.(Brahmi, Boswellia serrata Roxb.(Shallaki, Cedrus deodara (Roxb. Loud (Devadaru, Elaeocarpus sphaericus (Rudraksha, Ficus religiosa (Ashwatha, Inula racemosa (Pushkarmoola, Sphaeranthus indicus (Mundi and Vitex Negundo (Nirgundi. All of them have shown a certain degree of mast cell stabilizing activity as evidenced by various research studies.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Anti-Purkinje cell antibody as a biological marker in attention deficit/hyperactivity disorder: a pilot study.

    Science.gov (United States)

    Passarelli, Francesca; Donfrancesco, Renato; Nativio, Paola; Pascale, Esterina; Di Trani, Michela; Patti, Anna Maria; Vulcano, Antonella; Gozzo, Paolo; Villa, Maria Pia

    2013-05-15

    An autoimmune hypothesis has been suggested for several disorders in childhood. The aim of the study was to clarify the role of the cerebellum in ADHD and to evaluate the possible association between anti-Yo antibodies and ADHD. The presence/absence of antibodies was tested by indirect immunofluorescence assay on 30 combined subtype ADHD children, on 19 children with other psychiatric disorders (Oppositional-defiant and Conduct Disorders, Dyslexia) and 27 healthy controls. Results showed a significant positive response to the anti-Yo antibody immunoreactivity in the Purkinje cells of the cerebellum of ADHD children, compared with the control group and the psychiatric non-ADHD children. This association points to an immune dysregulation and the involvement of the cerebellum in ADHD. PMID:23510584

  20. Cognitive Function of Children and Adolescents with Attention Deficit Hyperactivity Disorder and Learning Difficulties: A Developmental Perspective

    Science.gov (United States)

    Huang, Fang; Sun, Li; Qian, Ying; Liu, Lu; Ma, Quan-Gang; Yang, Li; Cheng, Jia; Cao, Qing-Jiu; Su, Yi; Gao, Qian; Wu, Zhao-Min; Li, Hai-Mei; Qian, Qiu-Jin; Wang, Yu-Feng

    2016-01-01

    Background: The cognitive function of children with either attention deficit hyperactivity disorder (ADHD) or learning disabilities (LDs) is known to be impaired. However, little is known about the cognitive function of children with comorbid ADHD and LD. The present study aimed to explore the cognitive function of children and adolescents with ADHD and learning difficulties in comparison with children with ADHD and healthy controls in different age groups in a large Chinese sample. Methods: Totally, 1043 participants with ADHD and learning difficulties (the ADHD + learning difficulties group), 870 with pure ADHD (the pure ADHD group), and 496 healthy controls were recruited. To investigate the difference in cognitive impairment using a developmental approach, all participants were divided into three age groups (6–8, 9–11, and 12–14 years old). Measurements were the Chinese-Wechsler Intelligence Scale for Children, the Stroop Color-Word Test, the Trail-Making Test, and the Behavior Rating Inventory of Executive Function-Parents (BRIEF). Multivariate analysis of variance was used. Results: The results showed that after controlling for the effect of ADHD symptoms, the ADHD + learning difficulties group was still significantly worse than the pure ADHD group, which was, in turn, worse than the control group on full intelligence quotient (98.66 ± 13.87 vs. 105.17 ± 14.36 vs. 112.93 ± 13.87, P ADHD symptoms, intelligence quotient, age, and gender. As for the age groups, the differences among groups became nonsignificant in the 12–14 years old group for inhibition (meaning interference of the Stroop Color-Word Test, 18.00 [13.00, 25.00] s vs. 17.00 [15.00, 26.00] s vs. 17.00 [10.50, 20.00] s, P = 0.704) and shift function (shifting time of the Trail-Making Test, 62.00 [43.00, 97.00] s vs. 53.00 [38.00, 81.00] s vs. 101.00 [88.00, 114.00] s, P = 0.778). Conclusions: Children and adolescents with ADHD and learning difficulties have more severe cognitive

  1. 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. PMID:27656126

  2. Sleep-disordered breathing and nocturnal hypoxemia in young adults with sickle cell disease.

    Science.gov (United States)

    Whitesell, P L; Owoyemi, O; Oneal, P; Nouraie, M; Klings, E S; Rock, A; Mellman, T A; Berihun, T; Lavella, J; Taylor, R E; Perrine, S P

    2016-06-01

    Sleep-disordered breathing (SDB) is reported in up to 69% of adolescents and children with sickle cell disease (SCD) [1], but data regarding the prevalence of SDB in adults with SCD are limited. In order to obtain a preliminary assessment of the frequency and degree of sleep-related hypoxemia and potential associations with cardiovascular function in adults with SCD, we conducted overnight sleep studies, 6-min walk tests, echocardiograms, and hematologic and chemistry panels, calculated the Pittsburgh sleep quality index (PSQI), and conducted fatigue- and health-related quality-of-life measurement in 20 young adults with SCD visiting a sickle cell clinic for routine care. Sleep apnea, defined as an apnea-hypopnea index (AHI) > 5 events/h, was found in 50% of patients. Traditional clinical indicators, such as obesity, the presence of snoring, and reported sleep complaints, did not reliably differentiate them. The patients with AHI > 5 had higher mean systolic blood pressure (p = 0.03), evidence of impaired left ventricular diastolic function (i.e., increased mitral valve E/A ratio, p = 0.05), a trend toward higher reduction in 6-min walk distances (p = 0.06), and lower health-related quality-of-life scores (p ≤ 0.01). Three of nine patients with more severe anemia (total Hb sleep apnea. As prolonged and frequent hypoxemic episodes likely increase risks for vaso-occlusive, cardiovascular, and neurologic complications of SCD, these results suggest that the prevalence and severity of SDB should be investigated further in studies of larger patient populations. If confirmed, these findings could identify opportunities to prevent or reduce nocturnal hypoxia and improve outcomes. PMID:27544835

  3. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

    OpenAIRE

    Bourne, Sarah K.; Eckhardt, Christine A.; Sheth, Sameer A.; Eskandar, Emad N.

    2012-01-01

    Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions...

  4. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

    OpenAIRE

    Sarah Kathleen Bourne; Christine Ann Eckhardt; Sheth, Sameer A.; Eskandar, Emad N.

    2012-01-01

    Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive-compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions...

  5. “To Treat or Not To Treat?”: An Exploratory Study of Medical Practitioners' Perspective on Clinical Ethics in Stem Cell Therapies

    OpenAIRE

    Shariat, Sadaf

    2011-01-01

    This study investigates the practitioners‘ perception toward an ethical Stem Cell therapy. Reviewing literature, it is revealed that studies on Stem Cell therapies are predominately focus on ethical aspects of Stem Cell researches, commercialization, and concept of ethic support in clinical practice; whereas the notion of clinical ethics in Stem Cell therapies and particularly medical practitioners‘ perspective is noticeably absent from contemporary clinical ethics and Stem Cell therapy discu...

  6. 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.

  7. 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,…

  8. 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.

  9. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement

    OpenAIRE

    Gaspar, Nathalie; Van Den Neste, Eric; Boudou, Pascaline; Haroche, Julien; Wechsler, Bertrand; Hoang-Xuan, Khe; Amoura, Zahir; Guillevin, Remy; Savatovski, Julien; Azar, Nabih; Piette, Jean-Charles; Leblond, Veronique

    2006-01-01

    We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous hematopoietic stem cell transplantation might help to control refractory central nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS involvement were treated in this way. Two patients achieved non-active disease status, although one relapsed at 84 months. Two patients had regressive disease, one of whom progressed at 21 months. One patient had progressive disease at 14 months. One patie...

  10. 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

  11. 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.

  12. Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

    International Nuclear Information System (INIS)

    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 neuro-inflammation. (authors)

  13. Stem cells and lineages of the intestine: a developmental and evolutionary perspective

    OpenAIRE

    Takashima, Shigeo; Gold, David; Hartenstein, Volker

    2012-01-01

    The intestine consists of epithelial cells that secrete digestive enzymes and mucus (gland cells), absorb food particles (enterocytes), and produce hormones (endocrine cells). Intestinal cells are rapidly turned over and need to be replaced. In cnidarians, mitosis of differentiated intestinal cells accounts for much of the replacement; in addition, migratory, multipotent stem cells (interstitial cells) contribute to the production of intestinal cells. In other phyla, intestinal cell replaceme...

  14. The analysis of expanded cells from patients with lymphoproliferative disorders of granular lymphocytes may help to clarify the NK cell differentiation.

    Science.gov (United States)

    Zambello, R; Chisesi, T; De Rossi, G; Pandolfi, F; Trentin, L; Vespignani, M; Luciani, M; Cafaro, A; Agostini, C; Martelli, M

    1986-07-01

    Surface phenotype and functional in vitro activities were studied in 2 cases of lymphoproliferative disorders of granular lymphocytes. Cells from both patients presented the same, previously unreported, surface phenotype (i.e. T3+, T8+, T4-, HNK-1-, NK-15+, M1-), were unable to display either Natural Killer (NK) activity or suppressor function in a poke-weed-driven system, and showed a defective response to phytohemagglutinin (PHA). On the basis of available schemes for NK cells ontogenesis, we will discuss the phenotype and functional activities of patients' cells suggesting that the cell population expressing the T3+, T8+, HNK-1-, NK-15+, M1- phenotype might represent a discrete stage along the NK-cell differentiation pathway. PMID:3746877

  15. 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.

  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. 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.

  18. Light-scattering effectiveness of two-dimensional disordered surface textures in thin-film silicon solar cells.

    Science.gov (United States)

    Yeh, Pinghui S; Chen, Chien-Wei; Yang, Bing-Ru; Hong, Lu-Sheng

    2014-05-01

    To compare the light-scattering effectiveness of surface-textured solar cells of various design parameters such as density, diameter, refractive index, and location, this study used a new parameter, optical path length gain (OPLG), that is more sensitive than Haze. By modeling two-dimensional disordered textures as a structure that comprises many randomly distributed, small, spherical scatterers, ray-tracing simulations of surface-textured thin-film silicon solar cells were performed. The simulation results suggest that: (1) the optimal scatterer diameter for hydrogenated amorphous silicon (a-Si:H) solar cells is ~50 nm, producing an average OPLG of 3.5; and (2) the optimal scatterer diameter for a-Si:H/μc-Si:H (hydrogenated microcrystalline silicon) tandem cells is ~75 nm, producing an average OPLG of 3.4 and an increase in the bandwidth of the absorption spectrum of 14.5%. PMID:24921870

  19. 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…

  20. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.

    Science.gov (United States)

    Gubert, Carolina; Stertz, Laura; Pfaffenseller, Bianca; Panizzutti, Bruna Schilling; Rezin, Gislaine Tezza; Massuda, Raffael; Streck, Emilio Luiz; Gama, Clarissa Severino; Kapczinski, Flávio; Kunz, Maurício

    2013-10-01

    Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression. PMID:23870796

  1. 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. 

  2. Induced pluripotent stem cells: Mechanisms, achievements and perspectives in farm animals

    OpenAIRE

    Kumar, Dharmendra; Talluri, Thirumala R; Anand, Taruna; Kues, Wilfried A.

    2015-01-01

    Pluripotent stem cells are unspecialized cells with unlimited self-renewal, and they can be triggered to differentiate into desired specialized cell types. These features provide the basis for an unlimited cell source for innovative cell therapies. Pluripotent cells also allow to study developmental pathways, and to employ them or their differentiated cell derivatives in pharmaceutical testing and biotechnological applications. Via blastocyst complementation, pluripotent cells are a favoured ...

  3. Pathological Propagation through Cell-to-Cell Transmission of Non-Prion Protein Aggregates in Neurodegenerative Disorders

    Science.gov (United States)

    Lee, Seung-Jae; Desplats, Paula; Sigurdson, Christina; Tsigelny, Igor; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, fronto-temporal dementia, Huntington's Disease and Creutzfeldt-Jakob Disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. While protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has been reserved to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence suggests that prion-like spreading may occur in other neurodegenerative disorders, taking place with secreted proteins, such as amyloid-β,) and cytosolic proteins, such as tau, huntingtin and α-synuclein. Underlying molecular mechanisms and therapeutic implications are discussed. PMID:21045796

  4. 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

  5. [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

  6. 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.

  7. Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    2005-06-23

    I Cell Disease; Fucosidosis; Globoid Cell Leukodystrophy; Adrenoleukodystrophy; Mannosidosis; Niemann-Pick Disease; Pulmonary Complications; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Metachromatic Leukodystrophy; Gaucher's Disease; Wolman Disease

  8. Stem cells and lineages of the intestine: a developmental and evolutionary perspective.

    Science.gov (United States)

    Takashima, Shigeo; Gold, David; Hartenstein, Volker

    2013-03-01

    The intestine consists of epithelial cells that secrete digestive enzymes and mucus (gland cells), absorb food particles (enterocytes), and produce hormones (endocrine cells). Intestinal cells are rapidly turned over and need to be replaced. In cnidarians, mitosis of differentiated intestinal cells accounts for much of the replacement; in addition, migratory, multipotent stem cells (interstitial cells) contribute to the production of intestinal cells. In other phyla, intestinal cell replacement is solely the function of stem cells entering the gut from the outside (such as in case of the neoblasts of platyhelminths) or intestinal stem cells located within the midgut epithelium (as in both vertebrates or arthropods). We will attempt in the following to review important aspects of midgut stem cells in different animal groups: where are they located, what types of lineages do they produce, and how do they develop. We will start out with a comparative survey of midgut cell types found across the animal kingdom; then briefly look at the specification of these cells during embryonic development; and finally focus on the stem cells that regenerate midgut cells during adult life. In a number of model systems, including mouse, zebrafish and Drosophila, the molecular pathways controlling intestinal stem cells proliferation and the specification of intestinal cell types are under intensive investigation. We will highlight findings of the recent literature, focusing on aspects that are shared between the different models and that point at evolutionary ancient mechanisms of intestinal cell formation. PMID:23179635

  9. 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

  10. Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cells

    International Nuclear Information System (INIS)

    Highlights: → Primary proinsulin maturation disorder is inherent in Ins2+/Akita islets/β-cells. → A consequence is the inefficient conversion of proinsulin to insulin. → Post-translational defects occur as well in the involved PC1/3 and PC2 convertases. → Proinsulin maturation chaos results in defects in the following conversion process. → A link of the proinsulin maturation disorder and hyperproinsulinemia is suggested. -- Abstract: Disproportionate hyperproinsulinemia is an indicator of β-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 β-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 β-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+/Akita islets/β-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+/Akita islets. Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the β-cells of Ins2+/Akita islets in spite of no declines of these two convertases at the transcriptional and translational levels. Immunoblot analyses in cloned Ins2+/Akita β-cells further confirmed the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2 proteins were not reduced somehow

  11. 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

    OpenAIRE

    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 variou...

  12. RNA-binding proteins in mouse male germline stem cells: a mammalian perspective

    OpenAIRE

    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 ...

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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 ...

  18. 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…

  19. Treatment of cardiovascular disorders using the cell differentiation signaling protein Nell1

    Science.gov (United States)

    Culiat, Cymbeline T

    2014-05-13

    It has been identified in accordance with the present invention that Nell1 is essential for normal cardiovascular development by promoting proper formation of the heart and blood vessels. The present invention therefore provides therapeutic methods for treating cardiovascular disorders by employing a Nell1 protein or nucleic acid molecule.

  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

  1. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

    NARCIS (Netherlands)

    Baker, D.J.; Wijshake, T.; Tchkonia, T.; LeBrasseur, N.K.; Childs, B.G.; Sluis, B. van de; Kirkland, J.L.; Deursen, J.M.A. van

    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

  2. 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)).

  3. 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)). PMID:26341268

  4. 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.

  5. A fair comparison between ultrathin crystalline-silicon solar cells with either periodic or correlated disorder inverted pyramid textures.

    Science.gov (United States)

    Muller, Jérôme; Herman, Aline; Mayer, Alexandre; Deparis, Olivier

    2015-06-01

    Fabrication of competitive solar cells based on nano-textured ultrathin silicon technology is challenging nowadays. Attention is paid to the optimization of this type of texture, with a lot of simulation and experimental results published in the last few years. While previous studies discussed mainly the local features of the surface texture, we highlight here the importance of their filling fraction. In this work, we focus on a fair comparison between a technologically realizable correlated disorder pattern of inverted nano-pyramids on an ultrathin crystalline-silicon layer, and its periodically patterned counterpart. A fair comparison is made possible by defining an equivalent periodic structure for each hole filling fraction. Moreover, in order to be as realistic as possible, we consider patterns that could be fabricated by standard patterning techniques: hole-mask colloidal lithography, nanoimprint lithography and wet chemical etching. Based on numerical simulations, we show that inverted nano-pyramid patterns with correlated disorder provide typically greater efficiency than their periodic counterparts. However, the hole filling fraction of the etched pattern plays a crucial role and may limit the benefits of the correlated disorder due to experimental restrictions on pattern fabrication.

  6. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits.

    Science.gov (United States)

    Bourne, Sarah K; Eckhardt, Christine A; Sheth, Sameer A; Eskandar, Emad N

    2012-01-01

    Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level. PMID:22712007

  7. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

    Directory of Open Access Journals (Sweden)

    Sarah Kathleen Bourne

    2012-06-01

    Full Text Available Deep brain stimulation (DBS has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive-compulsive disorder (OCD, which is characterized by recurrent unwanted thoughts or ideas (obsessions and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions. Abnormal activity in cortico-striato-thalamo-cortical (CSTC circuits including the orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mediodorsal thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule, ventral capsule/ventral striatum, ventral caudate nucleus, subthalamic nucleus, nucleus accumbens, and the inferior thalamic peduncle have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

  8. T-Cell lymphoproliferative disorder of hand-mirror cell morphology presenting in an eosinophilic loculated peritoneal effusion, with omental "caking"

    Directory of Open Access Journals (Sweden)

    Tufankjian Dearon

    2006-01-01

    Full Text Available Abstract Background Cells with "hand mirror" morphology have not, to the best of our knowledge, been described in a primary effusion sample. This paper describes a case of T-cell lymphoma with eosinophilia in a patient with suspected peritoneal carcinomatosis. Rarely, a T-cell lymphoproliferative process may mimic primary peritoneal carcinomatosis, clinically suggested by a presentation in CT imaging of omental caking with bilateral massive loculated effusions in a patient without lymphadenopathy or splenomegaly. Methods A 60 year old caucasian male presented with vague abdominal discomfort and increasing abdominal girth. Computed tomography showed a two centimeter thick omental cake and a small loculated effusion. The clinical presentation and imaging findings were most consistent with peritoneal carcinomatosis. Cytologic evaluation of the effusion was undertaken for diagnostic study. Results Rapid intraprocedural interpretation of the effusion sample showed a monomorphic population of cells with "hand-mirror" cell morphology exhibiting cytoplasmic extensions (uropodia with 3–5 course dark cytoplasmic granules and a rim of vacuolated cytoplasm capping the opposing "mirror head" side. These cells were seen within a background of mature eosinophils. Flow cytometric evaluation of the ascites fluid demonstrated an atypical T-cell population with the following immunophenotype: CD2-, CD3+, CD4-, CD5-, CD7-, CD8+, CD56+. T-cell receptor (TCR gene rearrangement was positive for clonal TCR-gamma gene rearrangement, supporting the diagnosis of a T-lymphoprolifereative disorder. Conclusion A T-cell lymphoproliferative process may present with "hand mirror" morphology in an effusion sample. These cells may show polar cytoplasmic vacuolization and 3–5 course granules within the "handle" of these unique cells. Cytoplasm shows peripheral constriction around the nucleus.

  9. EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations.

    Science.gov (United States)

    Courville, Elizabeth L; Yohe, Sophia; Chou, David; Nardi, Valentina; Lazaryan, Aleksandr; Thakral, Beenu; Nelson, Andrew C; Ferry, Judith A; Sohani, Aliyah R

    2016-10-01

    Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (Pnegative (Ppost-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (Ppost-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.

  10. Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

    Directory of Open Access Journals (Sweden)

    Dae-Kwon Bae

    2016-01-01

    Full Text Available Since multiple sclerosis (MS is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG- induced experimental autoimmune encephalomyelitis (EAE model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP. The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, ciliary neurotrophic factor (CNTF, and leukemia inhibitory factor (LIF. In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

  11. Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy

    OpenAIRE

    Simerman, Ariel A; Daniel A Dumesic; 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...

  12. 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. PMID:26839690

  13. 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.

  14. Interstitial cells of Cajal as targets for pharmacological intervention in gastrointestinal motor disorders

    DEFF Research Database (Denmark)

    Huizinga, J D; Thuneberg, L; Vanderwinden, J M;

    1997-01-01

    Interstitial cells of Cajal (ICCs) have recently been identified as the pacemaker cells for contractile activity of the gastrointestinal tract. These cells generate the electrical 'slow-wave' activity that determines the characteristic frequency of phasic contractions of the stomach, intestine an...

  15. Mature B-cell lymphoma and leukemia in children and adolescents-review of standard chemotherapy regimen and perspectives.

    Science.gov (United States)

    Worch, Jennifer; Rohde, Marius; Burkhardt, Birgit

    2013-09-01

    Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. Many B-NHL subtypes frequently observed in adults are rarely diagnosed in children and adolescents. In this age group, Burkitt lymphoma (BL), Burkitt leukemia or FAB L3 leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBL), follicular lymphoma (FL), and aggressive mature B-NHL not further classifiable (B-NHL nfc) are the most common subtypes. Diverse clinical trials demonstrated similar results of current combination chemotherapy regimens succeeding in overall survival rates of more than 80%. However, treatment-related toxicity and the poor prognosis of relapse are serious concerns. Furthermore, specific histological B-NHL subtypes are rare in children and optimal treatment is not established. New treatment modalities are urgently needed for these patient groups. Rituximab, a monoclonal antibody that is already established in the treatment of adults with mature B-NHL, demonstrated promising results in pediatric patients. The definitive role of rituximab in the treatment of children and adolescents with B-NHL needs to be evaluated in prospective controlled clinical trials. This review provides a comprehensive overview of chemotherapy regimens and the perspectives for children and adolescents with mature B-cell lymphoma and leukemia. PMID:23570584

  16. Infiltration patterns in monoclonal plasma cell disorders: correlation of magnetic resonance imaging with matched bone marrow histology

    Energy Technology Data Exchange (ETDEWEB)

    Andrulis, Mindaugas [Institute of Pathology, University of Heidelberg, Heidelberg (Germany); Bäuerle, Tobias [Department of Diagnostic and Interventional Radiology, University of Hamburg, Hamburg (Germany); Goldschmidt, Hartmut [Department of Hematology and Oncology, University of Heidelberg, Heidelberg (Germany); Delorme, Stefan [Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Landgren, Ola [Multiple Myeloma Section, Metabolism Branch, National Cancer Institute, Bethesda (United States); Schirmacher, Peter [Institute of Pathology, University of Heidelberg, Heidelberg (Germany); Hillengass, Jens, E-mail: jens.hillengass@med.uni-heidelberg.de [Department of Hematology and Oncology, University of Heidelberg, Heidelberg (Germany); Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2014-06-15

    Objectives: To investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy. Methods: We assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region. Results: MRI revealed a minimal (n = 11, 22%), focal (n = 5, 10%), diffuse (n = 14, 28%) and mixed (n = 20, 40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with “focal component” (i.e. focal and mixed) were most common in symptomatic myeloma (p < 0.01). In histology an interstitial (n = 13, 26%), nodular (n = 23, 46%) and packed marrow (n = 14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology. Conclusions: Infiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells.

  17. Infiltration patterns in monoclonal plasma cell disorders: correlation of magnetic resonance imaging with matched bone marrow histology

    International Nuclear Information System (INIS)

    Objectives: To investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy. Methods: We assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region. Results: MRI revealed a minimal (n = 11, 22%), focal (n = 5, 10%), diffuse (n = 14, 28%) and mixed (n = 20, 40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with “focal component” (i.e. focal and mixed) were most common in symptomatic myeloma (p < 0.01). In histology an interstitial (n = 13, 26%), nodular (n = 23, 46%) and packed marrow (n = 14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology. Conclusions: Infiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells

  18. Borna disease virus induces acute fatal neurological disorders in neonatal gerbils without virus- and immune-mediated cell destructions

    International Nuclear Information System (INIS)

    Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that is known to cause neurological disturbances in various animal species. Our previous experiment demonstrated that neonate gerbils develop an acute fatal neurological disease following infection with BDV , Virology 282, 65-76). The study suggested that BDV directly causes functional damage of neuronal cells resulting in the lethal disorder in neonatal gerbils. To extend this finding, we examined whether BDV can induce neurological diseases in the absence of virus- and immune-mediated cell destruction, by using cyclosporine A (CsA)-treated neonatal gerbils. Although CsA completely suppressed specific antibody production and brain inflammation in the infected gerbil brains, the fatal neurological disorder was not inhibited by the treatment. Furthermore, we demonstrated that CsA treatment significantly decreased brain levels of cytokines, except interleukin (IL)-1β, in the infected gerbils. These results suggested that BDV replication, as well as brain cytokines, at least IL-1β, rapidly induces fatal disturbances in gerbil brain. We demonstrate here that BDV exhibits a unique neuropathogenesis in neonatal gerbil that may be pathologically and immunologically different from those in two other established rodent models, rats and mice. With this novel rodent model of virus infection it should be possible not only to examine acute neurological disturbances without severe neuroanatomical and immunopathological alterations but also to analyze molecular and cellular damage by virus replication in the central nervous system

  19. The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders.

    OpenAIRE

    Betancur, Catalina; Sakurai, Takeshi; Buxbaum, Joseph D

    2009-01-01

    International audience Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, includi...

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. Present state and future perspectives of using pluripotent stem cells in toxicology research

    OpenAIRE

    Wobus, Anna M.; Löser, Peter

    2011-01-01

    The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, a...

  5. Treadmill exercise ameliorates symptoms of attention deficit/hyperactivity disorder through reducing Purkinje cell loss and astrocytic reaction in spontaneous hypertensive rats

    OpenAIRE

    Yun, Hyo-Soon; Park, Mi-Sook; Ji, Eun-Sang; Kim, Tae-Woon; Ko, Il-Gyu; Kim, Hyun-Bae; Kim, Hong

    2014-01-01

    Attention deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder of cognition. We investigated the effects of treadmill exercise on Purkinje cell and astrocytic reaction in the cerebellum of the ADHD rat. Adult male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKYR) weighing 210± 10 g were used. The animals were randomly divided into four groups (n= 15): control group, ADHD group, ADHD and methylphenidate (MPH)-treated group, ADHD and treadmill exercise group. The...

  6. 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.

  7. 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…

  8. Dream disorders and treatment.

    Science.gov (United States)

    Eiser, Alan S

    2007-09-01

    Consensus does not exist regarding what should constitute a "dream disorder." Conditions with disordered dreaming may be thought of as primary (ie, arising from changes in dreaming per se) or secondary to extrinsic disorders that impinge on structures involved in dreaming. The major primary disorder of dreaming, nightmare disorder, is covered in depth in this article. Definition of nightmare, diagnostic criteria for nightmare disorder, and differential diagnosis are discussed. The value of a sleep-disorders perspective on nightmares, and the possible exacerbating effects of sleep disorders that cause arousals, are indicated. The importance of a perspective that appreciates nightmares as richly and personally meaningful, with links to complex psychological factors present and past, is emphasized. Two types of treatment approaches are discussed: approaches that target the symptom of nightmares in relative isolation, and approaches that aim at working out psychological issues viewed as causing nightmares and a variety of other interconnected symptoms and problems. The former type of treatment includes the cognitive-behavioral approach "imagery rehearsal therapy," and the medication prazosin. The latter approach entails exploratory or psychodynamic psychotherapies. The approaches are seen as so different in scope, aim, and conceptual framework as to defy ready comparison. I think that a thorough psychological/psychiatric evaluation is essential for informed consideration in conjunction with the patient's choice of treatment approach. Sleep terrors are discussed as a non-rapid eye movement sleep arousal disorder that at times may be linked to broader psychological issues warranting consideration of psychotherapy. Brief summaries are provided of dream disorders secondary to other sleep disorders, drug and alcohol effects, medical disorders, and organic brain damage.

  9. Challenges of stem cell-based pulp and dentin regeneration: a clinical perspective

    OpenAIRE

    Huang, George T.-J.; Al-Habib, Mey; Gauthier, Philippe

    2013-01-01

    There are two types of approaches to regenerate tissues: cell-based and cell-free. The former approach is to introduce exogenous cells into the host to regenerate tissues, and the latter is to use materials other than cells in an attempt to regenerate tissues. There has been a significant advancement in stem cell-based pulp and dentin regeneration research in the past few years. Studies in small and large animals have demonstrated that pulp/dentin-like tissues can be regenerated partially or ...

  10. Relevance of Cell-ECM Interactions: From a Biological Perspective to the Mathematical Modeling

    Directory of Open Access Journals (Sweden)

    Preziosi Luigi

    2015-01-01

    Full Text Available Cell migration across fibre networks and micro-channel structures has been widely demonstrated to be strongly influenced by the interactions between moving individuals and the surrounding extracellular matrix as well as by the mechanical properties of cell nucleus. In this respect, our work will be devoted to describe several mathematical models, which deal either with cell adhesion mechanics or with suitable analysis of the role played in cell movement by nucleus stiffness. In particular, the presented approaches span from discrete individual-based methods to continuous models and provide useful insights into selected determinant underlying cell migration within two-and three-dimensional matrix environments.

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

    NARCIS (Netherlands)

    P. Bárcena (Paloma); M. Jara-Acevedo (M.); M.D. Tabernero; A. López (Antonio); M.-L. Sánchez (M.); A.C. García-Montero (Andrés); N. Muñoz-García (Noemí); M.B. Vidriales (M.); A. Paiva (Artur); Q. Lecrevisse (Quentin); M. Lima (Margarida); A.W. Langerak (Ton); S. Böttcher (Stephan); J.J.M. van Dongen (Jacques); A. Orfao (Alberto); J. Almeida (Julia)

    2015-01-01

    textabstractCurrently, 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

  13. Further evidence that paroxysmal nocturnal haemoglobinuria is a disorder of defective cell membrane lipid rafts.

    Science.gov (United States)

    Ratajczak, Mariusz Z; Borkowska, Sylwia; Mierzejewska, Kasia; Kucia, Magda; Mendek-Czajkowska, Ewa; Suszynska, Malwina; Sharma, Vivek A; Deptala, Andrzej; Song, Wechao; Platzbecker, Uwe; Larratt, Loree; Janowska-Wieczorek, Anna; Maciejewski, Jarek; Ratajczak, Janina

    2015-09-01

    The glycolipid glycosylphosphatidylinositol anchor (GPI-A) plays an important role in lipid raft formation, which is required for proper expression on the cell surface of two inhibitors of the complement cascade, CD55 and CD59. The absence of these markers from the surface of blood cells, including erythrocytes, makes the cells susceptible to complement lysis, as seen in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). However, the explanation for why PNH-affected hematopoietic stem/progenitor cells (HSPCs) expand over time in BM is still unclear. Here, we propose an explanation for this phenomenon and provide evidence that a defect in lipid raft formation in HSPCs leads to defective CXCR4- and VLA-4-mediated retention of these cells in BM. In support of this possibility, BM-isolated CD34(+) cells from PNH patients show a defect in the incorporation of CXCR4 and VLA-4 into membrane lipid rafts, respond weakly to SDF-1 stimulation, and show defective adhesion to fibronectin. Similar data were obtained with the GPI-A(-) Jurkat cell line. Moreover, we also report that chimeric mice transplanted with CD55(-/-)  CD59(-/-) BM cells but with proper GPI-A expression do not expand over time in transplanted hosts. On the basis of these findings, we propose that a defect in lipid raft formation in PNH-mutated HSPCs makes these cells more mobile, so that they expand and out-compete normal HSPCs from their BM niches over time.

  14. Cell Cycle Phase Abnormalities Do Not Account for Disordered Proliferation in Barrett's Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pierre Lao-Sirieix

    2004-11-01

    Full Text Available Barrett's esophagus (BE epithelium is the precursor lesion for esophageal adenocarcinoma. Cell cycle proteins have been advocated as biomarkers to predict the malignant potential in BE. However, whether disruption of the cell cycle plays a causal role in Barrett's carcinogenesis is not clear. Specimens from the Barrett's dysplasia—carcinoma sequence were immunostained for cell cycle phase markers (cyclin D1 for G1; cyclin A for S, G2, and M; cytoplasmic cyclin B1 for G2; and phosphorylated histone 3 for M phase and expressed as a proportion of proliferating cells. Flow cytometric analysis of the cell cycle phase of prospective biopsies was also performed. The proliferation status of nondysplastic BE was similar to gastric antrum and D2, but the proliferative compartment extended to the luminal surface. In dysplastic samples, the number of proliferating cells correlated with the degree of dysplasia (P < .001. The overall levels of cyclins A and B1 correlated with the degree of dysplasia (P < .001. However, the cell cycle phase distribution measured with both immunostaining and flow cytometry was conserved during all stages of BE, dysplasia, and cancer. Hence, the increased proliferation seen in Barrett's carcinogenesis is due to abnormal cell cycle entry or exit, rather than a primary abnormality within the cell cycle.

  15. Potential role of stem cells in severe spinal cord injury: current perspectives and clinical data

    Directory of Open Access Journals (Sweden)

    Paspala SA

    2012-09-01

    Full Text Available Syed AB Paspala,1,2 Sandeep K Vishwakarma,1 Tenneti VRK Murthy,2 Thiriveedi N Rao,2 Aleem A Khan11PAN Research Foundation, CARE, 2The Institute of Medical Sciences, Hyderabad, IndiaAbstract: Stem cell transplantation for spinal cord injury (SCI along with new pharmacotherapy research offers the potential to restore function and ease the associated social and economic burden in the years ahead. Various sources of stem cells have been used in the treatment of SCI, but the most convincing results have been obtained with neural progenitor cells in preclinical models. Although the use of cell-based transplantation strategies for the repair of chronic SCI remains the long sought after holy grail, these approaches have been to date the most successful when applied in the subacute phase of injury. Application of cell-based strategies for the repair and regeneration of the chronically injured spinal cord will require a combinational strategy that may need to include approaches to overcome the effects of the glial scar, inhibitory molecules, and use of tissue engineering strategies to bridge the lesion. Nonetheless, cell transplantation strategies are promising, and it is anticipated that the Phase I clinical trials of some form of neural stem cell-based approach in SCI will commence very soon.Keywords: stem cell therapy, regeneration, spinal cord injury, cell dosing, cell tracking

  16. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders.

    Science.gov (United States)

    Brennand, Kristen J; Marchetto, M Carol; Benvenisty, Nissim; Brüstle, Oliver; Ebert, Allison; Izpisua Belmonte, Juan Carlos; Kaykas, Ajamete; Lancaster, Madeline A; Livesey, Frederick J; McConnell, Michael J; McKay, Ronald D; Morrow, Eric M; Muotri, Alysson R; Panchision, David M; Rubin, Lee L; Sawa, Akira; Soldner, Frank; Song, Hongjun; Studer, Lorenz; Temple, Sally; Vaccarino, Flora M; Wu, Jun; Vanderhaeghen, Pierre; Gage, Fred H; Jaenisch, Rudolf

    2015-12-01

    As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  17. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kristen J. Brennand

    2015-12-01

    Full Text Available As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  18. Rapid detection of dendritic cell and monocyte disorders using CD4 as a lineage marker of the human peripheral blood antigen presenting cell compartment

    Directory of Open Access Journals (Sweden)

    Laura eJardine

    2013-12-01

    Full Text Available Dendritic cells (DCs and monocytes are critical regulators and effectors of innate and adaptive immune responses. Monocyte expansion has been described in many pathological states while monocyte and DC deficiency syndromes are relatively recent additions to the catalogue of human primary immunodeficiency disorders. Clinically applicable screening tests to diagnose and monitor these conditions are lacking. Conventional strategies for identifying human DCs and monocytes have been based on the use of a lineage gate to exclude lymphocytes, thus preventing simultaneous detection of DCs, monocytes and lymphocyte subsets. Here we demonstrate that CD4 is a reliable lineage marker for the human peripheral blood antigen presenting cell compartment that can be used to identify DCs and monocytes in parallel with lymphocytes. Based on this principle, simple modification of a standard lymphocyte phenotyping assay permits simultaneous enumeration of four lymphocyte and five DC/monocyte populations from a single sample. This approach is applicable to clinical samples and facilitates the diagnosis of DC and monocyte disorders in a wide range of clinical settings, including genetic deficiency, neoplasia and inflammation.

  19. Intact mammalian cell function on semi-conductor nanowire arrays: new perspectives for cell-based biosensing

    DEFF Research Database (Denmark)

    Berthing, Trine; Bonde, Sara; Sørensen, Claus Birger;

    2011-01-01

    . A selection of critical cell functions and pathways are shown not to be impaired, including cell adhesion, membrane integrity, intracellular enzyme activity, DNA uptake, cytosolic and membrane protein expression, and the neuronal maturation pathway. The results demonstrate the low invasiveness of InAs NW...... arrays, which, combined with the unique physical properties of InAs, open up their potential for cellular investigations....

  20. Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders.

    Science.gov (United States)

    Rusanov, Alexander L; Luzgina, Natalia G; Barreto, George E; Aliev, Gjumrakch

    2016-01-01

    In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. PMID:26831260