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Sample records for disorders including multiple

  1. [Neuropsychological disorders in multiple sclerosis].

    PubMed

    Greim, B; Zettl, U K

    2009-08-01

    In multiple sclerosis (MS) neuropsychological disorders such as cognitive dysfunctions, depression, and fatigue are common and have a significant impact on everyday live. The three symptoms interact in different ways which has to be bore in mind in diagnostic and therapeutic proceedings. The clinical management of the three symptoms should include an assessment of overlapping cofactors and primary causes as well as a step-wise treatment approach that encompasses non-pharmacological and pharmacological interventions. PMID:19685387

  2. Bipolar disorder and multiple sclerosis.

    PubMed

    Ybarra, Mariana Inés; Moreira, Marcos Aurélio; Araújo, Carolina Reis; Lana-Peixoto, Marco Aurélio; Teixeira, Antonio Lucio

    2007-12-01

    Bipolar disorder may be overrepresented in multiple sclerosis (MS) patients. Although research in this area is limited, studies assessing the nature of this association have focused on genetic aspects, adverse reaction to drugs and brain demyelinating lesions. Herein we report three patients with MS that also presented bipolar disorder. The coexistence of neurological and psychiatric symptoms in most MS relapses highlights the relevance of biological factors in the emergence of mood disorders in these patients. PMID:18345425

  3. Autonomic Disorders in Multiple Sclerosis

    PubMed Central

    Lensch, E.; Jost, W. H.

    2011-01-01

    Multiple sclerosis is an inflammatory disease leading to disseminated lesions of the central nervous system resulting in both somatomotor and autonomic disturbances. These involve the central centers of the autonomic nervous system, as well as the automatic control and pathway systems. All autonomic functions may be disordered individually or in combined form. There is no other disease with a clinical picture so multifaceted. Besides cardiovascular dysfunctions disorders of bladder and rectum have become apparent. Somatomotor and autonomic disturbances occur with similar frequency; however the focused exam often heavily favors somatomotor symptoms. Autonomic disturbances should primarily be taken into account on history taking and clinical examination. Individual diagnosis and treatment is a secondary feature. Impairments of the autonomic nervous systems in multiple sclerosis are frequently overlooked. PMID:21603189

  4. Emotional Disorders in People with Multiple Sclerosis

    MedlinePlus

    ... and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the main findings of a ...

  5. Stomach Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Stomach Disorders URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Stomach Disorders - Multiple Languages To use the sharing features on ...

  6. Sleep Disorders in Multiple Sclerosis.

    PubMed

    Braley, Tiffany J; Boudreau, Eilis Ann

    2016-05-01

    Recent studies suggest that individuals with multiple sclerosis (MS) are at increased risk for sleep disturbances and that sleep disturbances contribute to fatigue and other chronic symptoms in MS. Although fatigue occurs commonly in people with MS, this symptom is often attributed to MS-specific pathology. Consequently, sleep disorders are often unrecognized and untreated in this population. Timely diagnosis and treatment of sleep problems in MS offer a new opportunity to ameliorate some of the daytime fatigue experienced by patients with MS. To increase this opportunity, the practitioner should be comfortable performing basic screening for common sleep complaints among patients with MS. The objectives of this review are to summarize the latest relevant data on sleep disorders in MS and offer a helpful approach to the identification and workup of the most common sleep problems in this population. Unexplored research avenues and opportunities to address important questions at the interface of sleep and MS are also discussed. PMID:27068547

  7. Cognitive and depressive disorders in multiple sclerosis.

    PubMed

    Alajbegović, Azra; Loga, Natasa; Tiro, Naida; Alajbegović, Salem; Cindro, Veselin; Hozo, Izet

    2009-03-01

    Among other symptoms, multiple sclerosis can also produce symptoms of affective and cognitive disorders. The majority of patients have certain cognitive dysfunctions, and the' most common affective disorder is reactive depression. The aim of the study was to determine the correlation of the Mini-Mental State (MMS) and Beck Depression Inventory (BDI) scale scores with the Expanded Disability Status Scale (EDSS) score in patients with multiple sclerosis treated at University Department of Neurology, Sarajevo University Clinical Center in Sarajevo. We evaluated 50 randomly selected patients with various types of multiple sclerosis using the MMS, BDI and EDSS instruments. The study included 33 women and 17 men (66% : 34%), mean age 40.74 years (SD 9.236). The mean value of EDSS score was 3.98, ranging from 1.0 to 8.5 in women and from 1.0 to 6.5 in men. BDI scale scores showed a mean value of 12.56. The mean MMS score in baseline sample was 26.88. Statistically significant positive correlation was found between age and EDSS score, and negative correlation between EDSS and MMS, as well as between BDI and MMS. Study results indicated older patients with multiple sclerosis to have a higher EDSS score with more pronounced cognitive disturbances. There was no statistically significant correlation between EDSS score and depression. PMID:19623864

  8. Progressive multiple sclerosis and mood disorders.

    PubMed

    Lorefice, Lorena; Fenu, G; Trincas, G; Moro, M F; Frau, J; Coghe, G C; Cocco, E; Marrosu, M G; Carta, M G

    2015-09-01

    Mood disorders are very common among multiple sclerosis (MS) patients, but their frequency in patients with progressive course (PMS) has not been adequately researched. Our study aimed to determine the frequency of mood disorders among patients with PMS compared with those with relapsing-remitting MS (RMS) and to explore the associations with disability and disease duration. The study included consecutive outpatients affected by MS according the 2010 revised Mc Donald diagnostic criteria. Psychiatric diagnoses were determined according to DSM-IV by psychiatrists using structured interview tools (ANTAS-SCID). Demographic and clinical data of patients were also collected. Disease courses were defined according to the re-examined phenotype descriptions by the Committee and MS Phenotype Group. Intergroup comparisons were performed by Chi-square test, while logistic regression analysis was performed to assess possible factors associated with mood disorders. In total, 240 MS patients (167 women) were enrolled; of these, 18 % (45/240) had PMS. The lifetime DSM-IV major depression diagnosis (MDD) was established in 40 and 23 % of the PMS and RMS patients, respectively. Using logistic regression analysis, the presence of MDD was independent from disease duration and disability and dependent on PMS course (P = 0.02; OR 2.2). Patients with PMS presented with MDD more frequently than those with RMS, independently from disease duration and physical disability. These findings highlight the importance of considering mood disorders, especially MDD, in the management of PMS patients. PMID:25899424

  9. Blood Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Blood Disorders URL of this page: https://www.nlm.nih.gov/medlineplus/languages/blooddisorders.html Other topics A-Z A B ...

  10. Multiple Peroxisomal Enzymatic Deficiency Disorders

    PubMed Central

    Vamecq, Joseph; Draye, Jean-Pierre; Van Hoof, François; Misson, Jean-Paul; Evrard, Philippe; Verellen, Gaston; Eyssen, Hendrik J.; Van Eldere, Johan; Schutgens, Ruud B. H.; Wanders, Ronald J. A.; Roels, Frank; Goldfischer, Sidney L.

    1986-01-01

    Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of Zellweger (CHRS) and neonatal adrenoleukodystrophy (NALD). Very long chain fatty acids, abnormal bile acids, including bile acid precursors (di- and trihydroxycoprostanoic acids), and C29-dicarboxylic acid accumulated in plasma in both patients. Generalized hyperaminoaciduria was also present. Peroxisomes could not be detected in CHRS liver and kidney; however, in the NALD patient, small and sparse cytoplasmic bodies resembling altered peroxisomes were found in hepatocytes. Hepatocellular and Kupffer cell lysosomes were engorged with ferritin and contained clefts and trilaminar structures believed to represent very long chain fatty acids. Enzymatic deficiencies reflected the peroxisomal defects. Hepatic glycolate oxidase and palmitoyl-CoA oxidase activities were deficient. No particle-bound catalase was found in cultured fibroblasts, and ether glycerolipid (plasmalogen) biosynthesis was markedly reduced. Administration of phenobarbital and clofibrate, an agent that induces peroxisomal proliferation and enzymatic activities, to the NALD patient did not bring about any changes in plasma metabolites, liver peroxisome population, or oxidizing activities. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:2879480

  11. Psychiatric disorders in multiple sclerosis patients.

    PubMed

    Fazzito, Mirella Martins; Jordy, Sérgio Semeraro; Tilbery, Charles Peter

    2009-09-01

    Multiple sclerosis (MS) is a demyelinating disease showing variable clinical presentation. Optic neuritis is the most common symptom, followed by motor and sensitive manifestations. It is known that this disease may be related to several psychiatric disorders, especially depression. In this study we will discribe 5 cases of MS patients harboring psychiatric disorder related or unchained by the disease itself. PMID:19722046

  12. Central ocular motor disorders, including gaze palsy and nystagmus.

    PubMed

    Strupp, M; Kremmyda, O; Adamczyk, C; Böttcher, N; Muth, C; Yip, C W; Bremova, T

    2014-09-01

    An impairment of eye movements, or nystagmus, is seen in many diseases of the central nervous system, in particular those affecting the brainstem and cerebellum, as well as in those of the vestibular system. The key to diagnosis is a systematic clinical examination of the different types of eye movements, including: eye position, range of eye movements, smooth pursuit, saccades, gaze-holding function and optokinetic nystagmus, as well as testing for the different types of nystagmus (e.g., central fixation nystagmus or peripheral vestibular nystagmus). Depending on the time course of the signs and symptoms, eye movements often indicate a specific underlying cause (e.g., stroke or neurodegenerative or metabolic disorders). A detailed knowledge of the anatomy and physiology of eye movements enables the physician to localize the disturbance to a specific area in the brainstem (midbrain, pons or medulla) or cerebellum (in particular the flocculus). For example, isolated dysfunction of vertical eye movements is due to a midbrain lesion affecting the rostral interstitial nucleus of the medial longitudinal fascicle, with impaired vertical saccades only, the interstitial nucleus of Cajal or the posterior commissure; common causes with an acute onset are an infarction or bleeding in the upper midbrain or in patients with chronic progressive supranuclear palsy (PSP) and Niemann-Pick type C (NP-C). Isolated dysfunction of horizontal saccades is due to a pontine lesion affecting the paramedian pontine reticular formation due, for instance, to brainstem bleeding, glioma or Gaucher disease type 3; an impairment of horizontal and vertical saccades is found in later stages of PSP, NP-C and Gaucher disease type 3. Gaze-evoked nystagmus (GEN) in all directions indicates a cerebellar dysfunction and can have multiple causes such as drugs, in particular antiepileptics, chronic alcohol abuse, neurodegenerative cerebellar disorders or cerebellar ataxias; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. The pathognomonic clinical sign of internuclear ophthalmoplegia is an impaired adduction while testing horizontal saccades on the side of the lesion in the ipsilateral medial longitudinal fascicule. The most common pathological types of central nystagmus are downbeat nystagmus (DBN) and upbeat nystagmus (UBN). DBN is generally due to cerebellar dysfunction affecting the flocculus bilaterally (e.g., due to a neurodegenerative disease). Treatment options exist for a few disorders: miglustat for NP-C and aminopyridines for DBN and UBN. It is therefore particularly important to identify treatable cases with these conditions. PMID:25145891

  13. Neuromuscular Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Neuromuscular Disorders - Multiple Languages To use the sharing features on this page, please enable JavaScript. French (français) Japanese (日本語) Korean (한국어) Russian (Русский) Somali ( ...

  14. Parathyroid Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Parathyroid Disorders - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Traditional (繁體中文) French (français) Hindi (हिन्दी) Japanese (日本語) Korean (한국어) ...

  15. Throat Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Throat Disorders - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Traditional (繁體中文) French (français) Hindi (हिन्दी) Japanese (日本語) Russian (Русский) ...

  16. Multiple Object Tracking in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Koldewyn, Kami; Weigelt, Sarah; Kanwisher, Nancy; Jiang, Yuhong

    2013-01-01

    Difficulties in visual attention are often implicated in autism spectrum disorders (ASD) but it remains unclear which aspects of attention are affected. Here, we used a multiple object tracking (MOT) task to quantitatively characterize dynamic attentional function in children with ASD aged 5-12. While the ASD group performed significantly worse…

  17. Multiple Object Tracking in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Koldewyn, Kami; Weigelt, Sarah; Kanwisher, Nancy; Jiang, Yuhong

    2013-01-01

    Difficulties in visual attention are often implicated in autism spectrum disorders (ASD) but it remains unclear which aspects of attention are affected. Here, we used a multiple object tracking (MOT) task to quantitatively characterize dynamic attentional function in children with ASD aged 5-12. While the ASD group performed significantly worse

  18. Multiple Personality Disorder: Concepts and Cases.

    ERIC Educational Resources Information Center

    Lindsley, Hope L.

    1992-01-01

    Presents two case examples illustrating nature and etiology of multiple personality disorder in two clients and describing their entry into counseling and progress through treatment. Compares and contrasts cases in areas of diagnosis, symptoms, history, and treatment. Suggests that mental health counselors combine firmness with flexibility in…

  19. Extending a clinical repository to include multiple sites.

    PubMed Central

    Marrs, K. A.; Kahn, M. G.

    1995-01-01

    With the consolidation of health care organizations and services, a clinical repository comprising data from a single site is no longer sufficient. Individual patient data are now spread across multiple sites comprising a single enterprise. Users require an integrated view, or at least a common view, of these clinical data across multiple sites. Many issues arise when one tries to merge data from multiple, distinct organizations into an existing schema. We have addressed these issues while extending our clinical repository for Barnes Hospital with data from Jewish Hospital, both of which are members of the recently formed BJC Health System. We describe the architecture of our existing repository, approaches and issues in extending this repository to include multiple sites, and the specific issues we addressed in our system. PMID:8563308

  20. 37 CFR 2.86 - Application may include multiple classes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Application may include multiple classes. 2.86 Section 2.86 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Classification 2.86 Application...

  1. Sleep disorders in multiple sclerosis. Review.

    PubMed

    Veauthier, Christian

    2015-05-01

    Sleep disorders are common in patients with multiple sclerosis (MS) and play a crucial role in health and quality of life; however, they are often overlooked. The most important sleep disorders in this context are as follows: insomnia, restless legs syndrome, periodic limb movement disorders, and sleep-related breathing disorders (SRBD). It is unclear if MS-related processes (lesions, brain atrophy) can cause symptomatic forms of sleep apnea. MS-related narcolepsy-like symptoms are described in the literature and, in some cases, have resolved with methylprednisolone pulse therapy. Similarly, REM sleep behavior disorder (RBD) is very rare in MS, but it can be an initial sign of MS where cortisone therapy may be helpful and can be taken into account in this specific context. Independent diagnosis and treatment is required for all of the abovementioned conditions. Treating physicians and neurologists should be aware of these comorbidities and initiate specific therapy. Highly fatigued or sleepy MS patients should have polysomnography in order not to overlook these diagnoses. PMID:25773000

  2. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

    PubMed Central

    Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

    2015-01-01

    Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

  3. Pharmacotherapy of vestibular and ocular motor disorders, including nystagmus.

    PubMed

    Strupp, Michael; Thurtell, Matthew J; Shaikh, Aasef G; Brandt, Thomas; Zee, David S; Leigh, R John

    2011-07-01

    We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological nystagmus. The prerequisites for successful pharmacotherapy of vertigo, dizziness, and abnormal eye movements are the "4 D's": correct diagnosis, correct drug, appropriate dosage, and sufficient duration. There are seven groups of drugs (the "7 A's") that can be used: antiemetics; anti-inflammatory, anti-Ménière's, and anti-migrainous medications; anti-depressants, anti-convulsants, and aminopyridines. A recovery from acute vestibular neuritis can be promoted by treatment with oral corticosteroids. Betahistine may reduce the frequency of attacks of Ménière's disease. The aminopyridines constitute a novel treatment approach for downbeat and upbeat nystagmus, as well as episodic ataxia type 2 (EA 2); these drugs may restore normal "pacemaker" activity to the Purkinje cells that govern vestibular and cerebellar nuclei. A limited number of trials indicate that baclofen improves periodic alternating nystagmus, and that gabapentin and memantine improve acquired pendular and infantile (congenital) nystagmus. Preliminary reports suggest suppression of square-wave saccadic intrusions by memantine, and ocular flutter by beta-blockers. Thus, although progress has been made in the treatment of vestibular neuritis, some forms of pathological nystagmus, and EA 2, controlled, masked trials are still needed to evaluate treatments for many vestibular and ocular motor disorders, including betahistine for Ménière's disease, oxcarbazepine for vestibular paroxysmia, or metoprolol for vestibular migraine. PMID:21461686

  4. Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS.

    PubMed

    Wang, Qian; Yang, Can; Gelernter, Joel; Zhao, Hongyu

    2015-11-01

    Although some existing epidemiological observations and molecular experiments suggested that brain disorders in the realm of psychiatry may be influenced by immune dysregulation, the degree of genetic overlap between psychiatric disorders and immune disorders has not been well established. We investigated this issue by integrative analysis of genome-wide association studies of 18 complex human traits/diseases (five psychiatric disorders, seven immune disorders, and others) and multiple genome-wide annotation resources (central nervous system genes, immune-related expression-quantitative trait loci (eQTL) and DNase I hypertensive sites from 98 cell lines). We detected pleiotropy in 24 of the 35 psychiatric-immune disorder pairs. The strongest pleiotropy was observed for schizophrenia-rheumatoid arthritis with MHC region included in the analysis (p = 3.9 x 10(-285), and schizophrenia-Crohn's disease with MHC region excluded (p = 1.1 x 10(-36). Significant enrichment (> 1.4 fold) of immune-related eQTL was observed in four psychiatric disorders. Genomic regions responsible for pleiotropy between psychiatric disorders and immune disorders were detected. The MHC region on chromosome 6 appears to be the most important with other regions, such as cytoband 1p13.2, also playing significant roles in pleiotropy. We also found that most alleles shared between schizophrenia and Crohn's disease have the same effect direction, with similar trend found for other disorder pairs, such as bipolar-Crohn's disease. Our results offer a novel bird's-eye view of the genetic relationship and demonstrate strong evidence for pervasive pleiotropy between psychiatric disorders and immune disorders. Our findings might open new routes for prevention and treatment strategies for these disorders based on a new appreciation of the importance of immunological mechanisms in mediating risk of many psychiatric diseases. PMID:26340901

  5. The Multiple Faces of Disordered Nucleoporins.

    PubMed

    Lemke, Edward A

    2016-05-22

    An evolutionary advantage of intrinsically disordered proteins (IDPs) is their ability to bind a variety of folded proteins-a paradigm that is central to the nucleocytoplasmic transport mechanism, in which nuclear transport receptors mediate the translocation of various cargo through the nuclear pore complex by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). FG-Nups are highly dynamic, which poses a substantial problem when trying to determine precisely their function using common experimental approaches. FG-Nups have been studied under a variety of conditions, ranging from those that constitute single-molecule measurements to physiological concentrations at which they can form supramolecular structures. In this review, I describe the physicochemical properties of FG-Nups and compare them to those of other disordered systems, including well-studied IDPs. From this comparison, it is apparent that FG-Nups not only share some properties with IDPs in general but also possess unique characteristics that might be key to their central role in the nucleocytoplasmic transport machinery. PMID:26791761

  6. Neck Injuries and Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Neck Injuries and Disorders URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Neck Injuries and Disorders - Multiple Languages To use the sharing features on ...

  7. Immune-mediated extrapyramidal movement disorders, including Sydenham chorea.

    PubMed

    Dale, Russell C

    2013-01-01

    Immune-mediated extrapyramidal movement disorders typically occur in previously healthy children. Immune-mediated movement disorders may occur as a postinfectious, paraneoplastic, or idiopathic process. Sydenham chorea (SC) is the classical poststreptococcal movement and psychiatric disorder, and may be associated with other features of rheumatic fever. The outcome is typically good, although residual chorea, psychiatric disturbance, and relapses are possible. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a syndrome of streptococcal-induced tics and obsessive-compulsive disorder. Although a number of investigators have reported an association between streptococcal infection and neuropsychiatric syndromes, the PANDAS hypothesis is controversial. Encephalitis lethargica is an encephalitic illness with parkinsonism, dyskinesias, and psychiatric disturbance as dominant features. The exact disease mechanism is not understood, although an autoimmune process is suspected. NMDA-R encephalitis is a new entity characterized by encephalitis with dramatic psychiatric disturbance, dyskinesias, cognitive alteration, and seizures. Patients have autoantibodies against the NMDA-R that appear to be pathogenic: immune therapies appear warranted to minimize disability. Movement disorders are also described associated with systemic lupus erythematosus and antiphospholipid syndrome. The differential diagnosis and investigation approach of acute-onset movement disorders are also discussed. PMID:23622334

  8. Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders

    PubMed Central

    Sebat, Jonathan; Levy, Deborah L.; McCarthy, Shane E.

    2009-01-01

    Recent studies have established an important role for rare genomic deletions and duplications in the etiology of schizophrenia. This research suggests that the genetic architecture of neuropsychiatric disorders includes a constellation of rare mutations in many different genes. Mutations that confer substantial risk for schizophrenia have been identified at several loci, most of which have also been implicated in other neurodevelopmental disorders, including autism. Genetic heterogeneity is a characteristic of schizophrenia; conversely, phenotypic heterogeneity is a characteristic of all schizophrenia-associated mutations. Both kinds of heterogeneity probably reflect the complexity of neurodevelopment. Research strategies must account for both genetic and clinical heterogeneity to identify the genes and pathways crucial for the development of neuropsychiatric disorders. PMID:19883952

  9. An additional monogenic disorder that masquerades as multiple sclerosis

    SciTech Connect

    Vahedi, K.; Tournier-Lasserve, E.; Vahedi, K.

    1996-11-11

    In their comprehensive differential diagnosis of monogenic diseases that can mimic multiple sclerosis, Natowicz and Bejjani did not include a newly recognized monogenic disorder known under the acronym of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy); this disorder can mimic MS clinically and radiologically to a remarkable extent. The underlying histopathological lesion of CADASIL is a non-atherosclerotic, non-amyloid arteriopathy affecting mainly the penetrating medullary arteries to the subcortical white matter and basal ganglia. Electron microscopy shows an abnormal deposit of granular osmiophilic material in the arterial wall. These arterial changes are observed in various tissues even though clinical manifestations seem to be restricted to the central nervous system. The CADASIL gene was mapped recently to chromosome 19 and gene identification is ongoing. 6 refs., 1 fig.

  10. Immunofluorescence Patterns in Selected Dermatoses, Including Blistering Skin Diseases Utilizing Multiple Fluorochromes

    PubMed Central

    Abreu-Velez, Ana Maria; Calle-Isaza, Juliana; Howard, Michael S.

    2015-01-01

    Background: Autoimmune vesiculobullous disorders represent a heterogeneous group of dermatoses whose diagnosis is made based on clinical history, histologic features, and immunopathologic features. The most commonly used techniques for the diagnosis of these diseases are direct and indirect immunofluorescence (DIF and IIF), including salt-split processing. NaCl split skin is used to determine the level of blister formation, and the localization of autoantibodies relative to the split. Classically, immunofluorescence has been performed with one fluorochrome in the diagnosis of autoimmune bullous skin diseases. Aims: To compare DIF and IIF of the skin, using a single fluorochrome versus multiple fluorochromes. Materials and Methods: We studied 20 autoimmune skin disease cases using fluorescein isothiocyanate (FITC) alone, in comparison to multiple fluorochromes (with or without DNA counterstaining). Results: The use of multiple fluorochromes helped to simultaneously visualize reactivity in multiple skin areas, in contrast to using FITC alone. Conclusions: Using multiple fluorochromes allows simultaneous labeling of two or more antigens within the same cell/or tissue section, assists in colocalization of unknown antigens with known molecules, and helps in ruling out “background” staining. PMID:26605203

  11. A review of multiple stressor studies that include ionising radiation.

    PubMed

    Vanhoudt, Nathalie; Vandenhove, Hildegarde; Real, Almudena; Bradshaw, Clare; Stark, Karolina

    2012-09-01

    Studies were reviewed that investigated the combined effects of ionising radiation and other stressors on non-human biota. The aim was to determine the state of research in this area of science, and determine if a review of the literature might permit a gross generalization as to whether the combined effects of multi-stressors and radiation are fundamentally additive, synergistic or antagonistic. A multiple stressor database was established for different organism groups. Information was collected on species, stressors applied and effects evaluated. Studies were mostly laboratory based and investigated two-component mixtures. Interactions declared positive occurred in 58% of the studies, while 26% found negative interactions. Interactions were dependent on dose/concentration, on organism's life stage and exposure time and differed among endpoints. Except for one study, none of the studies predicted combined effects following Concentration Addition or Independent Action, and hence, no justified conclusions can be made about synergism or antagonism. PMID:22634132

  12. Academic Choice for Included Students with Emotional and Behavioral Disorders

    ERIC Educational Resources Information Center

    Skerbetz, Mandi Davis; Kostewicz, Douglas E.

    2013-01-01

    Students with emotional disturbances present with behavioral and academic deficits that often limit their participation in general education settings. As an antecedent intervention, academic choice provides multiple choices surrounding academic work promoting academic and behavioral gains. The authors examined the effects of assignment choice with…

  13. Methylphenidate and Comorbid Anxiety Disorder in Children with both Chronic Multiple Tic Disorder and ADHD

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; Nolan, Edith E.

    2011-01-01

    Objective: To determine if comorbid anxiety disorder is associated with differential response to immediate release methylphenidate (MPH-IR) in children with both ADHD and chronic multiple tic disorder (CMTD). Method: Children with (n = 17) and without (n = 37) diagnosed anxiety disorder (ANX) were evaluated in an 8-week, placebo-controlled trial

  14. Methylphenidate and Comorbid Anxiety Disorder in Children with both Chronic Multiple Tic Disorder and ADHD

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; Nolan, Edith E.

    2011-01-01

    Objective: To determine if comorbid anxiety disorder is associated with differential response to immediate release methylphenidate (MPH-IR) in children with both ADHD and chronic multiple tic disorder (CMTD). Method: Children with (n = 17) and without (n = 37) diagnosed anxiety disorder (ANX) were evaluated in an 8-week, placebo-controlled trial…

  15. Multiple Complex Developmental Disorder Delineated from PDD-NOS

    ERIC Educational Resources Information Center

    de Bruin, Esther I.; de Nijs, Pieter F. A.; Verheij, Fop; Hartman, Catharina A.; Ferdinand, Robert F.

    2007-01-01

    The objective of this study was to identify behavioral differences between children with multiple complex developmental disorder (MCDD) and those with pervasive developmental disorder-not otherwise specified (PDD-NOS). Twenty-five children (6-12 years) with MCDD and 86 children with PDD-NOS were compared with respect to psychiatric co-morbidity,…

  16. The Proliferation of Categories for "New" Behavioral Disorders. The Struggle to Include the Handicapped.

    ERIC Educational Resources Information Center

    Forness, Steven R.; And Others

    1995-01-01

    Describes five disorders (attention deficit disorder, traumatic brain injury, fetal alcohol syndrome, prenatal substance abuse, and fragile X syndrome) that are part of a proliferation of categories of behavioral disorders, examining how special and general education might approach problems potentially inherent in the process of including students…

  17. The Proliferation of Categories for "New" Behavioral Disorders. The Struggle to Include the Handicapped.

    ERIC Educational Resources Information Center

    Forness, Steven R.; And Others

    1995-01-01

    Describes five disorders (attention deficit disorder, traumatic brain injury, fetal alcohol syndrome, prenatal substance abuse, and fragile X syndrome) that are part of a proliferation of categories of behavioral disorders, examining how special and general education might approach problems potentially inherent in the process of including students

  18. A systematic review of the incidence and prevalence of sleep disorders and seizure disorders in multiple sclerosis

    PubMed Central

    Reider, Nadia; Cohen, Jeffrey; Trojano, Maria; Sorensen, Per Soelberg; Cutter, Gary; Reingold, Stephen; Stuve, Olaf

    2015-01-01

    Background: Several studies have suggested that comorbid neurologic disorders are more common than expected in multiple sclerosis (MS). Objective: To estimate the incidence and prevalence of comorbid seizure disorders and sleep disorders in persons with MS and to evaluate the quality of studies included. Methods: The PUBMED, EMBASE, Web of Knowledge, and SCOPUS databases, conference proceedings, and reference lists of retrieved articles were searched. Two reviewers independently screened abstracts to identify relevant articles, followed by full-text review of selected articles. We assessed included studies qualitatively and quantitatively (I2 statistic), and conducted meta-analyses among population-based studies. Results: We reviewed 32 studies regarding seizure disorders. Among population-based studies the incidence of seizure disorders was 2.28% (95% CI: 1.11–3.44%), while the prevalence was 3.09% (95% CI: 2.01–4.16%). For sleep disorders we evaluated 18 studies; none were population-based. The prevalence ranged from 0–1.6% for narcolepsy, 14.4–57.5% for restless legs syndrome, 2.22–3.2% for REM behavior disorder, and 7.14–58.1% for obstructive sleep apnea. Conclusion: This review suggests that seizure disorders and sleep disorders are common in MS, but highlights gaps in the epidemiological knowledge of these conditions in MS worldwide. Other than central-western Europe and North America, most regions are understudied. PMID:25533301

  19. Multiple rare variants in the etiology of autism spectrum disorders

    PubMed Central

    Buxbaum, Joseph D.

    2009-01-01

    Recent studies in autism spectrum disorders (ASDs) support an important role for multiple rare variants in these conditions. This is a clinically important finding, as, with the demonstration that a significant proportion of ASDs are the result of rare, etiological genetic variants, it becomes possible to make use of genetic testing to supplement behavioral analyses for an earlier diagnosis. As it appears that earlier interventions in ASDs will produce better outcomes, the development of genetic testing to augment behaviorally based evaluations in ASDs holds promise for improved treatment. Furthermore, these rare variants involve synaptic and neuronal genes that implicate specific paihvi/ays, cells, and subcellular compartments in ASDs, which in turn will suggest novel therapeutic approaches in ASDs, Of particular recent interest are the synaptic cell adhesion and associated molecules, including neurexin 1, neuroligin 3 and 4, and SHANK3, which implicate glutamatergic synapse abnormalities in ASDs, In the current review we will overview the evidence for a genetic etiology for ASDs, and summarize recent genetic findings in these disorders. PMID:19432386

  20. Crime and multiple personality disorder: a case history and discussion.

    PubMed

    Perr, I N

    1991-01-01

    The application of the concept of multiple personality disorder (MPD) is one of the most complex and controversial issues facing forensic psychiatrists. The case presented is one in which a diagnosis of multiple personality disorder is not only well documented, but was so diagnosed at least 10 years before the ultimate homicide. Nonetheless, consideration of the legal issues was difficult. Other cases, particularly the Bianchi case, reflect the clinical difficulties in diagnosis. Subsequent cases have reflected a judicial review of the issues and a trend to disallow the concept of MPD as a defense; the author suggests that forensic psychiatrists incorporate these opinions in their future judgments. PMID:1873575

  1. Plasma cell morphology in multiple myeloma and related disorders.

    PubMed

    Ribourtout, B; Zandecki, M

    2015-06-01

    Normal and reactive plasma cells (PC) are easy to ascertain on human bone marrow films, due to their small mature-appearing nucleus and large cytoplasm, the latter usually deep blue after Giemsa staining. Cytoplasm is filled with long strands of rough endoplasmic reticulum and one large Golgi apparatus (paranuclear hof), demonstrating that PC are dedicated mainly to protein synthesis and excretion (immunoglobulin). Deregulation of the genome may induce clonal expansion of one PC that will lead to immunoglobulin overproduction and eventually to one among the so-called PC neoplasms. In multiple myeloma (MM), the number of PC is over 10% in most patients studied. Changes in the morphology of myeloma PC may be inconspicuous as compared to normal PC (30-50% patients). In other instances PC show one or several morphological changes. One is related to low amount of cytoplasm, defining lymphoplasmacytoid myeloma (10-15% patients). In other cases (40-50% patients), named immature myeloma cases, nuclear-cytoplasmic asynchrony is observed: presence of one nucleolus, finely dispersed chromatin and/or irregular nuclear contour contrast with a still large and blue (mature) cytoplasm. A peculiar morphological change, corresponding to the presence of very immature PC named plasmablasts, is observed in 10-15% cases. Several prognostic morphological classifications have been published, as mature myeloma is related to favorable outcome and immature myeloma, peculiarly plasmablastic myeloma, is related to dismal prognosis. However, such classifications are no longer included in current prognostic schemes. Changes related to the nucleus are very rare in monoclonal gammopathy of unknown significance (MGUS). In contrast, anomalies related to the cytoplasm of PC, including color (flaming cells), round inclusions (Mott cells, Russell bodies), Auer rod-like or crystalline inclusions, are reported in myeloma cases as well as in MGUS and at times in reactive disorders. They do not correspond to malignant changes of PC but are related to abnormal synthesis, trafficking, or excretion of the immunoglobulin that is stored in excess within the cytoplasm. Occurrence of crystalline inclusions within PC may be the first anomaly leading to the diagnosis of adult Fanconi syndrome. After a historical perspective, the authors report on the various morphological aspects of PC that may occur in multiple myeloma and related disorders, and discuss about their clinical and pathophysiological significance. Today, morphological identification and accurate determination of % PC within bone marrow remain ancillary criteria for the diagnosis of MM and help for the diagnosis of rare renal disorders. PMID:25899140

  2. Carrier Transport in Disordered Multiple Quantum Wells.

    NASA Astrophysics Data System (ADS)

    Shivamoggi, Jayasree B.

    We present in this dissertation, a study of the cross-well transport of carriers in annealed Multiple Quantum Wells (MQW). The design of the devices using MQW structures depends critically on the amount of time required by the photogenerated carriers to influence the optical properties. It is therefore very important from the design considerations to understand the basic mechanisms that control the carrier escape from the intrinsic region of the reverse biased p-i-n junction structure with the MQW fabricated in the intrinsic region. Fine-tuning of the performance of these devices can be achieved through band gap engineering. This can be done by selectively intermixing the well and the barrier region. In this work, we have identified and explored the effect of finite barrier width, initial barrier concentration and annealing time on the barrier height. We have used a more general method, the Runge-Kutta method, to calculate the energy levels in annealed quantum wells. The results from this method are in good agreement with those from other existing numerical methods. The advantage comes from the fact that Runge-Kutta method is accurate when Quantum wells of arbitrary shapes are used. We have also defined the superlattice limits and the essential difference between energy levels in the as-grown wells and the annealed quantum wells. We have presented a new formulation of the thermionic emission taking into account the effect of valence band mixing and 2D density of states in the calculation of the rate of carrier escape due to emission. We have also considered resonant non-resonant and thermally assisted tunneling time constants. We have used these time constants in the solution of the system of differential equations which represent the rate equations for the carrier escape from the intrinsic region. While no such experimental data is yet available for comparison, we have seen a qualitative agreement with existing measurements.

  3. Outpatient Art Therapy with Multiple Personality Disorder: A Survey of Current Practice.

    ERIC Educational Resources Information Center

    Mills, Anne

    1995-01-01

    Reports findings of a 1993 questionnaire completed by 46 North American art therapists that focuses on the outpatient treatment of multiple personality disorder. Includes information on role in diagnosing, fees and third-party payment, and therapeutic activities. Treatment issues include pacing and containment, and managing the client's chronic…

  4. Wrist Injuries and Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... All Topics All Wrist Injuries and Disorders - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) French (français) Russian (Русский) Somali (af Soomaali) Spanish (español) ...

  5. Hearing Disorders and Deafness - Multiple Languages: MedlinePlus

    MedlinePlus

    ... All Topics All Hearing Disorders and Deafness - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Simplified (简体中文) French (français) Hindi (हिन्दी) Japanese (日本語) Korean (한국어) ...

  6. Knee Injuries and Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... List of All Topics All Knee Injuries and Disorders - Multiple Languages To use the sharing features on this page, ... National Institute of Arthritis and Musculoskeletal and Skin Diseases ... page? See language display issues . Return to the MedlinePlus Health Information ...

  7. Indicators of Multiple Personality Disorder for the Clinician.

    ERIC Educational Resources Information Center

    Dalton, Thomas W.

    Multiple personality disorder (MPD) is now recognized as a valid diagnostic category. Occurrence may be higher than previously suspected. While physiological testing of MPD has shown significant differences between the various personalities of individuals in terms of galvanic skin response, electroencephalogram recordings, electrodermal response

  8. A More Unified View of the Multiple Personality Disorder.

    ERIC Educational Resources Information Center

    Kelley, Ronald L.; Kodman, Frank

    1987-01-01

    Offers perspective of Multiple Personality Disorder (MPD) phenomenon based on current clinical experience. Asserts that the Jmind is polypsychic with multitude of psychological systems and processes existing in conjunction with one another, that MPD individuals have fragmented or dissociated ego states due to stress on unity of sense of self, and…

  9. Indicators of Multiple Personality Disorder for the Clinician.

    ERIC Educational Resources Information Center

    Dalton, Thomas W.

    Multiple personality disorder (MPD) is now recognized as a valid diagnostic category. Occurrence may be higher than previously suspected. While physiological testing of MPD has shown significant differences between the various personalities of individuals in terms of galvanic skin response, electroencephalogram recordings, electrodermal response…

  10. A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum Disorders, Including a Comparison with Other Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Atladóttir, H. Ó.; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.

    2015-01-01

    The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all…

  11. A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum Disorders, Including a Comparison with Other Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Atladttir, H. .; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.

    2015-01-01

    The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all

  12. Multiple complex developmental disorder delineated from PDD-NOS.

    PubMed

    de Bruin, Esther I; de Nijs, Pieter F A; Verheij, Fop; Hartman, Catharina A; Ferdinand, Robert F

    2007-07-01

    The objective of this study was to identify behavioral differences between children with multiple complex developmental disorder (MCDD) and those with pervasive developmental disorder-not otherwise specified (PDD-NOS). Twenty-five children (6-12 years) with MCDD and 86 children with PDD-NOS were compared with respect to psychiatric co-morbidity, psychotic thought problems and social contact problems using the child behavior checklist/4-18, the Dutch version of the diagnostic interview schedule for children-Version IV, the child and adolescent functional assessment scale, and the autism diagnostic observation schedule-generic. MCDD was associated with anxiety disorders, disruptive behavior, and psychotic thought problems. PDD-NOS was associated with deficits in social contact. MCDD differs from autistic disorder, and can also be delineated from PDD-NOS. PMID:17066306

  13. Postnatal Diagnosis of a Baby With Multiple Rare Congenital Anomalies Including Syngnathia, Brain Dysmorphism, and Skin Pigmentation.

    PubMed

    Mahgoub, Linda; Joynt, Chloe; Bhargava, Ravi; Davies, Dawn; El-Hakim, Hamdy; Dobrovolsky, Walter

    2015-11-01

    Syngnathia is a rare congenital disorder of jaw fusion with a paucity of literature from developed countries. We present a case of an infant noted to have multiple anomalies at birth including syngnathia, microcephaly with a variant of brain abnormality between holoprosencephaly and syntelencephaly, optic nerve hypoplasia, ear canal anomalies, hemi-vertebrae, and suspected hypomelanosis of Ito. To our knowledge, this patient with syngnathia and multiple anomalies is the first to be reported, but whether they are a coincidence, a pathogenetic association, or a new syndrome remains unknown. This case is discussed with a brief review of the literature. PMID:25325328

  14. Should the current DSM-IV-TR definition for PTSD be expanded to include serial and multiple microtraumas as aetiologies?

    PubMed

    Seides, R

    2010-10-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops from events that are interpreted as traumatic. It may be secondary to witnessing trauma to someone close, an event that threatens one's life or childhood sexual trauma. Resultant feelings can be fear, helplessness or horror. Thresholds at which traumatic events cause PTSD, the individual's coping ability and support systems help determine occurrence and severity of symptoms. According to DSM-IV-TR (DSM) definition, PTSD can occur after childhood sexual abuse or a single trauma threatening life or safety. However, it is becoming clearer that symptoms of PTSD can arise from multiple less severe traumas ('microtraumas'), which can be a consequence of a history of longstanding emotional neglect, humiliation or inaccurate attribution of blame. The DSM should consider modifying the criteria to include multiple microtraumas that can lead to PTSD symptoms and may even be more destructive to psychological health. PMID:21050339

  15. 22q11 deletion syndrome and multiple complex developmental disorder: a case report.

    PubMed

    Scandurra, Valeria; Scordo, Maria R; Canitano, Roberto; de Bruin, Esther I

    2013-04-01

    22q11.2 Deletion Syndrome (22q11 DS) is a multisystemic condition that may also include neuropsychiatric disorders. We present a case of a 15-year-old boy that was evaluated for social difficulties, and anxiety with the above genetic abnormality. Clinical features were rather complex as different neuropsychiatric symptoms emerged from assessment and clinical evaluation. As a result we propose that Multiple Complex Developmental Disorder (MCDD) would be the best fitting comprehensive diagnosis to be added to the DSM-IV category of Pervasive Developmental Disorder-Not Otherwise Specified. PMID:23519073

  16. 22q11 Deletion Syndrome and Multiple Complex Developmental Disorder: A Case Report

    PubMed Central

    Scandurra, Valeria; Scordo, Maria R.; Canitano, Roberto; de Bruin, Esther I.

    2013-01-01

    22q11.2 Deletion Syndrome (22q11 DS) is a multisystemic condition that may also include neuropsychiatric disorders. We present a case of a 15-year-old boy that was evaluated for social difficulties, and anxiety with the above genetic abnormality. Clinical features were rather complex as different neuropsychiatric symptoms emerged from assessment and clinical evaluation. As a result we propose that Multiple Complex Developmental Disorder (MCDD) would be the best fitting comprehensive diagnosis to be added to the DSM-IV category of Pervasive Developmental Disorder-Not Otherwise Specified. PMID:23519073

  17. Inducing Order from Disordered Copolymers: On Demand Generation of Triblock Morphologies Including Networks

    SciTech Connect

    Tureau, Maëva S.; Kuan, Wei-Fan; Rong, Lixia; Hsiao, Benjamin S.; Epps, III, Thomas H.

    2015-10-15

    Disordered block copolymers are generally impractical in nanopatterning applications due to their inability to self-assemble into well-defined nanostructures. However, inducing order in low molecular weight disordered systems permits the design of periodic structures with smaller characteristic sizes. Here, we have induced nanoscale phase separation from disordered triblock copolymer melts to form well-ordered lamellae, hexagonally packed cylinders, and a triply periodic gyroid network structure, using a copolymer/homopolymer blending approach, which incorporates constituent homopolymers into selective block domains. This versatile blending approach allows one to precisely target multiple nanostructures from a single disordered material and can be applied to a wide variety of triblock copolymer systems for nanotemplating and nanoscale separation applications requiring nanoscale feature sizes and/or high areal feature densities.

  18. Hitting Closer to Home: A Multiple Family Prevention Group for Adolescent Disordered Eating

    ERIC Educational Resources Information Center

    Clemency, Colleen E.; Rayle, Andrea Dixon

    2006-01-01

    This article presents an innovative multiple family psychoeducational group for the prevention of disordered eating among adolescent females. An overview of the concerns facing adolescents today is presented, including sociocultural norms, body dissatisfaction associated with pubertal changes, teasing regarding weight and shape, and family…

  19. Childhood Trauma and Multiple Personality Disorder: The Case of a 9-Year-Old Girl.

    ERIC Educational Resources Information Center

    LaPorta, Lauren D.

    1992-01-01

    This paper reports the case of a nine-year-old female victim of sexual abuse, evaluated and diagnosed with multiple personality disorder over a six-month period. Included is a description of the child's presentation with historical and developmental data. A discussion of the dynamic and predisposing features of the case follows, along with…

  20. Anxiety Symptoms in Boys with Autism Spectrum Disorder, Attention-Deficit Hyperactivity Disorder, or Chronic Multiple Tic Disorder and Community Controls

    ERIC Educational Resources Information Center

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D.; DeVincent, Carla J.; Crowell, Judy

    2010-01-01

    We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were

  1. Anxiety Symptoms in Boys with Autism Spectrum Disorder, Attention-Deficit Hyperactivity Disorder, or Chronic Multiple Tic Disorder and Community Controls

    ERIC Educational Resources Information Center

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D.; DeVincent, Carla J.; Crowell, Judy

    2010-01-01

    We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were…

  2. Multiple traumatic experiences and the development of posttraumatic stress disorder.

    PubMed

    Scott, Sheryn T

    2007-07-01

    This study assesses the differential and combined impacts of multiple lifetime stressors in the development and severity of posttraumatic stress disorder (PTSD) symptoms. One hundred and four clinical and 64 nonclinical participants were assessed for their exposure to four types of interpersonal trauma: physical and sexual abuse in childhood, lifetime community violence, and domestic violence in adulthood. PTSD symptomatology was assessed using the Los Angeles Symptom Checklist (LASC). Results indicated that exposure to lifetime multiple traumatic experiences was positively correlated with severity of PTSD symptoms. Clinical participants had experienced significantly more multiple traumas and had a higher rate of PTSD than the nonclinical participants. Results also suggested that adults who had experienced childhood sexual abuse were at higher risk for the development of PTSD related to interpersonal violence than adults who were not sexually abused as children. PMID:17575070

  3. Should an Obsessive-Compulsive Spectrum Grouping of Disorders Be Included in DSM-V?

    PubMed Central

    Phillips, Katharine A.; Stein, Dan J.; Rauch, Scott; Hollander, Eric; Fallon, Brian A.; Barsky, Arthur; Fineberg, Naomi; Mataix-Cols, David; Ferrão, Ygor Arzeno; Saxena, Sanjaya; Wilhelm, Sabine; Kelly, Megan M.; Clark, Lee Anna; Pinto, Anthony; Bienvenu, O. Joseph; Farrow, Joanne; Leckman, James

    2014-01-01

    The obsessive-compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive-compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e., grouping, or “chapter”) in DSM. This paper addresses this topic and presents options and preliminary recommendations to be considered for DSM-V. The paper builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive-Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders be included in DSM-V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of “Anxiety and Obsessive-Compulsive Spectrum Disorders.” These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V. PMID:20533367

  4. Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage.

    PubMed

    Mattheij, Nadine J A; Braun, Attila; van Kruchten, Roger; Castoldi, Elisabetta; Pircher, Joachim; Baaten, Constance C F M J; Wülling, Manuela; Kuijpers, Marijke J E; Köhler, Ralf; Poole, Alastair W; Schreiber, Rainer; Vortkamp, Andrea; Collins, Peter W; Nieswandt, Bernhard; Kunzelmann, Karl; Cosemans, Judith M E M; Heemskerk, Johan W M

    2016-02-01

    Scott syndrome is a rare bleeding disorder, characterized by altered Ca(2+)-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano)6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca(2+)-dependent KCa3.1 Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6 min (control 6.4 min, P < 0.05). Platelets from the surviving Ano6-deficient mice resembled platelets from patients with Scott syndrome in: 1) normal collagen-induced aggregate formation (P > 0.05) with reduced PS exposure (-65 to 90%); 2) lowered Ca(2+)-dependent swelling (-80%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome.-Mattheij, N. J. A., Braun, A., van Kruchten, R., Castoldi, E., Pircher, J., Baaten, C. C. F. M. J., Wülling, M., Kuijpers, M. J. E., Köhler, R., Poole, A. W., Schreiber, R., Vortkamp, A., Collins, P. W., Nieswandt, B., Kunzelmann, K., Cosemans, J. M. E. M., Heemskerk, J. W. M. Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage. PMID:26481309

  5. A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

    ERIC Educational Resources Information Center

    McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

    2011-01-01

    Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

  6. Educators' Challenges of Including Children with Autism Spectrum Disorder in Mainstream Classrooms

    ERIC Educational Resources Information Center

    Lindsay, Sally; Proulx, Meghann; Thomson, Nicole; Scott, Helen

    2013-01-01

    Although children with autism spectrum disorder (ASD) are increasingly being placed within mainstream classes, little is known about the challenges that teachers encounter with including them as full participants in the class. This qualitative study draws on a purposive sample of 13 educators who have experience teaching children with ASD within…

  7. Should Sluggish Cognitive Tempo Symptoms Be Included in the Diagnosis of Attention-Deficit/hyperactivity Disorder?

    ERIC Educational Resources Information Center

    Todd, Richard D.; Rasmussen, Erik R.; Wood, Catherine; Levy, Florence; Hay, David A.

    2004-01-01

    Objective: To determine the impact of including sluggish cognitive tempo items on the factor and latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in boys and girls. Method: Parent report of two sluggish cognitive tempo items on a population-based sample of 1,430 female twins and 1,414 male twins were analyzed…

  8. Calculation of spin transfer torque in partially polarized spin valves including multiple reflections

    NASA Astrophysics Data System (ADS)

    Hernández, Stephanie; Victora, R. H.

    2010-08-01

    An analytic expression that includes the effect of multiple reflections within the interface of a spin-valve composed of materials with partial spin polarization was obtained. Inclusion of this term in a micromagnetic calculation demonstrates the effect of the spin polarization of the magnetic material on the current induced behavior of the structure. We show that neglecting to include interfacial scattering events results in an underestimation of the switching current compared to the method detailed in this letter. Multiple reflections also produce a strong dependence of the switching current on the magnetocrystalline anisotropy of the fixed layer.

  9. A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum Disorders, Including a Comparison with Other Neurodevelopmental Disorders.

    PubMed

    Atladóttir, H Ó; Schendel, D E; Parner, E T; Henriksen, T B

    2015-08-01

    The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all children born in Denmark from 1994, through 2010, and surviving the first year of life. Children with ASD as a whole have significantly elevated rates of a range of neurologic, respiratory, inflammatory, and metabolic problems in the neonatal period compared to the general population, but there are few if any indicators of a distinctive neonatal morbidity profile in ASD compared to other neurodevelopmental outcomes. PMID:25758820

  10. Unified description for hopping transport in organic semiconductors including both energetic disorder and polaronic contributions

    NASA Astrophysics Data System (ADS)

    Fishchuk, I. I.; Kadashchuk, A.; Hoffmann, S. T.; Athanasopoulos, S.; Genoe, J.; Bässler, H.; Köhler, A.

    2013-09-01

    We developed an analytical model to describe hopping transport in organic semiconductors including both energetic disorder and polaronic contributions due to geometric relaxation. The model is based on a Marcus jump rate in terms of the small-polaron concept with a Gaussian energetic disorder, and it is premised upon a generalized effective medium approach yet avoids shortcomings involved in the effective transport energy or percolation concepts. It is superior to our previous treatment [Phys. Rev. B1098-012110.1103/PhysRevB.76.045210 76, 045210 (2007)] since it is applicable at arbitrary polaron activation energy Ea with respect to the energy disorder parameter σ. It can be adapted to describe both charge-carrier mobility and triplet exciton diffusion. The model is compared with results from Monte Carlo simulations. We show (i) that the activation energy of the thermally activated hopping transport can be decoupled into disorder and polaron contributions whose relative weight depend nonlinearly on the σ/Ea ratio, and (ii) that the choice of the density of occupied and empty states considered in configurational averaging has a profound effect on the results of calculations of the Marcus hopping transport. The σ/Ea ratio governs also the carrier-concentration dependence of the charge-carrier mobility in the large-carrier-concentration transport regime as realized in organic field-effect transistors. The carrier-concentration dependence becomes considerably weaker when the polaron energy increases relative to the disorder energy, indicating the absence of universality. This model bridges a gap between disorder and polaron hopping concepts.

  11. Extension of the ADC Charge-Collection Model to Include Multiple Junctions

    NASA Technical Reports Server (NTRS)

    Edmonds, Larry D.

    2011-01-01

    The ADC model is a charge-collection model derived for simple p-n junction silicon diodes having a single reverse-biased p-n junction at one end and an ideal substrate contact at the other end. The present paper extends the model to include multiple junctions, and the goal is to estimate how collected charge is shared by the different junctions.

  12. Coenzyme Q10 treatment of cardiovascular disorders of ageing including heart failure, hypertension and endothelial dysfunction.

    PubMed

    Yang, Yan-Kun; Wang, Lin-Ping; Chen, Lei; Yao, Xiu-Ping; Yang, Kun-Qi; Gao, Ling-Gen; Zhou, Xian-Liang

    2015-10-23

    Advancing age is a major risk factor for the development of cardiovascular diseases. The aetiology of several cardiovascular disorders is thought to involve impaired mitochondrial function and oxidative stress. Coenzyme Q10 (CoQ10) acts as both an antioxidant and as an electron acceptor at the level of the mitochondria. Furthermore, in cardiac patients, plasma CoQ10 has been found to be an independent predictor of mortality. Based on the fundamental role of CoQ10 in mitochondrial bioenergetics and its well-acknowledged antioxidant properties, several clinical trials evaluating CoQ10 have been undertaken in cardiovascular disorders of ageing including chronic heart failure, hypertension, and endothelial dysfunction. CoQ10 as a therapy appears to be safe and well tolerated. PMID:26254995

  13. Plasma cell disorders in HIV-infected patients: from benign gammopathy to multiple myeloma.

    PubMed

    Dezube, Bruce J; Aboulafia, David M; Pantanowitz, Liron

    2004-07-01

    Plasma cell disorders are not uncommonly reported in young patients with HIV infection. These disorders range from benign polyclonal hypergammaglobulinemia to indeterminate monoclonal gammopathy of unknown significance (MGUS) to malignant dyscrasias, including multiple myeloma and plasma cell leukemia. Hypergammaglobulinemia and oligoclonal banding had been the most frequently reported disorders in the pre-HAART era. In HIV-infected persons, the incidence of MGUS is reported to be around 2.5%, with an approximate 4.5-fold increased risk of multiple myeloma. Many of these HIV-infected patients had been treated with alkylator-based regimens, and these reports predate the current widespread use of thalidomide-dexamethasone combination treatment in multiple myeloma. Although the optimal therapy for an HIV-infected person might with plasma cell dyscrasia is yet to be defined, in the current era of HAART the otherwise healthy HIV-infected patient might be tested like an HIV-negative person. Consequently, treatment with immunomodulatory agents (eg, thalidomide) and proteasome inhibitors (eg, bortezomib) may also be worth considering. High-dose chemotherapy with an autologous peripheral blood stem cell transplant is increasingly being considered as consolidation therapy in the younger non-HIV-infected myeloma patient. In the next few years, it is anticipated that these approaches will be applied more frequently to HIV-infected persons with myeloma. PMID:15282866

  14. Comparative Study of Children with ADHD Only, Autism Spectrum Disorder + ADHD, and Chronic Multiple Tic Disorder + ADHD

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; DeVincent, Carla J.; Schneider, Jayne

    2009-01-01

    Objective: Identification of differences among children with ADHD only, autism spectrum disorder (ASD)+ADHD, and chronic multiple tic disorder (CMTD)+ADHD may lead to better understanding of clinical phenotypes. Method: Children were evaluated using the parent- and teacher-completed questionnaires. Results: All three groups were highly similar in…

  15. Comparative Study of Children with ADHD Only, Autism Spectrum Disorder + ADHD, and Chronic Multiple Tic Disorder + ADHD

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; DeVincent, Carla J.; Schneider, Jayne

    2009-01-01

    Objective: Identification of differences among children with ADHD only, autism spectrum disorder (ASD)+ADHD, and chronic multiple tic disorder (CMTD)+ADHD may lead to better understanding of clinical phenotypes. Method: Children were evaluated using the parent- and teacher-completed questionnaires. Results: All three groups were highly similar in

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

    PubMed

    Mulhern, S

    1994-10-01

    During the past decade in North America, a growing number of mental health professionals have reported that between 25% and 50% of their patients in treatment for multiple personality disorder (MPD) have recovered early childhood traumatic memories of ritual torture, incestuous rape, sexual debauchery, sacrificial murder, infanticide, and cannibalism perpetrated by members of clandestine satanic cults. Although hundreds of local and federal police investigations have failed to corroborate patients' therapeutically constructed accounts, because the satanic etiology of MPD is logically coherent with the neodissociative, traumatic theory of psychopathology, conspiracy theory has emerged as the nucleus of a consistent pattern of contemporary clinical interpretation. Resolutely logical and thoroughly operational, ultrascientific psychodemonology remains paradoxically oblivious to its own irrational premises. When the hermetic logic of conspiracy theory is stripped away by historical and socio/psychological analysis, however, the hypothetical perpetrators of satanic ritual abuse simply disappear, leaving in their wake the very real human suffering of all those who have been caught up in the social delusion. PMID:7960286

  17. Multiple electron emission from noble gases colliding with proton beams, including postcollisional effects

    NASA Astrophysics Data System (ADS)

    Galassi, M. E.; Rivarola, R. D.; Fainstein, P. D.

    2007-05-01

    The process of multiple electron ionization of Ne and Ar noble gases produced by impact of proton beams is studied in the framework of the independent-electron model. The role played by different mechanisms is analyzed, including intershell Auger and intrashell Coster-Kronig electron emission, which follow the production of vacancies due to direct interaction of the projectile with the target electrons. The present results, obtained with the continuum distorted wave eikonal initial state (CDW-EIS) approximation, confirm previous predictions given by a different theoretical model. Semiempirical approximations are introduced by using analytical single-ionization probabilities with adjustable parameters determined from CDW-EIS total cross sections. The small computational time required to calculate multiple ionization cross sections with these semiempirical approximations and the good agreement found with existing experimental data and with results obtained with more elaborated theoretical models make them good candidates to study electron emission from complex targets.

  18. Analysis of Randomised Trials Including Multiple Births When Birth Size Is Informative

    PubMed Central

    Yelland, Lisa N.; Sullivan, Thomas R.; Pavlou, Menelaos; Seaman, Shaun R.

    2016-01-01

    Background Informative birth size occurs when the average outcome depends on the number of infants per birth. Although analysis methods have been proposed for handling informative birth size, their performance is not well understood. Our aim was to evaluate the performance of these methods and to provide recommendations for their application in randomised trials including infants from single and multiple births. Methods Three generalised estimating equation (GEE) approaches were considered for estimating the effect of treatment on a continuous or binary outcome: cluster weighted GEEs, which produce treatment effects with a mother-level interpretation when birth size is informative; standard GEEs with an independence working correlation structure, which produce treatment effects with an infant-level interpretation when birth size is informative; and standard GEEs with an exchangeable working correlation structure, which do not account for informative birth size. The methods were compared through simulation and analysis of an example dataset. Results Treatment effect estimates were affected by informative birth size in the simulation study when the effect of treatment in singletons differed from that in multiples (i.e. in the presence of a treatment group by multiple birth interaction). The strength of evidence supporting the effectiveness of treatment varied between methods in the example dataset. Conclusions Informative birth size is always a possibility in randomised trials including infants from both single and multiple births, and analysis methods should be pre-specified with this in mind. We recommend estimating treatment effects using standard GEEs with an independence working correlation structure to give an infant-level interpretation. PMID:26332368

  19. Annual Research Review: The neurobehavioral development of multiple memory systems: implications for childhood and adolescent psychiatric disorders

    PubMed Central

    Goodman, Jarid; Marsh, Rachel; Peterson, Bradley S.; Packard, Mark G.

    2014-01-01

    Extensive evidence indicates that mammalian memory is organized into multiple brains systems, including a “cognitive” memory system that depends upon the hippocampus and a stimulus-response “habit” memory system that depends upon the dorsolateral striatum. Dorsal striatal-dependent habit memory may in part influence the development and expression of some human psychopathologies, particularly those characterized by strong habit-like behavioral features. The present review considers this hypothesis as it pertains to psychopathologies that typically emerge during childhood and adolescence. These disorders include Tourette syndrome, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, eating disorders, and autism spectrum disorders. Human and nonhuman animal research shows that the typical development of memory systems comprises the early maturation of striatal-dependent habit memory and the relatively late maturation of hippocampal-dependent cognitive memory. We speculate that the differing rates of development of these memory systems may in part contribute to the early emergence of habit-like symptoms in childhood and adolescence. In addition, abnormalities in hippocampal and striatal brain regions have been observed consistently in youth with these disorders, suggesting that the aberrant development of memory systems may also contribute to the emergence of habit-like symptoms as core pathological features of these illnesses. Considering these disorders within the context of multiple memory systems may help elucidate the pathogenesis of habit-like symptoms in childhood and adolescence, and lead to novel treatments that lessen the habit-like behavioral features of these disorders. PMID:24286520

  20. The electronic and transport properties of two-dimensional conjugated polymer networks including disorder

    NASA Astrophysics Data System (ADS)

    Adjizian, Jean-Joseph; Lherbier, Aurélien; M.-M. Dubois, Simon; Botello-Méndez, Andrés Rafael; Charlier, Jean-Christophe

    2016-01-01

    Two-dimensional (2D) conjugated polymers exhibit electronic structures analogous to that of graphene with the peculiarity of π-π* bands which are fully symmetric and isolated. In the present letter, the suitability of these materials for electronic applications is analyzed and discussed. In particular, realistic 2D conjugated polymer networks with a structural disorder such as monomer vacancies are investigated. Indeed, during bottom-up synthesis, these irregularities are unavoidable and their impact on the electronic properties is investigated using both ab initio and tight-binding techniques. The tight-binding model is combined with a real space Kubo-Greenwood approach for the prediction of transport characteristics for monomer vacancy concentrations ranging from 0.5% to 2%. As expected, long mean free paths and high mobilities are predicted for low defect densities. At low temperatures and for high defect densities, strong localization phenomena originating from quantum interferences of multiple scattering paths are observed in the close vicinity of the Dirac energy region while the absence of localization effects is predicted away from this region suggesting a sharp mobility transition. These predictions show that 2D conjugated polymer networks are good candidates to pave the way for the ultimate scaling and performances of future molecular nanoelectronic devices.Two-dimensional (2D) conjugated polymers exhibit electronic structures analogous to that of graphene with the peculiarity of π-π* bands which are fully symmetric and isolated. In the present letter, the suitability of these materials for electronic applications is analyzed and discussed. In particular, realistic 2D conjugated polymer networks with a structural disorder such as monomer vacancies are investigated. Indeed, during bottom-up synthesis, these irregularities are unavoidable and their impact on the electronic properties is investigated using both ab initio and tight-binding techniques. The tight-binding model is combined with a real space Kubo-Greenwood approach for the prediction of transport characteristics for monomer vacancy concentrations ranging from 0.5% to 2%. As expected, long mean free paths and high mobilities are predicted for low defect densities. At low temperatures and for high defect densities, strong localization phenomena originating from quantum interferences of multiple scattering paths are observed in the close vicinity of the Dirac energy region while the absence of localization effects is predicted away from this region suggesting a sharp mobility transition. These predictions show that 2D conjugated polymer networks are good candidates to pave the way for the ultimate scaling and performances of future molecular nanoelectronic devices. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06825h

  1. Synergy of multiple partners, including freeloaders, increases host fitness in a multispecies mutualism

    PubMed Central

    Palmer, Todd M.; Doak, Daniel F.; Stanton, Maureen L.; Bronstein, Judith L.; Kiers, E. Toby; Young, Truman P.; Goheen, Jacob R.; Pringle, Robert M.

    2010-01-01

    Understanding cooperation is a central challenge in biology, because natural selection should favor “free-loaders” that reap benefits without reciprocating. For interspecific cooperation (mutualism), most approaches to this paradox focus on costs and benefits of individual partners and the strategies mutualists use to associate with beneficial partners. However, natural selection acts on lifetime fitness, and most mutualists, particularly longer-lived species interacting with shorter-lived partners (e.g., corals and zooxanthellae, tropical trees and mycorrhizae) interact with multiple partner species throughout ontogeny. Determining how multiple partnerships might interactively affect lifetime fitness is a crucial unexplored link in understanding the evolution and maintenance of cooperation. The tropical tree Acacia drepanolobium associates with four symbiotic ant species whose short-term individual effects range from mutualistic to parasitic. Using a long-term dataset, we show that tree fitness is enhanced by partnering sequentially with sets of different ant symbionts over the ontogeny of a tree. These sets include a “sterilization parasite” that prevents reproduction and another that reduces tree survivorship. Trees associating with partner sets that include these “parasites” enhance lifetime fitness by trading off survivorship and fecundity at different life stages. Our results demonstrate the importance of evaluating mutualism within a community context and suggest that lifespan inequalities among mutualists may help cooperation persist in the face of exploitation. PMID:20855614

  2. Synergy of multiple partners, including freeloaders, increases host fitness in a multispecies mutualism.

    PubMed

    Palmer, Todd M; Doak, Daniel F; Stanton, Maureen L; Bronstein, Judith L; Kiers, E Toby; Young, Truman P; Goheen, Jacob R; Pringle, Robert M

    2010-10-01

    Understanding cooperation is a central challenge in biology, because natural selection should favor "free-loaders" that reap benefits without reciprocating. For interspecific cooperation (mutualism), most approaches to this paradox focus on costs and benefits of individual partners and the strategies mutualists use to associate with beneficial partners. However, natural selection acts on lifetime fitness, and most mutualists, particularly longer-lived species interacting with shorter-lived partners (e.g., corals and zooxanthellae, tropical trees and mycorrhizae) interact with multiple partner species throughout ontogeny. Determining how multiple partnerships might interactively affect lifetime fitness is a crucial unexplored link in understanding the evolution and maintenance of cooperation. The tropical tree Acacia drepanolobium associates with four symbiotic ant species whose short-term individual effects range from mutualistic to parasitic. Using a long-term dataset, we show that tree fitness is enhanced by partnering sequentially with sets of different ant symbionts over the ontogeny of a tree. These sets include a "sterilization parasite" that prevents reproduction and another that reduces tree survivorship. Trees associating with partner sets that include these "parasites" enhance lifetime fitness by trading off survivorship and fecundity at different life stages. Our results demonstrate the importance of evaluating mutualism within a community context and suggest that lifespan inequalities among mutualists may help cooperation persist in the face of exploitation. PMID:20855614

  3. PTSD and Comorbid Disorders in a Representative Sample of Adolescents: The Risk Associated with Multiple Exposures to Potentially Traumatic Events

    ERIC Educational Resources Information Center

    Macdonald, Alexandra; Danielson, Carla Kmett; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

    2010-01-01

    Objective: This study compared the impact of multiple exposures to potentially traumatic events (PTEs), including sexual victimization, physical victimization, and witnessed violence, on posttraumatic stress disorder (PTSD) and comorbid conditions (i.e., major depressive episode [MDE], and substance use [SUD]). Methods: Participants were a…

  4. PTSD and Comorbid Disorders in a Representative Sample of Adolescents: The Risk Associated with Multiple Exposures to Potentially Traumatic Events

    ERIC Educational Resources Information Center

    Macdonald, Alexandra; Danielson, Carla Kmett; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

    2010-01-01

    Objective: This study compared the impact of multiple exposures to potentially traumatic events (PTEs), including sexual victimization, physical victimization, and witnessed violence, on posttraumatic stress disorder (PTSD) and comorbid conditions (i.e., major depressive episode [MDE], and substance use [SUD]). Methods: Participants were a

  5. The Effects of Including a Callous Unemotional Specifier for the Diagnosis of Conduct Disorder

    PubMed Central

    Kahn, Rachel E.; Frick, Paul J.; Youngstrom, Eric; Findling, Robert L.; Youngstrom, Jennifer Kogos

    2011-01-01

    Background “With Significant Callous-Unemotional Traits” has been proposed as a specifier for Conduct Disorder (CD) in the upcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The impact of this specifier on children diagnosed with CD should be considered. Methods A multi-site cross-sectional design with volunteers (n=1136) in the 3rd-7th grades and 566 consecutive referrals (ages 5-18) to a community mental health center were used to estimate the prevalence rates of CD with and without the proposed specifier. In addition, the degree of emotional and behavioral (especially physical aggression) disturbance and level of impairment in youth with and without CD and with and without the specifier was evaluated. Results In the community sample, 10% to 32% of those with CD and 2% to 7% of those without CD met the callous-unemotional (CU) specifier threshold depending on informant. In the clinic-referred sample, 21% to 50% of those with CD and 14% to 32% without CD met the CU specifier threshold depending on informant. Those with CD and the specifier showed higher rates of aggression in both samples and higher rates of cruelty in the clinic-referred sample. Conclusions Results indicate between 10% and 50% of youth with CD would be designated with the proposed CU specifier. Those with CD and the specifier appear to be more severe on a number of indices, including aggression and cruelty. PMID:21950481

  6. Child Abuse and Multiple Personality Disorders: Review of the Literature and Suggestions for Treatment.

    ERIC Educational Resources Information Center

    Coons, Philip M.

    1986-01-01

    Multiple personality disorder is associated with a high incidence of physical and sexual abuse during childhood. While difficult to diagnose, multiple personality is easier to treat if diagnosed early in childhood or adolescence. Treatment for multiple personality focuses on establishing trust and communicating with and integrating the…

  7. Pharmacotherapy in the Management of Voiding and Storage Disorders, Including Enuresis and Encopresis

    ERIC Educational Resources Information Center

    Reiner, William G.

    2008-01-01

    Enuresis and encopresis are disorders of the bladder and rectum, and this article helps in understanding the neurobiology of lower urinary tract and anorectal function to help in the treatment of these disorders. Treatment for children with these disorders emphasizes either a psychological or pharmacological approach.

  8. Behavior Disorders: The Need for Multiple and Integrated Treatment Activities.

    ERIC Educational Resources Information Center

    Bernes, Kerry

    In response to increasing demands that Canadian school boards provide behavior adaptation programs to counter the effects of disruptive home environments, school violence, and victimization, this paper explores definitions and diagnostic criteria for the following behavior disorders: attention-deficit hyperactivity disorder, oppositional defiant…

  9. Varieties of Preschool Hyperactivity: Multiple Pathways from Risk to Disorder

    ERIC Educational Resources Information Center

    Sonuga-Barke, Edmund J. S.; Auerbach, Judith; Campbell, Susan B.; Daley, David; Thompson, Margaret

    2005-01-01

    In this paper we examine the characteristics of preschool attention deficit hyperactivity disorder (ADHD) from both mental disorder and developmental psychopathology points of view. The equivalence of preschool and school-aged hyperactivity as a behavioral dimension is highlighted together with the potential value of extending the use of the ADHD…

  10. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)

    PubMed Central

    Takaki, Akinobu; Kawai, Daisuke; Yamamoto, Kazuhide

    2013-01-01

    Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. PMID:24132155

  11. Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up

    SciTech Connect

    Croft, Stephen; Evans, Louise G; Schear, Melissa A

    2010-01-01

    In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build-up (thermalization transient) within the detector cannot be ignored. Another example where signal build-up might be observed is when a {sup 3}He based system is used to track the evolution of the time correlated signal created by a higher multiplying item within a reflective configuration such as the measurement of a spent fuel assembly. In this work we develop expressions for the GUFs which include signal build-up.

  12. Multiple cell photoresponsive amorphous photo voltaic devices including graded ban gaps

    SciTech Connect

    Ovshinsky, S.R.; Adler, D.

    1990-09-04

    This patent describes an improved photoresponsive tandem multiple cell device. It comprises: at least first and second superimposed solar cells; the first cell being formed of an amorphous silicon alloy material; the second amorphous silicon alloy cell having an active photoresponsive region in which radiation can impinge to produce charge carriers. The amorphous silicon alloy cell body including at least one element for reducing the density of defect states to about 10{sup 16} defects per cubic centimeter and a band gap adjusting element graded through at least a portion of the photoresponsive region thereof to enhance the radiation absorption; the adjusting element being germanium, and the band gap of the cell being adjusted for a specified photoresponse wavelength threshold function different from the first cell; the second cell being a multi-layer body having deposited silicon alloy layers of opposite (p and n) conductivity type; and the first cell being formed with the second cell in substantially direct junction contact therebetween.

  13. Neuromyelitis Optica Spectrum Disorder with Tumefactive Demyelination mimicking Multiple Sclerosis: A Rare Case

    PubMed Central

    Roy, Ujjawal; Saini, Dinesh Satyanarayan; Pan, Koushik; Pandit, Alak; Ganguly, Goutam; Panwar, Ajay

    2016-01-01

    Neuromyelitis optica spectrum disorder (NMOSD) is a diverse condition which not only encompasses isolated longitudinally extensive transverse myelitis (LETM) and optic neuritis but also includes area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, and symptomatic cerebral syndrome. Imaging may reveal periependymal lesions surrounding the ventricular system or involvement of corticospinal tracts, area postrema, diencephalon, and corpus callosum. Rarely, there may be hemispheric tumefactive lesions that enhance in a “Cloud-like” fashion on gadolinium injection unlike in tumefactive multiple sclerosis where there is incomplete ring enhancement. Here, we present a case of aquaporin-4 positive relapsing NMOSD who presented to us with recurrent episodes of paraparesis with LETM and tumefactive lesions of brain on imaging, which enhanced in an incomplete ring like pattern resembling multiple sclerosis.

  14. Multiple chronic disorders - health care system’s modern challenge in the Maccabi Health Care System

    PubMed Central

    2014-01-01

    Background One of the major challenges health care systems face in modern time is treating chronic disorders. In recent years, the increasing occurrence of multiple chronic disorders (MCC) in single individuals has compounded the complexity of health care. In 2008, it was estimated that worldwide as many as one quarter of the population between the ages of sixty five to sixty nine suffered from two or more chronic conditions and this prevalence rose with age. Clinical guidelines provide guidance for management of single disorders, but not for MCC. The aim of the present study was the study of the prevalence, distribution and impact of MCC in a large Israeli health system. Methods We performed a cross-sectional study of MCC in the Maccabi Healthcare System (MHS), Israel’s second largest healthcare service, providing care for approximately two million people. Data regarding chronic conditions was collected through electronic medical records and organizational records, as was demographic and socioeconomic data. Age and sex specific data were compared with previously published data from Scotland. Results Two thirds of the population had two or more chronic disorders. This is significantly higher than previously published rates. A correlation between patient age and number of chronic disorders was found, as was a correlation between number of chronic disorders and low socioeconomic status, with the exception of children due to a high prevalence of learning disabilities, asthma, and visual disturbances. Discussion MCC is very prevalent in the MHS population, increases with age, and except for children is more prevalent in lower socioeconomic classes, possibly due to the a combination of the structure of the Israeli universal insurance and requirements of the ministry of education for exemptions and benefits. A higher than previously reported prevalence of MCC may be due to the longtime use of use of integrated electronic medical records. Conclusions To effectively deal with MCC health care systems must devise strategies, including but not limited to, information technologies that enable shared teamwork based on clinical guidelines which address the problem of multiple, as opposed to single chronic disorders in patients. PMID:25206971

  15. Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

    PubMed Central

    Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

    2013-01-01

    Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

  16. Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

    PubMed

    Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

    2013-01-01

    Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

  17. Ten rice peroxidases redundantly respond to multiple stresses including infection with rice blast fungus.

    PubMed

    Sasaki, Katsutomo; Iwai, Takayoshi; Hiraga, Susumu; Kuroda, Katsushi; Seo, Shigemi; Mitsuhara, Ichiro; Miyasaka, Atsushi; Iwano, Masataka; Ito, Hiroyuki; Matsui, Hirokazu; Ohashi, Yuko

    2004-10-01

    Class III plant peroxidases are believed to function in diverse physiological processes including disease resistance and wound response, but predicted low substrate specificities and the presence of 70 or more isoforms have made it difficult to define a specific physiological function(s) for each gene. To select pathogen-responsive POX genes, we analyzed the expression profiles of 22 rice POX genes after infection with rice blast fungus. The expression of 10 POX genes among the 22 genes was induced after fungal inoculation in both compatible and incompatible hosts. Seven of the 10 POX genes were expressed at higher levels in the incompatible host than in the compatible host 6-24 h after inoculation by which time no fungus-induced lesions have appeared. Organ-specific expression and stress-induced expression by wounding and treatment with probenazole, an agrichemical against blast fungus, jasmonic acid, salicylic acid and 1-aminocyclopropane-1-carboxylate, a precursor of ethylene, indicated that rice POXs have individual characteristics and can be classified into several types. A comparison of the amino acid sequences of POXs showed that multiple isoforms with a high sequence similarity respond to stress in different or similar ways. Such redundant responses of POX genes may guarantee POX activities that are necessary for self-defense in plant tissues against environmental stresses including pathogen infection. PMID:15564528

  18. RNA interference screening identifies lenalidomide sensitizers in multiple myeloma, including RSK2

    PubMed Central

    Zhu, Yuan Xiao; Yin, Hongwei; Bruins, Laura A.; Shi, Chang-Xin; Jedlowski, Patrick; Aziz, Meraj; Sereduk, Chris; Kortuem, Klaus Martin; Schmidt, Jessica E.; Champion, Mia; Braggio, Esteban

    2015-01-01

    To identify molecular targets that modify sensitivity to lenalidomide, we measured proliferation in multiple myeloma (MM) cells transfected with 27 968 small interfering RNAs in the presence of increasing concentrations of drug and identified 63 genes that enhance activity of lenalidomide upon silencing. Ribosomal protein S6 kinase (RPS6KA3 or RSK2) was the most potent sensitizer. Other notable gene targets included 5 RAB family members, 3 potassium channel proteins, and 2 peroxisome family members. Single genes of interest included I-κ-B kinase-α (CHUK), and a phosphorylation dependent transcription factor (CREB1), which associate with RSK2 to regulate several signaling pathways. RSK2 knockdown induced cytotoxicity across a panel of MM cell lines and consistently increased sensitivity to lenalidomide. Accordingly, 3 small molecular inhibitors of RSK2 demonstrated synergy with lenalidomide cytotoxicity in MM cells even in the presence of stromal contact. Both RSK2 knockdown and small molecule inhibition downregulate interferon regulatory factor 4 and MYC, and provides an explanation for the synergy between lenalidomide and RSK2 inhibition. Interestingly, RSK2 inhibition also sensitized MM cells to bortezomib, melphalan, and dexamethasone, but did not downregulate Ikaros or influence lenalidomide-mediated downregulation of tumor necrosis factor-α or increase lenalidomide-induced IL-2 upregulation. In summary, inhibition of RSK2 may prove a broadly useful adjunct to MM therapy. PMID:25395420

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

    PubMed Central

    2013-01-01

    Background A recent study of lateral septum (LS) suggested a large number of autism-related genes with altered expression in the postpartum state. However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. Results The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. Conclusions The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. To date, this is the first study to show a significant, quantitative link between the maternal brain and mental health disorders using large scale gene expression data. Thus, the postpartum brain may provide a novel and promising platform for understanding the complex genetics of improved sociability that may have direct relevance for multiple psychiatric illnesses. This study also provides an important new tool that fills a critical analysis gap and makes evaluation of enrichment using any database of interest possible with an emphasis on ease of use and methodological transparency. PMID:24245670

  20. Should DSM-V include dimensional diagnostic criteria for alcohol use disorders?

    PubMed

    Helzer, John E; Bucholz, Kathleen K; Bierut, Laura Jean; Regier, Darrel A; Schuckit, Marc A; Guth, Sarah E

    2006-02-01

    This program calls attention to the upcoming timetable for the revision of the Diagnostic and Statistical Manual (DSM)-IV and the publication of DSM-V. It is vitally important for Research Society of Alcoholism members to be aware of the current discussions of the important scientific questions related to the next DSM revision and to use the opportunity for input. The title of the symposium highlights 1 key question, i.e., whether the DSM definitions should remain strictly categorical as in the past or whether a dimensional component should be included in this revision. Two substantive and 1 conceptual paper are included in this portion of the symposium. The fourth and final presentation detailing the revision timetable and the opportunities for input is by Dr. Darrel Regier. Dr. Regier is the director of American Psychiatric Institute for Research and Education the research and education branch of the American Psychiatric Association and the organization within the APA that will oversee the DSM revision. The discussion is by Marc Schuckit, who was chair of the Substance Use disorders (SUD) Committee for DSM-IV and cochair of the international group of experts reviewing the SUD definitions for DSM-V. PMID:16441279

  1. The Parental Fitness of Mothers with Multiple Personality Disorder: A Preliminary Study.

    ERIC Educational Resources Information Center

    Kluft, Richard P.

    1987-01-01

    A review of the parenting patterns of 75 mothers with multiple personality disorders indicated 38.7% were competent or exceptional mothers, 16% were grossly abusive, and 45.3% were compromised or impaired as parents. (DB)

  2. Thymoquinone causes multiple effects, including cell death, on dividing plant cells.

    PubMed

    Hassanien, Sameh E; Ramadan, Ahmed M; Azeiz, Ahmed Z Abdel; Mohammed, Rasha A; Hassan, Sabah M; Shokry, Ahmed M; Atef, Ahmed; Kamal, Khalid B H; Rabah, Samar; Sabir, Jamal S M; Abuzinadah, Osama A; El-Domyati, Fotouh M; Martin, Gregory B; Bahieldin, Ahmed

    2013-01-01

    Thymoquinone (TQ) is a major constituent of Nigella sativa oil with reported anti-oxidative activity and anti-inflammatory activity in animal cells. It also inhibits proliferation and induces programmed cell death (apoptosis) in human skin cancer cells. The present study sought to detect the influence of TQ on dividing cells of three plant systems and on expression of Bcl2-associated athanogene-like (BAG-like) genes that might be involved during the process of cell death. BAG genes are known for the regulation of diverse physiological processes in animals, including apoptosis, tumorigenesis, stress responses, and cell division. Synthetic TQ at 0.1mg/mL greatly reduced wheat seed germination rate, whereas 0.2mg/mL completely inhibited germination. An Evans blue assay revealed moderate cell death in the meristematic zone of Glycine max roots after 1h of TQ treatment (0.2mg/mL), with severe cell death occurring in this zone after 2h of treatment. Light microscopy of TQ-treated (0.2mg/mL) onion hairy root tips for 1h revealed anti-mitotic activity and also cell death-associated changes, including nuclear membrane disruption and nuclear fragmentation. Transmission electron microscopy of TQ-treated cells (0.2mg/mL) for 1h revealed shrinkage of the plasma membrane, leakage of cell lysate, degradation of cell walls, enlargement of vacuoles and condensation of nuclei. Expression of one BAG-like gene, previously associated with cell death, was induced 20 min after TQ treatment in Glycine max root tip cells. Thus, TQ has multiple effects, including cell death, on dividing plant cells and plants may serve as a useful system to further investigate the mechanisms underlying the response of eukaryotic cells to TQ. PMID:24296078

  3. The epigenetics of multiple sclerosis and other related disorders.

    PubMed

    van den Elsen, Peter J; van Eggermond, Marja C J A; Puentes, Fabiola; van der Valk, Paul; Baker, David; Amor, Sandra

    2014-03-01

    Multiple Sclerosis (MS) is a demyelinating disease characterized by chronic inflammation of the central nervous system (CNS) gray and white matter. Although the cause of MS is unknown, it is widely appreciated that innate and adaptive immune processes contribute to its pathogenesis. These include microglia/macrophage activation, pro-inflammatory T-cell (Th1) responses and humoral responses. Additionally, there is evidence indicating that MS has a neurodegenerative component since neuronal and axonal loss occurs even in the absence of overt inflammation. These aspects also form the rationale for clinical management of the disease. However, the currently available therapies to control the disease are only partially effective at best indicating that more effective therapeutic solutions are urgently needed. It is appreciated that in the immune-driven and neurodegenerative processes MS-specific deregulation of gene expressions and resulting protein dysfunction are thought to play a central role. These deviations in gene expression patterns contribute to the inflammatory response in the CNS, and to neuronal or axonal loss. Epigenetic mechanisms control transcription of most, if not all genes, in nucleated cells including cells of the CNS and in haematopoietic cells. MS-specific alterations in epigenetic regulation of gene expression may therefore lie at the heart of the deregulation of gene expression in MS. As such, epigenetic mechanisms most likely play an important role in disease pathogenesis. In this review we discuss a role for MS-specific deregulation of epigenetic features that control gene expression in the CNS and in the periphery. Furthermore, we discuss the application of small molecule inhibitors that target the epigenetic machinery to ameliorate disease in experimental animal models, indicating that such approaches may be applicable to MS patients. PMID:25878004

  4. One-Year Change in Repetitive Behaviours in Young Children with Communication Disorders Including Autism

    ERIC Educational Resources Information Center

    Honey, Emma; McConachie, Helen; Randle, Val; Shearer, Heather; Le Couteur, Ann S.

    2008-01-01

    Repetitive behaviours are a relatively neglected area of study in autism. Previous research has concluded that repetitive behaviour is inversely related to ability and that it tends to increase over the preschool years. One-hundred and four children ages 24-48 months, with autism, autism spectrum disorder (ASD) or other disorders, were followed…

  5. The Effects of Including a Callous-Unemotional Specifier for the Diagnosis of Conduct Disorder

    ERIC Educational Resources Information Center

    Kahn, Rachel E.; Frick, Paul J.; Youngstrom, Eric; Findling, Robert L.; Youngstrom, Jennifer Kogos

    2012-01-01

    Background: "With Significant Callous-Unemotional Traits" has been proposed as a specifier for conduct disorder (CD) in the upcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). The impact of this specifier on children diagnosed with CD should be considered. Methods: A multi-site cross-sectional design with…

  6. Oxidative metabolism is associated with physiological disorders in fruits stored under multiple environmental stresses.

    PubMed

    Lum, Geoffrey B; Shelp, Barry J; DeEll, Jennifer R; Bozzo, Gale G

    2016-04-01

    In combination with low temperature, controlled atmosphere storage and 1-methylcyclopropene (ethylene antagonist) application are used to delay senescence of many fruits and vegetables. Controlled atmosphere consists of low O2 and elevated CO2. When sub-optimal partial pressures are used, these practices represent multiple abiotic stresses that can promote the development of physiological disorders in pome fruit, including flesh browning and cavities, although there is some evidence for genetic differences in susceptibility. In the absence of surface disorders, fruit with flesh injuries are not easily distinguished from asymptomatic fruit until these are consumed. Oxidative stress metabolites tend to accumulate (e.g., γ-aminobutyrate) or rapidly decline (e.g., ascorbate and glutathione) in vegetative tissues exposed to hypoxic and/or elevated CO2 environments. Moreover, these phenomena can be associated with altered energy and redox status. Biochemical investigations of Arabidopsis and tomato plants with genetically-altered levels of enzymes associated with the γ-aminobutyrate shunt and the ascorbate-glutathione pathway indicate that these metabolic processes are functionally related and critical for dampening the oxidative burst in vegetative and fruit tissues, respectively. Here, we hypothesize that γ-aminobutyrate accumulation, as well energy and antioxidant depletion are associated with the development of physiological injury in pome fruit under multiple environmental stresses. An improved understanding of this relationship could assist in maintaining the quality of stored fruit. PMID:26940499

  7. From Single to Multiple Deficit Models of Developmental Disorders

    ERIC Educational Resources Information Center

    Pennington, Bruce F.

    2006-01-01

    The emerging etiological model for developmental disorders, like dyslexia, is probabilistic and multifactorial while the prevailing cognitive model has been deterministic and often focused on a single cognitive cause, such as a phonological deficit as the cause of dyslexia. So there is a potential contradiction in our explanatory frameworks for…

  8. Children at Risk for Learning Disorders: Multiple Perspectives.

    ERIC Educational Resources Information Center

    Al-Yagon, Michal

    2003-01-01

    A study involving 145 Israeli mother-child dyads examined the contribution of a multidimensional model of risk factors in explaining adaptive functioning among kindergartners with mild developmental delays considered at risk for developing learning disorders. Results indicated a high fit between the theoretical model and empirical findings.

  9. The myth of Chinese Barbies: eating disorders in China including Hong Kong.

    PubMed

    Getz, M J

    2014-10-01

    Much of the literature on eating disorders deals with Western subjects. Although the majority of those seen in clinical settings are Caucasians, reports from Asia suggest that anorexia nervosa and bulimia nervosa do occur in the Chinese, sparking debate as to whether or not it is the result of Westernization. This project begins with a review of the current literature on eating disorders in Chinese populations and the role of culture as a mediating factor. A psychodynamic conceptualization and the potential role of traumatic experiences are explored in the emergence of pathological eating habits. Research suggests that applying Western models for Chinese subjects with eating disorders may not always be appropriate. PMID:25356465

  10. Coexistence of Munchausen's syndrome and multiple personality disorder: detailed report of a case and theoretical discussion.

    PubMed

    Toth, E L; Baggaley, A

    1991-05-01

    Patients with factitious disorders represent an important challenge to medical and psychiatric caregivers. The literature on Munchausen's syndrome abounds with entertaining descriptions of these flamboyant patients, but rarely is there significant understanding of the mechanisms of the disease. We present a case where Munchausen's syndrome coincided with multiple personality disorder (MPD). The patient has been known to us for over 10 years, and some resolution of the Munchausen's syndrome is occurring in response to appropriate therapy for the multiple personality disorder. We point out the need to seek out dissociative phenomena in self-abusive patients, as this may provide a clue for psychodynamic understanding and rational therapy. PMID:1852850

  11. Developmental trauma disorder: pros and cons of including formal criteria in the psychiatric diagnostic systems

    PubMed Central

    2013-01-01

    Background This article reviews the current debate on developmental trauma disorder (DTD) with respect to formalizing its diagnostic criteria. Victims of abuse, neglect, and maltreatment in childhood often develop a wide range of age-dependent psychopathologies with various mental comorbidities. The supporters of a formal DTD diagnosis argue that post-traumatic stress disorder (PTSD) does not cover all consequences of severe and complex traumatization in childhood. Discussion Traumatized individuals are difficult to treat, but clinical experience has shown that they tend to benefit from specific trauma therapy. A main argument against inclusion of formal DTD criteria into existing diagnostic systems is that emphasis on the etiology of the disorder might force current diagnostic systems to deviate from their purely descriptive nature. Furthermore, comorbidities and biological aspects of the disorder may be underdiagnosed using the DTD criteria. Summary Here, we discuss arguments for and against the proposal of DTD criteria and address implications and consequences for the clinical practice. PMID:23286319

  12. Thermoelectric material including a multiple transition metal-doped type I clathrate crystal structure

    DOEpatents

    Yang, Jihui; Shi, Xun; Bai, Shengqiang; Zhang, Wenqing; Chen, Lidong; Yang, Jiong

    2012-01-17

    A thermoelectric material includes a multiple transition metal-doped type I clathrate crystal structure having the formula A.sub.8TM.sub.y.sub.1.sup.1TM.sub.y.sub.2.sup.2 . . . TM.sub.y.sub.n.sup.nM.sub.zX.sub.46-y.sub.1.sub.-y.sub.2.sub.- . . . -y.sub.n.sub.-z. In the formula, A is selected from the group consisting of barium, strontium, and europium; X is selected from the group consisting of silicon, germanium, and tin; M is selected from the group consisting of aluminum, gallium, and indium; TM.sup.1, TM.sup.2, and TM.sup.n are independently selected from the group consisting of 3d, 4d, and 5d transition metals; and y.sub.1, y.sub.2, y.sub.n and Z are actual compositions of TM.sup.1, TM.sup.2, TM.sup.n, and M, respectively. The actual compositions are based upon nominal compositions derived from the following equation: z=8q.sub.A-|.DELTA.q.sub.1|y.sub.1-|.DELTA.q.sub.2|y.sub.2- . . . -|.DELTA.q.sub.n|y.sub.n, wherein q.sub.A is a charge state of A, and wherein .DELTA.q.sub.1, .DELTA.q.sub.2, .DELTA.q.sub.n are, respectively, the nominal charge state of the first, second, and n-th TM.

  13. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis.

    PubMed

    Benedict, Ralph H B; Carone, Dominic A; Bakshi, Rohit

    2004-07-01

    Neuropsychological impairment is a common feature of multiple sclerosis. Affected patients often have deficits in information-processing speed and memory and exhibit psychopathological states such as depression. A minority of patients have rarer affect/mood disorders such as euphoria sclerotica and pathological laughter/crying. Neuropsychological impairment is a major predictor of low quality of life, unemployment, and caregiver distress. Studies evaluating correlations between neuropsychological impairment and findings on magnetic resonance imaging show that neuropsychological dysfunction is associated with lesion burden and diffuse disease in normal-appearing brain tissue. However, measures of tissue atrophy including whole-brain and central atrophy are especially well correlated with and predictive of cognitive impairment. Moreover, recent studies have shown that conventional measures of brain atrophy explain more variance in neuropsychological dysfunction than do measures of lesion burden. In particular, neuropsychological outcomes correspond highly with linear measures of subcortical atrophy such as ventricle enlargement. Within the domain of emotional dysfunction, both lesion burden and atrophy are related to major depressive disorder. Brain atrophy also predicts euphoria and disinhibition. The preliminary data suggest that although lesion burden primarily predicts depressive disorder, both lesion burden and atrophy predict the presence of euphoria. Euphoria and disinhibition likely represent personality change associated with worsening cognition as the disease progresses. Taken together, this growing body of data on magnetic resonance imaging to neuropsychological correlations supports the clinical relevance and validity of brain atrophy as a measure of disease progression in multiple sclerosis. Continuing research focuses on the possible relationship between measures of regional brain atrophy and cognitive and emotional impairment. PMID:15228758

  14. A Case Study of Tack Tiles[R] Literacy Instruction for a Student with Multiple Disabilities Including Congenital Blindness

    ERIC Educational Resources Information Center

    Klenk, Jessicia A.; Pufpaff, Lisa A.

    2011-01-01

    Research on literacy instruction for students with multiple disabilities is limited. Empirical research on braille instruction for students with multiple disabilities that include congenital blindness is virtually nonexistent. This case study offers initial insight into possible methods of early braille literacy instruction for a student with…

  15. The incidence and prevalence of psychiatric disorders in multiple sclerosis: A systematic review

    PubMed Central

    Reingold, Stephen; Cohen, Jeffrey; Stuve, Olaf; Trojano, Maria; Sorensen, Per Soelberg; Cutter, Gary; Reider, Nadia

    2015-01-01

    Background: Psychiatric comorbidity is associated with lower quality of life, more fatigue, and reduced adherence to disease-modifying therapy in multiple sclerosis (MS). Objectives: The objectives of this review are to estimate the incidence and prevalence of selected comorbid psychiatric disorders in MS and evaluate the quality of included studies. Methods: We searched the PubMed, PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of retrieved articles. Abstracts were screened for relevance by two independent reviewers, followed by full-text review. Data were abstracted by one reviewer, and verified by a second reviewer. Study quality was evaluated using a standardized tool. For population-based studies we assessed heterogeneity quantitatively using the I2 statistic, and conducted meta-analyses. Results: We included 118 studies in this review. Among population-based studies, the prevalence of anxiety was 21.9% (95% CI: 8.76%–35.0%), while it was 14.8% for alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.4%–30.0%) for depression, 2.5% for substance abuse, and 4.3% (95% CI: 0%–10.3%) for psychosis. Conclusion: This review confirms that psychiatric comorbidity, particularly depression and anxiety, is common in MS. However, the incidence of psychiatric comorbidity remains understudied. Future comparisons across studies would be enhanced by developing a consistent approach to measuring psychiatric comorbidity, and reporting of age-, sex-, and ethnicity-specific estimates. PMID:25583845

  16. Benefits of Including Siblings in the Treatment of Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Ferraioli, Suzannah J.; Hansford, Amy; Harris, Sandra L.

    2012-01-01

    Having a brother or sister with an autism spectrum disorder (ASD) can significantly impact the life of a typically developing sibling. These relationships are generally characterized by less frequent and nurturing interactions than are evident in sibling constellations with neurotypical children or children with other developmental disabilities.

  17. School Factors Associated with Mainstream Progress in Secondary Education for Included Pupils with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Osborne, Lisa A.; Reed, Phil

    2011-01-01

    This research examined the factors promoting inclusion of young people with Autism Spectrum Disorders (ASD) in mainstream secondary schools, and noted high levels of behavioral difficulties in these pupils. The size of the secondary school, and the class size, impacted positively on the pupils with Autism, and the number of other pupils with…

  18. Benefits of Including Siblings in the Treatment of Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Ferraioli, Suzannah J.; Hansford, Amy; Harris, Sandra L.

    2012-01-01

    Having a brother or sister with an autism spectrum disorder (ASD) can significantly impact the life of a typically developing sibling. These relationships are generally characterized by less frequent and nurturing interactions than are evident in sibling constellations with neurotypical children or children with other developmental disabilities.…

  19. A new expanded host range of Cucurbit yellow stunting disorder virus includes three agricultural crops.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cucurbit yellow stunting disorder virus (CYSDV) was identified in the fall of 2006 affecting cucurbit production in the Imperial Valley of California, the adjacent Yuma, AZ region, as well as nearby Sonora, Mexico. There was nearly universal infection of fall melon crops in 2006 and 2007, and late,...

  20. Exploring Teachers' Strategies for Including Children with Autism Spectrum Disorder in Mainstream Classrooms

    ERIC Educational Resources Information Center

    Lindsay, Sally; Proulx, Meghann; Scott, Helen; Thomson, Nicole

    2014-01-01

    As the rates of diagnosis of autism spectrum disorder (ASD) increase and more students with ASD are enrolled in mainstream schools, educators face many challenges in teaching and managing social and behavioural development while ensuring academic success for all students. This descriptive, qualitative study, embedded within an inclusive…

  1. Including Students with Attention-Deficit/Hyperactivity Disorder in Mainstream Schools

    ERIC Educational Resources Information Center

    Humphrey, Neil

    2009-01-01

    Around 80% of pupils with attention deficit disorders are educated in mainstream schools. The difficulties relating to inattention, impulsivity and hyperactivity experienced by such pupils present mainstream educators with a unique set of challenges and opportunities. In this article, Neil Humphrey, Senior Lecturer in the Psychology of Education…

  2. Autistic Spectrum and Inclusion: Including Pupils with Autistic Spectrum Disorders in Mainstream Schools

    ERIC Educational Resources Information Center

    Humphrey, Neil

    2008-01-01

    The number of pupils with autistic spectrum disorders (ASD) being educated in mainstream schools is increasing. However, there is growing concern about their educational experiences. Research suggests that such pupils make easy targets for bullies, and are considered difficult to teach by teachers. Furthermore, pupils with ASD are more than 20…

  3. Temporomandibular joint disorder in a patient with multiple sclerosis--review of literature with a clinical report.

    PubMed

    Badel, Tomislav; Carek, Andreja; Podoreski, Dijana; Pavicin, Ivana Savić; Lovko, Sandra Kocijan

    2010-09-01

    Temporomandibular disorders are a form of musculoskeletal disorders, which reduce the function of stomatognathic system and they are related to some other diseases causing painful conditions and disorders of oral function. The aim of this paper is to describe a one year follow up clinical case of a female patient with comorbid multiple sclerosis and a relatively rare form of articular disc disorder. Primary clinical diagnostics encompassed manual methods of TMJ examination. Definite diagnosis included radiologic examination. Clinical hyperextensive condyle position was palpated bilaterally and subsequently confirmed by a functional panoramic radiograph of TMJ. The anterior displacement of disc with reduction was diagnosed by magnetic resonance and in the right joint there was a disc displacement upon excursive movement. From relevant literature, the relationship of a number of diseases that can be related to functional disorder of the orofacial system, such as multiple sclerosis, has been described from many aspects. Also, apart from the standard classification of one form of anterior displacement of the disc, made primarily by magnetic resonance, cases of disc displacement upon excursive mandibular movement can rarely be found in literature. PMID:20977121

  4. The effects of a multiple family therapy on adolescents with eating disorders: an outcome study.

    PubMed

    Gelin, Zoé; Fuso, Silvana; Hendrick, Stephan; Cook-Darzens, Solange; Simon, Yves

    2015-03-01

    Multiple Family Therapy (MFT) has gained increasing popularity in the treatment of eating disorders and many programs have been developed over the past decade. Still, there is little evidence in the literature on the effectiveness on MFT for treating eating disorders. The present study examines the effects of a particular model of Multiple Family Therapy on eating disorder symptoms, quality of life, and percentage of Expected Body Weight (%EBW) in adolescents with eating disorders (ED). Eighty-two adolescents with ED, aged between 11 and 19 years, were assessed before and after treatment using the Eating Disorders Inventory 2 (EDI-2), the Outcome Questionnaire 45 (OQ-45) and %EBW. Results showed a significant increase in %EBW between the beginning and end of treatment, with a large effect size. 52.4% of patients achieved an EBW above 85%. Symptoms relative to all EDI dimensions (except for bulimia) significantly decreased during treatment. The three dimensions related to quality of life assessment also improved over the course of MFT. At the end of treatment, 70.7% of patients had a total OQ-45 score below clinical significance. This study suggests that Multiple Family Therapy may benefit adolescents with eating disorders, with improvement on several outcome measures (%EBW, ED symptoms, and quality of life). However, the lack of a comparison group entails caution when drawing conclusions. PMID:25243337

  5. A practical approach to the diagnosis and management of sleep disorders in patients with multiple sclerosis

    PubMed Central

    Braley, Tiffany J.; Chervin, Ronald D.

    2015-01-01

    Patients with multiple sclerosis (MS) are at increased risk for comorbid sleep disturbances, which can profoundly contribute to poor functional status and fatigue. Insomnia, sleep-disordered breathing, and restless legs syndrome are among the most common sleep disorders experienced by patients with MS. Despite their impact, these underlying sleep disorders may escape routine clinical evaluations in persons with MS, thereby leading to missed opportunities to optimize functional status and quality of life in patients with MS. A practical, systematic approach to the evaluation and treatment of sleep disorders in MS, in the context of MS-specific variables that may influence risk for these conditions or response to therapy, is recommended to facilitate early diagnosis and successful treatment. This review summarizes the most common sleep disorders experienced by persons with MS, and offers a practical approach to diagnosis and management of these conditions. PMID:26600873

  6. Intellectual Disability and Multiple Co Morbid Psychiatric Disorders in a Child: A Case Report

    PubMed Central

    Gautam, Priyanka; Rathi, Anubhav

    2014-01-01

    Comorbid psychiatric Disorders are seen commonly in people with intellectual disability and in fact they are at greater risk for developing other health disorders. Most prevalent chronic health conditions in children with intellectual disability are epilepsy, cerebral palsy,anxiety disorders, sleep disorders and autism spectrum disorders. Co morbidities multiply the problem of people with intellectual impairment to a great extent and hence an accurate psychological assessment of multiple diagnoses is useful in detecting the specific underlying processes differentiating the co morbid syndrome and in planning an appropriate management and rehabilitation program. This case report is presented to emphasize the fact that though. It is common for intellectually disabled children to have other co-morbid psychiatric disorders, it is important to have accurate, suitable assessment and recording of every co-morbid disorder as it has its own implication in course and outcome of the disability in the child. A comprehensive management approach involving people from various spheres would be required to improve the quality of life and for reduction of burden of care giver.We describe a child of intellectual disability with multiple co morbidities. PMID:25584292

  7. Intellectual disability and multiple co morbid psychiatric disorders in a child: a case report.

    PubMed

    Gautam, Priyanka; Bhatia, M S; Rathi, Anubhav

    2014-11-01

    Comorbid psychiatric Disorders are seen commonly in people with intellectual disability and in fact they are at greater risk for developing other health disorders. Most prevalent chronic health conditions in children with intellectual disability are epilepsy, cerebral palsy,anxiety disorders, sleep disorders and autism spectrum disorders. Co morbidities multiply the problem of people with intellectual impairment to a great extent and hence an accurate psychological assessment of multiple diagnoses is useful in detecting the specific underlying processes differentiating the co morbid syndrome and in planning an appropriate management and rehabilitation program. This case report is presented to emphasize the fact that though. It is common for intellectually disabled children to have other co-morbid psychiatric disorders, it is important to have accurate, suitable assessment and recording of every co-morbid disorder as it has its own implication in course and outcome of the disability in the child. A comprehensive management approach involving people from various spheres would be required to improve the quality of life and for reduction of burden of care giver.We describe a child of intellectual disability with multiple co morbidities. PMID:25584292

  8. Multiple emergences of genetically diverse amphibian-infecting chytrids include a globalized hypervirulent recombinant lineage

    PubMed Central

    Farrer, Rhys A.; Weinert, Lucy A.; Bielby, Jon; Garner, Trenton W. J.; Balloux, Francois; Clare, Frances; Bosch, Jaime; Cunningham, Andrew A.; Weldon, Che; du Preez, Louis H.; Anderson, Lucy; Pond, Sergei L. Kosakovsky; Shahar-Golan, Revital; Henk, Daniel A.; Fisher, Matthew C.

    2011-01-01

    Batrachochytrium dendrobatidis (Bd) is a globally ubiquitous fungal infection that has emerged to become a primary driver of amphibian biodiversity loss. Despite widespread effort to understand the emergence of this panzootic, the origins of the infection, its patterns of global spread, and principle mode of evolution remain largely unknown. Using comparative population genomics, we discovered three deeply diverged lineages of Bd associated with amphibians. Two of these lineages were found in multiple continents and are associated with known introductions by the amphibian trade. We found that isolates belonging to one clade, the global panzootic lineage (BdGPL) have emerged across at least five continents during the 20th century and are associated with the onset of epizootics in North America, Central America, the Caribbean, Australia, and Europe. The two newly identified divergent lineages, Cape lineage (BdCAPE) and Swiss lineage (BdCH), were found to differ in morphological traits when compared against one another and BdGPL, and we show that BdGPL is hypervirulent. BdGPL uniquely bears the hallmarks of genomic recombination, manifested as extensive intergenomic phylogenetic conflict and patchily distributed heterozygosity. We postulate that contact between previously genetically isolated allopatric populations of Bd may have allowed recombination to occur, resulting in the generation, spread, and invasion of the hypervirulent BdGPL leading to contemporary disease-driven losses in amphibian biodiversity. PMID:22065772

  9. Marital and Family Therapy in the Treatment of Multiple Personality Disorder.

    ERIC Educational Resources Information Center

    Sachs, Roberta G.; And Others

    1988-01-01

    Explores marital and family therapy in treatment of Multiple Personality Disorder (MPD), discussing role of family of origin in MPD development and role of nuclear family in its perpetuation. Suggests family and marital interventions, illustrating them with case examples. Proposes involving MPD client in marital or family therapy, in addition to…

  10. Redefining the maximum sustainable yield for the Schaefer population model including multiplicative environmental noise.

    PubMed

    Bousquet, Nicolas; Duchesne, Thierry; Rivest, Louis-Paul

    2008-09-01

    The focus of this article is to investigate the biological reference points, such as the maximum sustainable yield (MSY), in a common Schaefer (logistic) surplus production model in the presence of a multiplicative environmental noise. This type of model is used in fisheries stock assessment as a first-hand tool for biomass modelling. Under the assumption that catches are proportional to the biomass, we derive new conditions on the environmental noise distribution such that stationarity exists and extinction is avoided. We then get new explicit results about the stationary behavior of the biomass distribution for a particular specification of the noise, namely the biomass distribution itself and a redefinition of the MSY and related quantities that now depend on the value of the variance of the noise. Consequently, we obtain a more precise vision of how less optimistic the stochastic version of the MSY can be than the traditionally used (deterministic) MSY. In addition, we give empirical conditions on the error variance to approximate our specific noise by a lognormal noise, the latter being more natural and leading to easier inference in this context. These conditions are mild enough to make the explicit results of this paper valid in a number of practical applications. The outcomes of two case-studies about northwest Atlantic haddock [Spencer, P.D., Collie, J.S., 1997. Effect of nonlinear predation rates on rebuilding the Georges Bank haddock (Melanogrammus aeglefinus) stock. Can. J. Fish. Aquat. Sci. 54, 2920-2929] and South Atlantic albacore tuna [Millar, R.B., Meyer, R., 2000. Non-linear state space modelling of fisheries biomass dynamics by using Metropolis-Hastings within-Gibbs sampling. Appl. Stat. 49, 327-342] are used to illustrate the impact of our results in bioeconomic terms. PMID:18571675

  11. Identification of Multiple Novel Viruses, Including a Parvovirus and a Hepevirus, in Feces of Red Foxes

    PubMed Central

    van der Giessen, Joke; Haagmans, Bart L.; Osterhaus, Albert D. M. E.; Smits, Saskia L.

    2013-01-01

    Red foxes (Vulpes vulpes) are the most widespread members of the order of Carnivora. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified. PMID:23616657

  12. Rethinking the comparison of borderline personality disorder and multiple personality disorder.

    PubMed

    Marmer, S S; Fink, D

    1994-12-01

    This article has made a number of points that assert what is today a minority position within the fields of MPD/DID and BPD. We hope our views will stimulate attempts by others to rethink their positions and test our assertions, so that issues surrounding these two disorders can be sharpened. For the sake of the clarity of future work, we summarize in outline form the essence of our viewpoint. 1. BPD and MPD/DID have similar appearing symptoms, such as identity problems, unstable affect modulation, self-destructive behaviors, chaotic impulse control, and troubled interpersonal relationships, but they have decisive differences in underlying dynamics, process, and structure. 2. DSM tends to blur these two disorders by its emphasis on phenomenology over inner structure, thus fostering misleading conclusions when DSM criteria are used to test for comorbidity or overlap between BPD and MPD/DID. 3. BPD and MPD/DID are both described dynamically as using the defense of splitting, but we contend that the splitting in each disorder is fundamentally different from the splitting in the other. BPD uses a polarization form of splitting, whereas MPD/DID uses ego splitting or identity division. 4. Both disorders partake in the process of dissociation, but the quality of dissociation in BPD is a "low-tech" spaced out type, whereas that of MPD/DID is a "high-tech" waking dream. 5. BPD structure is also "low tech," with polarization of self, object, and relationship. MPD/DID structure is "high tech," with heavily symbolic, highly nuanced variations of self, object, and relationship. 6. Although both conditions have etiologic elements of trauma, BPD has a larger degree of developmental deficiency, with a failure to complete the task of entering a repression hierarchy of defenses. MPD/DID, by use of primary process-linked symbolic dissociation, is able to continue development to the repression hierarchy, although at a profound cost of simultaneous suspension of reality testing. BPD patients suffer from the rigid use of too few defenses; MPD/DID patients suffer from the obsolete use of too many defenses. 7. BPD patients grow up in homes in which overtly expressed aggression is more tolerated, or at least more openly experienced. MPD/DID patients grow up in homes in which the fact of aggression is kept a secret. This has consequences for the formation of psychic structure in each disorder.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7877901

  13. Analytical model for investigation of interior noise characteristics in aircraft with multiple propellers including synchrophasing

    NASA Astrophysics Data System (ADS)

    Fuller, C. R.

    1986-08-01

    A simplified analytical model of transmission of noise into the interior of propeller-driven aircraft has been developed. The analysis includes directivity and relative phase effects of the propeller noise sources, and leads to a closed form solution for the coupled motion between the interior and exterior fields via the shell (fuselage) vibrational response. Various situations commonly encountered in considering sound transmission into aircraft fuselages are investigated analytically and the results obtained are compared to measurements in real aircraft. In general the model has proved successful in identifying basic mechanisms behind noise transmission phenomena.

  14. Transitions from order to disorder in multiple dark and multiple dark-bright soliton atomic clouds

    SciTech Connect

    Wang, Wenlong; Kevrekidis, P. G.

    2015-03-09

    We have performed a systematic study quantifying the variation of solitary wave behavior from that of an ordered cloud resembling a crystalline configuration to that of a disordered state that can be characterized as a soliton gas. As our illustrative examples, we use both one-component, as well as two-component, one-dimensional atomic gases very close to zero temperature, where in the presence of repulsive interatomic interactions and of a parabolic trap, a cloud of dark (dark-bright) solitons can form in the one- (two-) component system. We corroborate our findings through three distinct types of approaches, namely a Gross-Pitaevskii type of partial differential equation, particle-based ordinary differential equations describing the soliton dynamical system, and Monte Carlo simulations for the particle system. In addition, we define an empirical order parameter to characterize the order of the soliton lattices and study how this changes as a function of the strength of the thermally (i.e., kinetically) induced perturbations. As may be anticipated by the one-dimensional nature of our system, the transition from order to disorder is gradual without, apparently, a genuine phase transition ensuing in the intermediate regime.

  15. Transitions from order to disorder in multiple dark and multiple dark-bright soliton atomic clouds

    DOE PAGESBeta

    Wang, Wenlong; Kevrekidis, P. G.

    2015-03-09

    We have performed a systematic study quantifying the variation of solitary wave behavior from that of an ordered cloud resembling a “crystalline” configuration to that of a disordered state that can be characterized as a soliton “gas.” As our illustrative examples, we use both one-component, as well as two-component, one-dimensional atomic gases very close to zero temperature, where in the presence of repulsive interatomic interactions and of a parabolic trap, a cloud of dark (dark-bright) solitons can form in the one- (two-) component system. We corroborate our findings through three distinct types of approaches, namely a Gross-Pitaevskii type of partialmore » differential equation, particle-based ordinary differential equations describing the soliton dynamical system, and Monte Carlo simulations for the particle system. In addition, we define an “empirical” order parameter to characterize the order of the soliton lattices and study how this changes as a function of the strength of the “thermally” (i.e., kinetically) induced perturbations. As may be anticipated by the one-dimensional nature of our system, the transition from order to disorder is gradual without, apparently, a genuine phase transition ensuing in the intermediate regime.« less

  16. Transitions from order to disorder in multiple dark and multiple dark-bright soliton atomic clouds

    SciTech Connect

    Wang, Wenlong; Kevrekidis, P. G.

    2015-03-09

    We have performed a systematic study quantifying the variation of solitary wave behavior from that of an ordered cloud resembling a “crystalline” configuration to that of a disordered state that can be characterized as a soliton “gas.” As our illustrative examples, we use both one-component, as well as two-component, one-dimensional atomic gases very close to zero temperature, where in the presence of repulsive interatomic interactions and of a parabolic trap, a cloud of dark (dark-bright) solitons can form in the one- (two-) component system. We corroborate our findings through three distinct types of approaches, namely a Gross-Pitaevskii type of partial differential equation, particle-based ordinary differential equations describing the soliton dynamical system, and Monte Carlo simulations for the particle system. In addition, we define an “empirical” order parameter to characterize the order of the soliton lattices and study how this changes as a function of the strength of the “thermally” (i.e., kinetically) induced perturbations. As may be anticipated by the one-dimensional nature of our system, the transition from order to disorder is gradual without, apparently, a genuine phase transition ensuing in the intermediate regime.

  17. Statistical Analysis of EMIC Waves in Multiple Component Plasma Including Heavy Ions

    NASA Astrophysics Data System (ADS)

    Matsuda, S.; Kasahara, Y.; Goto, Y.

    2013-12-01

    It is well known that Earth's radiation belts are located around geomagnetic equator, where wide ranges of energetic particles from several hundred keV to several tens MeV are contained. According to the recent study, it is suggested that ELF/VLF waves such as EMIC waves and chorus emissions deeply contribute to the generation and loss mechanism of relativistic electrons in the radiation belt. The ERG mission[1] is expected to provide important clues for solving plasma dynamics in the Earth's radiation belts by means of integrated observation of wide energy range of plasma particles and high resolution plasma waves. On the other hand, long-term observation data which covers over 2 cycles of solar activity obtained by the Akebono satellite is very valuable to work out the strategy of the ERG mission. The ELF receiver, which is a sub-system of the VLF instruments onboard Akebono, measures waveforms below 50 Hz for one component of electric field and three components of magnetic field, or waveforms below 100 Hz for one component of electric and magnetic field, respectively. It was reported that ion cyclotron waves were observed near magnetic equator by the receiver[2]. In our previous study[3], we introduced four events of characteristic EMIC waves observed by Akebono in April, 1989. These waves have sudden decrease of intensity just above half of proton cyclotron frequency changing along the trajectories of Akebono. Comparing the observed data with the dispersion relation in multiple species of ions under cold plasma approximation, we demonstrate that a few percent of 'M / Z = 2 ions (M = mass of ions, Z = charge of ions)' such as alpha particles (He++) or deuterons (D+) cause such characteristic attenuation of EMIC at lower hybrid frequency. In the present study, we performed polarization analysis and direction finding of the waves. It was found that these EMIC waves were left-handed polarized in the higher frequency part, while the polarization gradually changes to linear and finally to right-handed in the lower frequency part of the waves. In general, cross-over frequency, at which EMIC wave undergoes polarization reversal, appears if more than two kinds of ions are coexisted in the plasma. It was demonstrated that the observed cross-over frequencies were a little higher than the ones where sudden attenuation occurring at approximately half of proton cyclotron frequency. The wave normal vectors were analyzed using Means' method[4]. It was found that the wave normal directions of these EMIC waves were close to 90 degrees against the geomagnetic field lines. Consequently, these results strongly support existence of 'M / Z = 2 ions' during this event. In other words, dispersion relation does not satisfy the observed EMIC wave if we only consider major ion constituents in the plasma. In order to investigate the generality of such minor ion existence, we picked up approximately 100 characteristic events from long-term observation data obtained by Akebono. We will also discuss more detailed analysis about several events, as well as statistical data analysis.

  18. The product of microbial uranium reduction includes multiple species with U(IV)-phosphate coordination

    NASA Astrophysics Data System (ADS)

    Alessi, Daniel S.; Lezama-Pacheco, Juan S.; Stubbs, Joanne E.; Janousch, Markus; Bargar, John R.; Persson, Per; Bernier-Latmani, Rizlan

    2014-04-01

    Until recently, the reduction of U(VI) to U(IV) during bioremediation was assumed to produce solely the sparingly soluble mineral uraninite, UO2(s). However, results from several laboratories reveal other species of U(IV) characterized by the absence of an EXAFS U-U pair correlation (referred to here as noncrystalline U(IV)). Because it lacks the crystalline structure of uraninite, this species is likely to be more labile and susceptible to reoxidation. In the case of single species cultures, analyses of U extended X-ray fine structure (EXAFS) spectra have previously suggested U(IV) coordination to carboxyl, phosphoryl or carbonate groups. In spite of this evidence, little is understood about the species that make up noncrystalline U(IV), their structural chemistry and the nature of the U(IV)-ligand interactions. Here, we use infrared spectroscopy (IR), uranium LIII-edge X-ray absorption spectroscopy (XAS), and phosphorus K-edge XAS analyses to constrain the binding environments of phosphate and uranium associated with Shewanella oneidensis MR-1 bacterial cells. Systems tested as a function of pH included: cells under metal-reducing conditions without uranium, cells under reducing conditions that produced primarily uraninite, and cells under reducing conditions that produced primarily biomass-associated noncrystalline U(IV). P X-ray absorption near-edge structure (XANES) results provided clear and direct evidence of U(IV) coordination to phosphate. Infrared (IR) spectroscopy revealed a pronounced perturbation of phosphate functional groups in the presence of uranium. Analysis of these data provides evidence that U(IV) is coordinated to a range of phosphate species, including monomers and polymerized networks. U EXAFS analyses and a chemical extraction measurements support these conclusions. The results of this study provide new insights into the binding mechanisms of biomass-associated U(IV) species which in turn sheds light on the mechanisms of biological U(VI) reduction.

  19. [A Case of Multiple HCC with Vp2 and Vv3 Invasion Controlled by Multidisciplinary Treatment Including Surgery].

    PubMed

    Deguchi, Sota; Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Yamamoto, Satoshi; Murata, Akihiro; Nakajima, Takayoshi; Sakae, Masayuki; Tachimori, Akiko; Tamamori, Yutaka; Yamamoto, Atsushi; Inoue, Toru; Yamashita, Yoshito; Nishiguchi, Yukio

    2015-11-01

    The prognosis of HCC with vascular invasion is dismal, but surgery is elected when the hepatic reserve is adequate. The case involved a 68-year-old male HCV carrier. A 10 cm diameter tumor occupying the central 2 segments of the liver and liver metastasis in the left lobe were detected. The patient was diagnosed with multiple HCC with severe vascular invasion of Vp2 and Vv3. The tumor shrunk dramatically after starting HAIC therapy with cisplatin and oral administration of sorafenib. A laparoscopic partial hepatectomy was performed for the viable lesion. The tumor showed almost complete coagulative necrosis. Multiple hepatic metastases were found 4 months after surgery, but the tumor was under control at 25 months after the first HAIC due to HAIC, oral administration of sorafenib, and RFA. An improved prognosis for multiple HCC with severe vascular invasion can be expected by performing multidisciplinary treatments including surgery. PMID:26805192

  20. Multiple trapping on a comb structure as a model of electron transport in disordered nanostructured semiconductors

    SciTech Connect

    Sibatov, R. T. Morozova, E. V.

    2015-05-15

    A model of dispersive transport in disordered nanostructured semiconductors has been proposed taking into account the percolation structure of a sample and joint action of several mechanisms. Topological and energy disorders have been simultaneously taken into account within the multiple trapping model on a comb structure modeling the percolation character of trajectories. The joint action of several mechanisms has been described within random walks with a mixture of waiting time distributions. Integral transport equations with fractional derivatives have been obtained for an arbitrary density of localized states. The kinetics of the transient current has been calculated within the proposed new model in order to analyze time-of-flight experiments for nanostructured semiconductors.

  1. Multiple trapping on a comb structure as a model of electron transport in disordered nanostructured semiconductors

    NASA Astrophysics Data System (ADS)

    Sibatov, R. T.; Morozova, E. V.

    2015-05-01

    A model of dispersive transport in disordered nanostructured semiconductors has been proposed taking into account the percolation structure of a sample and joint action of several mechanisms. Topological and energy disorders have been simultaneously taken into account within the multiple trapping model on a comb structure modeling the percolation character of trajectories. The joint action of several mechanisms has been described within random walks with a mixture of waiting time distributions. Integral transport equations with fractional derivatives have been obtained for an arbitrary density of localized states. The kinetics of the transient current has been calculated within the proposed new model in order to analyze time-of-flight experiments for nanostructured semiconductors.

  2. A multiple deficit model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for shared cognitive deficits

    PubMed Central

    McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

    2010-01-01

    Background This study tests a multiple cognitive deficit model of Reading Disability (RD), Attention-Deficit/Hyperactivity Disorder (ADHD), and their comorbidity. Methods A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique predictor of RD and response inhibition as a unique predictor of ADHD. Processing speed, naming speed, and verbal working memory were modeled as potential shared cognitive deficits. Results Model fit indices from the SEM indicated satisfactory fit. Closer inspection of the path weights revealed that processing speed was the only cognitive variable with significant unique relationships to RD and ADHD dimensions, particularly inattention. Moreover, the significant correlation between reading and inattention was reduced to nonsignificance when processing speed was included in the model, suggesting that processing speed primarily accounted for the phenotypic correlation (or comorbidity) between reading and inattention. Conclusions This study illustrates the power of a multiple deficit approach to complex developmental disorders and psychopathologies, particularly for exploring comorbidities. The theoretical role of processing speed in the developmental pathways of RD and ADHD and directions for future research are discussed. PMID:21126246

  3. Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders

    PubMed Central

    2014-01-01

    Background Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one’s personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. Methods We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 ± 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Results Among participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F = 9.2; p = .003) and Beauty in Life (F = 6.0; p = .015) were experienced significantly more often by women than men. However, the experience of Awe did not differ between women and men (F = 2.2; n.s.). In contrast to our hypothesis, Gratitude/Awe cannot explain any relevant variance in patients’ life satisfaction (R2 = .04). Regression analyses (R2 = .42) revealed that Gratitude/Awe can be predicted best by a person’s engagement in religious practices, followed by other forms of spiritual practices and life satisfaction. Female gender was a weak predictor and underlying disease showed no effect. Conclusions Gratitude/Awe could be regarded as a life orientation towards noticing and appreciating the positive in life - despite the symptoms of disease. Positive spirituality/religiosity seems to be a source of gratitude and appreciation in life, whereas patients with neither spiritual nor religious sentiments (R-S-) seem to have a lower awareness for these feelings. PMID:24779860

  4. Quantification of Electromyographic Activity During REM Sleep in Multiple Muscles in REM Sleep Behavior Disorder

    PubMed Central

    Frauscher, Birgit; Iranzo, Alex; Högl, Birgit; Casanova-Molla, Jordi; Salamero, Manel; Gschliesser, Viola; Tolosa, Eduardo; Poewe, Werner; Santamaria, Joan

    2008-01-01

    Study Objectives: The aim of our study was to determine which muscle or combination of muscles (either axial or limb muscles, lower or upper limb muscles, or proximal or distal limb muscles) provides the highest rates of rapid eye movement (REM) sleep phasic electromyographic (EMG) activity seen in patients with REM sleep behavior disorder (RBD). Setting: Two university hospital sleep disorders centers. Participants: Seventeen patients with idiopathic RBD (n = 8) and RBD secondary to Parkinson disease (n = 9). Interventions: Not applicable. Measurements and Results: Patients underwent polysomnography, including EMG recording of 13 different muscles. Phasic EMG activity in REM sleep was quantified for each muscle separately. A mean of 1459.6 ± 613.8 three-second REM sleep mini-epochs were scored per patient. Mean percentages of phasic EMG activity were mentalis (42 ± 19), flexor digitorum superficialis (29 ± 13), extensor digitorum brevis (23 ± 12), abductor pollicis brevis (22 ± 11), sternocleidomastoid (22 ± 12), deltoid (19 ± 11), biceps brachii (19 ± 11), gastrocnemius (18 ± 9), tibialis anterior (right, 17 ± 12; left, 16 ± 10), rectus femoris (left, 11 ± 6; right, 9 ± 6), and thoraco-lumbar paraspinal muscles (6 ± 5). The mentalis muscle provided significantly higher rates of excessive phasic EMG activity than all other muscles but only detected 55% of all the mini-epochs with phasic EMG activity. Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles detected 82% of all mini-epochs containing phasic EMG activity. This combination provided higher rates of EMG activity than any other 3-muscle combination. Excessive phasic EMG activity was more frequent in distal than in proximal muscles, both in upper and lower limbs. Conclusion: Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles provided the highest rates of REM sleep phasic EMG activity in subjects with RBD. Citation: Frauscher B; Iranzo A; Högl B; Casanova-Molla J; Salamero M; Gschliesser V; Tolosa E; Poewe W; Santamaria J;. Quantification of electromyographic activity during REM sleep in multiple muscles in REM sleep behavior disorder. SLEEP 2008;31(5):724-731. PMID:18517042

  5. Dubowitz Syndrome Is a Complex Comprised of Multiple, Genetically Distinct and Phenotypically Overlapping Disorders

    PubMed Central

    Stewart, Douglas R.; Pemov, Alexander; Johnston, Jennifer J.; Sapp, Julie C.; Yeager, Meredith; He, Ji; Boland, Joseph F.; Burdett, Laurie; Brown, Christina; Gatti, Richard A.; Alter, Blanche P.; Biesecker, Leslie G.; Savage, Sharon A.

    2014-01-01

    Dubowitz syndrome is a rare disorder characterized by multiple congenital anomalies, cognitive delay, growth failure, an immune defect, and an increased risk of blood dyscrasia and malignancy. There is considerable phenotypic variability, suggesting genetic heterogeneity. We clinically characterized and performed exome sequencing and high-density array SNP genotyping on three individuals with Dubowitz syndrome, including a pair of previously-described siblings (Patients 1 and 2, brother and sister) and an unpublished patient (Patient 3). Given the siblings' history of bone marrow abnormalities, we also evaluated telomere length and performed radiosensitivity assays. In the siblings, exome sequencing identified compound heterozygosity for a known rare nonsense substitution in the nuclear ligase gene LIG4 (rs104894419, NM_002312.3:c.2440C>T) that predicts p.Arg814X (MAF:0.0002) and an NM_002312.3:c.613delT variant that predicts a p.Ser205Leufs*29 frameshift. The frameshift mutation has not been reported in 1000 Genomes, ESP, or ClinSeq. These LIG4 mutations were previously reported in the sibling sister; her brother had not been previously tested. Western blotting showed an absence of a ligase IV band in both siblings. In the third patient, array SNP genotyping revealed a de novo ∼3.89 Mb interstitial deletion at chromosome 17q24.2 (chr 17:62,068,463–65,963,102, hg18), which spanned the known Carney complex gene PRKAR1A. In all three patients, a median lymphocyte telomere length of ≤1st centile was observed and radiosensitivity assays showed increased sensitivity to ionizing radiation. Our work suggests that, in addition to dyskeratosis congenita, LIG4 and 17q24.2 syndromes also feature shortened telomeres; to confirm this, telomere length testing should be considered in both disorders. Taken together, our work and other reports on Dubowitz syndrome, as currently recognized, suggest that it is not a unitary entity but instead a collection of phenotypically similar disorders. As a clinical entity, Dubowitz syndrome will need continual re-evaluation and re-definition as its constituent phenotypes are determined. PMID:24892279

  6. Diagnostic rules for children with PDD-NOS and multiple complex developmental disorder.

    PubMed

    Buitelaar, J K; van der Gaag, R J

    1998-09-01

    This study was designed to examine the classification performance of diagnostic rules for pervasive developmental disorder not otherwise specified (PDD-NOS) and multiple complex developmental disorder (McDD), with clinical diagnosis as the gold standard. McDD is an heuristic concept of a developmental disorder characterised by social impairments, affective dysregulation, and thought disturbance. Detailed information on the symptoms, reliably extracted from the charts of 103 children with PDD-NOS and McDD, 32 with autistic disorder, and 96 with non-PDD disorders, was used to determine the presence of the DSM-IV criteria of autistic disorder and the criteria of McDD. A scoring rule for PDD-NOS based on a short set of seven DSM-IV criteria with a cut-off point of three items and one social interaction item set as mandatory had the best balance between high sensitivity and high specificity. The most effective and simple rule based on McDD criteria had a cut-off of three items, out of six items of anxieties and thought disturbance. PMID:9758199

  7. Disorder-induced incoherent scattering losses in photonic crystal waveguides: Bloch mode reshaping, multiple scattering, and breakdown of the Beer-Lambert law

    NASA Astrophysics Data System (ADS)

    Patterson, M.; Hughes, S.; Schulz, S.; Beggs, D. M.; White, T. P.; O'Faolain, L.; Krauss, T. F.

    2009-11-01

    Through a combined theoretical and experimental study of disorder-induced incoherent scattering losses in slow-light photonic crystal slab waveguides, we show the importance of Bloch mode reshaping and multiple scattering. We describe a convenient and fully three-dimensional theoretical treatment of disorder-induced extrinsic scattering, including the calculation of backscatter and out-of-plane losses per unit cell, and the extrapolation of the unit-cell loss to the loss for an entire disordered waveguide. The theoretical predictions, which are also compared with recent measurements on dispersion engineered silicon waveguides, demonstrate the failure of the Beer-Lambert law due to multiple scattering. We also explain why the previously assumed group velocity scalings of disorder-induced loss break down in general.

  8. Ecosystemic needs assessment for children with developmental coordination disorder in elementary school: multiple case studies.

    PubMed

    Jasmin, Emmanuelle; Tétreault, Sylvie; Joly, Jacques

    2014-11-01

    This study explored the needs of children with developmental coordination disorder (DCD) from an ecosystemic viewpoint as part of a theory-driven program evaluation process. A multiple case study needs assessment was conducted. Participants included ten children with DCD, their parents (n = 12), teachers (n = 9), and service providers (n = 6). Data collection involved semi-structured interviews, validated questionnaires, and a review of the children's records. The results support the relevance of using an ecosystemic model to assess the needs of children with DCD in their life and social contexts. More specifically, the results highlight the need to provide additional services at school, such as occupational therapy and special education, as well as information and training regarding DCD for parents and teachers. The results also point to the relevant variables to consider in an intervention program based on theory-driven evaluations. This study shows how employing an ecosystemic frame of reference provides a better understanding of the needs of children with DCD. Future research should document the ecosystemic profiles and evolution of the needs of children with DCD with a larger sample from diverse socioeconomic backgrounds using a longitudinal study design. PMID:24649977

  9. Speech disorders reflect differing pathophysiology in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy.

    PubMed

    Rusz, Jan; Bonnet, Cecilia; Klempíř, Jiří; Tykalová, Tereza; Baborová, Eva; Novotný, Michal; Rulseh, Aaron; Růžička, Evžen

    2015-01-01

    Although speech disorder is frequently an early and prominent clinical feature of Parkinson's disease (PD) as well as atypical parkinsonian syndromes (APS) such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), there is a lack of objective and quantitative evidence to verify whether any specific speech characteristics allow differentiation between PD, PSP and MSA. Speech samples were acquired from 77 subjects including 15 PD, 12 PSP, 13 MSA and 37 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 16 speech dimensions. Dysarthria was uniformly present in all parkinsonian patients but was more severe in PSP and MSA than in PD. Whilst PD speakers manifested pure hypokinetic dysarthria, ataxic components were more affected in MSA whilst PSP subjects demonstrated severe deficits in hypokinetic and spastic elements of dysarthria. Dysarthria in PSP was dominated by increased dysfluency, decreased slow rate, inappropriate silences, deficits in vowel articulation and harsh voice quality whereas MSA by pitch fluctuations, excess intensity variations, prolonged phonemes, vocal tremor and strained-strangled voice quality. Objective speech measurements were able to discriminate between APS and PD with 95% accuracy and between PSP and MSA with 75% accuracy. Dysarthria severity in APS was related to overall disease severity (r = 0.54, p = 0.006). Dysarthria with various combinations of hypokinetic, spastic and ataxic components reflects differing pathophysiology in PD, PSP and MSA. Thus, motor speech examination may provide useful information in the evaluation of these diseases with similar manifestations. PMID:25683763

  10. Systems of Selves: the Construction of Meaning in Multiple Personality Disorder

    NASA Astrophysics Data System (ADS)

    Hughes, Dureen Jean

    Current models for understanding both Multiple Personality Disorder and human mentation in general are both linear in nature and self-perpetuating insofar as most research in this area has been informed and shaped by extant psychological concepts, paradigms and methods. The research for this dissertation made use of anthropological concepts and methods in an attempt to gain a richer understanding of both multiple personality and fundamental universal processes of the mind. Intensive fieldwork using in-depth, open-ended interviewing techniques was conducted with people diagnosed with Multiple Personality Disorder with the purpose of mapping their personality systems in order to discover the nature of the relationships between the various alternate personalities and subsystems comprising the overall personality systems. These data were then analyzed in terms of dynamical systems theory ("Chaos Theory") as a way of understanding various phenomena of multiple personality disorder as well as the overall structure of each system. It was found that the application of the formal characteristics of nonlinear models and equations to multiple personality systems provided a number of new perspectives on mental phenomena. The underlying organizational structure of multiple personality systems can be understood as a phenomenon of spontaneous self-organization in far-from -equilibrium states which characterizes dissipative structures. Chaos Theory allows the perspective that the nature of the process of the self and the nature of relationship are one and the same, and that both can be conceived as ideas in struggle at a fractal boundary. Further, such application makes it possible to postulate an iterative process which would have as one of its consequences the formation of a processural self who is conscious of self as separate self. Finally, given that the iterative application of a few simple rules (or instructions) can result in complex systems, an attempt was made to discern what the rules pertaining to human mentation might be.

  11. [Therapeutic indications in symptomatic cognitive and psychopathological disorders in multiple sclerosis].

    PubMed

    Lebrun, C

    2001-09-01

    Cognitive impairment and psychiatric disorders occur in about 60 p. cent of multiple sclerosis patients. In general, impairment develops in established cases, although it can present early in the disease course. The pattern of neuropsychological deficits is characterized by deficits in attention, memory and executive functions; No specific treatment seems to be effective in cognitive impairment but appropriate strategies could limit the negative impact on this disease. Depressive states are twice frequent and usual antidepressant drugs seems to demonstrate some efficacy. PMID:11787341

  12. An olfactory-limbic model of multiple chemical sensitivity syndrome: Possible relationships to kindling and affective spectrum disorders

    SciTech Connect

    Bell, I.R.; Miller, C.S.; Schwartz, G.E. )

    1992-08-01

    This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. 170 refs.

  13. Characteristics of first suicide attempts in single versus multiple suicide attempters with bipolar disorder.

    PubMed

    Michaelis, Benjamin H; Goldberg, Joseph F; Singer, Tara M; Garno, Jessica L; Ernst, Carrie L; Davis, Glen P

    2003-01-01

    Although suicidality remains highly prevalent among patients with bipolar disorder, little research exists examining the characteristics of successive attempts among individuals who make and survive a first suicide attempt. We compared bipolar subjects with a history of one suicide attempt to those with multiple attempts and assessed demographic characteristics, family histories, psychopathology, and clinical dimensions of suicidal behavior. Fifty-two DSM-IV bipolar patients (age 21 to 74 years) with a history of at least one suicide attempt were consecutively evaluated in the Bipolar Disorders Research Clinic of the New York Presbyterian Hospital. Circumstances surrounding each lifetime suicide attempt were assessed by direct interviews, questionnaires, and chart reviews along with family psychiatric histories, substance abuse histories, current psychopathology, and features of impulsivity and aggression. Multiple suicide attempts occurred in approximately two thirds of the study group. Single attempters were significantly more likely than multiple attempters to show high seriousness of intent at their first attempt (OR = 0.65, 95% CI = 0.43 to 0.99), and tended to be less likely than multiple attempters to exhibit mixed states at their first attempt (OR = 0.54, 95% CI = 0.28 to 1.01). Seriousness of intent was consistent across the first and second attempts (r =.48, P <.01) and second and third attempts (r =.74, P <.05). Single and multiple attempters differed in no other clinical or demographic characteristics studied. We conclude that multiple suicide attempts are common among bipolar patients. Those who survive an initial suicide attempt involving high seriousness of intent appear less likely than those with low intent to make subsequent attempts. Consequently, single attempters may represent a group more closely resembling those who complete suicide on a first attempt, in terms of the risk for death associated with their first attempt. However, multiple suicide attempts among bipolar patients are not necessarily associated with a higher risk for lethality in first suicide attempt survivors. PMID:12524631

  14. Shift, Interrupted: Strategies for Managing Difficult Patients Including Those with Personality Disorders and Somatic Symptoms in the Emergency Department.

    PubMed

    Moukaddam, Nidal; AufderHeide, Erin; Flores, Araceli; Tucci, Veronica

    2015-11-01

    Difficult patients are often those who present with a mix of physical and psychiatric symptoms, and seem refractory to usual treatments or reassurance. such patients can include those with personality disorders, those with somatization symptoms; they can come across as entitled, drug-seeking, manipulative, or simply draining to the provider. Such patients are often frequent visitors to Emergency Departments. Other reasons for difficult encounters could be rooted in provider bias or countertransference, rather than sole patient factors. Emergency providers need to have high awareness of these possibilities, and be prepared to manage such situations, otherwise workup can be sub-standard and dangerous medical mistakes can be made. PMID:26493524

  15. Childhood apraxia of speech and multiple phonological disorders in Cairo-Egyptian Arabic speaking children: language, speech, and oro-motor differences.

    PubMed

    Aziz, Azza Adel; Shohdi, Sahar; Osman, Dalia Mostafa; Habib, Emad Iskander

    2010-06-01

    Childhood apraxia of speech is a neurological childhood speech-sound disorder in which the precision and consistency of movements underlying speech are impaired in the absence of neuromuscular deficits. Children with childhood apraxia of speech and those with multiple phonological disorder share some common phonological errors that can be misleading in diagnosis. This study posed a question about a possible significant difference in language, speech and non-speech oral performances between children with childhood apraxia of speech, multiple phonological disorder and normal children that can be used for a differential diagnostic purpose. 30 pre-school children between the ages of 4 and 6 years served as participants. Each of these children represented one of 3 possible subject-groups: Group 1: multiple phonological disorder; Group 2: suspected cases of childhood apraxia of speech; Group 3: control group with no communication disorder. Assessment procedures included: parent interviews; testing of non-speech oral motor skills and testing of speech skills. Data showed that children with suspected childhood apraxia of speech showed significantly lower language score only in their expressive abilities. Non-speech tasks did not identify significant differences between childhood apraxia of speech and multiple phonological disorder groups except for those which required two sequential motor performances. In speech tasks, both consonant and vowel accuracy were significantly lower and inconsistent in childhood apraxia of speech group than in the multiple phonological disorder group. Syllable number, shape and sequence accuracy differed significantly in the childhood apraxia of speech group than the other two groups. In addition, children with childhood apraxia of speech showed greater difficulty in processing prosodic features indicating a clear need to address these variables for differential diagnosis and treatment of children with childhood apraxia of speech. PMID:20202694

  16. Connectivity mapping using a combined gene signature from multiple colorectal cancer datasets identified candidate drugs including existing chemotherapies

    PubMed Central

    2015-01-01

    Background While the discovery of new drugs is a complex, lengthy and costly process, identifying new uses for existing drugs is a cost-effective approach to therapeutic discovery. Connectivity mapping integrates gene expression profiling with advanced algorithms to connect genes, diseases and small molecule compounds and has been applied in a large number of studies to identify potential drugs, particularly to facilitate drug repurposing. Colorectal cancer (CRC) is a commonly diagnosed cancer with high mortality rates, presenting a worldwide health problem. With the advancement of high throughput omics technologies, a number of large scale gene expression profiling studies have been conducted on CRCs, providing multiple datasets in gene expression data repositories. In this work, we systematically apply gene expression connectivity mapping to multiple CRC datasets to identify candidate therapeutics to this disease. Results We developed a robust method to compile a combined gene signature for colorectal cancer across multiple datasets. Connectivity mapping analysis with this signature of 148 genes identified 10 candidate compounds, including irinotecan and etoposide, which are chemotherapy drugs currently used to treat CRCs. These results indicate that we have discovered high quality connections between the CRC disease state and the candidate compounds, and that the gene signature we created may be used as a potential therapeutic target in treating the disease. The method we proposed is highly effective in generating quality gene signature through multiple datasets; the publication of the combined CRC gene signature and the list of candidate compounds from this work will benefit both cancer and systems biology research communities for further development and investigations. PMID:26356760

  17. Mental Disorders

    MedlinePlus

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play ...

  18. Use of the mTOR inhibitor everolimus in a patient with multiple manifestations of tuberous sclerosis complex including epilepsy

    PubMed Central

    Wheless, James W.

    2015-01-01

    Tuberous sclerosis complex (TSC) is a genetic disease in which overactivation of mechanistic target of rapamycin (mTOR) signaling leads to the growth of benign hamartomas in multiple organs, including the brain, and is associated with a high rate of epilepsy and neurological deficits. The mTOR inhibitor everolimus has been used in the treatment of subependymal giant cell astrocytomas and renal angiomyolipomas in patients with TSC. This article describes the case of a 13-year-old girl with TSC-associated epilepsy with refractory generalized seizures who initiated treatment with everolimus and experienced subsequent improvement in several TSC manifestations, including a reduction in seizure frequency from clusters of two or three daily to one every 2 to 4 weeks after 1.5 years of treatment. PMID:26543807

  19. Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Anxiety in Children : A Multiple Baseline Design Analysis

    ERIC Educational Resources Information Center

    Jarrett, Matthew A.; Ollendick, Thomas H.

    2012-01-01

    Objective: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. Method: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety

  20. Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Anxiety in Children : A Multiple Baseline Design Analysis

    ERIC Educational Resources Information Center

    Jarrett, Matthew A.; Ollendick, Thomas H.

    2012-01-01

    Objective: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. Method: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety…

  1. Effects of multiple forms of childhood abuse and adult sexual assault on current eating disorder symptoms.

    PubMed

    Fischer, Sarah; Stojek, Monika; Hartzell, Erin

    2010-08-01

    The objective of this study is to examine the effect of recent adult sexual assault on current eating disorder symptoms when controlling for the effects of multiple forms of childhood abuse. A total of 489 undergraduate women completed the Eating Disorder Examination-Questionnaire, and surveys regarding childhood abuse and sexual assault that had occurred in the previous three months. Approximately 30% of the sample indicated recent unwanted sexual experiences. Childhood emotional abuse contributed unique variance to the prediction of current ED symptoms, but sexual and physical abuse did not. Recent sexual assault contributed additional unique variance to current ED symptoms when controlling for childhood abuse, thus both emotional abuse in childhood and sexual assault in adulthood contributed unique variance to ED symptoms. PMID:20434068

  2. Sensory and sensorimotor gating in children with multiple complex developmental disorders (MCDD) and autism.

    PubMed

    Oranje, Bob; Lahuis, Bertine; van Engeland, Herman; Jan van der Gaag, Rutger; Kemner, Chantal

    2013-04-30

    Multiple Complex Developmental Disorder (MCDD) is a well-defined and validated behavioral subtype of autism with a proposed elevated risk of developing a schizophrenic spectrum disorder. The current study investigated whether children with MCDD show the same deficits in sensory gating that are commonly reported in schizophrenia, or whether they are indistinguishable from children with autism in this respect. P50 suppression and prepulse inhibition (PPI) of the startle reflex were assessed in children with MCDD (n=14) or autism (n=13), and healthy controls (n=12), matched on age and IQ. All subjects showed high levels of PPI and P50 suppression. However, no group differences were found. No abnormalities in sensory filtering could be detected in children with autism or MCDD. Since sensory gating deficits are commonly regarded as possible endophenotypic markers for schizophrenia, the current results do not support a high level of similarity between schizophrenia and MCDD. PMID:23164481

  3. Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder.

    PubMed

    Chaudhry, A; Noor, A; Degagne, B; Baker, K; Bok, L A; Brady, A F; Chitayat, D; Chung, B H; Cytrynbaum, C; Dyment, D; Filges, I; Helm, B; Hutchison, H T; Jeng, L J B; Laumonnier, F; Marshall, C R; Menzel, M; Parkash, S; Parker, M J; Raymond, L F; Rideout, A L; Roberts, W; Rupps, R; Schanze, I; Schrander-Stumpel, C T R M; Speevak, M D; Stavropoulos, D J; Stevens, S J C; Thomas, E R A; Toutain, A; Vergano, S; Weksberg, R; Scherer, S W; Vincent, J B; Carter, M T

    2015-09-01

    Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype. PMID:25131214

  4. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE

    PubMed Central

    Nava, C; Lamari, F; Héron, D; Mignot, C; Rastetter, A; Keren, B; Cohen, D; Faudet, A; Bouteiller, D; Gilleron, M; Jacquette, A; Whalen, S; Afenjar, A; Périsse, D; Laurent, C; Dupuits, C; Gautier, C; Gérard, M; Huguet, G; Caillet, S; Leheup, B; Leboyer, M; Gillberg, C; Delorme, R; Bourgeron, T; Brice, A; Depienne, C

    2012-01-01

    The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID). A nonsense mutation in TMLHE, which encodes the ɛ-N-trimethyllysine hydroxylase catalyzing the first step of carnitine biosynthesis, was identified in two brothers with autism and ID. By screening the TMLHE coding sequence in 501 male patients with ASD, we identified two additional missense substitutions not found in controls and not reported in databases. Functional analyses confirmed that the mutations were associated with a loss-of-function and led to an increase in trimethyllysine, the precursor of carnitine biosynthesis, in the plasma of patients. This study supports the hypothesis that rare variants on the X chromosome are involved in the etiology of ASD and contribute to the sex-ratio disequilibrium. PMID:23092983

  5. Overcoming the diffraction limit using multiple light scattering in a highly disordered medium.

    PubMed

    Choi, Youngwoon; Yang, Taeseok Daniel; Fang-Yen, Christopher; Kang, Pilsung; Lee, Kyoung Jin; Dasari, Ramachandra R; Feld, Michael S; Choi, Wonshik

    2011-07-01

    We report that disordered media made of randomly distributed nanoparticles can be used to overcome the diffraction limit of a conventional imaging system. By developing a method to extract the original image information from the multiple scattering induced by the turbid media, we dramatically increase a numerical aperture of the imaging system. As a result, the resolution is enhanced by more than 5 times over the diffraction limit, and the field of view is extended over the physical area of the camera. Our technique lays the foundation to use a turbid medium as a far-field superlens. PMID:21797607

  6. Overcoming the Diffraction Limit Using Multiple Light Scattering in a Highly Disordered Medium

    NASA Astrophysics Data System (ADS)

    Choi, Youngwoon; Yang, Taeseok Daniel; Fang-Yen, Christopher; Kang, Pilsung; Lee, Kyoung Jin; Dasari, Ramachandra R.; Feld, Michael S.; Choi, Wonshik

    2011-07-01

    We report that disordered media made of randomly distributed nanoparticles can be used to overcome the diffraction limit of a conventional imaging system. By developing a method to extract the original image information from the multiple scattering induced by the turbid media, we dramatically increase a numerical aperture of the imaging system. As a result, the resolution is enhanced by more than 5 times over the diffraction limit, and the field of view is extended over the physical area of the camera. Our technique lays the foundation to use a turbid medium as a far-field superlens.

  7. Overcoming the Diffraction Limit Using Multiple Light Scattering in a Highly Disordered Medium

    PubMed Central

    Choi, Youngwoon; Yang, Taeseok Daniel; Fang-Yen, Christopher; Kang, Pilsung; Lee, Kyoung Jin; Dasari, Ramachandra R.; Feld, Michael S.; Choi, Wonshik

    2012-01-01

    We report that disordered media made of randomly distributed nanoparticles can be used to overcome the diffraction limit of a conventional imaging system. By developing a method to extract the original image information from the multiple scattering induced by the turbid media, we dramatically increase a numerical aperture of the imaging system. As a result, the the resolution is enhanced by more than five times over the diffraction limit and a field of view is extended over the physical area of the camera. Our technique lays the foundation to use a turbid medium as a far-field superlens. PMID:21797607

  8. Parents' Adoption of Social Communication Intervention Strategies: Families Including Children with Autism Spectrum Disorder Who are Minimally Verbal.

    PubMed

    Shire, Stephanie Y; Goods, Kelly; Shih, Wendy; Distefano, Charlotte; Kaiser, Ann; Wright, Courtney; Mathy, Pamela; Landa, Rebecca; Kasari, Connie

    2015-06-01

    Notably absent from the intervention literature are parent training programs targeting school-aged children with autism who have limited communication skills (Tager-Flusberg and Kasari in Autism Res 6:468-478, 2013). Sixty-one children with autism age 5-8 with minimal spontaneous communication received a 6-month social communication intervention including parent training. Parent-child play interactions were coded for parents' strategy implementation and children's time jointly engaged (Adamson et al. in J Autism Dev Disord 39:84-96, 2009). Parents mastered an average of 70% of the strategies. Further analyses indicated some gains in implementation occurred from mere observation of sessions, while the greatest gains occurred in the first month of active coaching and workshops. Children's joint engagement was associated with parents' implementation success across time demonstrating parents' implementation was relevant to children's social engagement. PMID:25475363

  9. The Cost Savings of Expanding Medicaid Eligibility to Include Currently Uninsured Homeless Adults with Substance Use Disorders

    PubMed Central

    Zur, Julia; Mojtabai, Ramin; Li, Suhui

    2013-01-01

    Following the June 2012 Supreme Court ruling that states are no longer mandated to expand their Medicaid programs in 2014 as part of the Affordable Care Act, many states plan to opt out of the expansion, citing affordability as their primary concern. In response to this controversy, the present study evaluated the cost savings of expanding Medicaid coverage to include currently ineligible homeless adults with substance use disorders, a subset of the population that incurs some of the greatest societal costs and is disproportionately impacted by uninsurance. Using a time horizon of 7 years, separate analyses were conducted for state and federal governments, and then a final analysis evaluated the combined costs for the other two models. Results of the study demonstrate that, although the expansion will be associated with a net cost when combining state and federal expenses and savings, states will experience tremendous savings if they choose to participate. PMID:24198085

  10. Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders.

    PubMed

    Moey, Ching; Hinze, Susan J; Brueton, Louise; Morton, Jenny; McMullan, Dominic J; Kamien, Benjamin; Barnett, Christopher P; Brunetti-Pierri, Nicola; Nicholl, Jillian; Gecz, Jozef; Shoubridge, Cheryl

    2016-03-01

    Copy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males. PMID:26059843

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

    PubMed

    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. PMID:26861102

  12. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects.

    PubMed

    Hanukoglu, A

    1991-11-01

    Type I pseudohypoaldosteronism (PHA) is a hereditary disease characterized by salt wasting resulting from target organ unresponsiveness to mineralocorticoids. We have studied two kindreds including a total of nine patients with PHA. In kindred I, the propositus presented with renal salt wasting in infancy (vomiting, failure to thrive, short stature, hyponatremia, hyperkalemia) and responded dramatically to a high salt diet (2.5 g/day). Sodium supplementation was discontinued at the age of two. In seven additional family members from three generations, clinical expression of PHA varied from asymptomatic to moderate. In affected members (propositus, mother, and two brothers), hyperaldosteronism persisted over 13 yr; however, the PRA decreased gradually to near normal values. Persistent hyperaldosteronism in the face of a decrease in PRA indicated the development of tertiary hyperaldosteronism due to autonomously functioning zona glomerulosa. The pedigree was consistent with an autosomal dominant mode of transmission with variable expression. In kindred II, the propositus, who was the product of a consanguineous marriage, developed severe renal salt losing at age 9 days. She had also increased salivary and sweat electrolytes consistent with PHA resulting from multiple organ unresponsiveness to mineralocorticoids. Life threatening episodes of salt wasting recurred beyond the age of 2 yr. At 5 yr of age she still requires high amounts of salt supplements (14 g/day). A sister died at 9 days of age with PHA symptoms. Six close relatives (parents, three siblings, maternal uncle) showed no biochemical abnormalities. This pedigree was consistent with an autosomal recessive mode of inheritance. In view of the findings on these two kindreds and the analysis of those in the literature, we conclude that type I PHA includes two clinically and genetically distinct entities with either renal or multiple target organ defects. PMID:1939532

  13. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions.

    PubMed

    Zhang, Zhiyu; Du, Guang-Jian; Wang, Chong-Zhi; Wen, Xiao-Dong; Calway, Tyler; Li, Zejuan; He, Tong-Chuan; Du, Wei; Bissonnette, Marc; Musch, Mark W; Chang, Eugene B; Yuan, Chun-Su

    2013-01-01

    Compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC). A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC. PMID:23434653

  14. Multiple victimizations before and after leaving home associated with PTSD, depression, and substance use disorder among homeless youth.

    PubMed

    Bender, Kimberly; Brown, Samantha M; Thompson, Sanna J; Ferguson, Kristin M; Langenderfer, Lisa

    2015-05-01

    Exposure to multiple forms of maltreatment during childhood is associated with serious mental health consequences among youth in the general population, but limited empirical attention has focused on homeless youth-a population with markedly high rates of childhood maltreatment followed by elevated rates of street victimization. This study investigated the rates of multiple childhood abuses (physical, sexual, and emotional abuse) and multiple street victimizations (robbery, physical assault, and sexual assault) and examined their relative relationships to mental health outcomes (meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for post-traumatic stress disorder [PTSD], depression, and substance use disorder) among a large (N = 601) multisite sample of homeless youth. Approximately 79% of youth retrospectively reported multiple childhood abuses (two or more types) and 28% reported multiple street victimizations (two or more types). Each additional type of street victimization nearly doubled youths' odds for meeting criteria for substance use disorder. Furthermore, each additional type of childhood abuse experienced more than doubled youths' odds for meeting criteria for PTSD. Both multiple abuses and multiple street victimizations were associated with an approximate twofold increase in meeting depression criteria. Findings suggest the need for screening, assessment, and trauma-informed services for homeless youth who consider multiple types of abuse and victimization experiences. PMID:25510502

  15. Multiple recurrent de novo copy number variations (CNVs), including duplications of the 7q11.23 Williams-Beuren syndrome region, are strongly associated with autism

    PubMed Central

    Sanders, Stephan J.; Ercan-Sencicek, A. Gulhan; Hus, Vanessa; Luo, Rui; Murtha, Michael T.; Moreno-De-Luca, Daniel; Chu, Su H.; Moreau, Michael P.; Gupta, Abha R.; Thomson, Susanne A.; Mason, Christopher E.; Bilguvar, Kaya; Celestino-Soper, Patricia B. S.; Choi, Murim; Crawford, Emily L.; Davis, Lea; Wright, Nicole R. Davis; Dhodapkar, Rahul M.; DiCola, Michael; DiLullo, Nicholas M.; Fernandez, Thomas V.; Fielding-Singh, Vikram; Fishman, Daniel O.; Frahm, Stephanie; Garagaloyan, Rouben; Goh, Gerald S.; Kammela, Sindhuja; Klei, Lambertus; Lowe, Jennifer K.; Lund, Sabata C.; McGrew, Anna D.; Meyer, Kyle A.; Moffat, William J.; Murdoch, John D.; O'Roak, Brian J.; Ober, Gordon T.; Pottenger, Rebecca S.; Raubeson, Melanie J.; Song, Youeun; Wang, Qi; Yaspan, Brian L.; Yu, Timothy W.; Yurkiewicz, Ilana R.; Beaudet, Arthur L.; Cantor, Rita M.; Curland, Martin; Grice, Dorothy E.; Günel, Murat; Lifton, Richard P.; Mane, Shrikant M.; Martin, Donna M.; Shaw, Chad A.; Sheldon, Michael; Tischfield, Jay A.; Walsh, Christopher A.; Morrow, Eric M.; Ledbetter, David H.; Fombonne, Eric; Lord, Catherine; Martin, Christa Lese; Brooks, Andrew I.; Sutcliffe, James S.; Cook, Edwin H.; Geschwind, Daniel; Roeder, Kathryn; Devlin, Bernie; State, Matthew W.

    2014-01-01

    Summary Given prior evidence for the contribution of rare copy number variations (CNVs) to autism spectrum disorders (ASD), we studied these events in 4,457 individuals from 1,174 simplex families, composed of parents, a proband and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, featuring a highly social personality. We identify rare recurrent de novo CNVs at five additional regions including two novel ASD loci, 16p13.2 (including the genes USP7 and C16orf72) and Cadherin13, and implement a rigorous new approach to evaluating the statistical significance of these observations. Overall, we find large de novo CNVs carry substantial risk (OR=3.55; CI =2.16-7.46, p=6.9 × 10−6); estimate the presence of 130-234 distinct ASD-related CNV intervals across the genome; and, based on data from multiple studies, present compelling evidence for the association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin1. PMID:21658581

  16. Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders

    PubMed Central

    Riedel, Michael; Messer, Thomas; Laux, Gerd; Pfeiffer, Herbert; Naber, Dieter; Schmidt, Lutz G.; Gaebel, Wolfgang; Huff, Wolfgang; Heuser, Isabella; Kühn, Kai-Uwe; Lemke, Matthias R.; Rüther, Eckart; Buchkremer, Gerhard; Gastpar, Markus; Bottlender, Ronald; Strauß, Anton; Möller, Hans-Jürgen

    2006-01-01

    Objective The aim was to investigate the hypothesis that patients with first episode schizophrenic disorders have a more favorable treatment response than those with multiple episodes. Method A total of 400 inpatients from an ongoing multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic disorders (F2) were assessed at admission to and discharge from hospital using the Positive and Negative Syndrome Scale (PANSS). Results At admission, first episode patients (n = 121) showed higher levels of positive symptoms (PANSS positive subscore) and lower ones of negative symptoms (PANSS negative subscore) than multiple episode patients (n = 279), whereas the global disease severity (PANSS total score) was comparable. Analyses of covariance revealed that treatment response (adjusted symptom levels at discharge) was more favorable in first-episode patients, with respect to both positive and negative symptoms. Conclusion The results are compatible with the hypothesis that treatment response becomes less favorable during the course of schizophrenic illness. This finding might be associated with progressive neurobiological alterations. PMID:17033915

  17. Differentiation between autism and multiple complex developmental disorder in response to psychosocial stress.

    PubMed

    Jansen, Lucres M C; Gispen-de Wied, Christine C; van der Gaag, Rutger-Jan; van Engeland, Herman

    2003-03-01

    Multiple Complex Developmental Disorder (MCDD) represents a distinct group within the autistic spectrum based on symptomatology. Unlike autistic children, part of MCDD children develop schizophrenia in adult life. Despite the differences, patients of both disorders are mainly characterized by abnormal reactions to their social environment. At the biological level, we showed in a previous study that MCDD children have a reduced cortisol response to psychosocial stress. Given the fact that autistic children clinically show more social impairments, it was hypothesized that they may have even further decreased cortisol responses to psychosocial stress than MCDD patients. Therefore, 10 autistic children were compared to 10 MCDD children and 12 healthy control children in their response to a psychosocial stressor, consisting of a public speaking task. In order to test whether any impairments in the biological stress response are specific for psychosocial stress, the autistic children were compared with 11 MCDD children and 15 control children in their response to a physical stressor, consisting of 10 min of bicycle exercise. Heart rate and salivary cortisol levels were used as indicators of response to the stress tests. Autistic children showed a relatively elevated cortisol response to psychosocial stress, in contrast to MCDD children who showed a reduced cortisol response. No differences in heart rate or cortisol responses to the physical stress test were found. The specific difference between autistic and MCDD children in their cortisol response to psychosocial stress indicates that the disturbed reactions to the social environment observed in these disorders may have different biological backgrounds. PMID:12629541

  18. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis

    PubMed Central

    Fu, Jie; Peng, Lilei; Li, Xiaogang

    2016-01-01

    Objective Vortioxetine is a novel antidepressant approved for the treatment of major depressive disorder by the US Food and Drug Administration in September 2013. This meta-analysis assessed the efficacy and safety of different doses of vortioxetine for generalized anxiety disorder of adults. Methods PubMed, Cochrane Library, PsycINFO, and Clinical Trials databases were searched from 2000 through 2015. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were searched to identify additional studies. The search was limited to individual randomized controlled trials (RCTs), and there was no language restriction. Four RCTs met the selection criteria. These studies included 1,843 adult patients. Results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The data were pooled with a random-effects or fixed-effects model. Results The results showed that multiple doses (2.5, 5, and 10 mg/d) of vortioxetine did not significantly improve the generalized anxiety disorder symptoms compared to placebo (OR=1.16, 95% CI=0.84–1.60, Z=0.89, P=0.38; OR=1.41, 95% CI=0.82–2.41, Z=1.25, P=0.21; OR=1.05, 95% CI=0.76–1.46, Z=0.32, P=0.75, respectively). We measured the efficacy of 2.5 mg/d vortioxetine compared to 10 mg/d, and no significant differences were observed. The common adverse effects included nausea and headache. With increased dose, nausea was found to be more frequent in the vortioxetine (5 and 10 mg/d) group (OR=2.99, 95% CI=1.31–6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85–4.25, Z=4.85, P<0.00001, respectively), but no significant differences were observed for headache. Conclusion The results showed no significant improvement in the treatment of generalized anxiety disorder for vortioxetine compared to placebo, and nausea was more frequent with higher doses. So the current evidences do not support using vortioxetine for the treatment of generalized anxiety disorder. Few RCTs were included in our meta-analysis, and more studies are needed to verify our results in the future. PMID:27143896

  19. Simulation of multiple personalities: a review of research comparing diagnosed and simulated dissociative identity disorder.

    PubMed

    Boysen, Guy A; VanBergen, Alexandra

    2014-02-01

    Dissociative Identity Disorder (DID) has long been surrounded by controversy due to disagreement about its etiology and the validity of its associated phenomena. Researchers have conducted studies comparing people diagnosed with DID and people simulating DID in order to better understand the disorder. The current research presents a systematic review of this DID simulation research. The literature consists of 20 studies and contains several replicated findings. Replicated differences between the groups include symptom presentation, identity presentation, and cognitive processing deficits. Replicated similarities between the groups include interidentity transfer of information as shown by measures of recall, recognition, and priming. Despite some consistent findings, this research literature is hindered by methodological flaws that reduce experimental validity. PMID:24291657

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

    PubMed

    Srinivas, Nuggehally R

    2006-05-01

    The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select disease areas and/or in clinically important drug-drug interaction studies. A tabular representation of select examples of analysis is provided covering areas of separation conditions, validation aspects and applicable conclusion. A limited discussion is provided on relevant aspects of the need for developing bioanalytical procedures for speedy drug discovery and development. Additionally, some key elements such as internal standard selection, likely issues of mass detection, matrix effect, chiral aspects etc. are provided for consideration during method development. PMID:16307470

  1. A call to include people with mental illness and substance use disorders alongside 'regular' smokers in smoking cessation research.

    PubMed

    Lembke, Anna; Humphreys, Keith

    2016-05-01

    This commentary points out that smoking is increasingly concentrated among people with psychiatric problems and other substance use disorders (eg, alcohol use disorder), and argues that for clinical, ethical and efficiency reasons, such individuals should be routinely enrolled in smoking cessation research. PMID:25882685

  2. Stem cell transplantation in multiple myeloma and other plasma cell disorders (report from an EBMT preceptorship meeting).

    PubMed

    Bruno, Benedetto; Auner, Holger W; Gahrton, Gösta; Garderet, Laurent; Festuccia, Moreno; Ladetto, Marco; Lemoli, Roberto M; Massaia, Massimo; Morris, Curly; Palumbo, Antonio; Schönland, Stefan; Boccadoro, Mario; Kröger, Nicolaus

    2016-06-01

    The European Society for Blood and Marrow Transplantation Chronic Malignancies Working Party held a preceptorship meeting in Turin, Italy on 25-26 September 2014, to discuss the role of stem cell transplantation (SCT) in the treatment of multiple myeloma and other plasma cell disorders. Scientists and clinicians working in the field gathered to discuss a variety of topics including the results of recent clinical trials, basic research, the concept of minimal residual disease, and immune modulation. As individual presentations revealed, important advances have occurred in our understanding of the pathophysiology of myeloma and the role that SCT, along with other forms of immunotherapy, plays in treating it. Each presentation stimulated discussion and exchange of ideas among the attendants. We decided to summarize and, importantly, to update the meeting proceedings in this review to share stimulating discussions and ideas on potentially novel treatment strategies among clinicians. PMID:26735310

  3. Relationship between Temporomandibular Disorders, Widespread Palpation Tenderness and Multiple Pain Conditions: A Case - Control Study

    PubMed Central

    Chen, Hong; Slade, Gary; Lim, Pei Feng; Miller, Vanessa; Maixner, William; Diatchenko, Luda

    2012-01-01

    The multiple bodily pain conditions in temporomandibular disorders (TMD) have been associated with generalized alterations in pain processing. The purpose of this study was to examine the relationship between the presence of widespread body palpation tenderness (WPT) and the likelihood of multiple comorbid pain conditions in TMD patients and controls. This case-control study was conducted in 76 TMD subjects with WPT, 83 TMD subjects without WPT, and 181 non-TMD matched control subjects. The study population was also characterized for clinical pain, experimental pain sensitivity, and related psychological phenotypes. Results showed that (1) TMD subjects reported an average of 1.7 comorbid pain conditions compared to 0.3 reported by the control subjects (p<0.001); (2) Compared to control subjects, the odds ratio (OR) for multiple comorbid pain conditions is higher for TMD subjects with WPT [OR 8.4 (95% CI 3.1–22.8) for TMD with WPT versus OR 3.3 (95% CI 1.3–8.4) for TMD without WPT]; (3) TMD subjects with WPT presented with reduced pressure pain thresholds (PPTs) in both cranial and extra-cranial regions compared to TMD subjects without WPT; and (4) TMD subjects with WPT reported increased somatic symptoms. These findings suggest that pain assessment outside of the orofacial region may prove valuable for the classification, diagnosis, and management of TMD patients. PMID:23031401

  4. The Histone Deacetylase Complex 1 Protein of Arabidopsis Has the Capacity to Interact with Multiple Proteins Including Histone 3-Binding Proteins and Histone 1 Variants1[OPEN

    PubMed Central

    Carr, Craig; Asensi-Fabado, Maria A.; Donald, Naomi A.; Hannah, Matthew A.; Amtmann, Anna

    2016-01-01

    Intrinsically disordered proteins can adopt multiple conformations, thereby enabling interaction with a wide variety of partners. They often serve as hubs in protein interaction networks. We have previously shown that the Histone Deacetylase Complex 1 (HDC1) protein from Arabidopsis (Arabidopsis thaliana) interacts with histone deacetylases and quantitatively determines histone acetylation levels, transcriptional activity, and several phenotypes, including abscisic acid sensitivity during germination, vegetative growth rate, and flowering time. HDC1-type proteins are ubiquitous in plants, but they contain no known structural or functional domains. Here, we explored the protein interaction spectrum of HDC1 using a quantitative bimolecular fluorescence complementation assay in tobacco (Nicotiana benthamiana) epidermal cells. In addition to binding histone deacetylases, HDC1 directly interacted with histone H3-binding proteins and corepressor-associated proteins but not with H3 or the corepressors themselves. Surprisingly, HDC1 also was able to interact with variants of the linker histone H1. Truncation of HDC1 to the ancestral core sequence narrowed the spectrum of interactions and of phenotypic outputs but maintained binding to a H3-binding protein and to H1. Thus, HDC1 provides a potential link between H1 and histone-modifying complexes. PMID:26951436

  5. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.

    PubMed

    Sanders, Stephan J; Ercan-Sencicek, A Gulhan; Hus, Vanessa; Luo, Rui; Murtha, Michael T; Moreno-De-Luca, Daniel; Chu, Su H; Moreau, Michael P; Gupta, Abha R; Thomson, Susanne A; Mason, Christopher E; Bilguvar, Kaya; Celestino-Soper, Patricia B S; Choi, Murim; Crawford, Emily L; Davis, Lea; Wright, Nicole R Davis; Dhodapkar, Rahul M; DiCola, Michael; DiLullo, Nicholas M; Fernandez, Thomas V; Fielding-Singh, Vikram; Fishman, Daniel O; Frahm, Stephanie; Garagaloyan, Rouben; Goh, Gerald S; Kammela, Sindhuja; Klei, Lambertus; Lowe, Jennifer K; Lund, Sabata C; McGrew, Anna D; Meyer, Kyle A; Moffat, William J; Murdoch, John D; O'Roak, Brian J; Ober, Gordon T; Pottenger, Rebecca S; Raubeson, Melanie J; Song, Youeun; Wang, Qi; Yaspan, Brian L; Yu, Timothy W; Yurkiewicz, Ilana R; Beaudet, Arthur L; Cantor, Rita M; Curland, Martin; Grice, Dorothy E; Günel, Murat; Lifton, Richard P; Mane, Shrikant M; Martin, Donna M; Shaw, Chad A; Sheldon, Michael; Tischfield, Jay A; Walsh, Christopher A; Morrow, Eric M; Ledbetter, David H; Fombonne, Eric; Lord, Catherine; Martin, Christa Lese; Brooks, Andrew I; Sutcliffe, James S; Cook, Edwin H; Geschwind, Daniel; Roeder, Kathryn; Devlin, Bernie; State, Matthew W

    2011-06-01

    We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10(-7)). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1. PMID:21658581

  6. Tryptophan protects hepatocytes against reactive oxygen species-dependent cell death via multiple pathways including Nrf2-dependent gene induction.

    PubMed

    Kimura, Takuya; Watanabe, Yoshifumi

    2016-05-01

    Hepatocyte apoptosis plays a key role in the pathogenesis of immune-mediated hepatitis. However, the detailed mechanisms of apoptosis signaling are still unclear and effective therapeutic drugs for hepatitis have been explored. Here, we show that tryptophan (Trp) suppressed IFN-γ-mediated hepatic apoptosis in vitro. Trp inhibited the downstream apoptotic events of mitochondria disruption, such as cell death and caspase-3 activation, while it did not influence upstream signaling including STAT1 activation and IRF1 expression. Trp suppressed reactive oxygen species (ROS) generation at the mitochondria. IFN-γ induced ROS in mitochondria by inhibiting complex I and III, but not II. This ROS generation by IFN-γ required de novo protein synthesis. Trp showed relatively weak direct scavenging activity but antagonized IFN-γ against the suppression of complex I. In addition, Trp increased the expression of the Nrf2-dependent antioxidant genes NQO1, HO-1 and GCS in hepatocytes both in vitro and in vivo. Finally, the administration of Trp in an acetaminophen-induced ROS-dependent hepatitis model suppressed the liver injury in vivo. Thus, Trp protects hepatocytes from ROS-dependent cell injury via multiple pathways. This study suggests Trp as a therapeutic antioxidant drug for hepatitis and a regulator for Nrf2-dependent genes. PMID:26795536

  7. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

    PubMed

    Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

    2014-01-01

    Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults. PMID:24723877

  8. Joint source based analysis of multiple brain structures in studying major depressive disorder

    NASA Astrophysics Data System (ADS)

    Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

    2014-03-01

    We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

  9. The comprehensive clinical management of multiple myeloma and related-plasma cell disorders.

    PubMed

    Richardson, Paul G; Blad, Joan

    2014-02-01

    Whilst we think of multiple myeloma and related plasma cell disorders as incurable to date, never before has there been such hope and enthusiasm about advances in the research and treatment of these various diseases. Translational research is very much at the forefront of progress for further refining targeted therapies and continuing to improve clinical efficacy. Whilst some of these advances in the last decade have been truly dramatic in their scope and timing, it is also worth noting that relatively incremental changes have favorably impacted on patient outcome, and this comprehensive clinical management review captures these accordingly. We hope therefore that this concise overview will give readers, be they specialist hemato-oncologists, or other providers and researchers in the field, an enlightening insight into the exciting future of therapeutic opportunities, as well as a practical 'hands on' approach. PMID:24483345

  10. KMAD: knowledge-based multiple sequence alignment for intrinsically disordered proteins

    PubMed Central

    Lange, Joanna; Wyrwicz, Lucjan S.; Vriend, Gert

    2016-01-01

    Summary: Intrinsically disordered proteins (IDPs) lack tertiary structure and thus differ from globular proteins in terms of their sequence–structure–function relations. IDPs have lower sequence conservation, different types of active sites and a different distribution of functionally important regions, which altogether make their multiple sequence alignment (MSA) difficult. The KMAD MSA software has been written specifically for the alignment and annotation of IDPs. It augments the substitution matrix with knowledge about post-translational modifications, functional domains and short linear motifs. Results: MSAs produced with KMAD describe well-conserved features among IDPs, tend to agree well with biological intuition, and are a good basis for designing new experiments to shed light on this large, understudied class of proteins. Availability and implementation: KMAD web server is accessible at http://www.cmbi.ru.nl/kmad/. A standalone version is freely available. Contact: vriend@cmbi.ru.nl PMID:26568635

  11. Unresponsiveness to psychosocial stress in a subgroup of autistic-like children, multiple complex developmental disorder.

    PubMed

    Jansen, L M; Gispen-de Wied, C C; Van der Gaag, R J; ten Hove, F; Willemsen-Swinkels, S W; Harteveld, E; Van Engeland, H

    2000-11-01

    In this study, we tried to replicate the finding of a diminished cortisol response to stress in autistic-like patients in a more homogenous Multiple Complex Developmental Disorder (MCDD) group. MCDD forms a distinct group within the autistic-like disorders, characterized by impaired regulation of anxiety and affective state, impaired social behavior/sensitivity, and thought disorder. A number of MCDD children develop schizophrenia in adult life. Responses to a psychosocial stressor, consisting of speaking in public while recorded on video, were measured in 10 MCDD children and 12 healthy control children. The public speaking test was imbedded in a two-hour test session, and compared to a control test session. Hypothalamic-pituitary-adrenal (HPA) responses were measured on salivary cortisol at about 20-minute intervals. Heart rate was measured continuously. Delta AUC's were computed for both heart rate (dAUCHR) and salivary cortisol (dAUCCORT), as a measure of response to the test.The public speaking task resulted in significant responses in heart rate and salivary cortisol in healthy control children, but not in MCDD children. dAUCHR was 3.28+/-2.37 in healthy control children, but -0.09+/-1.73 in MCDD children (t=3.31, P<0.01). dAUCCORT was 3.22+/-3.16 in healthy control children, but 0. 17+/-1.74 in MCDD children (t=2.72, P<0.05).The impaired responses to psychosocial stress found in MCDD children may be the result of their limited abilities to react adequately to their (social) environment. The same impairment in stress processing has been found in schizophrenia, and might be a factor in the vulnerability of these MCDD children to develop schizophrenia. PMID:10996471

  12. Early recognition of postural disorders in multiple sclerosis through movement analysis: a modeling study.

    PubMed

    Corradini, M L; Fioretti, S; Leo, T; Piperno, R

    1997-11-01

    In the present study, spontaneous postural behavior has been analyzed in freely standing multiple sclerosis (MS) patients, exhibiting no clinically assessable abnormalities of postural control. This population has been compared with two other groups, healthy people and hemiparetic patients. This latter group represents a situation where the central nervous system (CNS) lesion is precisely localized in one anatomical site and no signal-conduction disorders are present; i.e., it has an opposite anatomical character with respect to the MS at a preclinical stage. The hypothesis underlying the modeling study is the presence of a controller block working in a feedback posture control system. This controller block receives the body sway as input, and produces the corresponding ankle torque stabilizing the body, the latter being modeled as an inverted pendulum. The CNS damage, caused by MS, is supposed to be reflected in some detectable change in the structure of the controller of the posture control system. The identification of the controller has been performed by means of a parametric estimation procedure which employed as input sequences, data recorded by means of a movement-analysis (MA) system. Reported findings show a structural changes of the model of the controller block in the posture control system. This result may suggest the presence of an MS-specific reorganization of the posture control system. Some speculation is finally made on the black-box approach in comparison with traditional posturography, to arrive at hypothesizing a progression path for postural disorders. PMID:9353982

  13. The Presentation of Narcissistic Personality Disorder in an Octogenarian: Converging Evidence from Multiple Sources

    PubMed Central

    BALSIS, STEVE; EATON, NICHOLAS R.; COOPER, LUKE D.; OLTMANNS, THOMAS F.

    2011-01-01

    Little is known about personality disorders (PDs) in later life. One reason for this dearth of knowledge is that many investigators believe that PDs soften with age. Recent anecdotal and empirical evidence, however, suggests that PDs are still very relevant in later life and may actually have unique presentations and consequences. The DSM-IV PD criteria seem to overlook these possibilities, perhaps because the personalities of older adults were not sufficiently understood when these criteria were written. But without age-appropriate criteria, clinicians and investigators who work with older adults may be unable to measure PDs adequately in their clients and research participants. A starting point for better understanding these disorders in older adults is the presentation of rich, empirical, clinical descriptions of symptoms and related behaviors using data from multiple instruments and sources. To this end, we describe in depth a case of narcissistic PD (NPD) in a woman in her mid 80s. This case study reveals that NPD is indeed relevant in the context of later life and impairs functioning in significant ways. PMID:21637723

  14. Multiple Charge Transfer States at Ordered and Disordered Donor/Acceptor Interfaces

    NASA Astrophysics Data System (ADS)

    Fusella, Michael; Verreet, Bregt; Lin, Yunhui; Brigeman, Alyssa; Purdum, Geoffrey; Loo, Yueh-Lin; Giebink, Noel; Rand, Barry

    The presence of charge transfer (CT) states in organic solar cells is accepted, but their role in photocurrent generation is not well understood. Here we investigate solar cells based on rubrene and C60 to show that CT state properties are influenced by molecular ordering at the donor/acceptor (D/A) interface. Crystalline rubrene films are produced with domains of 100s of microns adopting the orthorhombic phase, as confirmed by grazing incidence XRD, with the (h00) planes parallel to the substrate. C60 grown atop these films adopts a highly oriented face-centered cubic phase with the (111) plane parallel to the substrate. For this highly ordered system we have discovered the presence of four CT states. Polarized external quantum efficiency (EQE) measurements assign three of these to crystalline origins with the remaining one well aligned with the disordered CT state. Varying the thickness of a disordered blend of rubrene:C60 atop the rubrene template modulates the degree of crystallinity at the D/A interface. Strikingly, this process alters the prominence of the four CT states measured via EQE, and results in a transition from single to multiple electroluminescence peaks. These results underscore the impact of molecular structure at the heterojunction on charge photogeneration.

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

    PubMed

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

    2016-01-01

    Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders. PMID:26941483

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

    PubMed Central

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

    2016-01-01

    Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders. PMID:26941483

  17. Transgenic Expression of miR-222 Disrupts Intestinal Epithelial Regeneration by Targeting Multiple Genes Including Frizzled-7

    PubMed Central

    Chung, Hee Kyoung; Chen, Yu; Rao, Jaladanki N; Liu, Lan; Xiao, Lan; Turner, Douglas J; Yang, Peixin; Gorospe, Myriam; Wang, Jian-Ying

    2015-01-01

    Defects in intestinal epithelial integrity occur commonly in various pathologies. miR-222 is implicated in many aspects of cellular function and plays an important role in several diseases, but its exact biological function in the intestinal epithelium is underexplored. We generated mice with intestinal epithelial tissue-specific overexpression of miR-222 to investigate the function of miR-222 in intestinal physiology and diseases in vivo. Transgenic expression of miR-222 inhibited mucosal growth and increased susceptibility to apoptosis in the small intestine, thus leading to mucosal atrophy. The miR-222–elevated intestinal epithelium was vulnerable to pathological stress, since local overexpression of miR-222 not only delayed mucosal repair after ischemia/reperfusion-induced injury, but also exacerbated gut barrier dysfunction induced by exposure to cecal ligation and puncture. miR-222 overexpression also decreased expression of the Wnt receptor Frizzled-7 (FZD7), cyclin-dependent kinase 4 and tight junctions in the mucosal tissue. Mechanistically, we identified the Fzd7 messenger ribonucleic acid (mRNA) as a novel target of miR-222 and found that [miR-222/Fzd7 mRNA] association repressed Fzd7 mRNA translation. These results implicate miR-222 as a negative regulator of normal intestinal epithelial regeneration and protection by downregulating expression of multiple genes including the Fzd7. Our findings also suggest a novel role of increased miR-222 in the pathogenesis of mucosal growth inhibition, delayed healing and barrier dysfunction. PMID:26252186

  18. Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

    PubMed

    Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

    2016-03-01

    Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility disorders were those between BCS and MET in both first and later lactations. Results indicated a limited value of a joint genetic evaluation model for metabolic disease traits and fertility disorders in Canadian Holsteins. PMID:26774726

  19. Delivery of Evidence-Based Treatment for Multiple Anxiety Disorders in Primary Care: A Randomized Controlled Trial

    PubMed Central

    Roy-Byrne, Peter; Craske, Michelle G.; Sullivan, Greer; Rose, Raphael D.; Edlund, Mark J.; Lang, Ariel J.; Bystritsky, Alexander; Welch, Stacy Shaw; Chavira, Denise A.; Golinelli, Daniela; Campbell-Sills, Laura; Sherbourne, Cathy D.; Stein, Murray B.

    2010-01-01

    Context Improving the quality of mental health care requires moving clinical interventions from controlled research settings into “real world” practice settings. While such advances have been made for depression, little work has been done for anxiety disorders. Objective To determine whether a flexible treatment-delivery model for multiple primary care anxiety disorders (panic, generalized anxiety, social anxiety, and/or posttraumatic stress disorders) would be superior to usual care. Design, Setting, and Participants Randomized controlled effectiveness trial of CALM (“Coordinated Anxiety Learning and Management”) compared to usual care (UC) in 17 primary care clinics in 4 US cities. Between June 2006 and April 2008, 1004 patients with anxiety disorders (with or without major depression), age 18–75, English- or Spanish-speaking, enrolled and subsequently received treatment for 3–12 months. Blinded follow-up assessments at 6, 12, and 18 months after baseline were completed in October 2009. Intervention(s) CALM allowed choice of cognitive behavioral therapy (CBT), medication, or both; included real-time web-based outcomes monitoring to optimize treatment decisions and a computer-assisted program to optimize delivery of CBT by non-expert care managers who also assisted primary care providers in promoting adherence and optimizing medications. Main Outcome Measure(s) 12-item Brief Symptom Inventory (anxiety and somatic symptoms) score. Secondary outcomes: Proportion of responders (≥ 50% reduction from pre-treatment BSI-12 score) and remitters (total BSI-12 score < 6). Results Significantly greater improvement for CALM than UC in global anxiety symptoms: BSI-12 group differences of −2.49 (95% CI, −3.59 to −1.40), −2.63 (95% CI, −3.73 to −1.54), and −1.63 (95% CI, −2.73 to −0.53) at 6, 12, and 18 months, respectively. At 12 months, response and remission rates (CALM vs. UC) were 63.66% (58.95–68.37) vs. 44.68% (39.76–49.59), and 51.49% (46.60–56.38) vs. 33.28% (28.62–37.93), with a number needed to treat (NNT) of 5.27 (4.18–7.13) for response and 5.5 (4.32–7.55) for remission. Conclusions For patients with anxiety disorders treated in primary care clinics, a collaborative care intervention, compared to usual care, resulted in greater improvement in anxiety symptoms, functional disability, and quality of care over 18 months. PMID:20483968

  20. Designing and recruiting to UK autism spectrum disorder research databases: do they include representative children with valid ASD diagnoses?

    PubMed Central

    Warnell, F; George, B; McConachie, H; Johnson, M; Hardy, R; Parr, J R

    2015-01-01

    Objectives (1) Describe how the Autism Spectrum Database-UK (ASD-UK) was established; (2) investigate the representativeness of the first 1000 children and families who participated, compared to those who chose not to; (3) investigate the reliability of the parent-reported Autism Spectrum Disorder (ASD) diagnoses, and present evidence about the validity of diagnoses, that is, whether children recruited actually have an ASD; (4) present evidence about the representativeness of the ASD-UK children and families, by comparing their characteristics with the first 1000 children and families from the regional Database of children with ASD living in the North East (Daslne), and children and families identified from epidemiological studies. Setting Recruitment through a network of 50 UK child health teams and self-referral. Patients Parents/carers with a child with ASD, aged 2–16 years, completed questionnaires about ASD and some gave professionals’ reports about their children. Results 1000 families registered with ASD-UK in 30 months. Children of families who participated, and of the 208 who chose not to, were found to be very similar on: gender ratio, year of birth, ASD diagnosis and social deprivation score. The reliability of parent-reported ASD diagnoses of children was very high when compared with clinical reports (over 96%); no database child without ASD was identified. A comparison of gender, ASD diagnosis, age at diagnosis, school placement, learning disability, and deprivation score of children and families from ASD-UK with 1084 children and families from Daslne, and families from population studies, showed that ASD-UK families are representative of families of children with ASD overall. Conclusions ASD-UK includes families providing parent-reported data about their child and family, who appear to be broadly representative of UK children with ASD. Families continue to join the databases and more than 3000 families can now be contacted by researchers about UK autism research. PMID:26341584

  1. Collaborative Care for patients with severe borderline and NOS personality disorders: A comparative multiple case study on processes and outcomes

    PubMed Central

    2011-01-01

    Background Structured psychotherapy is recommended as the preferred treatment of personality disorders. A substantial group of patients, however, has no access to these therapies or does not benefit. For those patients who have no (longer) access to psychotherapy a Collaborative Care Program (CCP) is developed. Collaborative Care originated in somatic health care to increase shared decision making and to enhance self management skills of chronic patients. Nurses have a prominent position in CCP's as they are responsible for optimal continuity and coordination of care. The aim of the CCP is to improve quality of life and self management skills, and reduce destructive behaviour and other manifestations of the personality disorder. Methods/design Quantitative and qualitative data are combined in a comparative multiple case study. This makes it possible to test the feasibility of the CCP, and also provides insight into the preliminary outcomes of CCP. Two treatment conditions will be compared, one in which the CCP is provided, the other in which Care as Usual is offered. In both conditions 16 patients will be included. The perspectives of patients, their informal carers and nurses are integrated in this study. Data (questionnaires, documents, and interviews) will be collected among these three groups of participants. The process of treatment and care within both research conditions is described with qualitative research methods. Additional quantitative data provide insight in the preliminary results of the CCP compared to CAU. With a stepped analysis plan the 'black box' of the application of the program will be revealed in order to understand which characteristics and influencing factors are indicative for positive or negative outcomes. Discussion The present study is, as to the best of our knowledge, the first to examine Collaborative Care for patients with severe personality disorders receiving outpatient mental health care. With the chosen design we want to examine how and which elements of the CC Program could contribute to a better quality of life for the patients. Trial registration Netherlands Trial Register (NTR): NTR2763 PMID:21699740

  2. Polysialic acid as an antigen for monoclonal antibody HIgM12 to treat multiple sclerosis and other neurodegenerative disorders.

    PubMed

    Watzlawik, Jens O; Kahoud, Robert J; Ng, Shermayne; Painter, Meghan M; Papke, Louisa M; Zoecklein, Laurie; Wootla, Bharath; Warrington, Arthur E; Carey, William A; Rodriguez, Moses

    2015-09-01

    CNS regeneration is a desirable goal for diseases of brain and spinal cord. Current therapeutic strategies for the treatment of multiple sclerosis (MS) aim to eliminate detrimental effects of the immune system, so far without reversing disability or affecting long-term prognosis in patients. Approachable molecular targets that stimulate CNS repair are not part of the clinical praxis or have not been identified yet. The purpose of this study was to identify the molecular target of the human monoclonal antibody HIgM12. HIgM12 reverses motor deficits in chronically demyelinated mice, a model of MS. Here, we identified polysialic acid (PSA) attached to the neural cell adhesion molecule (NCAM) as the antigen for HIgM12 by using different NCAM knockout strains and through PSA removal from the NCAM protein core. Antibody binding to CNS tissue and primary cells, antibody-mediated cell adhesion, and neurite outgrowth on HIgM12-coated nitrocellulose was detected only in the presence of PSA as assessed by western blotting, immunoprecipitation, immunocytochemistry, and histochemistry. We conclude that HIgM12 mediates its in vivo and in vitro effects through binding to PSA and has the potential to be an effective therapy for MS and neurodegenerative diseases. The human antibody HIgM12 stimulates neurite outgrowth in vitro and promotes function in chronically demyelinated mice, a model of multiple sclerosis. The cellular antigen for HIgM12 was undetermined. Here, we identified polysialic acid attached to NCAM (neural cell adhesion molecule) as the cellular target for HIgM12. This includes glial fibrillary acidic protein (GFAP)-positive mouse astrocytes (GFAP, red; HIgM12, green; DAPI, blue) among other cell types of the central nervous system. These findings indicate a new strategy for the treatment of neuro-motor disorders including multiple sclerosis. PMID:25866077

  3. Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis.

    PubMed

    Ghezzi, A; Zaffaroni, M

    2001-11-01

    Neurological manifestations of gastrointestinal disorders are described, with particular reference to those resembling multiple sclerosis (MS) on clinical or MRI grounds. Patients with celiac disease can present cerebellar ataxia, progressive myoclonic ataxia, myelopathy, or cerebral, brainstem and peripheral nerve involvement. Antigliadin antibodies can be found in subjects with neurological dysfunction of unknown cause, particularly in sporadic cerebellar ataxia ("gluten ataxia"). Patients with Whipple's disease can develop mental and psychiatric changes, supranuclear gaze palsy, upper motoneuron signs, hypothalamic dysfunction, cranial nerve abnormalities, seizures, ataxia, myorhythmia and sensory deficits. Neurological manifestations can complicate inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease) due to vascular or vasculitic mechanisms. Cases with both Crohn's disease and MS or cerebral vasculitis are described. Epilepsy, chronic inflammatory polyneuropathy, muscle involvement and myasthenia gravis are also reported. The central nervous system can be affected in patients with hepatitis C virus (HCV) infection because of vasculitis associated with HCV-related cryoglobulinemia. Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a disease caused by multiple deletions of mitochondrial DNA. It is characterized by peripheral neuropathy, ophthalmoplegia, deafness, leukoencephalopathy, and gastrointestinal symptoms due to visceral neuropathy. Neurological manifestations can be the consequence of vitamin B1, nicotinamide, vitamin B12, vitamin D, or vitamin E deficiency and from nutritional deficiency states following gastric surgery. PMID:11794474

  4. MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia.

    PubMed

    Boon, Mieke; Wallmeier, Julia; Ma, Lina; Loges, Niki Tomas; Jaspers, Martine; Olbrich, Heike; Dougherty, Gerard W; Raidt, Johanna; Werner, Claudius; Amirav, Israel; Hevroni, Avigdor; Abitbul, Revital; Avital, Avraham; Soferman, Ruth; Wessels, Marja; O'Callaghan, Christopher; Chung, Eddie M K; Rutman, Andrew; Hirst, Robert A; Moya, Eduardo; Mitchison, Hannah M; Van Daele, Sabine; De Boeck, Kris; Jorissen, Mark; Kintner, Chris; Cuppens, Harry; Omran, Heymut

    2014-01-01

    Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC. PMID:25048963

  5. Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: Developing treatments using an integrated translational approach

    PubMed Central

    Machado-Vieira, Rodrigo; Soeiro-De-Souza, Marcio G.; Richards, Erica M.; Teixeira, Antonio L.; Zarate, Carlos A.

    2014-01-01

    Objectives This paper reviews the neurobiology of bipolar disorder (BD), particularly findings associated with impaired cellular resilience and plasticity. Methods PubMed/Medline articles and book chapters published over the last 20 years were identified using the following keyword combinations: BD, calcium, cytokines, endoplasmic reticulum (ER), genetics, glucocorticoids, glutamate, imaging, ketamine, lithium, mania, mitochondria, neuroplasticity, neuroprotection, neurotrophic, oxidative stress, plasticity, resilience, and valproate. Results BD is associated with impaired cellular resilience and synaptic dysfunction at multiple levels, associated with impaired cellular resilience and plasticity. These findings were partially prevented or even reversed with the use of mood stabilizers, but longitudinal studies associated with clinical outcome remain scarce. Conclusions Evidence consistently suggests that BD involves impaired neural plasticity and cellular resilience at multiple levels. This includes the genetic and intra- and intercellular signalling levels, their impact on brain structure and function, as well as the final translation into behaviour/cognitive changes. Future studies are expected to adopt integrated translational approaches using a variety of methods (e.g., microarray approaches, neuroimaging, genetics, electrophysiology, and the new generation of –omics techniques). These studies will likely focus on more precise diagnoses and a personalized medicine paradigm in order to develop better treatments for those who need them most. PMID:23998912

  6. Multiple epigenetic factors predict the attention deficit/hyperactivity disorder among the Chinese Han children.

    PubMed

    Xu, Yi; Chen, Xiang-Tao; Luo, Man; Tang, Yuqing; Zhang, Guangxiang; Wu, De; Yang, Bin; Ruan, Di-Yun; Wang, Hui-Li

    2015-05-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. Despite its prevalence, the critical factors involved in its development remain to be identified. It was recently suggested that epigenetic mechanisms probably contribute to the etiology of ADHD. The present study was designed to examine the associations of epigenetic markers with ADHD among Chinese Han children, aiming to establish the prediction model for this syndrome from the epigenetic perspective. We conducted a pair-matching case-control study, and the ADHD children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised criteria (DSM-IV-R). The expression levels of risk genes DAT1, DRD4, DRD5, as well as their promoter methylation, were determined respectively, followed by the expression profiles of histone-modifying genes p300, MYST4, HDAC1, MeCP2. The multivariate logistic regressions were performed to establish ADHD prediction models. All of the seven genes tested were identified as risk factors for ADHD. The methylation of one critical CpG site located upstream of DRD4 was shown to affect its transcription, suggesting a role in ADHD's development. Aberrant DNA methylation and histone acetylation were indicated in ADHD patients. In addition, a prediction model was established using the combination of p300, MYST4 and HDAC1, with the accuracy of 0.9338. This is, to our knowledge, the first study to clearly demonstrate the associations between epigenetic markers and ADHD, shedding light on the preliminary diagnosis and etiological studies of this widespread disorder. PMID:25840828

  7. The Multiple, Distinct Ways that Personality Contributes to Alcohol Use Disorders

    PubMed Central

    Littlefield, Andrew K.; Sher, Kenneth J.

    2010-01-01

    There is little question of whether personality is associated with problematic alcohol involvement (such as alcohol use disorders; AUDs); it clearly is. However, the question remains: how or why is personality related to risky drinking and AUDs? To address this question, theoretical models have been posited regarding the causal effects of personality on alcohol use and related problems. In this article, several of these models are summarized and reviewed. Future research directions are discussed, including possible frameworks that serve to integrate various models of the personality-AUD relation. PMID:21170162

  8. Exploring the Social Impact of Being a Typical Peer Model for Included Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Locke, Jill; Rotheram-Fuller, Erin; Kasari, Connie

    2012-01-01

    This study examined the social impact of being a typical peer model as part of a social skills intervention for children with autism spectrum disorder (ASD). Participants were drawn from a randomized-controlled-treatment trial that examined the effects of targeted interventions on the social networks of 60 elementary-aged children with ASD.…

  9. An Overview of Multiple Sclerosis: Medical, Psychosocial, and Vocational Aspects of a Chronic and Unpredictable Neurological Disorder

    ERIC Educational Resources Information Center

    Rumrill, Phillip D., Jr.; Roessler, Richard T.

    2015-01-01

    This article presents an overview of multiple sclerosis (MS), one of the most common neurological disorders in the western hemisphere. Medical and psychosocial aspects of the disease such as causes and risk factors, diagnosis, incidence and prevalence, symptoms, courses, and treatment are described. Existing research regarding the employment…

  10. Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis

    PubMed Central

    Konradi, Christine; Sillivan, Stephanie E.; Clay, Hayley B.

    2011-01-01

    Gene expression studies of bipolar disorder (BPD) have shown changes in transcriptome profiles in multiple brain regions. Here we summarize the most consistent findings in the scientific literature, and compare them to data from schizophrenia (SZ) and major depressive disorder (MDD). The transcriptome profiles of all three disorders overlap, making the existence of a BPD-specific profile unlikely. Three groups of functionally related genes are consistently expressed at altered levels in BPD, SZ and MDD. Genes involved in energy metabolism and mitochondrial function are downregulated, genes involved in immune response and inflammation are upregulated, and genes expressed in oligodendrocytes are downregulated. Experimental paradigms for multiple sclerosis demonstrate a tight link between energy metabolism, inflammation and demyelination. These studies also show variabilities in the extent of oligodendrocyte stress, which can vary from a downregulation of oligodendrocyte genes, such as observed in psychiatric disorders, to cell death and brain lesions seen in multiple sclerosis. We conclude that experimental models of multiple sclerosis could be of interest for the research of BPD, SZ and MDD. PMID:21310238

  11. Multiple Channel Exposure Therapy: Combining Cognitive-Behavioral Therapies for the Treatment of Posttraumatic Stress Disorder with Panic Attacks

    ERIC Educational Resources Information Center

    Falsetti, Sherry A.; Resnick, Heidi S.; Davis, Joanne

    2005-01-01

    A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic…

  12. Patients with schizophrenia or schizoaffective disorder who receive multiple electroconvulsive therapy sessions: characteristics, indications, and results

    PubMed Central

    Iancu, Iulian; Pick, Nimrod; Seener-Lorsh, Orit; Dannon, Pinhas

    2015-01-01

    Background While electroconvulsive therapy (ECT) has been used for many years, there is insufficient research regarding the indications for continuation/maintenance (C/M)-ECT, its safety and efficacy, and the characteristics of patients with schizophrenia or schizoaffective disorder who receive multiple ECT sessions. The aims of this study were to characterize a series of patients who received 30 ECT sessions or more, to describe treatment regimens in actual practice, and to examine the results of C/M-ECT in terms of safety and efficacy, especially the effect on aggression and functioning. Methods We performed a retrospective chart review of 20 consecutive patients (mean age 64.6 years) with schizophrenia (n=16) or schizoaffective disorder (n=4) who received at least 30 ECT sessions at our ECT unit, and also interviewed the treating physician and filled out the Clinical Global Impression-Severity, Global Assessment of Functioning, and the Staff Observation Aggression Scale-Revised. Results Patients received a mean of 91.3 ECT sessions at a mean interval of 2.6 weeks. All had been hospitalized for most or all of the previous 3 years. There were no major adverse effects, and cognitive side effects were relatively minimal (cognitive deficit present for several hours after treatment). We found that ECT significantly reduced scores on the Staff Observation Aggression Scale-Revised subscales for verbal aggression and self-harm, and improved Global Assessment of Functioning scores. There were reductions in total aggression scores, subscale scores for harm to objects and to others, and Clinical Global Impression-Severity scores, these were not statistically significant. Conclusion C/M-ECT is safe and effective for chronically hospitalized patients. It improves general functioning and reduces verbal aggression and self-harm. More research using other aggression tools is needed to determine its effects and to reproduce our findings in prospective and controlled studies. PMID:25848283

  13. Single- or multiple-session viscosupplementation protocols for temporomandibular joint degenerative disorders: a randomized clinical trial.

    PubMed

    Guarda-Nardini, L; Rossi, A; Arboretti, R; Bonnini, S; Stellini, E; Manfredini, D

    2015-07-01

    The aim of the study was to compare the effectiveness of two single-session protocols, either adopting high- (protocol A) or medium-molecular weight hyaluronic acid (protocol B), with the reference five-session protocol of temporomandibular joint (TMJ) lavage plus viscosupplementation (protocol C) in the management of chronic TMJ degenerative disorders. A randomized clinical trial (RCT) with ten participants per treatment group was designed, with multiple observation points, ending at 6 months after treatment. Pain levels on a 10-point VAS scale were selected as the primary outcome variable to rate treatment effectiveness, along with a number of secondary outcome parameters. Findings showed that Group C patients had the highest decrease in pain levels. Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocols (P = 0·024). Pairwise comparisons showed that the differences of treatment effect between the two single-session interventions were negligible (global P-value = 0·93). On the contrary, the five-session protocol was significantly superior to both single-session protocols (global P-values ranging from 0·003 to 0·012). In conclusion, in a population of age-, sex-, and psychosocial aspects-matched study groups, the standard of reference five-session protocol proved to be superior at 6 months as far as the decrease in pain levels was concerned, whilst there were no differences between the two single-session interventions. The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation. PMID:25704621

  14. Periventricular Lesions Help Differentiate Neuromyelitis Optica Spectrum Disorders from Multiple Sclerosis

    PubMed Central

    Loh, John P.; Saba, Luca; Omari, Mirza; Herbert, Joseph; Kister, Ilya

    2014-01-01

    Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered (“type A”) or jagged-bordered (“type B”) pattern. On sagittal FLAIR, the images were evaluated for presence of “Dawson's fingers.” Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and “jagged-bordered” periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases. PMID:24665366

  15. Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis

    PubMed Central

    Gentile, Antonietta; De Vito, Francesca; Fresegna, Diego; Musella, Alessandra; Buttari, Fabio; Bullitta, Silvia; Mandolesi, Georgia; Centonze, Diego

    2015-01-01

    Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioral alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, that can regulate synaptic activity, thereby leading to perturbation of behavior. In multiple sclerosis (MS), the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioral studies in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioral syndrome. We review the experimental studies addressing behavioral symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS. PMID:26161070

  16. Imagery Rescripting for Body Dysmorphic Disorder: A Multiple-Baseline Single-Case Experimental Design.

    PubMed

    Willson, Rob; Veale, David; Freeston, Mark

    2016-03-01

    Individuals with body dysmorphic disorder (BDD) often experience negative distorted images of their appearance, and research suggests these may be linked to memories of adverse events such as bullying or teasing. This study evaluates imagery rescripting (ImR) as an intervention for BDD. In this article, we present a multiple-baseline single-case experimental design testing imagery rescripting as a brief, stand-alone intervention, with six individuals with BDD that related to aversive memories. The impact of the intervention was assessed by self-reported daily measures of symptom severity (preoccupation with appearance, appearance-related checking behaviors, appearance-related distress, and strength of belief that their main problem is their appearance) and standardized clinician ratings of BDD severity (Yale-Brown Obsessive Compulsive Scale modified for BDD). Four out of six of the participants responded positively to the intervention, with clinically meaningful improvement in symptomatology. Overall response was rapid; improvements began within the first week post-ImR intervention. From a small sample it is cautiously concluded that imagery rescripting may show promise as a module in cognitive-behavioral therapy for BDD, and is worthy of further investigation. PMID:26956656

  17. FUNDAMENTAL AREAS OF PHENOMENOLOGY (INCLUDING APPLICATIONS): Observation of Periodic Multiplication and Chaotic Phenomena in Atmospheric Cold Plasma Jets

    NASA Astrophysics Data System (ADS)

    Qi, Bing; Huang, Jian-Jun; Zhang, Zhe-Huang; Wang, De-Zhen

    2008-09-01

    We investigate the temporal evolution of the current pulses from an ac He cold plasma jet at atmospheric pressure and with driving frequency in the range 14.76-15.30 kHz. The driving frequency is used as the plasma system's bifurcation parameter in analogy with the evolution in which the current pulses undergoes multiplication and chaos. Such time-domain nonlinearity is important for controlling instabilities in atmospheric glow discharges. In addition, the observation can provide some data to support the simulation results reported previously [Appl. Phys. Lett. 90 (2007) 071501].

  18. Comorbid anxiety in bipolar disorder

    PubMed Central

    Nakagawa, Atsuo; Grunebaum, Michael F; Sullivan, Gregory M; Currier, Dianne; Ellis, Steven P; Burke, Ainsley K; Brent, David A; Mann, J John; Oquendo, Maria A

    2009-01-01

    Objective Comorbid anxiety disorder is reported to increase suicidality in bipolar disorder. However, studies of the impact of anxiety disorders on suicidal behavior in mood disorders have shown mixed results. The presence of personality disorders, often comorbid with anxiety and bipolar disorders, may explain these inconsistencies. This study examined the impact of comorbid Cluster B personality disorder and anxiety disorder on suicidality in bipolar disorder. Methods A total of 116 depressed bipolar patients with and without lifetime anxiety disorder were compared. Multiple regression analysis tested the association of comorbid anxiety disorder with past suicide attempts and severity of suicidal ideation, adjusting for the effect of Cluster B personality disorder. The specific effect of panic disorder was also explored. Results Bipolar patients with and without anxiety disorders did not differ in the rate of past suicide attempt. Suicidal ideation was less severe in those with anxiety disorders. In multiple regression analysis, anxiety disorder was not associated with past suicide attempts or with the severity of suicidal ideation, whereas Cluster B personality disorder was associated with both. The results were comparable when comorbid panic disorder was examined. Conclusions Comorbid Cluster B personality disorder appears to exert a stronger influence on suicidality than comorbid anxiety disorder in persons with bipolar disorder. Assessment of suicide risk in patients with bipolar disorder should include evaluation and treatment of Cluster B psychopathology. PMID:18452449

  19. Successful Improvement of Metabolic Disorders, Including Osteopenia, by a Dopamine Agonist in a Male Patient with Macro-Prolactinoma.

    PubMed

    Takeno, Ayumu; Yamamoto, Masahiro; Okazaki, Kyoko; Yamaguchi, Toru; Toshitsugu, Sugimoto

    2016-01-01

    BACKGROUND Bone metabolic disorders in patients with prolactinoma have not been fully characterized. The case presented herein illustrates potential causal associations between prolactinoma and osteopenia, with a reversal of the disorder by treatment with a dopamine agonist. CASE REPORT A 43-year-old male with macro-prolactinoma [PRL 7770 ng/mL] was referred to our hospital. He suffered was overweight [body mass index (BMI) 29.4 kg/m2] and had impaired glucose tolerance, hypertriglyceridemia, and osteopenia. The patient was administered cabergoline, a dopamine D2 receptor agonist, and the dose was gradually increased up to 9 mg/week over the period of 1 year. One year later, the patient's serum PRL levels decreased to within the normal range (19.1 ng/mL), and his pituitary tumor mass decreased to 1/4 of its initial size. His weight, dyslipidemia, and impaired glucose tolerance improved within 1 year. A marked increase in the bone mineral density (BMD) at the second to fourth lumbar spine (from 0.801 g/cm2 to 0.870 g/cm2, +8.6%) and at the femoral neck (from 0.785 g/cm2 to 0.864 g/cm2, +10.1%) were observed despite the presence of unresolved hypogonadism. CONCLUSIONS Treatments with dopamine agonists represent a beneficial strategy for patients with prolactinoma accompanied with bone loss, in addition to their established efficacy in shrinkage of the size of pituitary tumors, normalization of PRL levels, and improvement of metabolic disorders. PMID:26971354

  20. Successful Improvement of Metabolic Disorders, Including Osteopenia, by a Dopamine Agonist in a Male Patient with Macro-Prolactinoma

    PubMed Central

    Takeno, Ayumu; Yamamoto, Masahiro; Okazaki, Kyoko; Yamaguchi, Toru; Toshitsugu, Sugimoto

    2016-01-01

    Patient: Male, 43 Final Diagnosis: Prolactinoma Symptoms: — Medication: — Clinical Procedure: Treatments by a dopamine agonist Specialty: Endocrinology and Metabolic Objective: Unknown ethiology Background: Bone metabolic disorders in patients with prolactinoma have not been fully characterized. The case presented herein illustrates potential causal associations between prolactinoma and osteopenia, with a reversal of the disorder by treatment with a dopamine agonist. Case Report: A 43-year-old male with macro-prolactinoma [PRL 7770 ng/mL] was referred to our hospital. He suffered was overweight [body mass index (BMI) 29.4 kg/m2] and had impaired glucose tolerance, hypertriglyceridemia, and osteopenia. The patient was administered cabergoline, a dopamine D2 receptor agonist, and the dose was gradually increased up to 9 mg/week over the period of 1 year. One year later, the patient’s serum PRL levels decreased to within the normal range (19.1 ng/mL), and his pituitary tumor mass decreased to 1/4 of its initial size. His weight, dyslipidemia, and impaired glucose tolerance improved within 1 year. A marked increase in the bone mineral density (BMD) at the second to fourth lumbar spine (from 0.801 g/cm2 to 0.870 g/cm2, +8.6%) and at the femoral neck (from 0.785 g/cm2 to 0.864 g/cm2, +10.1%) were observed despite the presence of unresolved hypogonadism. Conclusions: Treatments with dopamine agonists represent a beneficial strategy for patients with prolactinoma accompanied with bone loss, in addition to their established efficacy in shrinkage of the size of pituitary tumors, normalization of PRL levels, and improvement of metabolic disorders. PMID:26971354

  1. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders.

    PubMed

    Rawstron, Andy C; Orfao, Alberto; Beksac, Meral; Bezdickova, Ludmila; Brooimans, Rik A; Bumbea, Horia; Dalva, Klara; Fuhler, Gwenny; Gratama, Jan; Hose, Dirk; Kovarova, Lucie; Lioznov, Michael; Mateo, Gema; Morilla, Ricardo; Mylin, Anne K; Omedé, Paola; Pellat-Deceunynck, Catherine; Perez Andres, Martin; Petrucci, Maria; Ruggeri, Marina; Rymkiewicz, Grzegorz; Schmitz, Alexander; Schreder, Martin; Seynaeve, Carine; Spacek, Martin; de Tute, Ruth M; Van Valckenborgh, Els; Weston-Bell, Nicky; Owen, Roger G; San Miguel, Jesús F; Sonneveld, Pieter; Johnsen, Hans E

    2008-03-01

    The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating laboratories. The second aimed to resolve outstanding technical issues and develop a consensus approach to analysis of plasma cells. The primary clinical applications identified were: differential diagnosis of neoplastic plasma cell disorders from reactive plasmacytosis; identifying risk of progression in patients with MGUS and detecting minimal residual disease. A range of technical recommendations were identified, including: 1) CD38, CD138 and CD45 should all be included in at least one tube for plasma cell identification and enumeration. The primary gate should be based on CD38 vs. CD138 expression; 2) after treatment, clonality assessment is only likely to be informative when combined with immunophenotype to detect abnormal cells. Flow cytometry is suitable for demonstrating a stringent complete remission; 3) for detection of abnormal plasma cells, a minimal panel should include CD19 and CD56. A preferred panel would also include CD20, CD117, CD28 and CD27; 4) discrepancies between the percentage of plasma cells detected by flow cytometry and morphology are primarily related to sample quality and it is, therefore, important to determine that marrow elements are present in follow-up samples, particularly normal plasma cells in MRD negative cases. PMID:18268286

  2. Hallucinogen persisting perception disorder and the serotonergic system: a comprehensive review including new MDMA-related clinical cases.

    PubMed

    Litjens, Ruud P W; Brunt, Tibor M; Alderliefste, Gerard-Jan; Westerink, Remco H S

    2014-08-01

    Hallucinogen persisting perception disorder (HPPD) is a drug-induced condition associated with inaccurate visual representations. Since the underlying mechanism(s) are largely unknown, this review aims to uncover aspects underlying its etiology. Available evidence on HPPD and drug-related altered visual processing was reviewed and the majority of HPPD cases were attributed to drugs with agonistic effects on serotonergic 5-HT₂A receptors. Moreover, we present 31 new HPPD cases that link HPPD to the use of ecstasy (MDMA), which is known to reverse serotonin reuptake and acts as agonist on 5-HT₂A receptors. The available evidence suggests that HPPD symptoms may be a result from a misbalance of inhibitory-excitatory activity in low-level visual processing and GABA-releasing inhibitory interneurons may be involved. However, high co-morbidities with anxiety, attention problems and derealization symptoms add complexity to the etiology of HPPD. Also, other perceptual disorders that show similarity to HPPD cannot be ruled out in presentations to clinical treatment. Taken together, evidence is still sparse, though low-level visual processing may play an important role. A novel finding of this review study, evidenced by our new cases, is that ecstasy (MDMA) use may also induce symptoms of HPPD. PMID:24933532

  3. Nonadiabatic dynamics of electron transfer in solution: Explicit and implicit solvent treatments that include multiple relaxation time scales

    SciTech Connect

    Schwerdtfeger, Christine A.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon

    2014-01-21

    The development of efficient theoretical methods for describing electron transfer (ET) reactions in condensed phases is important for a variety of chemical and biological applications. Previously, dynamical dielectric continuum theory was used to derive Langevin equations for a single collective solvent coordinate describing ET in a polar solvent. In this theory, the parameters are directly related to the physical properties of the system and can be determined from experimental data or explicit molecular dynamics simulations. Herein, we combine these Langevin equations with surface hopping nonadiabatic dynamics methods to calculate the rate constants for thermal ET reactions in polar solvents for a wide range of electronic couplings and reaction free energies. Comparison of explicit and implicit solvent calculations illustrates that the mapping from explicit to implicit solvent models is valid even for solvents exhibiting complex relaxation behavior with multiple relaxation time scales and a short-time inertial response. The rate constants calculated for implicit solvent models with a single solvent relaxation time scale corresponding to water, acetonitrile, and methanol agree well with analytical theories in the Golden rule and solvent-controlled regimes, as well as in the intermediate regime. The implicit solvent models with two relaxation time scales are in qualitative agreement with the analytical theories but quantitatively overestimate the rate constants compared to these theories. Analysis of these simulations elucidates the importance of multiple relaxation time scales and the inertial component of the solvent response, as well as potential shortcomings of the analytical theories based on single time scale solvent relaxation models. This implicit solvent approach will enable the simulation of a wide range of ET reactions via the stochastic dynamics of a single collective solvent coordinate with parameters that are relevant to experimentally accessible systems.

  4. Application of the Multiplicative-Additive Model in the Bone Marrow Transplantation Survival Data Including Competing Risks

    PubMed Central

    ASHOURI, Asieh; HAMIDIEH, Amirali; MAHMOODI, Mahmood; MOHAMMAD, Kazem; HADJIBABAIE, Molouk; ZERAATI, Hojjat; KARIMI, Akram; GHAVAMZADEH, Ardeshir

    2015-01-01

    Background: Cox proportional hazard model is a popular choice in modeling the survival data, but sometimes proportionality assumption is not satisfied. One of the tools for handling the non-proportional effects is the multiplicative-additive model named Cox-Aalen model. Recently these flexible regression models developed for competing risks setting. The aim of this paper is showing the application of the multiplicative-additive model in competing risks setting on real bone marrow transplantation (BMT) data when the proportionality assumption is violated. Methods: The data was from a retrospective study on class III thalassemia patients who undergo hematopoietic stem cell transplantation (HSCT) in BMT ward of Shariatei Hospital, Tehran, Iran. The neutrophil engraftment time as the early outcome of HSCT on37 patients who received mesenchymal stem cell infusion (MSC group) compared with 50 patients who did not. We fit the standard proportional models and flexible Cox-Aalen model in the sub distribution hazards. Results: By day 30 after transplantation, the cumulative incidence of neutrophil recovery was 97% (95%CI: 89%100%) and 76%(95%CI: 64%88%) in MSC and control group, respectively. Based on the Cox-Aalen model for cumulative incidence function, the MSC infusion had a significant delay effect on neutrophil engraftment (P=.044). In patients who did not neutrophil recovery immediately after HSCT, those who received MSC had faster recovery. Conclusion: Cox-Aalen model provides more accurate statistical description for time-varying covariate effects. There is a positive effect of MSCs on the neutrophil recovery, however further study on the advantages and disadvantages of MSCs are needed. PMID:26056673

  5. 38 CFR 4.130 - Schedule of ratings-mental disorders.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., poisons) 9327Organic mental disorder, other (including personality change due to a general medical... 9416Dissociative amnesia; dissociative fugue; dissociative identity disorder (multiple personality...

  6. Exploring the social impact of being a typical peer model for included children with autism spectrum disorder.

    PubMed

    Locke, Jill; Rotheram-Fuller, Erin; Kasari, Connie

    2012-09-01

    This study examined the social impact of being a typical peer model as part of a social skills intervention for children with autism spectrum disorder (ASD). Participants were drawn from a randomized-controlled-treatment trial that examined the effects of targeted interventions on the social networks of 60 elementary-aged children with ASD. Results demonstrated that typical peer models had higher social network centrality, received friendships, friendship quality, and less loneliness than non-peer models. Peer models were also more likely to be connected with children with ASD than non-peer models at baseline and exit. These results suggest that typical peers can be socially connected to children with ASD, as well as other classmates, and maintain a strong and positive role within the classroom. PMID:22215436

  7. Immune-related pathways including HLA-DRB1(∗)13:02 are associated with panic disorder.

    PubMed

    Shimada-Sugimoto, Mihoko; Otowa, Takeshi; Miyagawa, Taku; Khor, Seik-Soon; Kashiwase, Koichi; Sugaya, Nagisa; Kawamura, Yoshiya; Umekage, Tadashi; Kojima, Hiroto; Saji, Hiroh; Miyashita, Akinori; Kuwano, Ryozo; Kaiya, Hisanobu; Kasai, Kiyoto; Tanii, Hisashi; Okazaki, Yuji; Tokunaga, Katsushi; Sasaki, Tsukasa

    2015-05-01

    Panic disorder (PD) is an anxiety disorder characterized by panic attacks and anticipatory anxiety. Both genetic and environmental factors are thought to trigger PD onset. Previously, we performed a genome-wide association study (GWAS) for PD and focused on candidate SNPs with the lowest P values. However, there seemed to be a number of polymorphisms which did not reach genome-wide significance threshold due to their low allele frequencies and odds ratios, even though they were truly involved in pathogenesis. Therefore we performed pathway analyses in order to overcome the limitations of conventional single-marker analysis and identify associated SNPs with modest effects. Each pathway analysis indicated that pathways related to immunity showed the strongest association with PD (DAVID, P=2.08×10(-6); i-GSEA4GWAS, P<10(-3); ICSNPathway, P<10(-3)). Based on the results of pathway analyses and the previously performed GWAS for PD, we focused on and investigated HLA-B and HLA-DRB1 as candidate susceptibility genes for PD. We typed HLA-B and HLA-DRB1 in 744 subjects with PD and 1418 control subjects. Patients with PD were significantly more likely to carry HLA-DRB1(∗)13:02 (P=2.50×10(-4), odds ratio=1.54). Our study provided initial evidence that HLA-DRB1(∗)13:02 and genes involved in immune-related pathways are associated with PD. Future studies are necessary to confirm these results and clarify the underlying mechanisms causing PD. PMID:25582808

  8. SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation

    PubMed Central

    Ahlfors, Helena; Limaye, Amita; Elo, Laura L.; Tuomela, Soile; Burute, Mithila; Gottimukkala, Kamal Vishnu P.; Notani, Dimple; Rasool, Omid

    2010-01-01

    Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation. PMID:20522714

  9. Study Modules for Calculus-Based General Physics. [Includes Modules 3-5: Planar Motion; Newton's Laws; and Vector Multiplication].

    ERIC Educational Resources Information Center

    Fuller, Robert G., Ed.; And Others

    This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

  10. Multiple hypothesis correction is vital and undermines reported mtDNA links to diseases including AIDS, cancer, and Huntingdon's.

    PubMed

    Johnston, Iain G

    2016-09-01

    The ability to sequence mitochondrial genomes quickly and cheaply has led to an explosion in available mtDNA data. As a result, an expanding literature is exploring links between mtDNA features and susceptibility to, or prevalence of, a range of diseases. Unfortunately, this great technological power has not always been accompanied by great statistical responsibility. I will focus on one aspect of statistical analysis, multiple hypothesis correction, that is absolutely required, yet often absolutely ignored, for responsible interpretation of this literature. Many existing studies perform comparisons between incidences of a large number (N) of different mtDNA features and a given disease, reporting all those yielding p values under 0.05 as significant links. But when many comparisons are performed, it is highly likely that several p values under 0.05 will emerge, by chance, in the absence of any underlying link. A suitable correction (for example, Bonferroni correction, requiring p < 0.05/N) must, therefore, be employed to avoid reporting false positive results. The absence of such corrections means that there is good reason to believe that many links reported between mtDNA features and various diseases are false; a state of affairs that is profoundly negative both for fundamental biology and for public health. I will show that statistics matching those claimed to illustrate significant links can arise, with a high probability, when no such link exists, and that these claims should thus be discarded until results of suitable statistical reliability are provided. I also discuss some strategies for responsible analysis and interpretation of this literature. PMID:25884427

  11. Host cell interactome of HIV-1 Rev includes RNA helicases involved in multiple facets of virus production.

    PubMed

    Naji, Souad; Ambrus, Gza; Cimerman?i?, Peter; Reyes, Jason R; Johnson, Jeffrey R; Filbrandt, Rebecca; Huber, Michael D; Vesely, Paul; Krogan, Nevan J; Yates, John R; Saphire, Andrew C; Gerace, Larry

    2012-04-01

    The HIV-1 Rev protein plays a key role in the late phase of virus replication. It binds to the Rev Response Element found in underspliced HIV mRNAs, and drives their nuclear export by the CRM1 receptor pathway. Moreover, mounting evidence suggests that Rev has additional functions in viral replication. Here we employed proteomics and statistical analysis to identify candidate host cell factors that interact with Rev. For this we studied Rev complexes assembled in vitro with nuclear or cytosolic extracts under conditions emulating various intracellular environments of Rev. We ranked the protein-protein interactions by combining several statistical features derived from pairwise comparison of conditions in which the abundance of the binding partners changed. As a validation set, we selected the eight DEAD/H box proteins of the RNA helicase family from the top-ranking 5% of the proteins. These proteins all associate with ectopically expressed Rev in immunoprecipitates of cultured cells. From gene knockdown approaches, our work in combination with previous studies indicates that six of the eight DEAD/H proteins are linked to HIV production in our cell model. In a more detailed analysis of infected cells where either DDX3X, DDX5, DDX17, or DDX21 was silenced, we observed distinctive phenotypes for multiple replication features, variously involving virus particle release, the levels of unspliced and spliced HIV mRNAs, and the nuclear and cytoplasmic concentrations of these transcripts. Altogether the work indicates that our top-scoring data set is enriched in Rev-interacting proteins relevant to HIV replication. Our more detailed analysis of several Rev-interacting DEAD proteins suggests a complex set of functions for the helicases in regulation of HIV mRNAs. The strategy used here for identifying Rev interaction partners should prove effective for analyzing other viral and cellular proteins. PMID:22174317

  12. Host Cell Interactome of HIV-1 Rev Includes RNA Helicases Involved in Multiple Facets of Virus Production*

    PubMed Central

    Naji, Souad; Ambrus, Géza; Cimermančič, Peter; Reyes, Jason R.; Johnson, Jeffrey R.; Filbrandt, Rebecca; Huber, Michael D.; Vesely, Paul; Krogan, Nevan J.; Yates, John R.; Saphire, Andrew C.; Gerace, Larry

    2012-01-01

    The HIV-1 Rev protein plays a key role in the late phase of virus replication. It binds to the Rev Response Element found in underspliced HIV mRNAs, and drives their nuclear export by the CRM1 receptor pathway. Moreover, mounting evidence suggests that Rev has additional functions in viral replication. Here we employed proteomics and statistical analysis to identify candidate host cell factors that interact with Rev. For this we studied Rev complexes assembled in vitro with nuclear or cytosolic extracts under conditions emulating various intracellular environments of Rev. We ranked the protein-protein interactions by combining several statistical features derived from pairwise comparison of conditions in which the abundance of the binding partners changed. As a validation set, we selected the eight DEAD/H box proteins of the RNA helicase family from the top-ranking 5% of the proteins. These proteins all associate with ectopically expressed Rev in immunoprecipitates of cultured cells. From gene knockdown approaches, our work in combination with previous studies indicates that six of the eight DEAD/H proteins are linked to HIV production in our cell model. In a more detailed analysis of infected cells where either DDX3X, DDX5, DDX17, or DDX21 was silenced, we observed distinctive phenotypes for multiple replication features, variously involving virus particle release, the levels of unspliced and spliced HIV mRNAs, and the nuclear and cytoplasmic concentrations of these transcripts. Altogether the work indicates that our top-scoring data set is enriched in Rev-interacting proteins relevant to HIV replication. Our more detailed analysis of several Rev-interacting DEAD proteins suggests a complex set of functions for the helicases in regulation of HIV mRNAs. The strategy used here for identifying Rev interaction partners should prove effective for analyzing other viral and cellular proteins. PMID:22174317

  13. Clinical and neuroimaging correlation of movement disorders in multiple sclerosis: case series and review of the literature.

    PubMed

    Potulska-Chromik, Anna; Rudzinska, Monika; Nojszewska, Monika; Podlecka-Piętowska, Aleksandra; Szczudlik, Andrzej; Zakrzewska-Pniewska, Beata; Gołębiowski, Marek

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, in which movement disorders (MD) have been reported very rarely. Anatomopathological studies of MS indicate two main processes: inflammation and neurodegeneration. The occurrence of the movement disorders symptoms in MS revises the question of aetiology of these two diseases. During the 10 years of observation in our out-patient clinic and MS units we examined about 2500 patients with clinically definite MS diagnosed according to the revised McDonald's criteria. Only in 10 cases we found coexistence of MS and MD signs. Below we present rare cases of patients with coexistence of MS and chorea, pseudoathetosis, dystonia and parkinsonism. Searching for the strategic focal lesion in our case series showed demyelinating plaques placed in the thalamus most often. Detailed analysis of the clinical, pharmacological and neuroimaging correlations may help to explain the character of movement disorders in MS. PMID:24729346

  14. Multiple Beneficial Lipids Including Lecithin Detected in the Edible Invasive Mollusk Crepidula fornicata from the French Northeastern Atlantic Coast

    PubMed Central

    Dagorn, Flore; Buzin, Florence; Couzinet-Mossion, Aurélie; Decottignies, Priscilla; Viau, Michèle; Rabesaotra, Vony; Barnathan, Gilles; Wielgosz-Collin, Gaëtane

    2014-01-01

    The invasive mollusk Crepidula fornicata, occurring in large amounts in bays along the French Northeastern Atlantic coasts, may have huge environmental effects in highly productive ecosystems where shellfish are exploited. The present study aims at determining the potential economic value of this marine species in terms of exploitable substances with high added value. Lipid content and phospholipid (PL) composition of this mollusk collected on the Bourgneuf Bay were studied through four seasons. Winter specimens contained the highest lipid levels (5.3% dry weight), including 69% of PLs. Phosphatidylcholine (PC) was the major PL class all year, accounting for 63.9% to 88.9% of total PLs. Consequently, the winter specimens were then investigated for PL fatty acids (FAs), and free sterols. Dimethylacetals (DMAs) were present (10.7% of PL FA + DMA mixture) revealing the occurrence of plasmalogens. More than forty FAs were identified, including 20:5n-3 (9.4%) and 22:6n-3 (7.3%) acids. Fourteen free sterols were present, including cholesterol at 31.3% of the sterol mixture and about 40% of phytosterols. These data on lipids of C. fornicata demonstrate their positive attributes for human nutrition and health. The PL mixture, rich in PC and polyunsaturated FAs, offers an interesting alternative source of high value-added marine lecithin. PMID:25532566

  15. Improved sequence-based prediction of disordered regions with multilayer fusion of multiple information sources

    PubMed Central

    Mizianty, Marcin J.; Stach, Wojciech; Chen, Ke; Kedarisetti, Kanaka Durga; Disfani, Fatemeh Miri; Kurgan, Lukasz

    2010-01-01

    Motivation: Intrinsically disordered proteins play a crucial role in numerous regulatory processes. Their abundance and ubiquity combined with a relatively low quantity of their annotations motivate research toward the development of computational models that predict disordered regions from protein sequences. Although the prediction quality of these methods continues to rise, novel and improved predictors are urgently needed. Results: We propose a novel method, named MFDp (Multilayered Fusion-based Disorder predictor), that aims to improve over the current disorder predictors. MFDp is as an ensemble of 3 Support Vector Machines specialized for the prediction of short, long and generic disordered regions. It combines three complementary disorder predictors, sequence, sequence profiles, predicted secondary structure, solvent accessibility, backbone dihedral torsion angles, residue flexibility and B-factors. Our method utilizes a custom-designed set of features that are based on raw predictions and aggregated raw values and recognizes various types of disorder. The MFDp is compared at the residue level on two datasets against eight recent disorder predictors and top-performing methods from the most recent CASP8 experiment. In spite of using training chains with ≤25% similarity to the test sequences, our method consistently and significantly outperforms the other methods based on the MCC index. The MFDp outperforms modern disorder predictors for the binary disorder assignment and provides competitive real-valued predictions. The MFDp's outputs are also shown to outperform the other methods in the identification of proteins with long disordered regions. Availability: http://biomine.ece.ualberta.ca/MFDp.html Supplementary information: Supplementary data are available at Bioinformatics online. Contact: lkurgan@ece.ualberta.ca PMID:20823312

  16. Multiple micronutrient supplementation during pregnancy in low-income countries: Review of methods and characteristics of studies included in the meta-analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper reports on the methods and characteristics of 12 studies from developing countries included in a meta-analysis of the impact of antenatal supplements of multiple micronutrients compared with iron–folic acid on micronutrient status, maternal nutritional status, birth outcomes, and neonatal...

  17. Immediate-Release Methylphenidate for ADHD in Children with Comorbid Chronic Multiple Tic Disorder

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; Sverd, Jeffrey; Nolan, Edith E.; Sprafkin, Joyce; Schneider, Jayne

    2007-01-01

    Objective: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). Method: Two cohorts of prepubertal children (N = 71) received placebo and three doses of

  18. Immediate-Release Methylphenidate for ADHD in Children with Comorbid Chronic Multiple Tic Disorder

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; Sverd, Jeffrey; Nolan, Edith E.; Sprafkin, Joyce; Schneider, Jayne

    2007-01-01

    Objective: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). Method: Two cohorts of prepubertal children (N = 71) received placebo and three doses of…

  19. Commentary: Differentiated Measures of Temperament and Multiple Pathways to Childhood Disorders

    ERIC Educational Resources Information Center

    Rothbart, Mary K.

    2004-01-01

    Provided is a commentary on articles written for a special section on temperament and childhood disorders. Temperament's contributions to the development of childhood disorders are considered both generally and specifically. Questions are raised about the use of terminology in the field, particularly the term difficult. Differentiation of outcomes…

  20. The multiple effects of thyroid disorders on bone and mineral metabolism.

    PubMed

    Cardoso, Ludmilla F; Maciel, Léa M Z; Paula, Francisco J A de

    2014-07-01

    Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton. PMID:25166035

  1. RHD maternal-fetal genotype incompatibility and schizophrenia: extending the MFG test to include multiple siblings and birth order.

    PubMed

    Kraft, Peter; Palmer, Christina G S; Woodward, Arthur J; Turunen, Joni A; Minassian, Sonia; Paunio, Tiina; Lönnqvist, Jouko; Peltonen, Leena; Sinsheimer, Janet S

    2004-03-01

    Rh incompatibility disease (ie Rh hemolytic disease of the fetus and newborn) has been implicated as a risk factor for schizophrenia. Here, we extend the maternal-fetal genotype incompatibility (MFG) test used in an earlier case-parent trio study that found significant evidence for an increased risk of schizophrenia in RHD MFG-incompatible children. We modify the MFG test for case-parent trios to include any number of siblings. This modified test enables us to use more of the available data from the earlier study. The increased sample size not only gives us greater power to test for MFG incompatibility but it also enables us to model the impact of previous RHD MFG-incompatible pregnancies on the relative risk of RHD MFG incompatibility in later-born siblings. This modeling is important, because RHD MFG incompatibility is a proxy for Rh incompatibility disease, and the risk of Rh incompatibility disease increases with the number of previous RHD MFG-incompatible pregnancies. The best-fitting models are consistent with the hypothesized effect that previous incompatible pregnancies increase the risk of schizophrenia due to RHD MFG incompatibility. There was significant evidence that the relative risk of schizophrenia in the second- and later-born RHD MFG-incompatible children is 1.7, consistent with earlier estimates. Our extension of the MFG test has general application to family-based studies of maternal-genotype and MFG interaction effects. PMID:14735156

  2. A Drug-Sensitized Zebrafish Screen Identifies Multiple Genes, Including GINS3, as Regulators of Myocardial Repolarization

    PubMed Central

    Milan, David J.; Kim, Albert M.; Winterfield, Jeffrey R.; Jones, Ian L.; Pfeufer, Arne; Sanna, Serena; Arking, Dan E.; Amsterdam, Adam H.; Sabeh, Khaled M.; Mably, John D.; Rosenbaum, David S.; Peterson, Randall T.; Chakravarti, Aravinda; Kääb, Stefan; Roden, Dan M.; MacRae, Calum A.

    2009-01-01

    Background Cardiac repolarization, the process by which cardiomyocytes return to their resting potential after each beat, is a highly regulated process that is critical for heart rhythm stability. Perturbations of cardiac repolarization increase the risk for life-threatening arrhythmias and sudden cardiac death. While genetic studies of familial long QT syndromes have uncovered several key genes in cardiac repolarization, the major heritable contribution to this trait remains unexplained. Identification of additional genes may lead to a better understanding of the underlying biology, aid in identification of patients at risk for sudden death, and potentially enable new treatments for susceptible individuals. Methods and Results We extended and refined a zebrafish model of cardiac repolarization by using fluorescent reporters of transmembrane potential. We then conducted a drug-sensitized genetic screen in zebrafish, identifying 15 genes, including GINS3, that affect cardiac repolarization. Testing these genes for human relevance in two concurrently completed genome wide association studies revealed that the human GINS3 ortholog is located in the 16q21 locus which is strongly associated with QT interval. Conclusions This sensitized zebrafish screen identified 15 novel myocardial repolarization genes. Among these genes is GINS3, the human ortholog of which is a major locus in two concurrent human genome wide association studies of QT interval. These results reveal a novel network of genes that regulate cardiac repolarization. PMID:19652097

  3. Airborne electromagnetic detection of shallow seafloor topographic features, including resolution of multiple sub-parallel seafloor ridges

    NASA Astrophysics Data System (ADS)

    Vrbancich, Julian; Boyd, Graham

    2014-05-01

    The HoistEM helicopter time-domain electromagnetic (TEM) system was flown over waters in Backstairs Passage, South Australia, in 2003 to test the bathymetric accuracy and hence the ability to resolve seafloor structure in shallow and deeper waters (extending to ~40 m depth) that contain interesting seafloor topography. The topography that forms a rock peak (South Page) in the form of a mini-seamount that barely rises above the water surface was accurately delineated along its ridge from the start of its base (where the seafloor is relatively flat) in ~30 m water depth to its peak at the water surface, after an empirical correction was applied to the data to account for imperfect system calibration, consistent with earlier studies using the same HoistEM system. A much smaller submerged feature (Threshold Bank) of ~9 m peak height located in waters of 35 to 40 m depth was also accurately delineated. These observations when checked against known water depths in these two regions showed that the airborne TEM system, following empirical data correction, was effectively operating correctly. The third and most important component of the survey was flown over the Yatala Shoals region that includes a series of sub-parallel seafloor ridges (resembling large sandwaves rising up to ~20 m from the seafloor) that branch out and gradually decrease in height as the ridges spread out across the seafloor. These sub-parallel ridges provide an interesting topography because the interpreted water depths obtained from 1D inversion of TEM data highlight the limitations of the EM footprint size in resolving both the separation between the ridges (which vary up to ~300 m) and the height of individual ridges (which vary up to ~20 m), and possibly also the limitations of assuming a 1D model in areas where the topography is quasi-2D/3D.

  4. Identification of Multiple DNA Copy Number Alterations Including Frequent 8p11.22 Amplification in Conjunctival Squamous Cell Carcinoma

    PubMed Central

    Asnaghi, Laura; Alkatan, Hind; Mahale, Alka; Othman, Maha; Alwadani, Saeed; Al-Hussain, Hailah; Jastaneiah, Sabah; Yu, Wayne; Maktabi, Azza; Edward, Deepak P.; Eberhart, Charles G.

    2014-01-01

    Purpose. Little is known about the molecular alterations that drive formation and growth of conjunctival squamous cell carcinoma (cSCC). We therefore sought to identify genetic changes that could be used as diagnostic markers or therapeutic targets. Methods. The DNA extracted from 10 snap-frozen cSCC tumor specimens and 2 in situ carcinomas was analyzed using array-based comparative genomic hybridization (aCGH), and further examined with NanoString and quantitative PCR. Results. The number of regions of DNA loss ranged from 1 to 23 per tumor, whereas gains and amplifications ranged from 1 to 15 per tumor. Most large regions of chromosomal gain and loss were confirmed by NanoString karyotype analysis. The commonest alteration was amplification of 8p11.22 in 9 tumors (75%), and quantitative PCR analysis revealed 100-fold or greater overexpression of ADAM3A mRNA from 8p11.22 locus. In addition, recurring losses were observed at 14q13.2 and 22q11.23, both lost in 5 (42%) of the 12 tumors, and at 12p13.31, lost in 4 (33%) of the 12 samples. Of the eight loci associated with the DNA damage repair syndrome xeroderma pigmentosum, three showed loss of at least one allele in our aCGH analysis, including XPA (9q22.33, one tumor), XPE/DDB2 (11p11.2, one tumor) and XPG/ERCC5 (13q33.1, three tumors). Conclusions. Conjunctival SCC contains a range of chromosomal alterations potentially important in tumor formation and growth. Amplification of 8p11.22 and overexpression of ADAM3A suggests a potential role for this protease. Our findings also suggest that defects in DNA repair loci are important in sporadic cSCC. PMID:25491297

  5. Dehalococcoides mccartyi strain JNA dechlorinates multiple chlorinated phenols including pentachlorophenol and harbors at least 19 reductive dehalogenase homologous genes.

    PubMed

    Fricker, Ashwana D; LaRoe, Sarah L; Shea, Michael E; Bedard, Donna L

    2014-12-16

    Pentachlorophenol and other chlorinated phenols are highly toxic ubiquitous environmental pollutants. Using gas chromatographic analysis we determined that Dehalococcoides mccartyi strain JNA in pure culture dechlorinated pentachlorophenol to 3,5-dichlorophenol (DCP) via removal of the ortho and para chlorines in all of the three possible pathways. In addition, JNA dechlorinated 2,3,4,6-tetrachlorophenol via 2,4,6-trichlorophenol (TCP) and 2,4,5-TCP to 2,4-DCP and 3,4-DCP, respectively, and dechlorinated 2,3,6-TCP to 3-chlorophenol (CP) via 2,5-DCP. JNA converted 2,3,4-TCP to 3,4-DCP and 2,4-DCP by ortho and meta dechlorination, respectively. 2,3-DCP was dechlorinated to 3-CP, and, because cultures using it could be transferred with a low inoculum (0.5 to 1.5% vol/vol), it may act as an electron acceptor to support growth. Using PCR amplification with targeted and degenerate primers followed by cloning and sequencing, we determined that JNA harbors at least 19 reductive dehalogenase homologous (rdh) genes including orthologs of pcbA4 and pcbA5, pceA, and mbrA, but not tceA or vcrA. Many of these genes are shared with D. mccartyi strains CBDB1, DCMB5, GT, and CG5. Strain JNA has previously been shown to extensively dechlorinate the commercial polychlorinated biphenyl (PCB) mixture Aroclor 1260. Collectively the data suggest that strain JNA may be well adapted to survive in sites contaminated with chlorinated aromatics and may be useful for in situ bioremediation. PMID:25377868

  6. Pterosin B has multiple targets in gluconeogenic programs, including coenzyme Q in RORα-SRC2 signaling.

    PubMed

    Itoh, Yumi; Fuchino, Hiroyuki; Sanosaka, Masato; Kako, Koichiro; Hada, Kazumasa; Fukamizu, Akiyoshi; Takemori, Hiroshi; Kawahara, Nobuo

    2016-04-29

    Hepatic gluconeogenic programs are regulated by a variety of signaling cascades. Glucagon-cAMP signaling is the main initiator of the gluconeogenic programs, including glucose-6-phosphatase catalytic subunit (G6pc) gene expression. Pterosin B, an ingredient in Pteridium aquilinum, inhibits salt-inducible kinase 3 signaling that represses cAMP-response element-binding protein regulated transcription coactivator 2, an inducer of gluconeogenic programs. As the results, pterosin B promotes G6pc expression even in the absence of cAMP. In this work, however, we noticed that once cAMP signaling was initiated, pterosin B became a strong repressor of G6pc expression. The search for associated transcription factors for pterosin B actions revealed that retinoic acid receptor-related orphan receptor alpha-steroid receptor coactivator 2 (RORα-SRC2) complex on the G6pc promoter was the target. Meanwhile, pterosin B impaired the oxidation-reduction cycle of coenzyme Q in mitochondrial oxidative phosphorylation (OXPHOS); and antimycin A, an inhibitor of coenzyme Q: cytochrome c-oxidoreductase (termed mitochondrial complex III), also mimicked pterosin B actions on RORα-SRC2 signaling. Although other respiratory toxins (rotenone and oligomycin) also suppressed G6pc expression accompanied by lowered ATP levels following the activation of AMP-activated kinase, minimal or no effect of these other toxins on RORα-SRC2 activity was observed. These results suggested that individual components in OXPHOS differentially linked to different transcriptional machineries for hepatic gluconeogenic programs, and the RORα-SRC2 complex acted as a sensor for oxidation-reduction cycle of coenzyme Q and regulated G6Pc expression. This was a site disrupted by pterosin B in gluconeogenic programs. PMID:26970301

  7. Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial

    PubMed Central

    IJff, Marjoliek A; Huijbregts, Klaas ML; van Marwijk, Harm WJ; Beekman, Aartjan TF; Hakkaart-van Roijen, Leona; Rutten, Frans F; Unützer, Jürgen; van der Feltz-Cornelis, Christina M

    2007-01-01

    Background Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries. Methods/design This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months) are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36. Discussion In this study, an American model to enhance care for patients with a depressive disorder, the collaborative care model, will be evaluated for effectiveness in the primary care setting. If effective across the Atlantic and across different health care systems, it is also likely to be an effective strategy to implement in the treatment of major depressive disorder in the Netherlands. PMID:17331237

  8. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies

    PubMed Central

    Haque, Syed K.; Ariceta, Gema; Batlle, Daniel

    2012-01-01

    Proximal renal tubular acidosis (RTA) (Type II RTA) is characterized by a defect in the ability to reabsorb HCO3 in the proximal tubule. This is usually manifested as bicarbonate wastage in the urine reflecting that the defect in proximal tubular transport is severe enough that the capacity for bicarbonate reabsorption in the thick ascending limb of Henle's loop and more distal nephron segments is overwhelmed. More subtle defects in proximal bicarbonate transport likely go clinically unrecognized owing to compensatory reabsorption of bicarbonate distally. Inherited proximal RTA is more commonly autosomal recessive and has been associated with mutations in the basolateral sodium-bicarbonate cotransporter (NBCe1). Mutations in this transporter lead to reduced activity and/or trafficking, thus disrupting the normal bicarbonate reabsorption process of the proximal tubules. As an isolated defect for bicarbonate transport, proximal RTA is rare and is more often associated with the Fanconi syndrome characterized by urinary wastage of solutes like phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins as well as bicarbonate. A vast array of rare tubular disorders may cause proximal RTA but most commonly it is induced by drugs. With the exception of carbonic anhydrase inhibitors which cause isolated proximal RTA, drug-induced proximal RTA is associated with Fanconi syndrome. Drugs that have been recently recognized to cause severe proximal RTA with Fanconi syndrome include ifosfamide, valproic acid and various antiretrovirals such as Tenofovir particularly when given to human immunodeficiency virus patients receiving concomitantly protease inhibitors such as ritonavir or reverse transcriptase inhibitors such as didanosine. PMID:23235953

  9. Manual for the psychotherapeutic treatment of acute and post-traumatic stress disorders following multiple shocks from implantable cardioverter defibrillator (ICD)

    PubMed Central

    Jordan, Jochen; Titscher, Georg; Peregrinova, Ludmila; Kirsch, Holger

    2013-01-01

    Background: In view of the increasing number of implanted cardioverter defibrillators (ICD), the number of people suffering from so-called “multiple ICD shocks” is also increasing. The delivery of more than five shocks (appropriate or inappropriate) in 12 months or three or more shocks (so called multiple shocks) in a short time period (24 hours) leads to an increasing number of patients suffering from severe psychological distress (anxiety disorder, panic disorder, adjustment disorder, post-traumatic stress disorder). Untreated persons show chronic disease processes and a low rate of spontaneous remission and have an increased morbidity and mortality. Few papers have been published concerning the psychotherapeutic treatment for these patients. Objective: The aim of this study is to develop a psychotherapeutic treatment for patients with a post-traumatic stress disorder or adjustment disorder after multiple ICD shocks. Design: Explorative feasibility study: Treatment of 22 patients as a natural design without randomisation and without control group. The period of recruitment was three years, from March 2007 to March 2010. The study consisted of two phases: in the first phase (pilot study) we tested different components and dosages of psychotherapeutic treatments. The final intervention programme is presented in this paper. In the second phase (follow-up study) we assessed the residual post-traumatic stress symptoms in these ICD patients. The time between treatment and follow-up measurement was 12 to 30 months. Population: Thirty-one patients were assigned to the Department of Psychocardiology after multiple shocks. The sample consisted of 22 patients who had a post-traumatic stress disorder or an adjustment disorder and were willing and able to participate. They were invited for psychological treatment. 18 of them could be included into the follow-up study. Methods: After the clinical assessment at the beginning and at the end of the inpatient treatment a post-treatment assessment with questionnaires followed. In this follow-up measurement, minimum 12 months after inpatient treatment, posttraumatic stress was assessed using the “Impact of Event Scale” (IES-R). Setting: Inpatient treatment in a large Heart and Thorax Centre with a Department of Psychocardiology (Kerckhoff Heart Centre). Results: From the 18 patients in the follow-up study no one reported complaints of PTSD. 15 of them reported a high or even a very high decrease of anxiety and avoidance behaviour. Conclusions: The fist step of the treatment development seems to be successful. It shows encouraging results with an acceptable dosage. The second step of our work is in process now: we evaluate the treatment manual within other clinical institutions and a higher number of psychotherapists. This leads in the consequence to a controlled and randomised comparison study. PMID:24403967

  10. Cognitive impairment and memory disorders in relapsing-remitting multiple sclerosis: the role of white matter, gray matter and hippocampus.

    PubMed

    Sacco, R; Bisecco, A; Corbo, D; Della Corte, M; d'Ambrosio, A; Docimo, R; Gallo, A; Esposito, F; Esposito, S; Cirillo, M; Lavorgna, L; Tedeschi, G; Bonavita, S

    2015-07-01

    Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they have been correlated with different MRI measures of brain tissue damage, whole and regional brain atrophy. The hippocampal involvement has been poorly investigated in cognitively impaired (CI) MS patients. The objective of this study is to analyze and compare brain tissue abnormalities, including hippocampal atrophy, in relapsing-remitting MS (RRMS) patients with and without cognitive deficits, and to investigate their role in determining cognitive impairment in MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age, sex and education-matched healthy controls (HCs) underwent neuropsychological evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a semiautomatic method, gray matter volume and white matter volume were estimated using SIENAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain tissues volumes were compared among groups and correlated with cognitive performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM, left and right Hippocampus (p < 0.001). Compared to CP, CI RRMS patients showed higher T2-LL (p = 0.02) and WM atrophy (p = 0.01). In the whole RRMS group, several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and GM atrophy); only verbal memory performances correlated with left hippocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cognitive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients regardless of cognitive status. PMID:25957638

  11. Genetics Home Reference: multiple lentigines syndrome

    MedlinePlus

    ... signs and symptoms of multiple lentigines syndrome include learning disorders, mild developmental delay, a sunken or protruding chest, ... Mutations in the PTPN11 , RAF1 , or BRAF genes cause multiple lentigines syndrome . Approximately 90 percent of individuals ...

  12. Immune Parameters That Distinguish Multiple Sclerosis Patients from Patients with Other Neurological Disorders at Presentation

    PubMed Central

    Mouzaki, Athanasia; Rodi, Maria; Dimisianos, Nikolaos; Emmanuil, Andreas; Kalavrizioti, Dimitra; Lagoudaki, Rosa; Grigoriadis, Nikolaos C.; Papathanasopoulos, Panagiotis

    2015-01-01

    Background/Aim Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. Effector T helper cells, mainly Th1 and Th17, cytotoxic T-cells, B-cells, macrophages, microglia, and the cytokines they secrete, are implicated in the initiation and maintenance of a deregulated immune response to myelin antigens and the ensuing immune-mediated demyelination. In this study, we investigated whether signature cytokines exist in MS patients at presentation to gain an insight into the underlying immunopathogenic processes at the early stage of the disease. Methods We collected serum and cerebrospinal fluid (CSF) samples from 123 patients at presentation, eventually diagnosed with MS or non-inflammatory (NIND) or inflammatory neurological diseases (IND) or symptomatic controls (SC). The levels of cytokines IFN-γ, TNF-α, TGF-β1, IL-2, IL-4, IL-6, IL-10 and IL-17 were measured, and cytokine ratios, such as Th1/Th2, Th1/Th17, and Type-1/Type-2, were calculated. All parameters were tested for their correlations with the intrathecal IgG synthesis. Results Cytokine levels in CSF were lower than in serum in all the patients, with the exception of IL-6. Serum or CSF cytokine levels of MS patients did not differ significantly from NIND or SC, with the exception of serum IFN-γ and TNF-α that were significantly higher in NIND. IND patients presented with the highest levels of all cytokines in serum and CSF, with the exception of serum IL-10 and CSF IL-17. MS patients had a significantly lower serum Th1/Th2 ratio compared to the NIND and IND groups, and significantly lower serum Type-1/Type-2, IFN-γ/IL-10 and CSF Th1/Th17 ratios compared to IND patients. MS patients had a significantly higher CSF IL-17/IL-10 ratio compared to IND patients. The IgG index was higher in MS patients compared to the control groups; the differences reached statistical significance between the MS and the NIND and SC groups. Reiber-Felgenhauer analysis of the QIgG and QAlb indices revealed higher intrathecal IgG synthesis in MS patients, and higher blood-CSF barrier dysfunction in IND patients. The IgG index correlated with CSF IL-4 in MS patients only. Conclusions We found no signature cytokines or profiles thereof in MS patients at presentation. Only IND patients presented with a clear Th1 cytokine polarization in serum and CSF. The parameters that distinguished MS patients from patients with other neurological disorders were IgG intrathecal synthesis, the IgG index and its correlation with CSF IL-4 levels. PMID:26317430

  13. Multiple Consultee Consultation to Modify Behaviors in a Student with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Reynolds, Jennifer L.; Fisher, Sycarah D.

    2015-01-01

    Consultation is used to provide indirect services to students. The process typically occurs with a school psychologist consultant and a teacher consultee. Few cases exist demonstrating consultation with nontraditional or multiple consultees. The current study showed the use of consultation with multiple interdisciplinary consultees to implement…

  14. A disturbed processing of graviceptive pathways may be involved in the pathophysiology of balance disorders in patients with multiple sclerosis.

    PubMed

    Fonseca, Bruna Antinori Vignola da; Pereira, Cristiana Borges; Jorge, Frederico; Simm, Renata; Apostolos-Pereira, Samira; Callegaro, Dagoberto

    2016-02-01

    The purpose of this study was to determine the relationship between perception of verticality and balance disorders in multiple sclerosis patients. We evaluated patients and healthy controls. Patients were divided into two groups according to their risk of fall, with or without risk of fall, measured by a Dynamic Gait Index scale. Graviceptive perception was assessed using the subjective visual vertical test. Patients with risk of fall showed worse perception than those without risk of fall, p < 0.001. Misperception of verticality was correlated with the dynamic gait index scores (p < 0.001), suggesting that the larger the error for verticality judgment, the greater risk for falling. Considering that the perception of verticality is essential for postural control, our results suggested that the disturbed processing of graviceptive pathways may be involved in the pathophysiology of balance disorders in these patients. PMID:26982986

  15. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders

    PubMed Central

    Gridley, Gloria; Check, David; Landgren, Ola

    2008-01-01

    In a retrospective cohort of more than 4 million white and black male United States (US) veterans, we explored the role of specific prior autoimmune, infectious, inflammatory, and allergic disorders in the etiology of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Patients were selected from computerized inpatient discharge records at US Veterans Affairs hospitals. The analysis included 4641 patients (3040 white, 1601 black) and 2046 patients (1312 white; 734 black) with a discharge diagnosis of MM and MGUS, respectively. Using Poisson regression, we calculated age-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relationship between MM, MGUS, and specific prior medical conditions. Significantly elevated risks of MM were associated with broad categories of autoimmune (RR, 1.15; 95% CI, 1.02-1.28), infectious (RR, 1.29; 95% CI, 1.20-1.38), and inflammatory disorders (RR, 1.18; 95% CI, 1.10-1.27) and specific prior autoimmune (polymyositis/dermatomyositis, systemic sclerosis, autoimmune hemolytic anemia, pernicious anemia, and ankylosing spondylitis), infectious (pneumonia, hepatitis, meningitis, septicemia, herpes zoster, and poliomyelitis), and inflammatory (glomerulonephritis, nephrotic syndrome, and osteoarthritis) disorders. Risks for MGUS were generally of similar magnitude. Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development. PMID:18239085

  16. 76 FR 66006 - Revised Medical Criteria for Evaluating Congenital Disorders That Affect Multiple Body Systems

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... received since 2005.\\2\\ \\1\\ 70 FR 51252. \\2\\ We published an advance notice of proposed rulemaking (ANPRM) on November 10, 2009. 74 FR 57971. In the ANPRM, we invited interested people and organizations to... methods for establishing the existence of non-mosaic Down syndrome and other congenital disorders...

  17. Involvement of Youths with Autism Spectrum Disorders or Intellectual Disabilities in Multiple Public Service Systems

    ERIC Educational Resources Information Center

    Brookman-Frazee, Lauren; Baker-Ericzen, Mary; Stahmer, Aubyn; Mandell, David; Haine, Rachel A.; Hough, Richard L.

    2009-01-01

    The objectives of this study were to estimate the prevalence of autism spectrum disorders (ASD) and intellectual disability (ID) among youths active in at least one of five public service systems: mental health (MH), educational services for youth with serious emotional disturbance (SED), child welfare (CW), juvenile justice (JJ), and alcohol and

  18. Imaging Evidence for Disturbances in Multiple Learning and Memory Systems in Persons with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Goh, Suzanne; Peterson, Bradley S.

    2012-01-01

    Aim: The aim of this article is to review neuroimaging studies of autism spectrum disorders (ASD) that examine declarative, socio-emotional, and procedural learning and memory systems. Method: We conducted a search of PubMed from 1996 to 2010 using the terms "autism,""learning,""memory," and "neuroimaging." We limited our review to studies…

  19. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

  20. Temperament and Attention Deficit Hyperactivity Disorder: The Development of a Multiple Pathway Model

    ERIC Educational Resources Information Center

    Nigg, Joel T.; Goldsmith, H. Hill; Sachek, Jennifer

    2004-01-01

    This article outlines the parallels between major theories of attention deficit hyperactivity disorder (ADHD) and relevant temperament domains, summarizing recent research from our laboratories on (a) child temperament and (b) adult personality traits related to ADHD symptoms. These data are convergent in suggesting a role of effortful control and

  1. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in

  2. Imaging Evidence for Disturbances in Multiple Learning and Memory Systems in Persons with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Goh, Suzanne; Peterson, Bradley S.

    2012-01-01

    Aim: The aim of this article is to review neuroimaging studies of autism spectrum disorders (ASD) that examine declarative, socio-emotional, and procedural learning and memory systems. Method: We conducted a search of PubMed from 1996 to 2010 using the terms "autism,""learning,""memory," and "neuroimaging." We limited our review to studies

  3. The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53 and fibronectin

    PubMed Central

    Baron, Veronique; Adamson, Eileen D.; Calogero, Antonella; Ragona, Giuseppe; Mercola, Dan

    2008-01-01

    Recent studies are reviewed indicating that the transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53 and fibronectin. The downstream pathways of these factors display multiple nodes of interaction with each other suggesting the existence of a functional network of suppressor factors that serves to maintain normal growth regulation and resist the emergence of transformed variants. Paradoxically, Egr-1 is oncogenic in prostate cancer. In the majority of these cancers PTEN and/or p53 is inactive. It is suggested that these defects in the tumor suppressor network allow for the unopposed induction of TGFβ1 and fibronectin, which favor transformation and survival of prostate tumor epithelial cells, explain the role of Egr1 in prostate cancer. Egr1 is a novel and logical target for intervention by gene therapy methods and targeting methods are discussed. PMID:16138117

  4. Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans.

    PubMed Central

    Kniazeva, Marina; Sieber, Matt; McCauley, Scott; Zhang, Kang; Watts, Jennifer L; Han, Min

    2003-01-01

    While the general steps of fatty acid (FA) biosynthesis are well understood, the individual enzymes involved in the elongation of long chain saturated and polyunsaturated FA (PUFA) are largely unknown. Recent research indicates that these enzymes might be of considerable physiological importance for human health. We use Caenorhabditis elegans to study FA elongation activities and associated abnormal phenotypes. In this article we report that the predicted C. elegans F11E6.5/ELO-2 is a functional enzyme with the FA elongation activity. It is responsible for the elongation of palmitic acid and is involved in PUFA biosynthesis. RNAi-mediated suppression of ELO-2 causes an accumulation of palmitate and an associated decrease in the PUFA fraction in triacylglycerides and phospholipid classes. This imbalance in the FA composition results in multiple phenotypic defects such as slow growth, small body size, reproductive defects, and changes in rhythmic behavior. ELO-2 cooperates with the previously reported ELO-1 in 20-carbon PUFA production, and at least one of the enzymes must function to provide normal growth and development in C. elegans. The presented data indicate that suppression of a single enzyme of the FA elongation machinery is enough to affect various organs and systems in worms. This effect resembles syndromic disorders in humans. PMID:12586704

  5. Insertional translocation leading to a 4q13 duplication including the EPHA5 gene in two siblings with attention-deficit hyperactivity disorder.

    PubMed

    Matoso, Eunice; Melo, Joana B; Ferreira, Susana I; Jardim, Ana; Castelo, Teresa M; Weise, Anja; Carreira, Isabel M

    2013-08-01

    An insertional translocation (IT) can result in pure segmental aneusomy for the inserted genomic segment allowing to define a more accurate clinical phenotype. Here, we report on two siblings sharing an unbalanced IT inherited from the mother with a history of learning difficulty. An 8-year-old girl with developmental delay, speech disability, and attention-deficit hyperactivity disorder (ADHD), showed by GTG banding analysis a subtle interstitial alteration in 21q21. Oligonucleotide array comparative genomic hybridization (array-CGH) analysis showed a 4q13.1-q13.3 duplication spanning 8.6 Mb. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones confirmed the rearrangement, a der(21)ins(21;4)(q21;q13.1q13.3). The duplication described involves 50 RefSeq genes including the EPHA5 gene that encodes for the EphA5 receptor involved in embryonic development of the brain and also in synaptic remodeling and plasticity thought to underlie learning and memory. The same rearrangement was observed in a younger brother with behavioral problems and also exhibiting ADHD. ADHD is among the most heritable of neuropsychiatric disorders. There are few reports of patients with duplications involving the proximal region of 4q and a mild phenotype. To the best of our knowledge this is the first report of a duplication restricted to band 4q13. This abnormality could be easily missed in children who have nonspecific cognitive impairment. The presence of this behavioral disorder in the two siblings reinforces the hypothesis that the region involved could include genes involved in ADHD. PMID:23824631

  6. [Post-traumatic stress disorder (PTSD): the syndrome with multiple faces].

    PubMed

    Waddington, A; Ampelas, J-F; Mauriac, F; Bronchard, M; Zeltner, L; Mallat, V

    2003-01-01

    We choose to discuss from the PTSD's point of view because this diagnostic reference is commonly used. We wish outline its restrictive sight which could prevent the professional from having a diagnosis of PTSD. We don't want to say there is a PTSD everywhere but it appears to us that a traumatic reading can be a precious advantage for the clinician to establish a real therapeutic relation with some patients. Post-traumatic syndrome differs from the majority of other diagnostic categories as it includes in its criteria the presumptive cause of the trauma (criterion A). In the case that this syndrome originates in war experiences, the presumed cause presents itself as an exceptional event overcoming the individual's resources. The notion of war traumatisation has been extended to other events such as catastrophes, physical attacks, rapes, child and wife battering, and sexual abuses. But the events which cause PTSD (Post-Traumatic Stress Disorder) are significantly more numerous. It can be seen that medical events such as giving birth, miscarriage, heart attack, cancer, or hospitalisation following resuscitation may give rise to PTSD. Further, people experiencing prolonged periods of distress may equally develop a post-traumatic syndrome without any particular event having occurred to surpass their defences. It's the case of the Prolonged Duress Stress Disorder (PDSD). The series of discontinuous stress "waste" the psychic balance and may give rise, at one moment, to posttraumatic symptoms described in DSM, without any specific stressful event. The existence of criterion A is therefore not a necessary prerequisite in establishing a diagnosis of PTSD. It is, in fact, very difficult to predict which events could cause a PTSD, and this, especially, as the subjective aspects count at least as much as the objective aspects. The clinician should have to carefully explore how the patient experienced the event or, how he apprehended the event itself and it's outcome, if he wants get the traumatic range of a life event. The feeling of deep distress, the feeling of being trapped, the loss of control, the collapse of basic beliefs, the feeling that one's life is in jeopardy, that the physical integrity is (really or in one's imagination) threatened, the feeling of helplessness, are quite as much clues for a possible PTSD which hides behind others clinical manifestations either psychological or somatic. Furthermore, the "pure" form described in the DSM and grouping together three further criteria (reliving events, avoiding stimuli associated with the trauma, hyper-reactivity) is extremely rare in the chronic form. An untreated post-traumatic syndrome evolves with time and may present, initially, with very different pathological symptoms giving rise to equally varied diagnoses. Different etiopathogenic models propose to account for the PTSD 's heterogeneous appearance and instability with time. The comorbidity concept sees the PTSD as an independent entity other independent pathologies coexist with. The typologic concept suggests that the PTSD is an independent entity which shows different clinical appearances based on symptomatic descriptions. The "cascade" concept suggests to see the PTSD as an independent entity which offers, with time, different symptomatic appearances, in evolution, because of events caused by after effects, in different areas of the PTSD itself. All of these concepts outline the transnosologic appearance of the PTSD which makes it hardly recognizable. The "chronic" syndrome is rarely diagnosed forming a real challenge to prevention. In effect, the present authors insist on the crucial nature of early detection of PTSD since the greater the time elapsed the more difficult it becomes due to the evolutionary aspect of the syndrome, which initially has more readily recognizable symptoms. The consequences of an unrecognised PTSD are serious and affect both the individual and his immediate family and friends, contributing further to the aggravation of the problems. When a PTSD is diagnosed, it can allow the clinician to further a more global care which will help the patient to get a better recovery. With patients who suffered an infarct, the treatment of PTSD which prevents their recovery will help to go back to the way they lived before the event. It has been showed how important could be the PTSD detection on the severe burned people's pain control. Thus it seems to be crucial for the clinician to keep this diagnosis in mind alongside any other. PMID:12640323

  7. A model incorporating potential skewed X-inactivation in MZ girls suggests that X-linked QTLs exist for several social behaviours including autism spectrum disorder.

    PubMed

    Loat, C S; Haworth, C M A; Plomin, R; Craig, I W

    2008-11-01

    Sex differences in the frequency and patterns of behaviours are frequently observed and largely unexplained. We have investigated the possible role of X-linked genes in the aetiology of social behaviour problems, including those involved in autistic spectrum disorders. A novel approach has been implemented. This is based on predictions following from stochastic patterns of X-inactivation of lower concordance of monozygous female (MZF) twins than MZM twins for behaviours underpinned by X-linked QTLs and the converse that DZF twins are expected to correlate more strongly for X-linked traits than DZM twins because unlike males, females always have at least one X chromosome in common. These expectations were tested in an ongoing longitudinal cohort study in which all twins born in England and Wales between 1994 and 1996 were invited to take part. 1000 each of MZF, MZM, DZF and DZM pairs from TEDS were tested at 7 and 8 years of age. The results suggest the persistent influence of X-linked genes on cognition and social behaviour problems, including those involved in autistic spectrum disorders, from early to middle childhood. This emphasises the potential importance of X-linked genes in the developmental trajectories of behaviour and mental health and the need to stratify genetic analysis of behaviours by gender. PMID:18665976

  8. 78 FR 7659 - Revised Medical Criteria for Evaluating Congenital Disorders That Affect Multiple Body Systems

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ...We are revising the criteria in the Listing of Impairments (listings) that we use to evaluate cases involving impairments that affect multiple body systems in adults and children under titles II and XVI of the Social Security Act (Act). The revisions reflect our program experience and address adjudicator questions we have received since we last comprehensively revised this body system in 2005.......

  9. Endurance of Multiplication Fact Fluency for Students with Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Brady, Kelly K.; Kubina, Richard M., Jr.

    2010-01-01

    This study examines the relationship between a critical learning outcome of behavioral fluency and endurance, by comparing the effects of two practice procedures on multiplication facts two through nine. The first procedure, called whole time practice trial, consisted of an uninterrupted 1 minute practice time. The second procedure, endurance…

  10. Design of dual inhibitors of ROCK-I and NOX2 as potential leads for the treatment of neuroinflammation associated with various neurological diseases including autism spectrum disorder.

    PubMed

    Alokam, Reshma; Singhal, Sarthak; Srivathsav, Geetha Sai; Garigipati, Sowmya; Puppala, Sripriya; Sriram, Dharmarajan; Perumal, Yogeeswari

    2015-02-01

    Inhibition of both Rho kinase (ROCK-I) and NADPH oxidase (NOX2) to treat neuroinflammation could be very effective in the treatment of progressive neurological diseases like Alzheimer's disease, autism spectral disorder, and fragile X syndrome. NOX2 being a multi-enzyme component is activated during host defense in phagocytes such as microglia, to catalyze the production of superoxide from oxygen, while ROCK is an important mediator of fundamental cell processes like adhesion, proliferation and migration. Phosphorylated ROCK was found to activate NOX2 assembly via Ras related C3 botulinum toxin substrate (Rac) in disease conditions. Overexpression of ROCK-I and NOX2 in innate immune cells like microglial cells contribute to progressive neuronal damage early in neurological disease development. In the present study we employed a computer-aided methodology combining pharmacophores and molecular docking to identify new chemical entities that could inhibit ROCK-I as well as NOX2 (p47 phox). Among the huge dataset of a commercial database, top 18 molecules with crucial binding interactions were selected for biological evaluation. Seven among the lead molecules exhibited inhibitory potential against ROCK-I and NOX2 with IC50s ranging from 1.588 to 856.2 nM and 0.8942 to 10.24 μM, respectively, and emerged as potential hits as dual inhibitors with adequate selectivity index (SI = CC50/GIC50) in cell-based assays. The most active compound 3 was further found to show reduction of the pro-inflammatory mediators such as TNFα, interleukin-6 (IL-6) and interleukin-1beta (IL-1β) mRNA expression levels in activated (MeHg treated) human neuroblastoma (IMR32) cell lines. Hence the present work documented the utility of these dual inhibitors as prototypical leads to be useful for the treatment of neurological disorders including autism spectrum disorder and Alzheimer's disease. PMID:25465055

  11. The roles of FMRP-regulated genes in autism spectrum disorder: single- and multiple-hit genetic etiologies.

    PubMed

    Steinberg, Julia; Webber, Caleb

    2013-11-01

    Autism spectrum disorder (ASD) is a highly heritable complex neurodevelopmental condition characterized by impairments in social interaction and communication and restricted and repetitive behaviors. Although roles for both de novo and familial genetic variation have been documented, the underlying disease mechanisms remain poorly elucidated. In this study, we defined and explored distinct etiologies of genetic variants that affect genes regulated by Fragile-X mental retardation protein (FMRP), thought to play a key role in neuroplasticity and neuronal translation, in ASD-affected individuals. In particular, we developed the Trend test, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches. Exploiting detailed spatiotemporal maps of gene expression within the human brain, we identified four discrete FMRP-target subpopulations that exhibit distinct functional biases and contribute to ASD via different types of genetic variation. We also demonstrated that FMRP target genes are more likely than other genes with similar expression patterns to contribute to disease. We developed the hypothesis that FMRP targets contribute to ASD via two distinct etiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets ("single-hit etiology") or (2) the combination of multiple less penetrant disruptions of nonembryonic, synaptic FMRP targets ("multiple-hit etiology"). The Trend test provides rigorous support for a multiple-hit genetic etiology in a subset of autism cases and is easily extendible to combining information from multiple types of genetic variation (i.e., copy-number and exome variants), increasing its value to next-generation sequencing approaches. PMID:24207117

  12. The Roles of FMRP-Regulated Genes in Autism Spectrum Disorder: Single- and Multiple-Hit Genetic Etiologies

    PubMed Central

    Steinberg, Julia; Webber, Caleb

    2013-01-01

    Autism spectrum disorder (ASD) is a highly heritable complex neurodevelopmental condition characterized by impairments in social interaction and communication and restricted and repetitive behaviors. Although roles for both de novo and familial genetic variation have been documented, the underlying disease mechanisms remain poorly elucidated. In this study, we defined and explored distinct etiologies of genetic variants that affect genes regulated by Fragile-X mental retardation protein (FMRP), thought to play a key role in neuroplasticity and neuronal translation, in ASD-affected individuals. In particular, we developed the Trend test, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches. Exploiting detailed spatiotemporal maps of gene expression within the human brain, we identified four discrete FMRP-target subpopulations that exhibit distinct functional biases and contribute to ASD via different types of genetic variation. We also demonstrated that FMRP target genes are more likely than other genes with similar expression patterns to contribute to disease. We developed the hypothesis that FMRP targets contribute to ASD via two distinct etiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets (“single-hit etiology”) or (2) the combination of multiple less penetrant disruptions of nonembryonic, synaptic FMRP targets (“multiple-hit etiology”). The Trend test provides rigorous support for a multiple-hit genetic etiology in a subset of autism cases and is easily extendible to combining information from multiple types of genetic variation (i.e., copy-number and exome variants), increasing its value to next-generation sequencing approaches. PMID:24207117

  13. Enteric Bacterial Metabolites Propionic and Butyric Acid Modulate Gene Expression, Including CREB-Dependent Catecholaminergic Neurotransmission, in PC12 Cells - Possible Relevance to Autism Spectrum Disorders

    PubMed Central

    Nankova, Bistra B.; Agarwal, Raj; MacFabe, Derrick F.; La Gamma, Edmund F.

    2014-01-01

    Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA) like propionic (PPA), and butyric acid (BA), which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD). Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal) or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH) mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s) was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals such as increased levels of SCFA's can epigenetically modulate cell function further supporting their role as environmental contributors to ASD. PMID:25170769

  14. Interstitial microdeletions including the chromosome band 4q13.2 and the UBA6 gene as possible causes of intellectual disability and behavior disorder.

    PubMed

    Quintela, Ines; Barros, Francisco; Fernandez-Prieto, Montse; Martinez-Regueiro, Rocio; Castro-Gago, Manuel; Carracedo, Angel; Gomez-Lado, Carmen; Eiris, Jesus

    2015-12-01

    The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84 Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81 Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene for these phenotypes. © 2015 Wiley Periodicals, Inc. PMID:26284580

  15. Vehement Competition of Multiple Superexchange Interactions and Peculiar Magnetically Disordered State in Cu(OH)F

    NASA Astrophysics Data System (ADS)

    Danilovich, Igor; Merkulova, Anna; Polovkova, Anastasia; Zvereva, Elena; Ovchenkov, Yevgeniy; Morozov, Igor; Rahaman, Badiur; Saha-Dasgupta, Tanusri; Balz, Christian; Luetkens, Hubertus; Volkova, Olga; Shakin, Alexander; Vasiliev, Alexander

    2016-02-01

    The mixed anion copper compound Cu(OH)F was studied in measurements of dc- and ac-magnetic susceptibility, static and pulsed field magnetization, specific heat, X-band electron magnetic resonance and muon-spin spectroscopy. In variance with its layered structure, the magnetic behavior shows no evidence of low-dimensionality. Cu(OH)F reaches short range static antiferromagnetic order at TN = 9.5-11.5 K and experiences the spin-flop transition at B ˜ 3.5 T. This behavior is in a sharp contrast with physical properties of earlier reported isostructural compound Cu(OH)Cl. The first principle calculations reveal highly competitive nature of ferromagnetic and antiferromagnetic superexchange interactions, the details being rather sensitive to choice of magnetic structure employed in the extraction of magnetic interaction. Rather broad anomaly in Cp(T) dependence at phase transition and smeared magnetization curve M(B) at low temperatures suggest static disorder at low temperatures however no frequency dependence of the magnetization peak inherent for a spin-glass state was detected. Zero-field μSR data confirm transition into a static magnetically disordered state. The inter-substitutions of (OH)- and F- ions and relevant variations of exchange interaction parameters may be responsible for the formation of this peculiar ground state.

  16. "All children can and should have the opportunity to learn": general education teachers' perspectives on including children with autism spectrum disorder who require AAC.

    PubMed

    Finke, Erinn H; McNaughton, David B; Drager, Kathryn D R

    2009-06-01

    A qualitative online focus group methodology was used to investigate the experiences of five elementary school teachers (grades K-5) who had included in their general education classrooms children with autism spectrum disorders (ASD) who required augmentative and alternative communication (AAC). Information was obtained from the participants in the following areas: (a) the benefits of educational inclusion, (b) the negative impacts of educational inclusion, (c) the challenges of educational inclusion, (d) the supports for educational inclusion, and (e) recommendations for other teachers and individuals involved in the inclusion process. Participants primarily chose to focus on inclusion as a beneficial practice for all involved, but did describe a few barriers and challenges of inclusion. The results are discussed as they relate to these themes and with reference to published literature. Recommendations for future directions are also presented. PMID:19444682

  17. Field-induced multiple order-by-disorder state selection in an antiferromagnetic honeycomb bilayer lattice

    NASA Astrophysics Data System (ADS)

    Gómez Albarracín, F. A.; Rosales, H. D.

    2016-04-01

    In this paper we present a detailed study of the antiferromagnetic classical Heisenberg model on a bilayer honeycomb lattice in a highly frustrated regime in the presence of a magnetic field. This study shows strong evidence of entropic order-by-disorder selection in different sectors of the magnetization curve. For antiferromagnetic couplings J1=Jx=Jp/3 , we find that at low temperatures there are two different regions in the magnetization curve selected by this mechanism with different number of soft and zero modes. These regions present broken Z2 symmetry and are separated by a not fully collinear classical plateau at M =1 /2 . At higher temperatures, there is a crossover from the conventional paramagnet to a cooperative magnet. Finally, we also discuss the low-temperature behavior of the system for a less frustrated region, J1=Jx

  18. Multiple therapeutic and preventive effects of 3,3′-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

    PubMed Central

    Zhang, William Weiben; Feng, Zhenqing; Narod, Steven A.

    2014-01-01

    Abstract Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross. These vegetables are an abundant source of dietary phytochemicals, including glucosinolates and their hydrolysis products such as indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM). By 2013, the total number of natural glucosinolates that have been documented is estimated to be 132. Recently, cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer, antiviral infections, human sex hormone regulation, and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia (HGPIN). DIM is a hydrolysis product of glucosinolates and has been used in various trials. This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN. PMID:25332705

  19. An 11q11-q13.3 duplication, including FGF3 and FGF4 genes, in a patient with syndromic multiple craniosynostoses.

    PubMed

    Jehee, Fernanda S; Bertola, Débora R; Yelavarthi, Krishna K; Krepischi-Santos, Ana C V; Kim, Chong; Vianna-Morgante, Angela M; Vermeesch, Joris R; Passos-Bueno, Maria Rita

    2007-08-15

    Interstitial duplications of 11q are very rare and seldom reported. In this paper we describe the first case of a duplication involving bands 11q11 and 11q12. This newly described patient has multiple craniosynostoses, congenital heart defect and developmental delay, and is a carrier of a mosaic duplication: 46,XY,dup(11)(q11-->q13.3)(29)/46,XY(6). The breakpoints were further delimited by comparative genomic hybridization microarray. We also performed fluorescent in situ hybridization analysis to determine the extension of the duplication in a patient described earlier with a duplication 11q13.5-q21. An overlapping region of less than 1.2 Mb was identified and included the duplication of genes FGF3 and FGF4 in both individuals. We discuss the possible implications of dosage effects of these genes in the onset of craniosynostosis. PMID:17632770

  20. Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

    PubMed Central

    Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

    2012-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

  1. Health supervision and anticipatory guidance for children with genetic disorders (including specific recommendations for trisomy 21, trisomy 18, and neurofibromatosis I).

    PubMed

    Carey, J C

    1992-02-01

    A new model for care of children with genetic disorders has emerged from the pediatric and genetic communities in the last decade. This strategy incorporates the basic principles of well-child care, including ongoing psychological support for families, health screening, and prevention, into health supervision visits for children with these conditions. The same types of guidelines that have been developed for well children can also be applied to the routine follow-up and screening of children with these special health care needs. A number of general issues are applicable in the discussion of health supervision guidelines: correct diagnosis, analysis of the natural history of the condition, critical review of screening modalities and interventions, ongoing psychological support, and genetic counseling. With these points in mind and after a thorough review of the natural history of a disorder, guidelines can be developed and often applied to the primary care setting. Down syndrome is an ideal condition to which one can apply such a model because most children are cared for by primary care pediatricians, and the natural history is relatively well studied. Discussion of health provision in Down syndrome brings out some of the controversies regarding routine screening and review of interventions. Discussion of the natural history and uncertainties evident in the care of infants with trisomy 18 exemplifies the important issue of ongoing psychological support. Review of the natural history of neurofibromatosis emphasizes all of the principles involved in providing this model as a framework for health supervision. One of the key identified but unresolved issues is the decision as to when a primary care pediatrician can orchestrate the care on his or her own versus referral to a multidisciplinary team of specialists. In some conditions such as Down syndrome, it seems obvious that the primary care pediatrician can manage most of the care with periodic and appropriate referral to the necessary specialists. On the other hand, children with cystic fibrosis, meningomyelocele, and craniofacial syndromes almost always need referral to the specialist team because of the rarity of the disorder and the complex number of specialists involved in management. A condition such as NF-1 falls somewhere in between. Most children can be cared for in their childhood years by the pediatrician with referral when a symptom or sign emerges, but others would argue that all children with NF-1 need to be seen by a multidisciplinary team.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1531255

  2. CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8; 21).

    PubMed

    Sano, Hitoshi; Ohki, Kentaro; Park, Myoung-Ja; Shiba, Norio; Hara, Yusuke; Sotomatsu, Manabu; Tomizawa, Daisuke; Taga, Takashi; Kiyokawa, Nobutaka; Tawa, Akio; Horibe, Keizo; Adachi, Souichi; Hayashi, Yasuhide

    2015-08-01

    Mutations in the colony-stimulating factor 3 receptor (CSF3R) and calreticulin (CALR) genes have been reported in a proportion of adults with myeloproliferative disease. However, little is known about CSF3R or CALR mutations in paediatric myeloid disorders. We analysed CSF3R exons 14 and 17, and CALR exon 9, using direct sequencing in samples of paediatric acute myeloid leukaemia (AML; n = 521), juvenile myelomonocytic leukaemia (JMML; n = 40), myelodysplastic syndrome (MDS; n = 20) and essential thrombocythaemia (ET; n = 21). CSF3R mutations were found in 10 (1.2%) of 521 patients with AML; two in exon 14 (both missense mutations resulting in p.T618I) and eight in exon 17 (three frameshift mutations: p.S715X, p.Q774R, and p.S783Q; and five novel missense mutations: p.Q754K, p.R769H, p.L777F, p.T781I, and S795R). All of the patients with mutations in CSF3R exon 17 had chromosomal translocations, including four with t(8;21). At the time of reporting, seven of these ten patients are alive; three have died, due to side effects of chemotherapy. No CSF3R mutations were found in cases of MDS, JMML or ET. The only mutation found in the CALR gene was a frameshift (p.L367 fs) in one ET patient. We discuss the potential impact of these findings for the leukaemogenesis and clinical features of paediatric myeloid disorders. PMID:25858548

  3. A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

    PubMed Central

    Gau, Susan Shur-Fen; Méndez, Luis; Montgomery, William; Monk, Julie A.; Altin, Murat; Wu, Shenghu; Lin, Chaucer C.H.; Dueñas, Héctor J.

    2013-01-01

    Abstract Objective The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Methods Literature databases (MEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Results Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Conclusions Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success. PMID:23560600

  4. Multiple sclerosis

    MedlinePlus

    Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord ( central nervous system ). ... Multiple sclerosis (MS) affects women more than men. The disorder is most commonly diagnosed between ages 20 to ...

  5. Intrinsic disorder and multiple phosphorylations constrain the evolution of the flightin N-terminal region.

    PubMed

    Lemas, Dominick; Lekkas, Panagiotis; Ballif, Bryan A; Vigoreaux, Jim O

    2016-03-01

    Flightin is a myosin binding phosphoprotein that originated in the ancestor to Pancrustacea ~500MYA. In Drosophila melanogaster, flightin is essential for length determination and flexural rigidity of thick filaments. Here, we show that among 12 Drosophila species, the N-terminal region is characterized by low sequence conservation, low pI, a cluster of phosphorylation sites, and a high propensity to intrinsic disorder (ID) that is augmented by phosphorylation. Using mass spectrometry, we identified eight phosphorylation sites within a 29 amino acid segment in the N-terminal region of D. melanogaster flightin. We show that phosphorylation of D. melanogaster flightin is modulated during flight and, through a comparative analysis to orthologs from other Drosophila species, we found phosphorylation sites that remain invariant, sites that retain the charge character, and sites that are clade-specific. While the number of predicted phosphorylation sites differs across species, we uncovered a conserved pattern that relates the number of phosphorylation sites to pI and ID. Extending the analysis to orthologs of other insects, we found additional conserved features in flightin despite the near absence of sequence identity. Collectively, our results demonstrate that structural constraints demarcate the evolution of the highly variable N-terminal region. PMID:26691840

  6. Multiplicity of metastable nonergodic states of a dispersed nonwetting liquid in a disordered nanoporous medium

    NASA Astrophysics Data System (ADS)

    Borman, Vladimir D.; Belogorlov, Anton A.; Grekhov, Alexey M.; Tronin, Vladimir N.

    2014-10-01

    Three different metastable nonergodic states of a dispersed nonwetting liquid (water) in the Fluka 100 C8 and Fluka 100 C18 disordered porous media, as well as transitions between these states under variation of the temperature and the degree of filling, have been qualitatively described. It has been shown that the appearance of such states is due to spatial variations of the number of the nearest neighbors because of the broadening of the pore size distribution function f( R), fluctuations of various local configurations of neighbors in the system of pores, and fluctuations of a configuration of a pore and its environment consisting of filled and empty pores on a percolation cluster. These states and transitions are caused by the competition between the effective repulsion of the nonwetting liquid from the wall of the pore, which is responsible for the "extrusion" of the liquid from the pore, and the effective collective multiparticle attraction of the liquid cluster in the pore to clusters in the neighboring connected pores. The theoretical dependences obtained make it possible to qualitatively describe experimental data.

  7. Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.

    PubMed

    D'Gama, Alissa M; Pochareddy, Sirisha; Li, Mingfeng; Jamuar, Saumya S; Reiff, Rachel E; Lam, Anh-Thu N; Sestan, Nenad; Walsh, Christopher A

    2015-12-01

    Single nucleotide variants (SNVs), particularly loss-of-function mutations, are significant contributors to autism spectrum disorder (ASD) risk. Here we report the first systematic deep sequencing study of 55 postmortem ASD brains for SNVs in 78 known ASD candidate genes. Remarkably, even without parental samples, we find more ASD brains with mutations that are protein-altering (26/55 cases versus 12/50 controls, p = 0.015), deleterious (16/55 versus 5/50, p = 0.016), or loss-of-function (6/55 versus 0/50, p = 0.028) compared to controls, with recurrent deleterious mutations in ARID1B, SCN1A, SCN2A, and SETD2, suggesting these mutations contribute to ASD risk. In several cases, the identified mutations and medical records suggest syndromic ASD diagnoses. Two ASD and one Fragile X premutation case showed deleterious somatic mutations, providing evidence that somatic mutations occur in ASD cases, and supporting a model in which a combination of germline and/or somatic mutations may contribute to ASD risk on a case-by-case basis. PMID:26637798

  8. Binding of multiple features in memory by high-functioning adults with autism spectrum disorder.

    PubMed

    Bowler, Dermot M; Gaigg, Sebastian B; Gardiner, John M

    2014-09-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) would be tested in a later memory test. In a second experiment, participants studied similar grids and were told that they would be tested on object-location or object-colour combinations. Recognition of combinations was significantly diminished in ASD, which survived covarying performance on the Color Trails Test (D'Elia et al. Color trails test. Professional manual. Psychological Assessment Resources, Lutz, 1996), a test of executive difficulties. The findings raise the possibility that medial temporal as well as frontal lobe processes are dysfunctional in ASD. PMID:24696375

  9. Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder.

    PubMed

    Gérard, M; Morin, G; Bourillon, A; Colson, C; Mathieu, S; Rabier, D; Billette de Villemeur, T; Ogier de Baulny, H; Benoist, J F

    2015-03-01

    The cobalamin type C deficiency is a rare condition that results from impaired biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Hemizygous mutations of the HCFC1 gene explain the majority of clinically and biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We report a family with two maternal half-brothers with multiple congenital anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with dysmorphic features (flat profile, cleft lip for one), increased nuchal translucency, prenatal onset microcephaly and hypospadias. Additionally to early onset intractable epilepsy and profound neurocognitive impairment, this familial observation suggests that HCFC1 gene should be considered in boys with midline malformations, even without proven cobalamin C deficiency. PMID:25595573

  10. Functional MRI Evaluation of Multiple Neural Networks Underlying Auditory Verbal Hallucinations in Schizophrenia Spectrum Disorders

    PubMed Central

    Thoma, Robert. J.; Chaze, Charlotte; Lewine, Jeffrey David; Calhoun, Vince D.; Clark, Vincent P.; Bustillo, Juan; Houck, Jon; Ford, Judith; Bigelow, Rose; Wilhelmi, Corbin; Stephen, Julia M.; Turner, Jessica A.

    2016-01-01

    Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH). However, very little is known about how activated brain regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate onset and offset of AVH during fMRI scanning. When a general linear model was used to compare blood oxygenation level dependence signals during periods in which subjects indicated that they were versus were not experiencing AVH (“AVH-on” versus “AVH-off”), it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule, and extranuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICAs). Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated to the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital–temporal and medial prefrontal), not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures. PMID:27065889

  11. Multiple Comorbidities of 21 Psychological Disorders and Relationships With Psychosocial Variables: A Study of the Online Assessment and Diagnostic System Within a Web-Based Population

    PubMed Central

    Klein, Britt; Meyer, Denny

    2015-01-01

    Background While research in the area of e-mental health has received considerable attention over the last decade, there are still many areas that have not been addressed. One such area is the comorbidity of psychological disorders in a Web-based sample using online assessment and diagnostic tools, and the relationships between comorbidities and psychosocial variables. Objective We aimed to identify comorbidities of psychological disorders of an online sample using an online diagnostic tool. Based on diagnoses made by an automated online assessment and diagnostic system administered to a large group of online participants, multiple comorbidities (co-occurrences) of 21 psychological disorders for males and females were identified. We examined the relationships between dyadic comorbidities of anxiety and depressive disorders and the psychosocial variables sex, age, suicidal ideation, social support, and quality of life. Methods An online complex algorithm based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, was used to assign primary and secondary diagnoses of 21 psychological disorders to 12,665 online participants. The frequency of co-occurrences of psychological disorders for males and females were calculated for all disorders. A series of hierarchical loglinear analyses were performed to examine the relationships between the dyadic comorbidities of depression and various anxiety disorders and the variables suicidal ideation, social support, quality of life, sex, and age. Results A 21-by-21 frequency of co-occurrences of psychological disorders matrix revealed the presence of multiple significant dyadic comorbidities for males and females. Also, for those with some of the dyadic depression and the anxiety disorders, the odds for having suicidal ideation, reporting inadequate social support, and poorer quality of life increased for those with two-disorder comorbidity than for those with only one of the same two disorders. Conclusions Comorbidities of several psychological disorders using an online assessment tool within a Web-based population were similar to those found in face-to-face clinics using traditional assessment tools. Results provided support for the transdiagnostic approaches and confirmed the positive relationship between comorbidity and suicidal ideation, the negative relationship between comorbidity and social support, and the negative relationship comorbidity and quality of life. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG) PMID:25803420

  12. Transgenic Expression of MicroRNA-185 Causes a Developmental Arrest of T Cells by Targeting Multiple Genes Including Mzb1*

    PubMed Central

    Belkaya, Serkan; Murray, Sean E.; Eitson, Jennifer L.; de la Morena, M. Teresa; Forman, James A.; van Oers, Nicolai S. C.

    2013-01-01

    miR-185 is a microRNA (miR) that targets Bruton's tyrosine kinase in B cells, with reductions in miR-185 linked to B cell autoantibody production. In hippocampal neurons, miR-185 targets both sarcoplasmic/endoplasmic reticulum calcium ATPase 2 and a novel Golgi inhibitor. This miR is haploinsufficient in 90–95% of individuals with chromosome 22q11.2 deletion syndrome, patients who can present with immune, cardiac, and parathyroid problems, learning disorders, and a high incidence of schizophrenia in adults. The reduced levels of miR-185 in neurons cause presynaptic neurotransmitter release. Many of the 22q11.2 deletion syndrome patients have a thymic hypoplasia, which results in a peripheral T cell lymphopenia and unusual T helper cell skewing. The molecular targets of miR-185 in thymocytes are unknown. Using an miR-185 T cell transgenic approach, increasing levels of miR-185 attenuated T cell development at the T cell receptor β (TCRβ) selection checkpoint and during positive selection. This caused a peripheral T cell lymphopenia. Mzb1, Nfatc3, and Camk4 were identified as novel miR-185 targets. Elevations in miR-185 enhanced TCR-dependent intracellular calcium levels, whereas a knockdown of miR-185 diminished these calcium responses. These effects concur with reductions in Mzb1, an endoplasmic reticulum calcium regulator. Consistent with their haploinsufficiency of miR-185, Mzb1 levels were elevated in thymocyte extracts from several 22q11.2 deletion syndrome patients. Our findings indicate that miR-185 regulates T cell development through its targeting of several mRNAs including Mzb1. PMID:24014023

  13. Parental Perspectives on the Importance and Likelihood of Adult Outcomes for Children with Autism Spectrum Disorders, Intellectual Disabilities or Multiple Disabilities

    ERIC Educational Resources Information Center

    Poon, Kenneth K.; Koh, Lynette; Magiati, Iliana

    2013-01-01

    Aims: This study examined parental perspectives on the importance and likelihood of future adult outcomes for children with Autism Spectrum Disorders (ASD), Intellectual Disabilities (ID), or Multiple Disabilities (MD) and some of the factors that may affect parental aspirations. Methods: Parents of 105 children with ASD, ID, or MD were presented…

  14. "Helpful People in Touch" Consumer Led Self Help Programs for People with Multiple Disorders, Mental Illness, Drug Addiction, and Alcoholism (MIDAA).

    ERIC Educational Resources Information Center

    Sciacca, Kathleen

    This paper describes the consumer program, "Helpful People in Touch," a self-help treatment program for people with the multiple disorders of mental illness, drug addiction, and/or alcoholism. First, the terms, "Mentally Ill Chemical Abusers and Addicted" (MICAA) and "Chemical Abusing Mentally Ill" (CAMI) are defined and differentiated, with

  15. The Diagnostic Drawing Series and the Tree Rating Scale: An Isomorphic Representation of Multiple Personality Disorder, Major Depression, and Schizophrenic Populations.

    ERIC Educational Resources Information Center

    Morris, Maureen Batza

    1995-01-01

    The tree drawings of 80 subjects, who were diagnosed with either multiple personality disorder, schizophrenia, or major depression, and a control group, were rated. Patterns were examined and graphs were used to depict results. Certain features were found to distinguish each category. The descriptive statistical findings were both consistent and

  16. The Diagnostic Drawing Series and the Tree Rating Scale: An Isomorphic Representation of Multiple Personality Disorder, Major Depression, and Schizophrenic Populations.

    ERIC Educational Resources Information Center

    Morris, Maureen Batza

    1995-01-01

    The tree drawings of 80 subjects, who were diagnosed with either multiple personality disorder, schizophrenia, or major depression, and a control group, were rated. Patterns were examined and graphs were used to depict results. Certain features were found to distinguish each category. The descriptive statistical findings were both consistent and…

  17. The utility of multiple molecular methods including whole genome sequencing as tools to differentiate Escherichia coli O157:H7 outbreaks.

    PubMed

    Berenger, Byron M; Berry, Chrystal; Peterson, Trevor; Fach, Patrick; Delannoy, Sabine; Li, Vincent; Tschetter, Lorelee; Nadon, Celine; Honish, Lance; Louie, Marie; Chui, Linda

    2015-11-26

    A standardised method for determining Escherichia coli O157:H7 strain relatedness using whole genome sequencing or virulence gene profiling is not yet established. We sought to assess the capacity of either high-throughput polymerase chain reaction (PCR) of 49 virulence genes, core-genome single nt variants (SNVs) or k-mer clustering to discriminate between outbreak-associated and sporadic E. coli O157:H7 isolates. Three outbreaks and multiple sporadic isolates from the province of Alberta, Canada were included in the study. Two of the outbreaks occurred concurrently in 2014 and one occurred in 2012. Pulsed-field gel electrophoresis (PFGE) and multilocus variable-number tandem repeat analysis (MLVA) were employed as comparator typing methods. The virulence gene profiles of isolates from the 2012 and 2014 Alberta outbreak events and contemporary sporadic isolates were mostly identical; therefore the set of virulence genes chosen in this study were not discriminatory enough to distinguish between outbreak clusters. Concordant with PFGE and MLVA results, core genome SNV and k-mer phylogenies clustered isolates from the 2012 and 2014 outbreaks as distinct events. k-mer phylogenies demonstrated increased discriminatory power compared with core SNV phylogenies. Prior to the widespread implementation of whole genome sequencing for routine public health use, issues surrounding cost, technical expertise, software standardisation, and data sharing/comparisons must be addressed. PMID:26625187

  18. The effect of intellectual ability on functional activation in a neurodevelopmental disorder: preliminary evidence from multiple fMRI studies in Williams syndrome

    PubMed Central

    2012-01-01

    Background Williams syndrome (WS) is a rare genetic disorder caused by the deletion of approximately 25 genes at 7q11.23 that involves mild to moderate intellectual disability (ID). When using functional magnetic resonance imaging (fMRI) to compare individuals with ID to typically developing individuals, there is a possibility that differences in IQ contribute to between-group differences in BOLD signal. If IQ is correlated with BOLD signal, then group-level analyses should adjust for IQ, or else IQ should be matched between groups. If, however, IQ is not correlated with BOLD signal, no such adjustment or criteria for matching (and exclusion) based on IQ is necessary. Methods In this study, we aimed to test this hypothesis systematically using four extant fMRI datasets in WS. Participants included 29 adult subjects with WS (17 men) demonstrating a wide range of standardized IQ scores (composite IQ mean = 67, SD = 17.2). We extracted average BOLD activation for both cognitive and task-specific anatomically defined regions of interest (ROIs) in each individual and correlated BOLD with composite IQ scores, verbal IQ scores and non-verbal IQ scores in Spearman rank correlation tests. Results Of the 312 correlations performed, only six correlations (2%) in four ROIs reached statistical significance at a P value < 0.01, but none survived correction for multiple testing. All six correlations were positive. Therefore, none supports the hypothesis that IQ is negatively correlated with BOLD response. Conclusions These data suggest that the inclusion of subjects with below normal IQ does not introduce a confounding factor, at least for some types of fMRI studies with low cognitive load. By including subjects who are representative of IQ range for the targeted disorder, findings are more likely to generalize to that population. PMID:23102261

  19. Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients.

    PubMed

    König, C; Kleber, M; Reinhardt, H; Knop, S; Wäsch, R; Engelhardt, M

    2014-03-01

    In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach. PMID:24318541

  20. Behavioral inhibition and anxiety disorders: multiple levels of a resilience process.

    PubMed

    Degnan, Kathryn Amey; Fox, Nathan A

    2007-01-01

    Behavioral inhibition is reported to be one of the most stable temperamental characteristics in childhood. However, there is also evidence for discontinuity of this trait, with infants and toddlers who were extremely inhibited displaying less withdrawn social behavior as school-age children or adolescents. There are many possible explanations for the discontinuity in this temperament over time. They include the development of adaptive attention and regulatory skills, the influence of particular styles of parenting or caregiving contexts, and individual characteristics of the child such as their level of approach-withdrawal motivation or their gender. These discontinuous trajectories of behaviorally inhibited children and the factors that form them are discussed as examples of the resilience process. PMID:17705900

  1. Cerebellar Disorders

    MedlinePlus

    ... Problems with the cerebellum include Cancer Genetic disorders Ataxias - failure of muscle control in the arms and legs that result in movement disorders Degeneration - disorders caused by brain cells decreasing in ...

  2. The incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in multiple sclerosis: A systematic review

    PubMed Central

    Reider, Nadia; Stuve, Olaf; Trojano, Maria; Sorensen, Per Soelberg; Cutter, Gary R; Reingold, Stephen C; Cohen, Jeffrey

    2015-01-01

    Background: As new disease-modifying therapies emerge a better knowledge of the risk of comorbid disease in multiple sclerosis (MS) is needed. Objective: To estimate the incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in MS. Methods: We systematically reviewed the world literature by searching PUBMED, EMBASE, SCOPUS, the Web of Knowledge, and reference lists of retrieved articles. For selected articles, one reviewer abstracted data using a standardized form. The abstraction was verified by a second reviewer. The quality of all selected studies was assessed. For population-based studies we quantitatively assessed studies using the I2 statistic, and conducted random effects meta-analyses. Results: Study designs were heterogeneous with respect to populations, case definitions, and methods of ascertainment. Incidence of the studied comorbidities was rarely reported. Irritable bowel syndrome and chronic lung disease had a prevalence of more than 10% in the MS population. Irritable bowel syndrome, fibromyalgia, cataracts and glaucoma were more common than expected in the MS population. Conclusion: Although they have been the subject of less study than other comorbidities, irritable bowel syndrome, arthritis, and chronic lung disease are common in the MS population and occur more often than expected when compared to the general population. PMID:25538150

  3. Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.

    PubMed

    Andreassen, O A; Harbo, H F; Wang, Y; Thompson, W K; Schork, A J; Mattingsdal, M; Zuber, V; Bettella, F; Ripke, S; Kelsoe, J R; Kendler, K S; O'Donovan, M C; Sklar, P; McEvoy, L K; Desikan, R S; Lie, B A; Djurovic, S; Dale, A M

    2015-02-01

    Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility. PMID:24468824

  4. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas.

    PubMed

    Piotrowski, Arkadiusz; Xie, Jing; Liu, Ying F; Poplawski, Andrzej B; Gomes, Alicia R; Madanecki, Piotr; Fu, Chuanhua; Crowley, Michael R; Crossman, David K; Armstrong, Linlea; Babovic-Vuksanovic, Dusica; Bergner, Amanda; Blakeley, Jaishri O; Blumenthal, Andrea L; Daniels, Molly S; Feit, Howard; Gardner, Kathy; Hurst, Stephanie; Kobelka, Christine; Lee, Chung; Nagy, Rebecca; Rauen, Katherine A; Slopis, John M; Suwannarat, Pim; Westman, Judith A; Zanko, Andrea; Korf, Bruce R; Messiaen, Ludwine M

    2014-02-01

    Constitutional SMARCB1 mutations at 22q11.23 have been found in ∼50% of familial and <10% of sporadic schwannomatosis cases. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ∼80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1. PMID:24362817

  5. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas

    PubMed Central

    Piotrowski, Arkadiusz; Xie, Jing; Liu, Ying F; Poplawski, Andrzej B; Gomes, Alicia R; Madanecki, Piotr; Fu, Chuanhua; Crowley, Michael R; Crossman, David K; Armstrong, Linlea; Babovic-Vuksanovic, Dusica; Bergner, Amanda; Blakeley, Jaishri O; Blumenthal, Andrea L; Daniels, Molly S; Feit, Howard; Gardner, Kathy; Hurst, Stephanie; Kobelka, Christine; Lee, Chung; Nagy, Rebecca; Rauen, Katherine A; Slopis, John M; Suwannarat, Pim; Westman, Judith A; Zanko, Andrea; Korf, Bruce R; Messiaen, Ludwine M

    2015-01-01

    Constitutional SMARCB1 mutations at 22q11.23 have been found in ~50% of familial and <10% of sporadic schwannomatosis cases1. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ~80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1. PMID:24362817

  6. Prospective Follow-up of Girls with Attention-deficit/Hyperactivity Disorder into Early Adulthood: Continuing Impairment Includes Elevated Risk for Suicide Attempts and Self-Injury

    PubMed Central

    Hinshaw, Stephen P.; Owens, Elizabeth B.; Zalecki, Christine; Huggins, Suzanne Perrigue; Montenegro-Nevado, Adriana J.; Schrodek, Emily; Swanson, Erika N.

    2012-01-01

    Objective To perform a 10-year prospective follow-up of a childhood-ascertained (612 years), ethnically and socioeconomically diverse sample of girls with attention-deficit/hyperactivity disorder (ADHD) (N = 140: Combined type [ADHD-C} n = 93; Inattentive Type [ADHD-I] n = 47) plus a matched comparison group (N = 88). Girls were recruited from schools, mental health centers, pediatricians, and via advertisements; extensive evaluations confirmed ADHD vs. comparison status. Method Ten-year outcomes (age range 1724 years; retention rate = 95%) included symptoms (ADHD, externalizing, internalizing), substance use, eating pathology, self-perceptions, functional impairment (global, academic, service utilization), self-harm (suicide attempts, self-injury), and driving behavior. Results Participants with childhood-diagnosed ADHD continued to display higher rates of ADHD and comorbid symptoms, showed more serious impairment (both global and specific), and had higher rates of suicide attempts and self-injury than the comparison sample, with effect sizes from medium to very large; yet the groups did not differ significantly in terms of eating pathology, substance use, or driving behavior. ADHD-C and ADHD-I types rarely differed significantly, except for suicide attempts and self-injury, which were highly concentrated in ADHD-C. Domains of externalizing behavior, global impairment, and service utilization, and self-harm (suicide attempts and self-injury) survived stringent control of crucial childhood covariates (age, demographics, comorbidities, IQ). Conclusions Girls with childhood ADHD maintain marked impairment by early adulthood, spreading from symptoms to risk for serious self-harm. In future research we address the viability of different diagnostic conceptions of adult ADHD and their linkages with core life impairments. PMID:22889337

  7. Bofu-Tsu-Shosan, an Oriental Herbal Medicine, Exerts a Combinatorial Favorable Metabolic Modulation Including Antihypertensive Effect on a Mouse Model of Human Metabolic Disorders with Visceral Obesity

    PubMed Central

    Azushima, Kengo; Tamura, Kouichi; Wakui, Hiromichi; Maeda, Akinobu; Ohsawa, Masato; Uneda, Kazushi; Kobayashi, Ryu; Kanaoka, Tomohiko; Dejima, Toru; Fujikawa, Tetsuya; Yamashita, Akio; Toya, Yoshiyuki; Umemura, Satoshi

    2013-01-01

    Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM) and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF) is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT) were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system. PMID:24130717

  8. The etiology of multiple personalities.

    PubMed

    Stern, C R

    1984-03-01

    This article reviews the four major categories of explanations into the etiology of multiple personality disorder including supernatural, physiologic, psychologic, and sociologic. From these categories and their subdivisions, a series of hypotheses was developed. A paradigmatic description of a typical case of multiple personality was then created from a synthesis of the findings of case history and interview analyses. PMID:6718265

  9. Low self–esteem in women with eating disorders and alcohol abuse as a psycho–social factor to be included in their psychotherapeutic approach

    PubMed Central

    2010-01-01

    Author have analyzed the psycho–social peculiarities of the women from Romania who are affected by eating disorders and alcohol excessive consumption, and studied the manner of the link between these disease and the psycho–sexual. 120 participants at the study (Oltenia district) were divided into 2 groups: 60 healthy women, 30 with eating disorders and 30 alcohol dependent women. In all subjects were applied the following tests: Scale for compulsive appetite (SCA) and Scale of interest for own weight, both for eating disorders, CAGE questionnaire for alcohol dependence and two scales for determining: the gender–role ambivalence (O'Neil and Caroll Scale) and the masculinity and feminity index (A. Chelcea). The results obtained in both lots of Romanian women with pathologic behavior (food and/or alcohol consumption) have indicated a low psycho–sexual identity versus control group but no correlation with masculinity/feminity index. PMID:21254749

  10. Reliable disease biomarkers characterizing and identifying electrohypersensitivity and multiple chemical sensitivity as two etiopathogenic aspects of a unique pathological disorder.

    PubMed

    Belpomme, Dominique; Campagnac, Christine; Irigaray, Philippe

    2015-12-01

    Much of the controversy over the causes of electro-hypersensitivity (EHS) and multiple chemical sensitivity (MCS) lies in the absence of both recognized clinical criteria and objective biomarkers for widely accepted diagnosis. Since 2009, we have prospectively investigated, clinically and biologically, 1216 consecutive EHS and/or MCS-self reporting cases, in an attempt to answer both questions. We report here our preliminary data, based on 727 evaluable of 839 enrolled cases: 521 (71.6%) were diagnosed with EHS, 52 (7.2%) with MCS, and 154 (21.2%) with both EHS and MCS. Two out of three patients with EHS and/or MCS were female; mean age (years) was 47. As inflammation appears to be a key process resulting from electromagnetic field (EMF) and/or chemical effects on tissues, and histamine release is potentially a major mediator of inflammation, we systematically measured histamine in the blood of patients. Near 40% had a increase in histaminemia (especially when both conditions were present), indicating a chronic inflammatory response can be detected in these patients. Oxidative stress is part of inflammation and is a key contributor to damage and response. Nitrotyrosin, a marker of both peroxynitrite (ONOO-) production and opening of the blood-brain barrier (BBB), was increased in 28% the cases. Protein S100B, another marker of BBB opening was increased in 15%. Circulating autoantibodies against O-myelin were detected in 23%, indicating EHS and MCS may be associated with autoimmune response. Confirming animal experiments showing the increase of Hsp27 and/or Hsp70 chaperone proteins under the influence of EMF, we found increased Hsp27 and/or Hsp70 in 33% of the patients. As most patients reported chronic insomnia and fatigue, we determined the 24 h urine 6-hydroxymelatonin sulfate (6-OHMS)/creatinin ratio and found it was decreased (<0.8) in all investigated cases. Finally, considering the self-reported symptoms of EHS and MCS, we serially measured the brain blood flow (BBF) in the temporal lobes of each case with pulsed cerebral ultrasound computed tomosphygmography. Both disorders were associated with hypoperfusion in the capsulothalamic area, suggesting that the inflammatory process involve the limbic system and the thalamus. Our data strongly suggest that EHS and MCS can be objectively characterized and routinely diagnosed by commercially available simple tests. Both disorders appear to involve inflammation-related hyper-histaminemia, oxidative stress, autoimmune response, capsulothalamic hypoperfusion and BBB opening, and a deficit in melatonin metabolic availability; suggesting a risk of chronic neurodegenerative disease. Finally the common co-occurrence of EHS and MCS strongly suggests a common pathological mechanism. PMID:26613326

  11. Language Disorders in Multilingual and Multicultural Populations

    PubMed Central

    Goral, Mira; Conner, Peggy S.

    2014-01-01

    We review the characteristics of developmental language disorders (primary language impairment, reading disorders, autism, Down syndrome) and acquired language disorders (aphasia, dementia, traumatic brain injury) among multilingual and multicultural individuals. We highlight the unique assessment and treatment considerations pertinent to this population, including, for example, concerns of language choice and availability of measures and of normative data in multiple languages. A summary of relevant, recent research studies is provided for each of the language disorders selected. PMID:26257455

  12. GLUT1 deficiency syndrome as a cause of encephalopathy that includes cognitive disability, treatment-resistant infantile epilepsy and a complex movement disorder

    PubMed Central

    Graham, John M.

    2012-01-01

    Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point is illustrated by the natural history of this disorder in a 21-year-old woman with severe, progressive neurological disabilities. Her encephalopathy consisted of treatment-resistant seizures, a complex movement disorder, progressive intellectual disability, and deceleration of her head growth after late infancy. Focused evaluation at age 21 revealed GLUT1 deficiency caused by a novel heterozygous missence mutation in exon 7 (c.938C > A; p.Ser313Try) in SLC2A1 as the cause for her disabilities. PMID:22212417

  13. Prospective Follow-Up of Girls with Attention-Deficit/Hyperactivity Disorder into Early Adulthood: Continuing Impairment Includes Elevated Risk for Suicide Attempts and Self-Injury

    ERIC Educational Resources Information Center

    Hinshaw, Stephen P.; Owens, Elizabeth B.; Zalecki, Christine; Huggins, Suzanne Perrigue; Montenegro-Nevado, Adriana J.; Schrodek, Emily; Swanson, Erika N.

    2012-01-01

    Objective: We performed a 10-year prospective follow-up of a childhood-ascertained (6-12 years), ethnically and socioeconomically diverse sample of girls with attention-deficit/hyperactivity disorder (ADHD; N = 140: combined type [ADHD-C] n = 93; inattentive type [ADHD-I] n = 47) plus a matched comparison group (N = 88). Girls were recruited from

  14. The Social Validation of Behaviors Included in the Critical Events Index of the Systematic Screening for Behavior Disorders in Male Saudi Arabia Primary Schools

    ERIC Educational Resources Information Center

    Alwan, Emad

    2012-01-01

    The purpose of this study was to: (a) identify which behaviors from the Systematic Screening for Behavior Disorders (SSBD) Critical Events Index occur in male Saudi Arabia primary schools and how often teachers perceive their occurrence; (b) determine the extent of concern male Saudi Arabia primary school teachers report regarding these behaviors;…

  15. Prospective Follow-Up of Girls with Attention-Deficit/Hyperactivity Disorder into Early Adulthood: Continuing Impairment Includes Elevated Risk for Suicide Attempts and Self-Injury

    ERIC Educational Resources Information Center

    Hinshaw, Stephen P.; Owens, Elizabeth B.; Zalecki, Christine; Huggins, Suzanne Perrigue; Montenegro-Nevado, Adriana J.; Schrodek, Emily; Swanson, Erika N.

    2012-01-01

    Objective: We performed a 10-year prospective follow-up of a childhood-ascertained (6-12 years), ethnically and socioeconomically diverse sample of girls with attention-deficit/hyperactivity disorder (ADHD; N = 140: combined type [ADHD-C] n = 93; inattentive type [ADHD-I] n = 47) plus a matched comparison group (N = 88). Girls were recruited from…

  16. A Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorder Arising in a Patient With Multiple Myeloma and Cutaneous Amyloidosis.

    PubMed

    Romano, Ryan C; Cohen, Daniel N; Howard, Matthew T; Wieland, Carilyn N

    2016-05-01

    CD30-positive cutaneous lymphoproliferative disorders, a group of T-cell neoplasms, including lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma, require careful clinicopathologic correlation for diagnosis. An association between LyP and the development of a second hematolymphoid malignancy has been established in the literature. LyP has also been reported with systemic amyloidosis, but no such reports have documented coexisting cutaneous amyloid deposition with LyP to our knowledge. A 66-year-old woman with cutaneous amyloidosis, secondary to multiple myeloma, in remission, presented with erythematous and dark-brown papules involving the right arm, scalp, and torso. Punch biopsy of the arm showed a dermal infiltrate of intermediate-sized lymphocytes, some of which displayed a plasmacytoid morphology and prominent nodular subepidermal amyloid deposition. Punch biopsy of the scalp similarly showed a nonepidermotropic dense dermal infiltrate of intermediate-sized plasmacytoid lymphocytes and multifocal amyloid deposition. Both infiltrates were immunophenotypically CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoproliferative processes. Subsequent studies showed no systemic involvement, and clinical correlation suggested a final diagnosis of LyP. We present this case of LyP, which histologically mimics a B-cell proliferation with a plasmacytoid morphology arising in association with cutaneous amyloidosis to highlight the importance of clinicopathologic correlation, a thorough battery of immunohistochemical studies, and consideration for a second hematologic malignancy arising in the setting of LyP. PMID:26981738

  17. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis

    PubMed Central

    Kalaitzidis, Demetrios; Usenko, Tatiana; Kutok, Jeffery L.; Yang, Wentian; Mohi, M. Golam; Neel, Benjamin G.

    2009-01-01

    PTPN11, which encodes the tyrosine phosphatase SHP2, is mutated in approximately 35% of patients with juvenile myelomonocytic leukemia (JMML) and at a lower incidence in other neoplasms. To model JMML pathogenesis, we generated knockin mice that conditionally express the leukemia-associated mutant Ptpn11D61Y. Expression of Ptpn11D61Y in all hematopoietic cells evokes a fatal myeloproliferative disorder (MPD), featuring leukocytosis, anemia, hepatosplenomegaly, and factor-independent colony formation by bone marrow (BM) and spleen cells. The Lin−Sca1+cKit+ (LSK) compartment is expanded and “right-shifted,” accompanied by increased stem cell factor (SCF)–evoked colony formation and Erk and Akt activation. However, repopulating activity is decreased in diseased mice, and mice that do engraft with Ptpn11D61Y stem cells fail to develop MPD. Ptpn11D61Y common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs) produce cytokine-independent colonies in a cell-autonomous manner and demonstrate elevated Erk and Stat5 activation in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation. Ptpn11D61Y megakaryocyte-erythrocyte progenitors (MEPs) yield increased numbers of erythrocyte burst-forming units (BFU-Es), but MEPs and erythrocyte-committed progenitors (EPs) produce fewer erythrocyte colony-forming units (CFU-Es), indicating defective erythroid differentiation. Our studies provide a mouse model for Ptpn11-evoked MPD and show that this disease results from cell-autonomous and distinct lineage-specific effects of mutant Ptpn11 on multiple stages of hematopoiesis. PMID:19179468

  18. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis.

    PubMed

    Chan, Gordon; Kalaitzidis, Demetrios; Usenko, Tatiana; Kutok, Jeffery L; Yang, Wentian; Mohi, M Golam; Neel, Benjamin G

    2009-04-30

    PTPN11, which encodes the tyrosine phosphatase SHP2, is mutated in approximately 35% of patients with juvenile myelomonocytic leukemia (JMML) and at a lower incidence in other neoplasms. To model JMML pathogenesis, we generated knockin mice that conditionally express the leukemia-associated mutant Ptpn11(D61Y). Expression of Ptpn11(D61Y) in all hematopoietic cells evokes a fatal myeloproliferative disorder (MPD), featuring leukocytosis, anemia, hepatosplenomegaly, and factor-independent colony formation by bone marrow (BM) and spleen cells. The Lin(-)Sca1(+)cKit(+) (LSK) compartment is expanded and "right-shifted," accompanied by increased stem cell factor (SCF)-evoked colony formation and Erk and Akt activation. However, repopulating activity is decreased in diseased mice, and mice that do engraft with Ptpn11(D61Y) stem cells fail to develop MPD. Ptpn11(D61Y) common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs) produce cytokine-independent colonies in a cell-autonomous manner and demonstrate elevated Erk and Stat5 activation in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation. Ptpn11(D61Y) megakaryocyte-erythrocyte progenitors (MEPs) yield increased numbers of erythrocyte burst-forming units (BFU-Es), but MEPs and erythrocyte-committed progenitors (EPs) produce fewer erythrocyte colony-forming units (CFU-Es), indicating defective erythroid differentiation. Our studies provide a mouse model for Ptpn11-evoked MPD and show that this disease results from cell-autonomous and distinct lineage-specific effects of mutant Ptpn11 on multiple stages of hematopoiesis. PMID:19179468

  19. Patterns of Risk for Multiple Co‐Occurring Medical Conditions Replicate Across Distinct Cohorts of Children with Autism Spectrum Disorder

    PubMed Central

    Aldinger, Kimberly A.; Lane, Christianne J.; Veenstra‐VanderWeele, Jeremy

    2015-01-01

    Children with autism spectrum disorder (ASD) may present with multiple medical conditions in addition to ASD symptoms. This study investigated whether there are predictive patterns of medical conditions that co‐occur with ASD, which could inform medical evaluation and treatment in ASD, as well as potentially identify etiologically meaningful subgroups. Medical history data were queried in the multiplex family Autism Genetic Resource Exchange (AGRE). Fourteen medical conditions were analyzed. Replication in the Simons Simplex Collection (SSC) was attempted using available medical condition data on gastrointestinal disturbances (GID), sleep problems, allergy and epilepsy. In the AGRE cohort, no discrete clusters emerged among 14 medical conditions. GID and seizures were enriched in unaffected family members, and together with sleep problems, were represented in both AGRE and SSC. Further analysis of these medical conditions identified predictive co‐occurring patterns in both samples. For a child with ASD, the presence of GID predicts sleep problems and vice versa, with an approximately 2‐fold odds ratio in each direction. These risk patterns were replicated in the SSC sample, and in addition, there was increased risk for seizures and sleep problems to co‐occur with GID. In these cohorts, seizure alone was not predictive of the other conditions co‐occurring, but behavioral impairments were more severe as the number of co‐occurring medical symptoms increased. These findings indicate that interdisciplinary clinical care for children with ASD will benefit from evaluation for specific patterns of medical conditions in the affected child and their family members. Autism Res 2015, 8: 771–781. © 015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. PMID:26011086

  20. Multiple tasks and neuroimaging modalities increase the likelihood of detecting covert awareness in patients with disorders of consciousness

    PubMed Central

    Gibson, Raechelle M.; Fernández-Espejo, Davinia; Gonzalez-Lara, Laura E.; Kwan, Benjamin Y.; Lee, Donald H.; Owen, Adrian M.; Cruse, Damian

    2014-01-01

    Minimal or inconsistent behavioral responses to command make it challenging to accurately diagnose the level of awareness of a patient with a Disorder of consciousness (DOC). By identifying markers of mental imagery being covertly performed to command, functional neuroimaging (fMRI), electroencephalography (EEG) has shown that some of these patients are aware despite their lack of behavioral responsiveness. We report the findings of behavioral, fMRI, and EEG approaches to detecting command-following in a group of patients with DOC. From an initial sample of 14 patients, complete data across all tasks was obtained in six cases. Behavioral evaluations were performed with the Coma Recovery Scale—Revised. Both fMRI and EEG evaluations involved the completion of previously validated mental imagery tasks—i.e., motor imagery (EEG and fMRI) and spatial navigation imagery (fMRI). One patient exhibited statistically significant evidence of motor imagery in both the fMRI and EEG tasks, despite being unable to follow commands behaviorally. Two behaviorally non-responsive patients produced appropriate activation during the spatial navigation fMRI task. However, neither of these patients successfully completed the motor imagery tasks, likely due to specific motor area damage in at least one of these cases. A further patient demonstrated command following only in the EEG motor imagery task, and two patients did not demonstrate command following in any of the behavioral, EEG, or fMRI assessments. Due to the heterogeneity of etiology and pathology in this group, DOC patients vary in terms of their suitability for some forms of neuroimaging, the preservation of specific neural structures, and the cognitive resources that may be available to them. Assessments of a range of cognitive abilities supported by spatially-distinct brain regions and indexed by multiple neural signatures are therefore required in order to accurately characterize a patient's level of residual cognition and awareness. PMID:25505400

  1. Atomoxetine Augmentation in a Case of Treatment Resistant Panic Disorder with Multiple Augments Failure: A Case Report

    PubMed Central

    Ram, Dushad; Patil, Shwetha; Gowdappa, Basavana; Rajalakshmi, Iyshwarya

    2015-01-01

    Atomoxetine, a selective norepinephrine inhibitor, is effective in comorbid anxiety and attention deficit hyperactivity disorder, however its role in panic disorder is unknown. We are presenting a case of panic disorder, who initially partially responded to clonazepam. When clonazepam was added with sertraline, escitalopram, desvenlafaxin, she did not improve significantly until paroxetine was added. When clonazepam-paroxetine combination was added with propranolol, etizolam, olanzepine, risperidone and amisulpride the symptom remission did not occur until a trial of Atomoxetine was done. PMID:26598594

  2. Atomoxetine Augmentation in a Case of Treatment Resistant Panic Disorder with Multiple Augments Failure: A Case Report.

    PubMed

    Ram, Dushad; Patil, Shwetha; Gowdappa, Basavana; Rajalakshmi, Iyshwarya

    2015-12-31

    Atomoxetine, a selective norepinephrine inhibitor, is effective in comorbid anxiety and attention deficit hyperactivity disorder, however its role in panic disorder is unknown. We are presenting a case of panic disorder, who initially partially responded to clonazepam. When clonazepam was added with sertraline, escitalopram, desvenlafaxin, she did not improve significantly until paroxetine was added. When clonazepam-paroxetine combination was added with propranolol, etizolam, olanzepine, risperidone and amisulpride the symptom remission did not occur until a trial of Atomoxetine was done. PMID:26598594

  3. Subthreshold Conditions as Precursors for Full Syndrome Disorders: A 15-Year Longitudinal Study of Multiple Diagnostic Classes

    ERIC Educational Resources Information Center

    Shankman, Stewart A.; Lewinsohn, Peter M.; Klein, Daniel N.; Small, Jason W.; Seeley, John R.; Altman, Sarah E.

    2009-01-01

    Background: There has been increasing interest in the distinction between subthreshold and full syndrome disorders and specifically whether subthreshold conditions escalate or predict the onset of full syndrome disorders over time. Most of these studies, however, examined whether a single subthreshold condition escalates into the full syndrome…

  4. Eating Disorders

    MedlinePlus

    Eating disorders are serious behavior problems. They can include severe overeating or not consuming enough food to stay ... concern about your shape or weight. Types of eating disorders include Anorexia nervosa, in which you become too ...

  5. Tailbone Disorders

    MedlinePlus

    ... at the bottom of your backbone, or spine. Tailbone disorders include tailbone injuries, pain, infections, cysts and tumors. ... common cause of such injuries. Symptoms of various tailbone disorders include pain in the tailbone area, pain upon ...

  6. Coarse-Grained HiRE-RNA Model for ab Initio RNA Folding beyond Simple Molecules, Including Noncanonical and Multiple Base Pairings.

    PubMed

    Cragnolini, Tristan; Laurin, Yoann; Derreumaux, Philippe; Pasquali, Samuela

    2015-07-14

    HiRE-RNA is a coarse-grained model for RNA structure prediction and the dynamical study of RNA folding. Using a reduced set of particles and detailed interactions accounting for base-pairing and stacking, we show that noncanonical and multiple base interactions are necessary to capture the full physical behavior of complex RNAs. In this paper, we give a full account of the model and present results on the folding, stability, and free energy surfaces of 16 systems with 12 to 76 nucleotides of increasingly complex architectures, ranging from monomers to dimers, using a total of 850 μs of simulation time. PMID:26575783

  7. Reliability and Diagnostic Efficiency of the Diagnostic Inventory for Disharmony (DID) in Youths with Pervasive Developmental Disorder and Multiple Complex Developmental Disorder

    ERIC Educational Resources Information Center

    Xavier, Jean; Vannetzel, Leonard; Viaux, Sylvie; Leroy, Arthur; Plaza, Monique; Tordjman, Sylvie; Mille, Christian; Bursztejn, Claude; Cohen, David; Guile, Jean-Marc

    2011-01-01

    The Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) category is a psychopathological entity few have described and is poorly, and mainly negatively, defined by autism exclusion. In order to limit PDD-NOS heterogeneity, alternative clinical constructs have been developed. This study explored the reliability and the diagnostic…

  8. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder.

    PubMed

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; Hollywood, Katherine A; Jüllig, Mia; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. PMID:26957286

  9. Multiple Approaches to Investigate the Transport and Activity-Dependent Release of BDNF and Their Application in Neurogenetic Disorders

    PubMed Central

    Hartmann, David; Drummond, Jana; Handberg, Erik; Ewell, Sharday; Pozzo-Miller, Lucas

    2012-01-01

    Studies utilizing genetic and pharmacological manipulations in rodent models and neuronal cultures have revealed myriad roles of brain-derived neurotrophic factor (BDNF). Currently, this knowledge of BDNF function is being translated into improvement strategies for several debilitating neurological disorders in which BDNF abnormalities play a prominent role. Common among the BDNF-related disorders are irregular trafficking and release of mature BDNF (mBDNF) and/or its prodomain predecessor, proBDNF. Thus, investigating the conditions required for proper trafficking and release of BDNF is an essential step toward understanding and potentially improving these neurological disorders. This paper will provide examples of disorders related to BDNF release and serve as a review of the techniques being used to study the trafficking and release of BDNF. PMID:22720171

  10. Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders

    PubMed Central

    2012-01-01

    Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1, DTNBP1, JARID2, and NHLRC1 that we propose may be responsible for ASDs and developmental delay. PMID:22480366

  11. Kinetics of 3H-serotonin uptake by platelets in infantile autism and developmental language disorder (including five pairs of twins)

    SciTech Connect

    Katsui, T.; Okuda, M.; Usuda, S.; Koizumi, T.

    1986-03-01

    The kinetics of 5-HT uptake by platelets was studied in cases of infantile autism and developmental language disorder (DLD) and normal subjects. Two patients of the autism group were twins, and the seven patients of the DLD group were members of four pairs of twins. The Vmax values (means +/- SD) for autism and DLD were 6.46 +/- .90 pmol 5-HT/10(7) cells/min and 4.85 +/- 1.50 pmol 5-HT/10(7) cells/min, respectively. These values were both significantly higher than that of 2.25 +/- .97 pmole 5-HT/10(7) cells/min for normal children. The Km values of the three groups were not significantly different. Data on the five pairs of twins examined suggested that the elevated Vmax of 5-HT uptake by platelets was determined genetically.

  12. Comparing Factor, Class, and Mixture Models of Cannabis Initiation and DSM Cannabis Use Disorder Criteria, Including Craving, in the Brisbane Longitudinal Twin Study

    PubMed Central

    Kubarych, Thomas S.; Kendler, Kenneth S.; Aggen, Steven H.; Estabrook, Ryne; Edwards, Alexis C.; Clark, Shaunna L.; Martin, Nicholas G.; Hickie, Ian B.; Neale, Michael C.; Gillespie, Nathan A.

    2014-01-01

    Accumulating evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying factor. However, it remains possible that models with additional factors, or latent class models or hybrid models, may better explain the data. Using structured interviews, 626 adult male and female twins provided complete data on symptoms of cannabis abuse and dependence, plus a craving criterion. We compared latent factor analysis, latent class analysis, and factor mixture modeling using normal theory marginal maximum likelihood for ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5 craving loads onto a general factor. When compared with latent class and mixture models, factor models provided a better fit to the data. When conditioned on initiation and cannabis use, the association between criteria for abuse, dependence, withdrawal, and craving were best explained by two correlated latent factors for males and females: a general risk factor to CUD and a factor capturing the symptoms of social and occupational impairment as a consequence of frequent use. Secondary analyses revealed a modest increase in the prevalence of DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded that, in addition to a general factor with loadings on cannabis use and symptoms of abuse, dependence, withdrawal, and craving, a second clinically relevant factor defined by features of social and occupational impairment was also found for frequent cannabis use. PMID:24588857

  13. Significant Low Prevalence of Antibodies Reacting with Simian Virus 40 Mimotopes in Serum Samples from Patients Affected by Inflammatory Neurologic Diseases, Including Multiple Sclerosis

    PubMed Central

    Mazzoni, Elisa; Pietrobon, Silvia; Masini, Irene; Rotondo, John Charles; Gentile, Mauro; Fainardi, Enrico; Casetta, Ilaria; Castellazzi, Massimiliano; Granieri, Enrico; Caniati, Maria Luisa; Tola, Maria Rosaria; Guerra, Giovanni; Martini, Fernanda; Tognon, Mauro

    2014-01-01

    Many investigations were carried out on the association between viruses and multiple sclerosis (MS). Indeed, early studies reported the detections of neurotropic virus footprints in the CNS of patients with MS. In this study, sera from patients affected by MS, other inflammatory (OIND) and non-inflammatory neurologic diseases (NIND) were analyzed for antibodies against the polyomavirus, Simian Virus 40 (SV40). An indirect enzyme-linked immunosorbent assay (ELISA), with two synthetic peptides, which mimic SV40 antigens, was employed to detect specific antibodies in sera from patients affected by MS, OIND, NIND and healthy subjects (HS). Immunologic data indicate that in sera from MS patients antibodies against SV40 mimotopes are detectable with a low prevalence, 6%, whereas in HS of the same mean age, 40 yrs, the prevalence was 22%. The difference is statistically significant (P = 0.001). Significant is also the difference between MS vs. NIND patients (6% vs. 17%; P = 0.0254), whereas no significant difference was detected between MS vs OIND (6% vs 10%; P>0.05). The prevalence of SV40 antibodies in MS patients is 70% lower than that revealed in HS. PMID:25365364

  14. Receptors and Entry Cofactors for Retroviruses Include Single and Multiple Transmembrane-Spanning Proteins as well as Newly Described Glycophosphatidylinositol-Anchored and Secreted Proteins

    PubMed Central

    Overbaugh, Julie; Miller, A. Dusty; Eiden, Maribeth V.

    2001-01-01

    In the past few years, many retrovirus receptors, coreceptors, and cofactors have been identified. These molecules are important for some aspects of viral entry, although in some cases it remains to be determined whether they are required for binding or postbinding stages in entry, such as fusion. There are certain common features to the molecules that many retroviruses use to gain entry into the cell. For example, the receptors for most mammalian oncoretroviruses are multiple membrane-spanning transport proteins. However, avian retroviruses use single-pass membrane proteins, and a sheep retrovirus uses a glycosylphosphatidylinositol-anchored molecule as its receptor. For some retroviruses, particularly the lentiviruses, two cell surface molecules are required for efficient entry. More recently, a soluble protein that is required for viral entry has been identified for a feline oncoretrovirus. In this review, we will focus on the various strategies used by mammalian retroviruses to gain entry into the cell. The choice of receptors will also be discussed in light of pressures that drive viral evolution and persistence. PMID:11528001

  15. The Interaction between Candida krusei and Murine Macrophages Results in Multiple Outcomes, Including Intracellular Survival and Escape from Killing ▿ † ‡

    PubMed Central

    García-Rodas, Rocío; González-Camacho, Fernando; Rodríguez-Tudela, Juan Luis; Cuenca-Estrella, Manuel; Zaragoza, Oscar

    2011-01-01

    Candida krusei is a fungal pathogen of interest for the scientific community for its intrinsic resistance to fluconazole. Little is known about the interaction of this yeast with host immune cells. In this work, we have characterized the outcome of the interaction between C. krusei and murine macrophages. Once C. krusei was internalized, we observed different phenomena. In a macrophage-like cell line, C. krusei survived in a significant number of macrophages and induced filamentation and macrophage explosion. Phagocytosis of C. krusei led to actin polymerization around the yeast cells at the site of entry. Fluorescent specific staining with anti-Lamp1 and LysoTracker indicated that after fungal internalization, there was a phagolysosome maturation defect, a phenomenon that was more efficient when the macrophages phagocytosed killed yeast cells. Using cell line macrophages, we also observed macrophage fusion after cell division. When we used primary resident peritoneal macrophages in addition to macrophage explosion, we also observed a strong chemotaxis of uninfected macrophages to regions where C. krusei-infected macrophages were present. We also noticed yeast transfer phenomena between infected macrophages. Primary macrophages inhibited pseudohypha elongation more efficiently than the macrophage-like cell line, suggesting that C. krusei infection was better controlled by the former macrophages. Primary macrophages induced more tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) than the macrophage-like cell line. Our results demonstrate that C. krusei can exploit the macrophages for replication, although other different outcomes are also possible, indicating that the interaction of this pathogen with phagocytic cells is very complex and regulated by multiple factors. PMID:21422181

  16. Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)

    SciTech Connect

    Sloan, J.W.

    1984-01-01

    These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) have been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.

  17. The Lyme Disease Spirochete Borrelia burgdorferi Utilizes Multiple Ligands, Including RNA, for Interferon Regulatory Factor 3-Dependent Induction of Type I Interferon-Responsive Genes ▿

    PubMed Central

    Miller, Jennifer C.; Maylor-Hagen, Heather; Ma, Ying; Weis, John H.; Weis, Janis J.

    2010-01-01

    We recently discovered a critical role for type I interferon (IFN) in the development of murine Lyme arthritis. Borrelia burgdorferi-mediated induction of IFN-responsive genes by bone marrow-derived macrophages (BMDMs) was dependent upon a functional type I IFN receptor but independent of Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adapter molecule MyD88. We now demonstrate that induction of the IFN transcriptional profile in B. burgdorferi-stimulated BMDMs occurs independently of the adapter TRIF and of the cytoplasmic sensor NOD2. In contrast, B. burgdorferi-induced transcription of these genes was dependent upon a rapid STAT1 feedback amplification pathway. IFN profile gene transcription was IRF3 dependent but did not utilize B. burgdorferi-derived DNA or DNase-sensitive ligands. Instead, IFN-responsive gene expression could be induced by B. burgdorferi-derived RNA. Interferon regulatory factor 3 (IRF3)-dependent IFN profile gene transcription was also induced by sonicated bacteria, by the lipoprotein OspA, and by factors released into the BSKII medium during culture of B. burgdorferi. The IFN-stimulatory activity of B. burgdorferi culture supernatants was not destroyed by nuclease treatment. Nuclease digestion also had no effect on IFN profile induction mediated by sonicated B. burgdorferi. Thus, B. burgdorferi-derived RNA, OspA, and non-nucleic acid ligands present in both sonicated bacteria and B. burgdorferi culture medium contribute to type I IFN-responsive gene induction. These findings suggest that B. burgdorferi invasion of joint tissue and the resultant type I IFN induction associated with Lyme arthritis development may involve multiple triggering ligands. PMID:20404081

  18. Deep RNA sequencing of L. monocytogenes reveals overlapping and extensive stationary phase and sigma B-dependent transcriptomes, including multiple highly transcribed noncoding RNAs

    PubMed Central

    2009-01-01

    Background Identification of specific genes and gene expression patterns important for bacterial survival, transmission and pathogenesis is critically needed to enable development of more effective pathogen control strategies. The stationary phase stress response transcriptome, including many σB-dependent genes, was defined for the human bacterial pathogen Listeria monocytogenes using RNA sequencing (RNA-Seq) with the Illumina Genome Analyzer. Specifically, bacterial transcriptomes were compared between stationary phase cells of L. monocytogenes 10403S and an otherwise isogenic ΔsigB mutant, which does not express the alternative σ factor σB, a major regulator of genes contributing to stress response, including stresses encountered upon entry into stationary phase. Results Overall, 83% of all L. monocytogenes genes were transcribed in stationary phase cells; 42% of currently annotated L. monocytogenes genes showed medium to high transcript levels under these conditions. A total of 96 genes had significantly higher transcript levels in 10403S than in ΔsigB, indicating σB-dependent transcription of these genes. RNA-Seq analyses indicate that a total of 67 noncoding RNA molecules (ncRNAs) are transcribed in stationary phase L. monocytogenes, including 7 previously unrecognized putative ncRNAs. Application of a dynamically trained Hidden Markov Model, in combination with RNA-Seq data, identified 65 putative σB promoters upstream of 82 of the 96 σB-dependent genes and upstream of the one σB-dependent ncRNA. The RNA-Seq data also enabled annotation of putative operons as well as visualization of 5'- and 3'-UTR regions. Conclusions The results from these studies provide powerful evidence that RNA-Seq data combined with appropriate bioinformatics tools allow quantitative characterization of prokaryotic transcriptomes, thus providing exciting new strategies for exploring transcriptional regulatory networks in bacteria. See minireivew http://jbiol.com/content/8/12/107. PMID:20042087

  19. A Novel N-Tetrasaccharide in Patients with Congenital Disorders of Glycosylation Including Asparagine-Linked Glycosylation Protein 1, Phosphomannomutase 2, and Phosphomannose Isomerase Deficiencies

    PubMed Central

    Zhang, Wenyue; James, Philip M.; Ng, Bobby G.; Li, Xueli; Xia, Baoyun; Rong, Jiang; Asif, Ghazia; Raymond, Kimiyo; Jones, Melanie A.; Hegde, Madhuri; Ju, Tongzhong; Cummings, Richard D.; Clarkson, Katie; Wood, Tim; Boerkoel, Cornelius F.; Freeze, Hudson H.; He, Miao

    2016-01-01

    Background Primary deficiencies in mannosylation of N-glycans are seen in a majority of patients with congenital disorders of glycosylation (CDG). We report the discovery of a series of novel N-glycans in sera, plasma, and cultured skin fibroblasts from patients with CDG having deficient mannosylation. Method We used LC-MS/MS and MALDI-TOF-MS analysis to identify and quantify a novel N-linked tetrasccharide linked to the protein core, an N-tetrasaccharide (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) in plasma, serum glycoproteins, and a fibroblast lysate from patients with CDG caused by ALG1 (ALG1, chitobiosyldiphosphodolichol β-mannosyltransferase), PMM2 (phosphomannomutase 2), and MPI (mannose phosphate isomerase). Results Glycoproteins in sera, plasma, or cell lysate from ALG1-CDG, PMM2-CDG, and MPI-CDG patients had substantially more N-tetrasaccharide than unaffected controls. We observed a >80% decline in relative concentrations of the N-tetrasaccharide in MPI-CDG plasma after mannose therapy in 1 patient and in ALG1-CDG fibroblasts in vitro supplemented with mannose. Conclusions This novel N-tetrasaccharide could serve as a diagnostic marker of ALG1-, PMM2-, or MPI-CDG for screening of these 3 common CDG subtypes that comprise >70% of CDG type I patients. Its quantification by LC-MS/MS may be useful for monitoring therapeutic efficacy of mannose. The discovery of these small N-glycans also indicates the presence of an alternative pathway in N-glycosylation not recognized previously, but its biological significance remains to be studied. PMID:26430078

  20. Adult hemophagocytic lymphohistiocytosis causing multi organ dysfunction in a patient with multiple autoimmune disorders: when the immune system runs amok.

    PubMed

    Fleischmann, Robert; Böhmerle, Wolfgang; von Laffert, Maximilian; Jöhrens, Korinna; Mengel, Annerose; Hotter, Benjamin; Lindenberg, Robert; Scheibe, Franziska; Köhnlein, Martin; von Bahr Greenwood, Tatiana; Henter, Jan Inge; Meisel, Andreas

    2016-02-01

    We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis (HLH). Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as HLH shares common features with sepsis and immune-mediated systemic inflammatory response syndromes. PMID:26862416

  1. Becoming a Teacher in Multiple Voices: An Exploration of Teacher Identity Formation among Teachers of Students with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Wilt, Mary E.

    2013-01-01

    The purpose of this study was to explore the formation of teacher identity among four teachers of students with autism spectrum disorder (ASD) and my own by examining our perspectives, influences, and experiences at different points in our careers and determining the similarities and differences that exist in our professional and educational…

  2. Becoming a Teacher in Multiple Voices: An Exploration of Teacher Identity Formation among Teachers of Students with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Wilt, Mary E.

    2013-01-01

    The purpose of this study was to explore the formation of teacher identity among four teachers of students with autism spectrum disorder (ASD) and my own by examining our perspectives, influences, and experiences at different points in our careers and determining the similarities and differences that exist in our professional and educational

  3. Identification of Multiple Phytotoxins Produced by Fusarium virguliforme Including a Phytotoxic Effector (FvNIS1) Associated With Sudden Death Syndrome Foliar Symptoms.

    PubMed

    Chang, Hao-Xun; Domier, Leslie L; Radwan, Osman; Yendrek, Craig R; Hudson, Matthew E; Hartman, Glen L

    2016-02-01

    Sudden death syndrome (SDS) of soybean is caused by a soilborne pathogen, Fusarium virguliforme. Phytotoxins produced by F. virguliforme are translocated from infected roots to leaves, in which they cause SDS foliar symptoms. In this study, additional putative phytotoxins of F. virguliforme were identified, including three secondary metabolites and 11 effectors. While citrinin, fusaric acid, and radicicol induced foliar chlorosis and wilting, Soybean mosaic virus (SMV)-mediated overexpression of F. virguliforme necrosis-inducing secreted protein 1 (FvNIS1) induced SDS foliar symptoms that mimicked the development of foliar symptoms in the field. The expression level of fvnis1 remained steady over time, although foliar symptoms were delayed compared with the expression levels. SMV::FvNIS1 also displayed genotype-specific toxicity to which 75 of 80 soybean cultivars were susceptible. Genome-wide association mapping further identified three single nucleotide polymorphisms at two loci, where three leucine-rich repeat receptor-like protein kinase (LRR-RLK) genes were found. Culture filtrates of fvnis1 knockout mutants displayed a mild reduction in phytotoxicity, indicating that FvNIS1 is one of the phytotoxins responsible for SDS foliar symptoms and may contribute to the quantitative susceptibility of soybean by interacting with the LRR-RLK genes. PMID:26646532

  4. Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA' Multiple Case Design Examining Dosing and Generalization to the Home and Community

    ERIC Educational Resources Information Center

    Holm, Margo B.; Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D'Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

    2014-01-01

    We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years…

  5. A Case of Metastatic Head and Neck Squamous Cell Carcinoma with Multiple Treatments Including Stereotactic Ablative Body Radiotherapy Alone for Oligometastases to the Parotid Gland.

    PubMed

    Sharrett, Jonathan; Pederson, Aaron

    2015-01-01

    Head and neck squamous cell carcinoma (HNSCC) has a reported average of around 15% metastases at presentation with chemotherapy being the mainstay of treatment for widely metastatic disease. However, in select patients with oligometastatic disease, local ablative therapy (commonly including surgery or radiotherapy) can be utilized with the possibility of improving survival, decreasing morbidity from the metastases, and obviating the need for systemic therapy with its possible side effects. However, most research has been of ablative therapy has been performed for pulmonary and hepatic oligometastatic lesions.  In this case, we present a patient who initially presented with a metastatic base of tongue malignancy with left axilla metastases who was treated palliatively with systemic therapy with an initial complete response. She subsequently progressed on maintenance therapy with a locoregional recurrence that was treated with definitive chemoradiation with complete response. There was a subsequent recurrence again in the left axilla that was treated as well with chemoradiation with complete response. Next, there was a recurrence in the right occipital lobe and left parotid gland with treatment with surgical resection, plus stereotactic radiotherapy boost and stereotactic ablative body radiotherapy (SABR), respectively. This all occurred over a 30-month time frame from initial therapy to her last treatment, with an additional 42 months at the present time with no recurrence.  This case highlights the future of care of oligometastatic disease of HNSCC with potential long-term survival in appropriately selected patients treated with stereotactic ablative body radiotherapy. Furthermore, this is one of the first reported cases in the literature of SABR for an oligometastatic lesion of the parotid gland, especially from squamous cell carcinoma (SCC) of the oral cavity, with no recurrence of disease over 40 months removed from treatment. PMID:26858919

  6. Point mutations at multiple sites including highly conserved amino acids maintain activity, but render O6-alkylguanine-DNA alkyltransferase insensitive to O6-benzylguanine.

    PubMed Central

    Xu-Welliver, M; Pegg, A E

    2000-01-01

    The DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase (AGT), is inactivated by reaction with the pseudosubstrate, O(6)-benzylguanine (BG). This inactivation sensitizes tumour cells to chemotherapeutic alkylating agents, and BG is aimed at enhancing cancer treatment in clinical trials. Point mutations in a 24 amino acid sequence likely to form the BG-binding pocket were identified using a screening method designed to identify BG-resistant mutants. It was found that alterations in 21 of these residues were able to render AGT resistant to BG. These included mutations at the highly conserved residues Lys(165), Leu(168) and Leu(169). The two positions at which changes led to the largest increase in resistance to BG were Gly(156) and Lys(165). Eleven mutants at Gly(156) were identified, with increases in resistance ranging from 190-fold (G156V) to 4400-fold (G156P). Two mutants at Lys(165) found in the screen (K165S and K165A) showed 620-fold and 100-fold increases in resistance to BG. Two mutants at the Ser(159) position (S159I and S159V) were >80-fold more resistant than wild-type AGT. Eleven active mutants at Leu(169) were also resistant to BG, but with lower increases (5-86-fold). Fourteen BG-resistant mutants were found for position Cys(150), with 3-26-fold increases in the amount of inhibitor needed to produce a 50% loss of activity in a 30 min incubation. Six BG-resistant mutants at Asn(157) were found with increases of 4-13-fold. These results show that many changes can render human AGT resistant to BG without preventing the ability to protect tumour cells from therapeutic alkylating agents. PMID:10749682

  7. The Clinical Obesity Maintenance Model: An Integration of Psychological Constructs including Mood, Emotional Regulation, Disordered Overeating, Habitual Cluster Behaviours, Health Literacy and Cognitive Function

    PubMed Central

    Raman, Jayanthi; Smith, Evelyn; Hay, Phillipa

    2013-01-01

    Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM). It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided. PMID:23710346

  8. Autism and Related Disorders

    PubMed Central

    McPartland, James; Volkmar, Fred R.

    2012-01-01

    The Pervasive Developmental Disorders are a group of neurodevelopmental disorders that include Autistic Disorder, Asperger’s Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Childhood Disintegrative Disorder (CDD), and Rett’s Disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (Autistic Disorder, Asperger’s Disorder, and PDD-NOS) are currently referred to as Autism Spectrum Disorders, reflecting divergent phenotypic and etiologic characteristics compared to Rett’s Disorder and CDD. This chapter reviews relevant research and clinical information relevant to appropriate medical diagnosis and treatment. PMID:22608634

  9. CNS demyelinating disorder with mixed features of neuromyelitis optica and multiple sclerosis in HIV-1 infection. Case report and literature review.

    PubMed

    Delgado, Silvia R; Maldonado, Janice; Rammohan, Kottil W

    2014-10-01

    An African-American male presented with bilateral visual impairment, gait difficulties, and bladder and bowel incontinence raising concerns for multiple sclerosis (MS) or neuromyelitis optica (NMO). He was identified to be HIV-1 infected with high viral load and low CD4+ counts. Magnetic resonance imaging (MRI) of the brain was abnormal, but atypical for MS. MRI of the cervical and thoracic spinal cord showed multiple areas of myelitis with a longitudinally extensive thoracic transverse myelitis that showed enhancement with gadolinium suggestive of NMO. Cerebrospinal fluid showed oligoclonal IgG bands but did not show reactivity to aquaporin 4. Patient underwent treatment for the acute exacerbation with intravenous corticosteroids and treatment of the HIV infection with highly active antiretroviral therapy (HAART). A year later, his viral load was <20 copies/ml and CD4+ counts were normal. Vision did not significantly improve, but his ambulation improved from a near total non-ambulatory state to ambulating without aids and resolution of the bladder and bowel incontinence. A demyelinating disorder of the central nervous system (CNS) like MS or NMO has been previously reported in the context of HIV infection. The remarkable improvement of symptoms has also been previously reported with HAART, and these observations have led to clinical trials of MS with HAART therapy in the absence of HIV infection. We reviewed the few cases of CNS demyelinating disorders with HIV infection reported in the literature and speculate on the mechanisms of pathogenesis. PMID:24981832

  10. Multiple Interactions of the Intrinsically Disordered Region between the Helicase and Nuclease Domains of the Archaeal Hef Protein*

    PubMed Central

    Ishino, Sonoko; Yamagami, Takeshi; Kitamura, Makoto; Kodera, Noriyuki; Mori, Tetsuya; Sugiyama, Shyogo; Ando, Toshio; Goda, Natsuko; Tenno, Takeshi; Hiroaki, Hidekazu; Ishino, Yoshizumi

    2014-01-01

    Hef is an archaeal protein that probably functions mainly in stalled replication fork repair. The presence of an unstructured region was predicted between the two distinct domains of the Hef protein. We analyzed the interdomain region of Thermococcus kodakarensis Hef and demonstrated its disordered structure by CD, NMR, and high speed atomic force microscopy (AFM). To investigate the functions of this intrinsically disordered region (IDR), we screened for proteins interacting with the IDR of Hef by a yeast two-hybrid method, and 10 candidate proteins were obtained. We found that PCNA1 and a RecJ-like protein specifically bind to the IDR in vitro. These results suggested that the Hef protein interacts with several different proteins that work together in the pathways downstream from stalled replication fork repair by converting the IDR structure depending on the partner protein. PMID:24947516

  11. Multiple interactions of the intrinsically disordered region between the helicase and nuclease domains of the archaeal Hef protein.

    PubMed

    Ishino, Sonoko; Yamagami, Takeshi; Kitamura, Makoto; Kodera, Noriyuki; Mori, Tetsuya; Sugiyama, Shyogo; Ando, Toshio; Goda, Natsuko; Tenno, Takeshi; Hiroaki, Hidekazu; Ishino, Yoshizumi

    2014-08-01

    Hef is an archaeal protein that probably functions mainly in stalled replication fork repair. The presence of an unstructured region was predicted between the two distinct domains of the Hef protein. We analyzed the interdomain region of Thermococcus kodakarensis Hef and demonstrated its disordered structure by CD, NMR, and high speed atomic force microscopy (AFM). To investigate the functions of this intrinsically disordered region (IDR), we screened for proteins interacting with the IDR of Hef by a yeast two-hybrid method, and 10 candidate proteins were obtained. We found that PCNA1 and a RecJ-like protein specifically bind to the IDR in vitro. These results suggested that the Hef protein interacts with several different proteins that work together in the pathways downstream from stalled replication fork repair by converting the IDR structure depending on the partner protein. PMID:24947516

  12. Multiple Intrinsically Disordered Sequences Alter DNA Binding by the Homeodomain of the Drosophila Hox Protein Ultrabithorax*S⃞

    PubMed Central

    Liu, Ying; Matthews, Kathleen S.; Bondos, Sarah E.

    2008-01-01

    During animal development, distinct tissues, organs, and appendages are specified through differential gene transcription by Hox transcription factors. However, the conserved Hox homeodomains bind DNA with high affinity yet low specificity. We have therefore explored the structure of the Drosophila melanogaster Hox protein Ultrabithorax and the impact of its nonhomeodomain regions on DNA binding properties. Computational and experimental approaches identified several conserved, intrinsically disordered regions outside the homeodomain of Ultrabithorax that impact DNA binding by the homeodomain. Full-length Ultrabithorax bound to target DNA 2.5-fold weaker than its isolated homeodomain. Using N-terminal and C-terminal deletion mutants, we demonstrate that the YPWM region and the disordered microexons (termed the I1 region) inhibit DNA binding ∼2-fold, whereas the disordered I2 region inhibits homeodomain-DNA interaction a further ∼40-fold. Binding is restored almost to homeodomain affinity by the mostly disordered N-terminal 174 amino acids (R region) in a length-dependent manner. Both the I2 and R regions contain portions of the activation domain, functionally linking DNA binding and transcription regulation. Given that (i) the I1 region and a portion of the R region alter homeodomain-DNA binding as a function of pH and (ii) an internal deletion within I1 increases Ultrabithorax-DNA affinity, I1 must directly impact homeodomain-DNA interaction energetics. However, I2 appears to indirectly affect DNA binding in a manner countered by the N terminus. The amino acid sequences of I2 and much of the I1 and R regions vary significantly among Ultrabithorax orthologues, potentially diversifying Hox-DNA interactions. PMID:18508761

  13. First-principles study of multiple order-disorder transitions in Cd{sub 2}AgAu Heusler alloys

    SciTech Connect

    McCormack, R.; de Fontaine, D.

    1996-10-01

    The bcc-based Heusler alloys exhibit a series of order-disorder phase transitions as a function of temperature. The high-temperature phase is a disordered bcc solid solution, and the low-temperature phase is the Heusler structure. An intermediate ordered phase is also typically observed in real systems. A prototype cluster variation method (CVM) analysis is presented that shows that the relative stabilities of the Heusler and intermediate phases can vary continuously, depending on a fine balance between ordering tendencies in the constituent binary systems. Given these basic conclusions, a first-principles analysis of order-disorder transitions in Cd{sub 2}AgAu was performed. A cluster expansion Hamiltonian was constructed based on a series of linearized muffin-tin orbital calculations in the atomic sphere approximation. CVM calculations were then performed in the ternary bcc tetrahedron approximation. In addition to the transition temperatures, long-range order parameters, and sublattice occupations for Cd{sub 2}AgAu, an isoplethal section of the ternary phase diagram was also calculated. In general, agreement with experiment is excellent, given the first-principles nature of the calculation. This study clearly demonstrates the ability of first-principles statistical-mechanical calculations to treat complex ordering phenomena in {ital ternary} systems. {copyright} {ital 1996 The American Physical Society.}

  14. Risk Factors for Onset of Eating Disorders: Evidence of Multiple Risk Pathways from an 8-Year Prospective Study

    PubMed Central

    Stice, Eric; Marti, C. Nathan; Durant, Shelley

    2014-01-01

    Objective Use classification tree analysis with lagged predictors to determine empirically derived cut-points for identifying adolescent girls at risk for future onset of threshold, subthreshold, and partial eating disorders and test for interactions between risk factors that may implicate qualitatively distinct risk pathways. Method Data were drawn from a prospective study of 496 adolescent girls who completed diagnostic interviews and surveys annually for 8 years. Results Body dissatisfaction emerged as the most potent predictor; adolescent girls in the upper 24% of body dissatisfaction showed a 4.0-fold increased incidence of eating disorder onset (24% vs. 6%). Among participants in the high body dissatisfaction branch, those in the upper 32% of depressive symptoms showed a 2.9-fold increased incidence of onset (43% vs. 15%). Among participants in the low body dissatisfaction branch, those in the upper 12% of dieting showed a 3.6-fold increased incidence onset (18% vs. 5%). Conclusion This three-way interaction suggests a body dissatisfaction pathway to eating disorder onset that is amplified by depressive symptoms, as well as a pathway characterized by self-reported dieting among young women who are more satisfied with their bodies. It may be possible to increase the effectiveness of prevention programs by targeting each of these qualitatively distinct risk groups, rather than only individuals with a single risk factor. PMID:21764035

  15. Relationship of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to multiple indicators of functioning in people with schizophrenia and bipolar disorder

    PubMed Central

    Mausbach, Brent T; Harvey, Philip D; Pulver, Ann E; Depp, Colin A; Wolyniec, Paula S; Thornquist, Mary H; Luke, James R; McGrath, John A; Bowie, Christopher; Patterson, Thomas L

    2010-01-01

    Objective This study assessed the relationship between multiple indicators of ‘real-world’ functioning and scores on a brief performance-based measure of functional capacity known as the Brief University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA-B) in a sample of 205 patients with either serious bipolar disorder (n = 89) or schizophrenia (n = 116). Methods Participants were administered the UPSA-B and assessed on the following functional domains: (i) independent living status (e.g., residing independently as head of household, living in residential care facility); (ii) informant reports of functioning (e.g., work skills, daily living skills); (iii) educational attainment and estimated premorbid IQ as measured by years of education and Wide Range Achievement Test reading scores, respectively; and (iv) employment. Results Better scores on the UPSA-B were associated with greater residential independence after controlling for age, diagnosis, and symptoms of psychopathology. Among both bipolar disorder and schizophrenia patients, higher UPSA-B scores were significantly related to better informant reports of functioning in daily living skills and work skills domains. Greater estimated premorbid IQ was associated with higher scores on the UPSA-B for both schizophrenia and bipolar disorder participants. Participants who were employed scored higher on the UPSA-B when controlling for age and diagnosis, but not when controlling for symptoms of psychopathology. Conclusions These data suggest the UPSA-B may be useful for assessing capacity for functioning in a number of domains in both people diagnosed with schizophrenia and bipolar disorder. PMID:20148866

  16. "Nothing like Pretend": Difference, Disorder, and Dystopia in the Multiple World Spaces of Philip Pullman's "His Dark Materials"

    ERIC Educational Resources Information Center

    Cantrell, Sarah K.

    2010-01-01

    This article examines the multiple worlds in Philip Pullman's "His Dark Materials" trilogy in light Pierre Bourdieu's "space of possibles" and the combination of chance and choice that impact Lyra and Will's decisions. Rather than viewing chance or destiny as disempowering, this article considers how the protagonists' choices also encourage

  17. "Nothing like Pretend": Difference, Disorder, and Dystopia in the Multiple World Spaces of Philip Pullman's "His Dark Materials"

    ERIC Educational Resources Information Center

    Cantrell, Sarah K.

    2010-01-01

    This article examines the multiple worlds in Philip Pullman's "His Dark Materials" trilogy in light Pierre Bourdieu's "space of possibles" and the combination of chance and choice that impact Lyra and Will's decisions. Rather than viewing chance or destiny as disempowering, this article considers how the protagonists' choices also encourage…

  18. Mood Disorders

    MedlinePlus

    ... They may say they're in a bad mood. A mood disorder is different. It affects a person's everyday emotional state. Nearly one in ten people aged 18 and older have mood disorders. These include depression and bipolar disorder (also ...

  19. Intricate Crystal Structure of Dihydrolipoamide Dehydrogenase (E3) with its Binding Protein: Multiple Copies, Dynamic and Static Disorders

    NASA Technical Reports Server (NTRS)

    Makal, A.; Hong, Y. S.; Potter, R.; Vettaikkorumakankauv, A. K.; Korotchkina, L. G.; Patel, M. S.; Ciszak, E.

    2004-01-01

    Human E3 and binding protein E3BP are two components of the pyruvate dehydrogenase complex. Crystallization of E3 with 221-amino acid fragment of E3BP (E3BPdd) led to crystals that diffracted to a resolution of 2.6 Angstroms. Structure determination involved molecular replacement using a dimer of E3 homolog as a search model and de novo building of the E3BPdd peptide. Solution was achieved by inclusion of one E3 dimer at a time, followed by refinement until five E3 dimers were located. This complete content of E3 provided electron density maps suitable for tracing nine peptide chains of E3BPdd, eight of them being identified with partial occupancies. Final content of the asymmetric unit consists of five E3 dimers, each binding one E3BPdd molecule. In four of these molecular complexes, E3BPdd is in static disorder resulting in E3BPdd binding to either one or the other monomer of the E3 dimer. However, E3BPdd of the fifth E3 dimer forms specific contacts that lock it at one monomer. In addition to this static disorder, E3BPdd reveals high mobility in the limited space of the crystal lattice. Support from NIH and NASA.

  20. Eosinophilic Disorders

    MedlinePlus

    ... parasites , particularly ones that invade tissue, cause eosinophilia. Cancers that cause eosinophilia include Hodgkin lymphoma , leukemia , and myeloproliferative disorders . If the number of eosinophils is only ...

  1. Integrated Treatment of Substance Use and Psychiatric Disorders

    PubMed Central

    Kelly, Thomas M.; Daley, Dennis C.

    2013-01-01

    Epidemiological studies find that psychiatric disorders, including mental disorders and substance use disorders, are common among adults and highly comorbid. Integrated treatment refers to the focus of treatment on two or more conditions and to the use of multiple treatments such as the combination of psychotherapy and pharmacotherapy. Integrated treatment for comorbidity has been found to be consistently superior compared to treatment of individual disorders with separate treatment plans. This article focuses on a review of the risks for developing comorbid disorders and the combinations of treatments that appear to be most effective for clients with particular comorbid disorders. PMID:23731427

  2. [Developmental disorders].

    PubMed

    Kushima, Itaru; Okada, Takashi; Ozaki, Norio

    2012-02-01

    Developmental disorders, which are usually diagnosed in infancy, childhood, or adolescence, include mental retardation, learning disorders, motor skills disorder, communication disorders, pervasive developmental disorders (PDD), attention-deficit hyperactivity disorder (ADHD), and tic disorders. Epidemiological studies have indicated that these disorders are characterized not only by high heritability (e.g., 0.80 for PDD) but also by their shared genetic etiology. Furthermore, retrospective or prospective longitudinal studies have revealed that adult psychiatric disorders are often preceded either by their juvenile counterparts (homotypic continuity) or by different disorders (heterotypic continuity). Recent genetic studies have detected copy number variants (CNVs; e.g., deletions on 1q21.1, 3q29, and 22q.11.21 and duplications on 16p11.2) as shared genetic factors for PDD, mental retardation, and schizophrenia. While these CNVs are generally very rare (<1%), their effect size is much larger than that of single nucleotide polymorphisms. Although the mechanism by which CNVs cause these abnormalities remains unclear, pleiotropic effect of CNVs may provide insights into the high rate of comorbidity among developmental disorders and heterotypic continuity between developmental disorders and adult disorders. In addition, longitudinal neuroimaging studies have provided evidence for irregularities in the typical trajectories in developmental disorders. For instance, retarded cortical development is identified in ADHD in cortical trajectory, and early acceleration of brain growth is identified in PDD. Finally, we outlined several research topics as the future direction for investigation of developmental disorders: a longitudinal clinical study in subjects with specific disorder-related CNVs; detailed analysis of genetic factors relevant to developmental disorders, including smaller CNVs and INDELs; and functional analysis of genetic factors by using induced pluripotent stem cell technology or non-human primate animal models. PMID:22308259

  3. Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins.

    PubMed

    Dierks, Thomas; Schlotawa, Lars; Frese, Marc-André; Radhakrishnan, Karthikeyan; von Figura, Kurt; Schmidt, Bernhard

    2009-04-01

    Multiple sulfatase deficiency (MSD), mucolipidosis (ML) II/III and Niemann-Pick type C1 (NPC1) disease are rare but fatal lysosomal storage disorders caused by the genetic defect of non-lysosomal proteins. The NPC1 protein mainly localizes to late endosomes and is essential for cholesterol redistribution from endocytosed LDL to cellular membranes. NPC1 deficiency leads to lysosomal accumulation of a broad range of lipids. The precise functional mechanism of this membrane protein, however, remains puzzling. ML II, also termed I cell disease, and the less severe ML III result from deficiencies of the Golgi enzyme N-acetylglucosamine 1-phosphotransferase leading to a global defect of lysosome biogenesis. In patient cells, newly synthesized lysosomal proteins are not equipped with the critical lysosomal trafficking marker mannose 6-phosphate, thus escaping from lysosomal sorting at the trans Golgi network. MSD affects the entire sulfatase family, at least seven members of which are lysosomal enzymes that are specifically involved in the degradation of sulfated glycosaminoglycans, sulfolipids or other sulfated molecules. The combined deficiencies of all sulfatases result from a defective post-translational modification by the ER-localized formylglycine-generating enzyme (FGE), which oxidizes a specific cysteine residue to formylglycine, the catalytic residue enabling a unique mechanism of sulfate ester hydrolysis. This review gives an update on the molecular bases of these enigmatic diseases, which have been challenging researchers since many decades and so far led to a number of surprising findings that give deeper insight into both the cell biology and the pathobiochemistry underlying these complex disorders. In case of MSD, considerable progress has been made in recent years towards an understanding of disease-causing FGE mutations. First approaches to link molecular parameters with clinical manifestation have been described and even therapeutical options have been addressed. Further, the discovery of FGE as an essential sulfatase activating enzyme has considerable impact on enzyme replacement or gene therapy of lysosomal storage disorders caused by single sulfatase deficiencies. PMID:19124046

  4. Multiple myeloma.

    PubMed

    Peller, Patrick J

    2015-04-01

    This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography (CT) and the potential to improve the management of patients with multiple myeloma are discussed. The clinical and research data supporting the utility of PET/CT use in evaluating myeloma and other plasma cell dyscrasias continues to grow. PMID:25829088

  5. Treating Post-traumatic Stress Disorder in Patients with Multiple Sclerosis: A Randomized Controlled Trial Comparing the Efficacy of Eye Movement Desensitization and Reprocessing and Relaxation Therapy

    PubMed Central

    Carletto, Sara; Borghi, Martina; Bertino, Gabriella; Oliva, Francesco; Cavallo, Marco; Hofmann, Arne; Zennaro, Alessandro; Malucchi, Simona; Ostacoli, Luca

    2016-01-01

    Objective: Multiple Sclerosis (MS) is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences. Several studies have investigated the association between MS and mental disorders such as depression and anxiety, and recently researchers have focused also on Post-traumatic Stress Disorder (PTSD). This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS. Methods: A randomized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing (EMDR; n = 20) and Relaxation Therapy (RT; n = 22). The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale 6-months after the treatment. Results: The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions. EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD. Both treatments are effective in reducing PTSD severity, anxiety and depression symptoms, and to improve Quality of Life. Conclusion: Although our results can only be considered preliminary, this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients, in order to help them to reduce the psychological burden associated with their neurological condition. Trial registration: NCT01743664, https://clinicaltrials.gov/ct2/show/NCT01743664 PMID:27148134

  6. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

    PubMed Central

    Teuscher, Nathan S; Adjei, Akwete; Findling, Robert L; Greenhill, Laurence L; Kupper, Robert J; Wigal, Sharon

    2015-01-01

    A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR) has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD). Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS)-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg), increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased). Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. PMID:26060393

  7. Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein

    PubMed Central

    Huang, Yongqi; Liu, Zhirong

    2011-01-01

    Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs) which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N) which are involved in binding with two different targets (MDM2 and Taz2), and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex). We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs). PMID:21541066

  8. Bone biopsy in haematological disorders.

    PubMed Central

    Burkhardt, R; Frisch, B; Bartl, R

    1982-01-01

    Bone marrow biopsies are now widely used in the investigation and follow-up of many diseases. Semi-thin sections of 8216 undecalcified biopsies of patients with haematological disorders were studied. Observations were made on the cytopenias and the myelodysplastic syndromes, the acute leukaemias the myeloproliferative disorders, Hodgkin's disease and the malignant lymphomas including multiple myeloma, hairy cell leukaemia and angioimmunoblastic lymphadenopathy. Bone marrow biopsies are essential for the differential diagnosis of most cytopenias and for the early recognition of fibrosis which most frequently occurred as a consequence of megakaryocytic proliferation in the myeloproliferative disorders. Different patterns of bone marrow involvement were found in the lymphoproliferative disorders and both their type and extent constituted factors of prognostic significance. A survey of the literature is given and the conclusion is drawn that bone marrow biopsies provide indispensible information for the diagnostic evaluation and the follow-up of patients with haematological disorders. Images PMID:7040489

  9. Structural Conversion of A?17-42 Peptides from Disordered Oligomers to U-Shape Protofilaments via Multiple Kinetic Pathways.

    PubMed

    Cheon, Mookyung; Hall, Carol K; Chang, Iksoo

    2015-05-01

    Discovering the mechanisms by which proteins aggregate into fibrils is an essential first step in understanding the molecular level processes underlying neurodegenerative diseases such as Alzheimer's and Parkinson's. The goal of this work is to provide insights into the structural changes that characterize the kinetic pathways by which amyloid-? peptides convert from monomers to oligomers to fibrils. By applying discontinuous molecular dynamics simulations to PRIME20, a force field designed to capture the chemical and physical aspects of protein aggregation, we have been able to trace out the entire aggregation process for a system containing 8 A?17-42 peptides. We uncovered two fibrillization mechanisms that govern the structural conversion of A?17-42 peptides from disordered oligomers into protofilaments. The first mechanism is monomeric conversion templated by a U-shape oligomeric nucleus into U-shape protofilament. The second mechanism involves a long-lived and on-pathway metastable oligomer with S-shape chains, having a C-terminal turn, en route to the final U-shape protofilament. Oligomers with this C-terminal turn have been regarded in recent experiments as a major contributing element to cell toxicity in Alzheimer's disease. The internal structures of the U-shape protofilaments from our PRIME20/DMD simulation agree well with those from solid state NMR experiments. The approach presented here offers a simple molecular-level framework to describe protein aggregation in general and to visualize the kinetic evolution of a putative toxic element in Alzheimer's disease in particular. PMID:25955249

  10. Advantages of the multiple case series approach to the study of cognitive deficits in autism spectrum disorder.

    PubMed

    Towgood, Karren J; Meuwese, Julia D I; Gilbert, Sam J; Turner, Martha S; Burgess, Paul W

    2009-11-01

    In the neuropsychological case series approach, tasks are administered that tap different cognitive domains, and differences within rather than across individuals are the basis for theorising; each individual is effectively their own control. This approach is a mainstay of cognitive neuropsychology, and is particularly suited to the study of populations with heterogeneous deficits. However it has very rarely been applied to the study of cognitive differences in autism spectrum disorder (ASD). Here, we investigate whether this approach can yield information beyond that given by the typical group study method, when applied to an ASD population. Twenty-one high-functioning adult ASD participants and 22 IQ, age, and gender-matched control participants were administered a large battery of neuropsychological tests that would represent a typical neuropsychological assessment for neurological patients in the United Kingdom. The data were analysed using both group and single-case study methods. The group analysis revealed a limited number of deficits, principally on tests with a large executive function component, with no impairment in more routine abilities such as basic attending, language and perception. Single-case study analysis proved more fruitful revealing evidence of considerable variation in abilities both between and within ASD participants. Both sub-normal and supra-normal performance were observed, with the most defining feature of the ASD group being this variability. We conclude that the use of group-level analysis alone in the study of cognitive deficits in ASD risks missing cognitive characteristics that may be vitally important both theoretically and clinically, and even may be misleading because of averaging artifact. PMID:19580821

  11. Pediatric intestinal motility disorders.

    PubMed

    Gfroerer, Stefan; Rolle, Udo

    2015-09-01

    Pediatric intestinal motility disorders affect many children and thus not only impose a significant impact on pediatric health care in general but also on the quality of life of the affected patient. Furthermore, some of these conditions might also have implications for adulthood. Pediatric intestinal motility disorders frequently present as chronic constipation in toddler age children. Most of these conditions are functional, meaning that constipation does not have an organic etiology, but in 5% of the cases, an underlying, clearly organic disorder can be identified. Patients with organic causes for intestinal motility disorders usually present in early infancy or even right after birth. The most striking clinical feature of children with severe intestinal motility disorders is the delayed passage of meconium in the newborn period. This sign is highly indicative of the presence of Hirschsprung disease (HD), which is the most frequent congenital disorder of intestinal motility. HD is a rare but important congenital disease and the most significant entity of pediatric intestinal motility disorders. The etiology and pathogenesis of HD have been extensively studied over the last several decades. A defect in neural crest derived cell migration has been proven as an underlying cause of HD, leading to an aganglionic distal end of the gut. Numerous basic science and clinical research related studies have been conducted to better diagnose and treat HD. Resection of the aganglionic bowel remains the gold standard for treatment of HD. Most recent studies show, at least experimentally, the possibility of a stem cell based therapy for HD. This editorial also includes rare causes of pediatric intestinal motility disorders such as hypoganglionosis, dysganglionosis, chronic intestinal pseudo-obstruction and ganglioneuromatosis in multiple endocrine metaplasia. Underlying organic pathologies are rare in pediatric intestinal motility disorders but must be recognized as early as possible. PMID:26361414

  12. Pediatric intestinal motility disorders

    PubMed Central

    Gfroerer, Stefan; Rolle, Udo

    2015-01-01

    Pediatric intestinal motility disorders affect many children and thus not only impose a significant impact on pediatric health care in general but also on the quality of life of the affected patient. Furthermore, some of these conditions might also have implications for adulthood. Pediatric intestinal motility disorders frequently present as chronic constipation in toddler age children. Most of these conditions are functional, meaning that constipation does not have an organic etiology, but in 5% of the cases, an underlying, clearly organic disorder can be identified. Patients with organic causes for intestinal motility disorders usually present in early infancy or even right after birth. The most striking clinical feature of children with severe intestinal motility disorders is the delayed passage of meconium in the newborn period. This sign is highly indicative of the presence of Hirschsprung disease (HD), which is the most frequent congenital disorder of intestinal motility. HD is a rare but important congenital disease and the most significant entity of pediatric intestinal motility disorders. The etiology and pathogenesis of HD have been extensively studied over the last several decades. A defect in neural crest derived cell migration has been proven as an underlying cause of HD, leading to an aganglionic distal end of the gut. Numerous basic science and clinical research related studies have been conducted to better diagnose and treat HD. Resection of the aganglionic bowel remains the gold standard for treatment of HD. Most recent studies show, at least experimentally, the possibility of a stem cell based therapy for HD. This editorial also includes rare causes of pediatric intestinal motility disorders such as hypoganglionosis, dysganglionosis, chronic intestinal pseudo-obstruction and ganglioneuromatosis in multiple endocrine metaplasia. Underlying organic pathologies are rare in pediatric intestinal motility disorders but must be recognized as early as possible. PMID:26361414

  13. Oppositional Defiant and Conduct Disorder Behaviors in Boys with Autism Spectrum Disorder with and without Attention-Deficit Hyperactivity Disorder versus Several Comparison Samples

    ERIC Educational Resources Information Center

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D.; DeVincent, Carla J.

    2009-01-01

    We compared disruptive behaviors in boys with either autism spectrum disorder (ASD) plus ADHD (n = 74), chronic multiple tic disorder plus ADHD (n = 47), ADHD Only (n = 59), or ASD Only (n = 107). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 including parent- (n = 168) and teacher-rated (n = 173)…

  14. Oppositional Defiant and Conduct Disorder Behaviors in Boys with Autism Spectrum Disorder with and without Attention-Deficit Hyperactivity Disorder versus Several Comparison Samples

    ERIC Educational Resources Information Center

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D.; DeVincent, Carla J.

    2009-01-01

    We compared disruptive behaviors in boys with either autism spectrum disorder (ASD) plus ADHD (n = 74), chronic multiple tic disorder plus ADHD (n = 47), ADHD Only (n = 59), or ASD Only (n = 107). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 including parent- (n = 168) and teacher-rated (n = 173)

  15. Tooth Disorders

    MedlinePlus

    ... made of a hard, bonelike material. Inside the tooth are nerves and blood vessels. You need your ... These include eating, speaking and even smiling. But tooth disorders are nothing to smile about. They include ...

  16. Development of a universal psycho-educational intervention to prevent common postpartum mental disorders in primiparous women: a multiple method approach

    PubMed Central

    2010-01-01

    Background Prevention of postnatal mental disorders in women is an important component of comprehensive health service delivery because of the substantial potential benefits for population health. However, diverse approaches to prevention of postnatal depression have had limited success, possibly because anxiety and adjustment disorders are also problematic, mental health problems are multifactorially determined, and because relationships amongst psychosocial risk factors are complex and difficult to modify. The aim of this paper is to describe the development of a novel psycho-educational intervention to prevent postnatal mental disorders in mothers of firstborn infants. Methods Data from a variety of sources were synthesised: a literature review summarised epidemiological evidence about neglected modifiable risk factors; clinical research evidence identified successful psychosocial treatments for postnatal mental health problems; consultations with clinicians, health professionals, policy makers and consumers informed the proposed program and psychological and health promotion theories underpinned the proposed mechanisms of effect. The intervention was pilot-tested with small groups of mothers and fathers and their first newborn infants. Results What Were We Thinking! is a psycho-educational intervention, designed for universal implementation, that addresses heightened learning needs of parents of first newborns. It re-conceptualises mental health problems in mothers of infants as reflecting unmet needs for adaptations in the intimate partner relationship after the birth of a baby, and skills to promote settled infant behaviour. It addresses these two risk factors in half-day seminars, facilitated by trained maternal and child health nurses using non-psychiatric language, in groups of up to five couples and their four-week old infants in primary care. It is designed to promote confidence and reduce mental disorders by providing skills in sustainable sleep and settling strategies, and the re-negotiation of the unpaid household workload in non-confrontational ways. Materials include a Facilitators' Handbook, creatively designed worksheets for use in seminars, and a book for couples to take home for reference. A website provides an alternative means of access to the intervention. Conclusions What Were We Thinking! is a postnatal mental health intervention which has the potential to contribute to psychologically-informed routine primary postnatal health care and prevent common mental disorders in women. PMID:20718991

  17. Heterogeneous ordered-disordered structure of the mesodomain in frozen sucrose-water solutions revealed by multiple electron paramagnetic resonance spectroscopies.

    PubMed

    Chen, Hanlin; Sun, Li; Warncke, Kurt

    2013-04-01

    The microscopic structure of frozen aqueous sucrose solutions, over concentrations of 0-75% (w/v), is characterized by using multiple continuous-wave and pulsed electron paramagnetic resonance (EPR) spectroscopic and relaxation techniques and the paramagnetic spin probe, TEMPOL. The temperature dependence of the TEMPOL EPR line-shape anisotropy reveals a mobility transition, specified at 205 K in pure water and 255 ± 5 K for >1% (w/v) added sucrose. The transition temperature is >Tg, where Tg is the homogeneous water glass transition temperature, which shows that TEMPOL resides in the mesoscopic domain (mesodomain) at water-ice crystallite boundaries and that the mesodomain sucrose concentrations are comparable at >1% (w/v) added sucrose. Electron spin-echo envelope modulation (ESEEM) spectroscopy of TEMPOL-(2)H2-sucrose hyperfine interactions also indicates comparable sucrose concentrations in mesodomains at >1% (w/v) added sucrose. Electron spin-echo (ESE) detected longitudinal and phase memory relaxation times (T1 and TM, respectively) at 6 K indicate a general trend of increased mesodomain volume with added sucrose, in three stages: 1-15, 20-50, and >50% (w/v). The calibrated TEMPOL concentrations indicate that the mesodomain volume is less than the predicted maximally freeze-concentrated value [80 (w/w); 120% (w/v)], with transitions at 15-20% and 50% (w/v) starting sucrose. An ordered sucrose hydrate phase, which excludes TEMPOL, and a disordered, amorphous sucrose-water glass phase, in which TEMPOL resides, are proposed to compose a heterogeneous mesodomain. The results show that the ratio of ordered and disordered volume fractions in the mesodomain is exquisitely sensitive to the starting sucrose concentration. PMID:23464733

  18. Borderline personality disorder

    MedlinePlus

    Personality disorder - borderline ... Cause of borderline personality disorder (BPD) is unknown. Genetic, family, and social factors are thought to play roles. Risk factors for BPD include: Abandonment ...

  19. Recognizing, managing medical consequences of eating disorders in primary care.

    PubMed

    Dickstein, Leah P; Franco, Kathleen N; Rome, Ellen S; Auron, Moises

    2014-04-01

    Eating disorders can lead to serious health problems, and as in many other disorders, primary care physicians are on the front line. Problems that can arise from intentional malnutrition and from purging affect multiple organ systems. Treatment challenges include maximizing weight gain while avoiding the refeeding syndrome. PMID:24692444

  20. Diversity in Pathways to Common Childhood Disruptive Behavior Disorders

    ERIC Educational Resources Information Center

    Martel, Michelle M.; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Nigg, Joel T.

    2012-01-01

    Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological factors and mechanisms. Little work has attempted to chart multiple-level-of-analysis pathways (i.e., simultaneously including biological, environmental, and trait influences) to ODD and

  1. Diversity in Pathways to Common Childhood Disruptive Behavior Disorders

    ERIC Educational Resources Information Center

    Martel, Michelle M.; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Nigg, Joel T.

    2012-01-01

    Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological factors and mechanisms. Little work has attempted to chart multiple-level-of-analysis pathways (i.e., simultaneously including biological, environmental, and trait influences) to ODD and…

  2. Stereotypic movement disorder

    MedlinePlus

    ... include repetitive and purposeless picking, hand wringing, head tics, or lip-biting. Long-term stimulant use may ... disorders Obsessive compulsive disorder Tourette syndrome or other tic disorder

  3. Overview of Tooth Disorders

    MedlinePlus

    ... Version Tooth Disorders Overview of Tooth Disorders Cavities Pulpitis Periapical Abscess Impacted Teeth Dental Appliances Common tooth disorders include cavities (caused by tooth decay), pulpitis, periapical abscess, impacted teeth, and malocclusion (see page ...

  4. Neuropathology of sleep disorders: a review.

    PubMed

    Hauw, Jean-Jacques; Hausser-Hauw, Chantal; De Girolami, Umberto; Hasboun, Dominique; Seilhean, Danielle

    2011-04-01

    Sleep disorders are important manifestations of neurodegenerativediseases and sometimes are clinically evident well before the onset of other neurological manifestations. This review addresses theneuroanatomical basis and the mechanisms of sleep regulation in humans in relation to the neuropathology of entities associated with sleep disturbances in selected diseases, including Alzheimer disease, progressive supranuclear palsy, Lewy body disorders, multiple-system atrophy, and fatal familial insomnia. This includes abnormalities of circadian rhythm, insomnia, narcolepsy, rapid eye movements sleep behavior disorders, and excessive daytime sleepiness. PMID:21412175

  5. Structural characterization and in vitro antioxidant activity of kojic dipalmitate loaded w/o/w multiple emulsions intended for skin disorders.

    PubMed

    Gonçalez, Maíra Lima; Marcussi, Diana Gleide; Calixto, Giovana Maria Fioramonti; Corrêa, Marcos Antonio; Chorilli, Marlus

    2015-01-01

    Multiple emulsions (MEs) are intensively being studied for drug delivery due to their ability to load and increase the bioavailability of active lipophilic antioxidant, such as kojic dipalmitate (KDP). The aim of this study was to structurally characterize developed MEs by determining the average droplet size (Dnm) and zeta potential (ZP), performing macroscopic and microscopic analysis and analyzing their rheological behavior and in vitro bioadhesion. Furthermore, the in vitro safety profile and antioxidant activity of KDP-loaded MEs were evaluated. The developed MEs showed a Dnm of approximately 1 micrometer and a ZP of -13 mV, and no change was observed in Dnm or ZP of the system with the addition of KDP. KDP-unloaded MEs exhibited ''shear thinning" flow behavior whereas KDP-loaded MEs exhibited Newtonian behavior, which are both characteristic of antithixotropic materials. MEs have bioadhesion properties that were not influenced by the incorporation of KDP. The results showed that the incorporation of KDP into MEs improved the safety profile of the drug. The in vitro antioxidant activity assay suggested that MEs presented a higher capacity for maintaining the antioxidant activity of KDP. ME-based systems may be a promising platform for the topical application of KDP in the treatment of skin disorders. PMID:25785265

  6. Structural Characterization and In Vitro Antioxidant Activity of Kojic Dipalmitate Loaded W/O/W Multiple Emulsions Intended for Skin Disorders

    PubMed Central

    Marcussi, Diana Gleide; Calixto, Giovana Maria Fioramonti; Corrêa, Marcos Antonio

    2015-01-01

    Multiple emulsions (MEs) are intensively being studied for drug delivery due to their ability to load and increase the bioavailability of active lipophilic antioxidant, such as kojic dipalmitate (KDP). The aim of this study was to structurally characterize developed MEs by determining the average droplet size (Dnm) and zeta potential (ZP), performing macroscopic and microscopic analysis and analyzing their rheological behavior and in vitro bioadhesion. Furthermore, the in vitro safety profile and antioxidant activity of KDP-loaded MEs were evaluated. The developed MEs showed a Dnm of approximately 1 micrometer and a ZP of −13 mV, and no change was observed in Dnm or ZP of the system with the addition of KDP. KDP-unloaded MEs exhibited ‘‘shear thinning” flow behavior whereas KDP-loaded MEs exhibited Newtonian behavior, which are both characteristic of antithixotropic materials. MEs have bioadhesion properties that were not influenced by the incorporation of KDP. The results showed that the incorporation of KDP into MEs improved the safety profile of the drug. The in vitro antioxidant activity assay suggested that MEs presented a higher capacity for maintaining the antioxidant activity of KDP. ME-based systems may be a promising platform for the topical application of KDP in the treatment of skin disorders. PMID:25785265

  7. [Eating disorders].

    PubMed

    Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

    2015-02-01

    Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders. PMID:25681363

  8. Dissociative Identity Disorder

    ERIC Educational Resources Information Center

    Schmidt, Tom

    2007-01-01

    Few psychological disorders in the Diagnostic Statistical Manual have generated as much controversy as Dissociative Identity Disorder (DID). For the past 35 years diagnoses of DID, previously referred to as Multiple Personality Disorder (MPD), have increased exponentially, causing various psychological researchers and clinicians to question the…

  9. Peritoneal Disorders

    MedlinePlus

    ... of the peritoneum are not common. They include Peritonitis - an inflammation of the peritoneum Cancer Complications from ... peritoneal fluid to diagnose the problem. Treatment of peritoneal disorders depends on the cause.

  10. Disorderly Light.

    ERIC Educational Resources Information Center

    Peterson, Ivars

    1991-01-01

    The relationship between theories about electrical conductivity in microscopic wires and laser speckle patterns is described. Practical applications of laser speckle patterns are included. Wave ideas are being used to describe and predict novel phenomena in disordered solids. (KR)

  11. Pleural Disorders

    MedlinePlus

    ... in and out. Disorders of the pleura include Pleurisy - inflammation of the pleura that causes sharp pain ... Viral infection is the most common cause of pleurisy. The most common cause of pleural effusion is ...

  12. Assessment Tools for Adult Bipolar Disorder

    PubMed Central

    Miller, Christopher J.; Johnson, Sheri L.; Eisner, Lori

    2010-01-01

    This article reviews the current state of the literature on the assessment of bipolar disorder in adults. Research on reliable and valid measures for bipolar disorder has unfortunately lagged behind assessment research for other disorders, such as major depression. We review diagnostic tools, self-report measures to facilitate screening for bipolar diagnoses, and symptom severity measures. We briefly review other assessment domains, including measures designed to facilitate self-monitoring of symptoms. We highlight particular gaps in the field, including an absence of research on the reliable diagnosis of bipolar II and milder forms of disorder, a lack of empirical data on the best ways to integrate data from multiple domains, and a shortage of measures targeting a broader set of illness-related constructs relevant to bipolar disorder. PMID:20360999

  13. Multiple structural states exist throughout the helical nucleation sequence of the intrinsically disordered protein stathmin, as reported by electron paramagnetic resonance spectroscopy.

    PubMed

    Chui, Ashley J; López, Carlos J; Brooks, Evan K; Chua, Katherina C; Doupey, Tonia G; Foltz, Gretchen N; Kamel, Joseph G; Larrosa, Estefania; Sadiki, Amissi; Bridges, Michael D

    2015-03-10

    The intrinsically disordered protein (IDP) stathmin plays an important regulatory role in cytoskeletal maintenance through its helical binding to tubulin and microtubules. However, it lacks a stable fold in the absence of its binding partner. Although stathmin has been a focus of research over the past two decades, the solution-phase conformational dynamics of this IDP are poorly understood. It has been reported that stathmin is purely monomeric in solution and that it bears a short helical region of persistent foldedness, which may act to nucleate helical folding in the C-terminal direction. Here we report a comprehensive study of the structural equilibria local to this region in stathmin that contradicts these two claims. Using the technique of electron paramagnetic resonance (EPR) spectroscopy on spin-labeled stathmin mutants in the solution-phase and when immobilized on Sepharose solid support, we show that all sites in the helical nucleation region of stathmin exhibit multiple spectral components that correspond to dynamic states of differing mobilities and stabilities. Importantly, a state with relatively low mobility dominates each spectrum with an average population greater than 50%, which we suggest corresponds to an oligomerized state of the protein. This is in contrast to a less populated, more mobile state, which likely represents a helically folded monomeric state of stathmin, and a highly mobile state, which we propose is the random coil conformer of the protein. Our interpretation of the EPR data is confirmed by further characterization of the protein using the techniques of native and SDS PAGE, gel filtration chromatography, and multiangle and dynamic light scattering, all of which show the presence of oligomeric stathmin in solution. Collectively, these data suggest that stathmin exists in a diverse equilibrium of states throughout the purported helical nucleation region and that this IDP exhibits a propensity toward oligomerization. PMID:25715079

  14. Multiple chemical sensitivity syndrome.

    PubMed

    Magill, M K; Suruda, A

    1998-09-01

    Multiple chemical sensitivity (MCS) is a syndrome in which multiple symptoms reportedly occur with low-level chemical exposure. Several theories have been advanced to explain the cause of MCS, including allergy, toxic effects and neurobiologic sensitization. There is insufficient scientific evidence to confirm a relationship between any of these possible causes and symptoms. Patients with MCS have high rates of depression, anxiety and somatoform disorders, but it is unclear if a causal relationship or merely an association exists between MCS and psychiatric problems. Physicians should compassionately evaluate and care for patients who have this distressing condition, while avoiding the use of unproven, expensive or potentially harmful tests and treatments. The first goal of management is to establish an effective physician-patient relationship. The patient's efforts to return to work and to a normal social life should be encouraged and supported. PMID:9750540

  15. Unique contributions of individual eating disorder symptoms to eating disorder-related impairment.

    PubMed

    Hovrud, Lindsey; De Young, Kyle P

    2015-08-01

    This study examined the unique contribution of individual eating disorder symptoms and related features to overall eating disorder-related impairment. Participants (N=113) from the community with eating disorders completed assessments including the Clinical Impairment Assessment (CIA) and the Eating Disorder Examination Questionnaire. A multiple linear regression analysis indicated that 58.6% of variance in the CIA was accounted for by binge eating frequency, weight and shape concerns, and depression. These findings indicate that certain eating disorder symptoms uniquely account for impairment and that depression is a substantial contributor. It is possible that purging, restrictive eating, and body mass index did not significantly contribute to impairment because these features are consistent with many individuals' weight and shape goals. The results imply that eating disorder-related impairment may be more a result of cognitive features and binge eating rather than body weight and compensatory behaviors. PMID:26026614

  16. Atomic Disorder in Tetrahedrite

    NASA Astrophysics Data System (ADS)

    Salasin, John Robert; Chakoumakos, Bryan; Rawn, Claudia; May, Andrew; Lara-Curzio, Edgar; McGuire, Michael; Cao, Huibo

    2015-03-01

    Thermoelectrics (TE) are materials which turn heat energy into electrical energy with applications spanning multiple disciplines including space exploration, Peltier cooling, and engine efficiency. Tetrahedrite is a copper sulfosalt with the general formula Cu12-xMx(Sb,As)4S13. Where M denotes a Cu2+ site frequently replaced in natural tetrahedrite with Zn, Fe, Hg, or Mn. It has a cubic structure with an I-43m symmetry, a = 10.4 Å, and only a handful of adjustable parameters. This structural study corroborates theoretical calculations on atomic disorder. Positional disorder of the trigonally coordinated Cu(2) site is suggested from the temperature dependence of the atomic displacement parameters determine from single-crystal x-ray and neutron diffraction. The displacements are extremely anisotropic for Cu(2) with a maximum rms static displacement of ~ 0.25 Å.

  17. Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders

    PubMed Central

    Rossignol, E.

    2011-01-01

    A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders. PMID:21876820

  18. Primary Sleep Disorders.

    PubMed

    Khoury, John; Doghramji, Karl

    2015-12-01

    Primary sleep disorders include those not attributable to another medical or psychiatric condition: insomnia disorder, hypersomnolence disorder, narcolepsy, obstructive sleep apnea hypopnea syndrome, central sleep apnea syndrome, and the parasomnias. They are commonly encountered and are comorbid with many psychiatric disorders. It is important to recognize these disorders and be comfortable treating them or to know when to refer to a sleep disorders center and sleep specialist. Treatment of a comorbid sleep disorder can improve the overall quality of life, symptoms in mood disorders, and symptoms of excessive daytime sleepiness, and decrease cardiovascular morbidity and mortality. PMID:26600103

  19. Disordered photonics

    NASA Astrophysics Data System (ADS)

    Wiersma, Diederik S.

    2013-03-01

    What do lotus flowers have in common with human bones, liquid crystals with colloidal suspensions, and white beetles with the beautiful stones of the Taj Mahal? The answer is they all feature disordered structures that strongly scatter light, in which light waves entering the material are scattered several times before exiting in random directions. These randomly distributed rays interfere with each other, leading to interesting, and sometimes unexpected, physical phenomena. This Review describes the physics behind the optical properties of disordered structures and how knowledge of multiple light scattering can be used to develop new applications. The field of disordered photonics has grown immensely over the past decade, ranging from investigations into fundamental topics such as Anderson localization and other transport phenomena, to applications in imaging, random lasing and solar energy.

  20. Multiple osteochondromas

    PubMed Central

    Bovée, Judith VMG

    2008-01-01

    Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed. PMID:18271966

  1. Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders

    PubMed Central

    Glinskii, Anna B; Ma, Shuang; Ma, Jun; Grant, Denise; Lim, Chang-Uk; Guest, Ian; Sell, Stewart; Buttyan, Ralph

    2011-01-01

    The mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here, we present experimental and clinical evidence supporting the importantance of the role of IDAGL in human diseases. A targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple IDAGL and identifies 96 small noncoding trans-regulatory RNAs of ∼100–300 nt in length containing SNPs (snpRNAs) associated with 21 common disorders. Multiple independent lines of experimental evidence support functionality of snpRNAs by documenting their cell type-specific expression and evolutionary conservation of sequences, genomic coordinates and biological effects. Chromatin state signatures, expression profiling experiments and luciferase reporter assays demonstrate that many IDAGL are Polycomb-regulated long-range enhancers. Expression of snpRNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically relevant phenotypic changes: NLRP1-locus snpRNAs rs2670660 exert regulatory effects on monocyte/macrophage transdifferentiation, induce prostate cancer (PC) susceptibility snpRNAs and transform low-malignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCR analysis and luciferase reporter assays demonstrate that snpRNA sequences represent allele-specific “decoy” targets of microRNAs that function as SNP allele-specific modifiers of microRNA expression and activity. We demonstrate that trans-acting RNA molecules facilitating resistance to androgen depletion (RAD) in vitro and castration-resistant phenotype (CRP) in vivo of PC contain intergenic 8q24-locus SNP variants (rs1447295; rs16901979; rs6983267) that were recently linked with increased risk of PC. Q-PCR analysis of clinical samples reveals markedly increased and highly concordant (r = 0.896; p < 0.0001) snpRNA expression levels in tumor tissues compared with the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001) for NLRP1-locus and 8q24-locus snpRNAs, respectively]. Our experiments indicate that RAD and CR phenotype of human PC cells can be triggered by ncRNA molecules transcribed from the NLRP1-locus intergenic enhancer at 17p13 and by downstream activation of the 8q24-locus snpRNAs. Our results define the IDAGL at 17p13 and 8q24 as candidate regulatory loci of RAD and CR phenotypes of PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC and identify novel molecular and genetic targets with diagnostic and therapeutic potentials, exploration of which should be highly beneficial for personalized clinical management of PC. PMID:22067658

  2. Bipolar Disorder

    MedlinePlus

    ... Prevention (2 items) Treatments (4 items) Publications About Bipolar Disorder Bipolar Disorder A brochure on bipolar disorder that ... En Espaol Continue Reading Share More Information About Bipolar Disorder Bipolar Disorder Page Information about Bipolar Disorder from ...

  3. Dysthymic Disorder

    PubMed Central

    Sansone, Lori A.

    2009-01-01

    This ongoing column is dedicated to the challenging clinical interface between psychiatry and primary care—two fields that are inexorably linked. Dysthymic disorder is a smoldering mood disturbance characterized by a long duration (at least two years in adults) as well as transient periods of normal mood. The disorder is fairly common in the US general population (3–6%) as well as in primary care (7%) and mental health settings (up to one-third of psychiatric outpatients). While the etiology of dysthymia remains unknown, there appears to be a genetic susceptibility, which may manifest in the presence of various psychosocial stressors. While the Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria are fairly clear, the disorder can be easily under-recognized for a variety of reasons. Treatment may include pharmacotherapy and psychotherapy, although the overall treatment course is oftentimes characterized by protracted symptoms and relapses. PMID:19724735

  4. Quality of life in multiple sclerosis patients with urinary disorders: reliability and validity of the Turkish version of King's Health Questionnaire.

    PubMed

    Akkoc, Yeşim; Karapolat, Hale; Eyigor, Sibel; Yesil, Hilal; Yüceyar, Nur

    2011-06-01

    MS patients frequently present with urinary system symptoms, which have a negative effect on the quality life. The aim of our study was to demonstrate the validity and reliability of the Turkish King's Health Questionnaire (KHQ) in MS patients. The study included 37 patients. For analysis of test-retest reliability, the Turkish version of the KHQ developed and the "translation-back translation" method was performed. To assess the validity of these results, Multiple Sclerosis Quality of Life Scale (MQoL-54) and Expanded Disability Status Scale (EDSS) were used. The internal consistency (intra-class correlation coefficient: 0.59-0.94) and test-retest reliability (Cronbach's α-score 0.59-0.94) of KHQ were found to be high (p < 0.05). A significant correlation was detected between most of the KHQ subscores and the physical and mental MQoL-54 and EDSS (total and bowel/bladder, p < 0.05) subscores. The KHQ may be used to determine the effect of incontinence on the quality of life for MS patients. PMID:21479614

  5. Multiple homicides.

    PubMed

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered. PMID:2782297

  6. Quantitative proteome-based guidelines for intrinsic disorder characterization.

    PubMed

    Vincent, Michael; Whidden, Mark; Schnell, Santiago

    2016-06-01

    Intrinsically disordered proteins fail to adopt a stable three-dimensional structure under physiological conditions. It is now understood that many disordered proteins are not dysfunctional, but instead engage in numerous cellular processes, including signaling and regulation. Disorder characterization from amino acid sequence relies on computational disorder prediction algorithms. While numerous large-scale investigations of disorder have been performed using these algorithms, and have offered valuable insight regarding the prevalence of protein disorder in many organisms, critical proteome-based descriptive statistical guidelines that would enable the objective assessment of intrinsic disorder in a protein of interest remain to be established. Here we present a quantitative characterization of numerous disorder features using a rigorous non-parametric statistical approach, providing expected values and percentile cutoffs for each feature in ten eukaryotic proteomes. Our estimates utilize multiple ab initio disorder prediction algorithms grounded on physicochemical principles. Furthermore, we present novel threshold values, specific to both the prediction algorithms and the proteomes, defining the longest primary sequence length in which the significance of a continuous disordered region can be evaluated on the basis of length alone. The guidelines presented here are intended to improve the interpretation of disorder content and continuous disorder predictions from the proteomic point of view. PMID:27085142

  7. MRI mimics of multiple sclerosis.

    PubMed

    Aliaga, Esther Sánchez; Barkhof, Frederik

    2014-01-01

    Diagnosis of multiple sclerosis (MS) is based on the demonstration of dissemination of lesions in space (DIS) and in time (DIT), as well as on the exclusion of an alternative neurologic disorder. As a paraclinical tool brain and/or spinal cord magnetic resonance imaging (MRI), showing typical lesion morphology, characteristic distribution of lesions, or involvement or specific anatomic structures, can support the diagnosis of MS. But from an imaging perspective a considerable amount of inherited and acquired disorders may manifest with radiologic evidence of DIT, DIS, or both. Hypoxic-ischemic vasculopathy, specially small-vessel disease, inflammatory disorders, vasculitis, and non-MS idiopathic inflammatory disorders, as well as some toxic, metabolic, and infectious disorders, may present mimicking MS on MR examinations and should be included in the differential diagnosis of MS-like lesions. Careful evaluation of associated findings on MRI, the so-called MRI red flags, such as the presence of infarcts, microbleeds, meningeal enhancement, and calcifications among others, are very helpful in suggesting a diagnosis other than MS. Complement MRI findings to patient's history, demographics, and serologic findings are crucial to achieve the correct diagnosis. We will review the most frequent radiologic appearance and differential features from the most frequent MS mimickers. PMID:24507523

  8. Prevention of eating disorders in female athletes.

    PubMed

    Coelho, Gabriela Morgado de Oliveira; Gomes, Ain Innocencio da Silva; Ribeiro, Beatriz Gonalves; Soares, Eliane de Abreu

    2014-01-01

    Eating disorders are serious mental diseases that frequently appear in female athletes. They are abnormal eating behaviors that can be diagnosed only by strict criteria. Disordered eating, although also characterized as abnormal eating behavior, does not include all the criteria for diagnosing eating disorders and is therefore a way to recognize the problem in its early stages. It is important to identify factors to avoid clinical progression in this high-risk population. Therefore, the purpose of this review is to discuss critical information for the prevention of eating disorders in female athletes. This review discusses the major correlates for the development of an eating disorder. We also discuss which athletes are possibly at highest risk for eating disorders, including those from lean sports and female adolescent athletes. There is an urgent need for the demystification of myths surrounding body weight and performance in sports. This review includes studies that tested different prevention programs' effectiveness, and the majority showed positive results. Educational programs are the best method for primary prevention of eating disorders. For secondary prevention, early identification is essential and should be performed by preparticipation exams, the recognition of dietary markers, and the use of validated self-report questionnaires or clinical interviews. In addition, more randomized clinical trials are needed with athletes from multiple sports in order for the most reliable recommendations to be made and for some sporting regulations to be changed. PMID:24891817

  9. Prevention of eating disorders in female athletes

    PubMed Central

    Coelho, Gabriela Morgado de Oliveira; Gomes, Ainá Innocencio da Silva; Ribeiro, Beatriz Gonçalves; Soares, Eliane de Abreu

    2014-01-01

    Eating disorders are serious mental diseases that frequently appear in female athletes. They are abnormal eating behaviors that can be diagnosed only by strict criteria. Disordered eating, although also characterized as abnormal eating behavior, does not include all the criteria for diagnosing eating disorders and is therefore a way to recognize the problem in its early stages. It is important to identify factors to avoid clinical progression in this high-risk population. Therefore, the purpose of this review is to discuss critical information for the prevention of eating disorders in female athletes. This review discusses the major correlates for the development of an eating disorder. We also discuss which athletes are possibly at highest risk for eating disorders, including those from lean sports and female adolescent athletes. There is an urgent need for the demystification of myths surrounding body weight and performance in sports. This review includes studies that tested different prevention programs’ effectiveness, and the majority showed positive results. Educational programs are the best method for primary prevention of eating disorders. For secondary prevention, early identification is essential and should be performed by preparticipation exams, the recognition of dietary markers, and the use of validated self-report questionnaires or clinical interviews. In addition, more randomized clinical trials are needed with athletes from multiple sports in order for the most reliable recommendations to be made and for some sporting regulations to be changed. PMID:24891817

  10. Plasma Cell Disorders

    MedlinePlus

    ... of Undetermined Significance (MGUS) Multiple Myeloma Macroglobulinemia Heavy Chain Diseases Plasma cell disorders are uncommon. They begin ... antibody produced is incomplete, consisting of only light chains or heavy chains (functional antibodies normally consist of ...

  11. Peer Victimization in Youth with Tourette Syndrome and Other Chronic Tic Disorders

    ERIC Educational Resources Information Center

    Zinner, Samuel H.; Conelea, Christine A.; Glew, Gwen M.; Woods, Douglas W.; Budman, Cathy L.

    2012-01-01

    Chronic tic disorders including Tourette syndrome have negative impact across multiple functional domains. We explored associations between peer victimization status and tic subtypes, premonitory urges, internalizing symptoms, explosive outbursts, and quality of life among youth with chronic tic disorders, as part of the internet-based omnibus

  12. Peer Victimization in Youth with Tourette Syndrome and Other Chronic Tic Disorders

    ERIC Educational Resources Information Center

    Zinner, Samuel H.; Conelea, Christine A.; Glew, Gwen M.; Woods, Douglas W.; Budman, Cathy L.

    2012-01-01

    Chronic tic disorders including Tourette syndrome have negative impact across multiple functional domains. We explored associations between peer victimization status and tic subtypes, premonitory urges, internalizing symptoms, explosive outbursts, and quality of life among youth with chronic tic disorders, as part of the internet-based omnibus…

  13. [Headache disorders].

    PubMed

    Takeshima, Takao; Kikui, Shoji

    2013-09-01

    Primary headache disorders such as migraine, tension-type headache, and cluster headache are prevalent and disabling neurological disorders. Although most headache disorders are largely treatable, they are under-recognized, under-diagnosed, and under-treated. Many headache sufferers in Japan do not receive appropriate and effective health care; hence, the illness, which should be relieved, persists and acts as an individual and societal burden. One of the barriers most responsible for this is poor awareness of the disorders. For lifting the burden, health care must be improved. Education is an essential way to resolve these issues at multiple levels. We have a Japanese version of the international headache classification and diagnostic criteria II (ICHD-II) and guidelines for the management of chronic headaches. Utilization of these resources is key for the improvement of headache management in our country. Not only neurologists, but also neurosurgeons and other medical specialists are participating in headache care in Japan. The Japanese Headache Society and the Japanese Society for Neurology should play major roles in health care service, education programs, as well as clinical and basic research for headache disorders. The road map for realizing our aim on headache treatment is as follows: (1) increase the number of units concerning headache in lectures for medical students, implement training programs for residents and neurologists, and offer continuous medical educations for physicians and neurologists; (2) secure more funding for headache research; (3) propagate medical care for headache in primary care settings and regional fundamental hospitals; (4) reform the health care system for headache and incentivize appropriate compensation for headache care in public health insurance; and (5) spread appropriate information on medical and socio-ethical issues related to headache for the sufferers and citizens. The authors expect that many neurologists have an interest in headache and understanding headaches, and better health care for headache disorders will bring great benefits for the sufferers. PMID:24018741

  14. Binge eating disorder

    MedlinePlus

    The exact cause of binge eating is unknown. Things that may lead to this disorder include: Genes, such as having close relatives who also have an eating disorder Changes in brain chemicals Depression ...

  15. Sleep disorders - overview

    MedlinePlus

    Sleep disorders are problems with sleeping. These include: Trouble falling or staying asleep Falling asleep at the wrong ... Mononucleosis or other viral illnesses Narcolepsy and other sleep disorders Obesity, especially if it causes obstructive sleep apnea ...

  16. Peroxisomal disorders.

    PubMed

    Aubourg, Patrick; Wanders, Ronald

    2013-01-01

    The peroxisomal disorders represent a group of genetic diseases in man in which there is an impairment in one or more peroxisomal functions. The peroxisomal disorders are subdivided into three subgroups comprising: (1) the peroxisome biogenesis disorders (PBDs); (2) the single peroxisomal (enzyme-) protein deficiencies; and (3) the single peroxisomal substrate transport deficiencies. The PBD group comprises four different disorders that include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). ZS, NALD, and IRD are clearly distinct from RCDP and are usually referred to as the Zellweger spectrum with ZS being the most severe, and IRD the less severe disorder, with sometimes onset in adulthood. The single peroxisomal enzyme deficiency group comprises seven different disorders, of which D-bifunctional protein and phytanoyl-CoA hydroxylase (adult Refsum disease) deficiencies are the most frequent. The single peroxisomal substrate transport deficiency group consists of only one disease, X-linked adrenoleukodystrophy. It is the purpose of this chapter to describe the current state of knowledge about the clinical, biochemical, cellular, and molecular aspects of peroxisomal diseases, and to provide guidelines for their post- and prenatal diagnosis. Therapeutic interventions are mostly limited to X-linked adrenoleukodystrophy. PMID:23622381

  17. Eating disorders.

    PubMed

    Patel, D R; Phillips, E L; Pratt, H D

    1998-01-01

    Anorexia nervosa and bulimia nervosa are primarily psychiatric disorders characterized by severe disturbances of eating behaviour. Anorexia nervosa has been well documented in pre-pubertal children. Eating disorders are most prevalent in the Western cultures where food is in abundance and for females attractiveness is equated with thinness. Eating disorders are rare in countries like India. As Western sociocultural ideals become more widespread one may expect to see an increase in number of cases of eating disorders in non-Western societies. Etiological theories suggest a complex interaction among psychological, sociocultural, and biological factors. Patients with anorexia nervosa manifest weight loss, fear of becoming fat, and disturbances in how they experience their body weight and shape. Patients with bulimia nervosa present with recurrent episodes of binge eating and inappropriate methods of weight control such as self-induced vomiting, and abuse of diuretics and laxatives. Major complications of eating disorders include severe fluid and electrolyte disturbances and cardiac arrhythmias. The most common cause of death in anorexia nervosa is suicide. Management requires a team approach in which different professionals work together. Individual and family psychotherapy are effective in patients with anorexia nervosa and cognitive-behavioral therapy is effective in bulimia nervosa. Pharmacotherapy is not universally effective by itself. Patients with eating disorders suffer a chronic course of illness. The pediatrician plays important role in early diagnosis, management of medical complications, and psychological support to the patient and the family. PMID:10773895

  18. Aquatherapy for neurodegenerative disorders.

    PubMed

    Plecash, Alyson R; Leavitt, Blair R

    2014-01-01

    Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders. PMID:25062761

  19. Gastroduodenal Disorders.

    PubMed

    Stanghellini, Vincenzo; Chan, Francis K L; Hasler, William L; Malagelada, Juan R; Suzuki, Hidekazu; Tack, Jan; Talley, Nicholas J

    2016-05-01

    Symptoms that can be attributed to the gastroduodenal region represent one of the main subgroups among functional gastrointestinal disorders. A slightly modified classification into the following 4 categories is proposed: (1) functional dyspepsia, characterized by 1 or more of the following: postprandial fullness, early satiation, epigastric pain, and epigastric burning, which are unexplained after a routine clinical evaluation; and includes 2 subcategories: postprandial distress syndrome that is characterized by meal-induced dyspeptic symptoms and epigastric pain syndrome that does not occur exclusively postprandially; the 2 subgroups can overlap; (2) belching disorders, defined as audible escapes of air from the esophagus or the stomach, are classified into 2 subcategories, depending on the origin of the refluxed gas as detected by intraluminal impedance measurement belching: gastric and supragastric belch; (3) nausea and vomiting disorders, which include 3 subcategories: chronic nausea and vomiting syndrome; cyclic vomiting syndrome; and cannabinoid hyperemesis syndrome; and (4) rumination syndrome. PMID:27147122

  20. Bipolar Disorder

    MedlinePlus

    ... Treatments and Therapies Join a Study Learn More Bipolar Disorder Definition Bipolar disorder, also known as manic- ... known as major depressive disorder with mixed features. Bipolar Disorder and Other Illnesses Some bipolar disorder symptoms ...

  1. Bipolar Disorder

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Bipolar Disorder KidsHealth > For Teens > Bipolar Disorder Print A ... Bipolar Disorder en español Trastorno bipolar What Is Bipolar Disorder? Bipolar disorders are one of several medical ...

  2. The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting

    ERIC Educational Resources Information Center

    Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.

    2007-01-01

    Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…

  3. Multiple List Learning in Adults with Autism Spectrum Disorder: Parallels with Frontal Lobe Damage or Further Evidence of Diminished Relational Processing?

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2010-01-01

    To test the effects of providing relational cues at encoding and/or retrieval on multi-trial, multi-list free recall in adults with high-functioning autism spectrum disorder (ASD), 16 adults with ASD and 16 matched typical adults learned a first followed by a second categorised list of 24 words. Category labels were provided at encoding,…

  4. Integrating Case Topics in Medical School Curriculum to Enhance Multiple Skill Learning: Using Fetal Alcohol Spectrum Disorders as an Exemplary Case

    ERIC Educational Resources Information Center

    Paley, Blair; O'Connor, Mary J.; Baillie, Susan J.; Guiton, Gretchen; Stuber, Margaret L.

    2009-01-01

    Objectives: This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. Methods: In collaboration with the Centers for Disease…

  5. Integrating Case Topics in Medical School Curriculum to Enhance Multiple Skill Learning: Using Fetal Alcohol Spectrum Disorders as an Exemplary Case

    ERIC Educational Resources Information Center

    Paley, Blair; O'Connor, Mary J.; Baillie, Susan J.; Guiton, Gretchen; Stuber, Margaret L.

    2009-01-01

    Objectives: This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. Methods: In collaboration with the Centers for Disease

  6. Community Report from the Autism and Developmental Disabilities Monitoring (ADDM) Network: Prevalence of Autism Spectrum Disorders (ASDs) among Multiple Areas of the United States in 2008

    ERIC Educational Resources Information Center

    Centers for Disease Control and Prevention, 2012

    2012-01-01

    The Centers for Disease Control and Prevention (CDC) estimates that about 1 in 88 children has been identified with an autism spectrum disorder (ASD). CDC's estimate comes from the Autism and Developmental Disabilities Monitoring (ADDM) Network, which monitors the number of 8-year-old children with ASDs living in diverse communities throughout the…

  7. Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA′ Multiple Case Design Examining Dosing and Generalization to the Home and Community

    PubMed Central

    Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D’Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

    2014-01-01

    We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6–8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70 % of the target behaviors were better during Intervention and improvement was retained in 63 % of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469

  8. Therapeutic horseback riding outcomes of parent-identified goals for children with autism spectrum disorder: an ABA' multiple case design examining dosing and generalization to the home and community.

    PubMed

    Holm, Margo B; Baird, Joanne M; Kim, Young Joo; Rajora, Kuwar B; D'Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

    2014-04-01

    We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70% of the target behaviors were better during Intervention and improvement was retained in 63% of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469

  9. Common anorectal disorders.

    PubMed

    Foxx-Orenstein, Amy E; Umar, Sarah B; Crowell, Michael D

    2014-05-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management. PMID:24987313

  10. Common Anorectal Disorders

    PubMed Central

    Foxx-Orenstein, Amy E.; Umar, Sarah B.; Crowell, Michael D.

    2014-01-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management. PMID:24987313

  11. Depression and anxiety disorders.

    PubMed

    Brown, C S

    2001-06-01

    Depressive and anxiety disorders are common problems facing obstetrician-gynecologists. Although psychiatric disorders are equally common in men and women, women are at least twice as likely to present with depressive disorders and most anxiety disorders. The depressive disorders include major depression, dysthymia, seasonal affective disorder, and premenstrual dysphoric disorder. The anxiety disorders are panic disorder (with and without agoraphobia), generalized anxiety disorder, social phobia, obsessive compulsive disorder, and PTSD. One must diagnose and manage depressive and anxiety disorders during pregnancy, the purpureum, and while breastfeeding. General treatment principles include assessing suicide risk, psychotherapy, pharmacologic treatment, and an appropriate medical work-up for depressive and anxiety disorders. The SSRIs are the first-line treatment for most depressive and anxiety disorders because of data supporting their efficacy, the minimal need for dosage titration, the overall favorable side-effect profile, and the length of available clinical experience. Newer antidepressants, such as venlafaxine, bupropion, nefazodone, and mirtazapine, are options for patients unresponsive to, or intolerant of, the SSRIs. Treatment considerations include acute, maintenance, and continuation therapy, dosage regimens, adverse effects, and drug interactions. Specific guidelines are available for referring patients to a mental health specialist. PMID:11430175

  12. Eating disorders

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The incidence of eating disorders is increasing, and health care professionals are faced with the difficult task of treating these refractory conditions. The first clinical description of anorexia nervosa (AN) was reported in 1694 and included symptoms such as decreased appetite, amenorrhea, food av...

  13. Penis Disorders

    MedlinePlus

    Problems with the penis can cause pain and affect a man's sexual function and fertility. Penis disorders include Erectile dysfunction - inability to get or ... not go away Peyronie's disease - bending of the penis during an erection due to a hard lump ...

  14. [Attention deficit hyperactivity disorder].

    PubMed

    Cunill, Ruth; Castells, Xavier

    2015-04-20

    Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders and can persist into the adulthood. ADHD has important social, academic and occupational consequences. ADHD diagnosis is based on the fulfillment of several clinical criteria, which can vary depending on the diagnostic system used. The clinical presentation can show great between-patient variability and it has been related to a dysfunction in the fronto-striatal and meso-limbic circuits. Recent investigations support a model in which multiple genetic and environmental factors interact to create a neurobiological susceptibility to develop the disorder. However, no clear causal association has yet been identified. Although multimodal treatment including both pharmacological and psychosocial interventions is usually recommended, no convincing evidence exists to support this recommendation. Pharmacological treatment has fundamentally shown to improve ADHD symptoms in the short term, while efficacy data for psychosocial interventions are scarce and inconsistent. Yet, drug treatment is increasingly popular and the last 2 decades have witnessed a sharp increase in the prescription of anti-ADHD medications coinciding with the marketing of new drugs to treat ADHD. PMID:24787685

  15. PSYCHIATRIC DISORDERS ASSOCIATED WITH FXTAS

    PubMed Central

    Seritan, Andreea L.; Ortigas, Melina; Seritan, Stefan; Bourgeois, James A.; Hagerman, Randi J.

    2015-01-01

    Carriers of the FMR1 premutation (with 55-200 CGG repeats) may present with multiple medical and psychiatric disorders. Middle-aged carriers (males more often than females) may suffer from fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS is a newly discovered neurodegenerative disease characterized by intention tremor and ataxia, along with several other neurological features. Psychiatric manifestations are common in premutation carriers of both genders and include attention deficits, anxiety, depression, irritability, impulse dyscontrol, and substance abuse or dependence. Major depressive disorder, panic disorder with or without agoraphobia, generalized anxiety disorder, social phobia, and specific phobia are among the psychiatric diagnoses often encountered in premutation carriers, including those with FXTAS. Later in the course of the illness, cognitive deficits (including dementia) may occur. In this paper, we discuss common psychiatric phenotypes in FXTAS, based on a thorough review of the literature, as well as our own research experience. Symptomatic pharmacologic treatments are available, although disease modifying agents have not yet been developed. PMID:25620899

  16. Common Questions About Oppositional Defiant Disorder.

    PubMed

    Riley, Margaret; Ahmed, Sana; Locke, Amy

    2016-04-01

    Oppositional defiant disorder (ODD) is a disruptive behavior disorder characterized by a pattern of angry or irritable mood, argumentative or defiant behavior, or vindictiveness lasting for at least six months. Children and adolescents with ODD may have trouble controlling their temper and are often disobedient and defiant toward others. There are no tools specifically designed for diagnosing ODD, but multiple questionnaires can aid in diagnosis while assessing for other psychiatric conditions. ODD is often comorbid with attention-deficit/hyperactivity disorder, conduct disorder, and mood disorders, including anxiety and depression. Behavioral therapy for the child and family members improves symptoms of ODD. Medications are not recommended as first-line treatment for ODD; however, treatment of comorbid mental health conditions with medications often improves ODD symptoms. Adults and adolescents with a history of ODD have a greater than 90% chance of being diagnosed with another mental illness in their lifetime. They are at high risk of developing social and emotional problems as adults, including suicide and substance use disorders. Early intervention seeks to prevent the development of conduct disorder, substance abuse, and delinquency that can cause lifelong social, occupational, and academic impairments. PMID:27035043

  17. Traumatic brain injury-induced sleep disorders.

    PubMed

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%-70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  18. Traumatic Brain Injury and Sleep Disorders

    PubMed Central

    Viola-Saltzman, Mari; Watson, Nathaniel F.

    2012-01-01

    SYNOPSIS Sleep disturbance is common following traumatic brain injury (TBI), affecting 30–70% of individuals, many occurring after mild injuries. Insomnia, fatigue and sleepiness are the most frequent post-TBI sleep complaints with narcolepsy (with or without cataplexy), sleep apnea (obstructive and/or central), periodic limb movement disorder, and parasomnias occurring less commonly. In addition, depression, anxiety and pain are common TBI co-morbidities with substantial influence on sleep quality. Two types of TBI negatively impact sleep: contact injuries causing focal brain damage and acceleration/deceleration injuries causing more generalized brain damage. Diagnosis of sleep disorders after TBI may involve polysomnography, multiple sleep latency testing and/or actigraphy. Treatment is disorder specific and may include the use of medications, continuous positive airway pressure (or similar device) and/or behavioral modifications. Unfortunately, treatment of sleep disorders associated with TBI often does not improve sleepiness or neuropsychological function. PMID:23099139

  19. Neurodegenerative disorders and nanoformulated drug development

    PubMed Central

    Nowacek, Ari; Kosloski, Lisa M; Gendelman, Howard E

    2009-01-01

    Degenerative and inflammatory diseases of the CNS include, but are not limited to, Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, stroke, multiple sclerosis and HIV-1-associated neurocognitive disorders. These are common, debilitating and, unfortunately, hold few therapeutic options. In recent years, the application of nanotechnologies as commonly used or developing medicines has served to improve pharmacokinetics and drug delivery specifically to CNS-diseased areas. In addition, nanomedical advances are leading to therapies that target CNS pathobiology and as such, can interrupt disordered protein aggregation, deliver functional neuroprotective proteins and alter the oxidant state of affected neural tissues. This article focuses on the pathobiology of common neurodegenerative disorders with a view towards how nanomedicine may be used to improve the clinical course of neurodegenerative disorders. PMID:19572820

  20. Neurodegenerative disorders and nanoformulated drug development.

    PubMed

    Nowacek, Ari; Kosloski, Lisa M; Gendelman, Howard E

    2009-07-01

    Degenerative and inflammatory diseases of the CNS include, but are not limited to, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, stroke, multiple sclerosis and HIV-1-associated neurocognitive disorders. These are common, debilitating and, unfortunately, hold few therapeutic options. In recent years, the application of nanotechnologies as commonly used or developing medicines has served to improve pharmacokinetics and drug delivery specifically to CNS-diseased areas. In addition, nanomedical advances are leading to therapies that target CNS pathobiology and as such, can interrupt disordered protein aggregation, deliver functional neuroprotective proteins and alter the oxidant state of affected neural tissues. This article focuses on the pathobiology of common neurodegenerative disorders with a view towards how nanomedicine may be used to improve the clinical course of neurodegenerative disorders. PMID:19572820

  1. Traumatic brain injury-induced sleep disorders

    PubMed Central

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  2. The relationship between creativity and mood disorders

    PubMed Central

    Andreasen, Nancy C.

    2008-01-01

    Research designed to examine the relationship between creativity and mental illnesses must confront multiple challenges. What is the optimal sample to study? How should creativity be defined? What is the most appropriate comparison group? Only a limited number of studies have examined highly creative individuals using personal interviews and a noncreative comparison group. The majority of these have examined writers. The preponderance of the evidence suggests that in these creative individuals the rate of mood disorder is high, and that both bipolar disorder and unipolar depression are quite common. Clinicians who treat creative individuals with mood disorders must also confronta variety of challenges, including the fear that treatment may diminish creativity, in the case of bipolar disorder, hovt/ever, it is likely that reducing severe manic episodes may actually enhance creativity in many individuals. PMID:18689294

  3. NEUROLOGICAL ASPECTS OF HUMAN GLYCOSYLATION DISORDERS

    PubMed Central

    Freeze, Hudson H.; Eklund, Erik A.; Ng, Bobby G.; Patterson, Marc C.

    2016-01-01

    This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed. PMID:25840006

  4. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

    PubMed Central

    Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

    1992-01-01

    Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

  5. Expansion of a PBPK model to predict disposition in pregnant women of drugs cleared via multiple CYP enzymes, including CYP2B6, CYP2C9 and CYP2C19

    PubMed Central

    Ke, Alice Ban; Nallani, Srikanth C; Zhao, Ping; Rostami-Hodjegan, Amin; Unadkat, Jashvant D

    2014-01-01

    Aim Conducting PK studies in pregnant women is challenging. Therefore, we asked if a physiologically-based pharmacokinetic (PBPK) model could be used to predict the disposition in pregnant women of drugs cleared by multiple CYP enzymes. Methods We expanded and verified our previously published pregnancy PBPK model by incorporating hepatic CYP2B6 induction (based on in vitro data), CYP2C9 induction (based on phenytoin PK) and CYP2C19 suppression (based on proguanil PK), into the model. This model accounted for gestational age-dependent changes in maternal physiology and hepatic CYP3A, CYP1A2 and CYP2D6 activity. For verification, the pregnancy-related changes in the disposition of methadone (cleared by CYP2B6, 3A and 2C19) and glyburide (cleared by CYP3A, 2C9 and 2C19) were predicted. Results Predicted mean post-partum to second trimester (PP : T2) ratios of methadone AUC, Cmax and Cmin were 1.9, 1.7 and 2.0, vs. observed values 2.0, 2.0 and 2.6, respectively. Predicted mean post-partum to third trimester (PP : T3) ratios of methadone AUC, Cmax and Cmin were 2.1, 2.0 and 2.4, vs. observed values 1.7, 1.7 and 1.8, respectively. Predicted PP : T3 ratios of glyburide AUC, Cmax and Cmin were 2.6, 2.2 and 7.0 vs. observed values 2.1, 2.2 and 3.2, respectively. Conclusions Our PBPK model integrating prior physiological knowledge, in vitro and in vivo data, allowed successful prediction of methadone and glyburide disposition during pregnancy. We propose this expanded PBPK model can be used to evaluate different dosing scenarios, during pregnancy, of drugs cleared by single or multiple CYP enzymes. PMID:23834474

  6. On the Complexity of Brain Disorders: A Symptom-Based Approach.

    PubMed

    Moustafa, Ahmed A; Phillips, Joseph; Kéri, Szabolcs; Misiak, Blazej; Frydecka, Dorota

    2016-01-01

    Mounting evidence shows that brain disorders involve multiple and different neural dysfunctions, including regional brain damage, change to cell structure, chemical imbalance, and/or connectivity loss among different brain regions. Understanding the complexity of brain disorders can help us map these neural dysfunctions to different symptom clusters as well as understand subcategories of different brain disorders. Here, we discuss data on the mapping of symptom clusters to different neural dysfunctions using examples from brain disorders such as major depressive disorder (MDD), Parkinson's disease (PD), schizophrenia, posttraumatic stress disorder (PTSD) and Alzheimer's disease (AD). In addition, we discuss data on the similarities of symptoms in different disorders. Importantly, computational modeling work may be able to shed light on plausible links between various symptoms and neural damage in brain disorders. PMID:26941635

  7. On the Complexity of Brain Disorders: A Symptom-Based Approach

    PubMed Central

    Moustafa, Ahmed A.; Phillips, Joseph; Kéri, Szabolcs; Misiak, Blazej; Frydecka, Dorota

    2016-01-01

    Mounting evidence shows that brain disorders involve multiple and different neural dysfunctions, including regional brain damage, change to cell structure, chemical imbalance, and/or connectivity loss among different brain regions. Understanding the complexity of brain disorders can help us map these neural dysfunctions to different symptom clusters as well as understand subcategories of different brain disorders. Here, we discuss data on the mapping of symptom clusters to different neural dysfunctions using examples from brain disorders such as major depressive disorder (MDD), Parkinson’s disease (PD), schizophrenia, posttraumatic stress disorder (PTSD) and Alzheimer’s disease (AD). In addition, we discuss data on the similarities of symptoms in different disorders. Importantly, computational modeling work may be able to shed light on plausible links between various symptoms and neural damage in brain disorders. PMID:26941635

  8. [Sleep and autonomic function: sleep related breathing disorders in Parkinson's disease and related disorders].

    PubMed

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Hirata, Koichi

    2014-01-01

    In patients with multiple system atrophy (MSA), sleep related breathing disorders (SRBD), including obstructive and central sleep apnea, vocal cord abductor paralysis and dysrhythmic breathing pattern, are frequently observed. SRBD may have a considerable impact on variation of autonomic nervous activity during sleep. The previous studies correlated upper airway muscle dysfunction related parkinsonism with increased prevalence of SRBD in patients with Parkinson's disease (PD). However, recently, the clinical significance of SRBD and its impact on sleepiness and disease severity have been debated. In this review, we discuss sleep and autonomic function, especially, SRBD in PD and related disorders, including the previous studies from our department. PMID:25672703

  9. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  10. Personality disorders, but not cancer severity or treatment type, are risk factors for later generalised anxiety disorder and major depressive disorder in non metastatic breast cancer patients.

    PubMed

    Champagne, Anne-Laure; Brunault, Paul; Huguet, Grégoire; Suzanne, Isabelle; Senon, Jean-Louis; Body, Gilles; Rusch, Emmanuel; Magnin, Guillaume; Voyer, Mélanie; Réveillère, Christian; Camus, Vincent

    2016-02-28

    This study aimed to determine whether personality disorders were associated with later Major Depressive Disorder (MDD) or Generalised Anxiety Disorder (GAD) in breast cancer patients. This longitudinal and multicentric study included 120 French non-metastatic breast cancer patients. After cancer diagnosis (T1) and 7 months after diagnosis (T3), we assessed MDD and GAD (Mini International Neuropsychiatric Interview 5.0). We assessed personality disorders 3 months after diagnosis (VKP). We used multiple logistic regression analysis to determine what were the factors associated with GAD and MDD at T3. At T3, prevalence rate was 10.8% for MDD and 19.2% for GAD. GAD at T3 was significantly and independently associated with GAD at T1 and with existence of a personality disorder, no matter the cluster type. MDD at T3 was significantly and independently associated with MDD at T1 and with the existence of a cluster C personality disorder. Initial cancer severity and the type of treatment used were not associated with GAD or MDD at T3. Breast cancer patients with personality disorders are at higher risk for GAD and MDD at the end of treatment. Patients with GAD should be screened for personality disorders. Specific interventions for patients with personality disorders could prevent psychiatric disorders. PMID:26747215

  11. Mindful Curriculum Leadership for Students with Attention Deficit Hyperactivity Disorder (ADHD): Leading in Elementary Schools by Using Multiple Intelligences Theory (SUMIT[C]).

    ERIC Educational Resources Information Center

    Schirduan, Victoria; Case, Karen I.

    This paper provides an example of how elementary school curriculum leaders can be mindful of student intelligences and can utilize the strengths of their student populations. It presents the findings from a national study that examined how 17 schools using a curriculum based on Multiple Intelligences Theory improved the self-concept and positive…

  12. Attention deficit hyperactivity disorder.

    PubMed

    Thapar, Anita; Cooper, Miriam

    2016-03-19

    Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a prevalence of 1·4-3·0%. It is more common in boys than girls. Comorbidity with childhood-onset neurodevelopmental disorders and psychiatric disorders is substantial. ADHD is highly heritable and multifactorial; multiple genes and non-inherited factors contribute to the disorder. Prenatal and perinatal factors have been implicated as risks, but definite causes remain unknown. Most guidelines recommend a stepwise approach to treatment, beginning with non-drug interventions and then moving to pharmacological treatment in those most severely affected. Randomised controlled trials show short-term benefits of stimulant medication and atomoxetine. Meta-analyses of blinded trials of non-drug treatments have not yet proven the efficacy of such interventions. Longitudinal studies of ADHD show heightened risk of multiple mental health and social difficulties as well as premature mortality in adult life. PMID:26386541

  13. Central nervous system stimulants for secondary attention deficit-hyperactivity disorder after paediatric traumatic brain injury: a rationale and protocol for single patient (n-of-1) multiple cross-over trials

    PubMed Central

    2013-01-01

    Background It is estimated that 22,800 children were living with an Acquired Brain Injury (ABI) (0.6% of children aged under 15 years) in Australia during 2003. Many children after a traumatic brain injury will experience difficulties with attention and concentration; a condition termed secondary Attention Deficit-Hyperactivity Disorder. There is conflicting evidence on whether treatment with stimulant therapy with medications such as methylphenidate or dexamphetamine will improve the attention and behavior of children with this condition. Methods/Design Single patient trials (n-of-1s or SPTs) evaluate the effect of titrated doses of psychostimulants methylphenidate or dexamphetamine compared to placebo on attention and behavior, in children with TBI and secondary ADHD. The aggregation of multiple SPTs will produce a population estimate of the benefit. Forty-two children will be registered into the trial through rehabilitation services at three large children’s hospitals in Australia. Patients will complete up to 3 cycles of treatment. Each cycle is 2 weeks long comprising seven days each of treatment and placebo, with the first two days of each cycle considered a washout period and the data not analysed. The order of treatment and placebo is randomly allocated for each cycle. The Conners’ Parent Rating Scales long forms will be employed to measure change in attention-deficit/hyperactivity and related problems of the child, and the primary outcome measure is the Conners’ Global Index Parent Version. Secondary outcomes include the teacher and child (if aged > 12 years) Conners’ Rating Scales, the Behaviour Rating Inventory of Executive Function among other measures. This study will provide high-level evidence using a novel methodological approach to inform clinicians about the most appropriate treatment for individual children. Through aggregation of individual trials, a population estimate of treatment effect will be provided to guide clinical practice in the treatment of children with secondary ADHD after a traumatic brain injury. Discussion This study employs an innovative methodological approach on the effectiveness of CNS stimulants for secondary ADHD from a brain injury. The findings will both guide clinicians on treatment recommendations, and inform the concept and acceptance of SPTs in paediatric research. Trial registration Australian New Zealand Clinical Trials Registry. ACTRN12609000873224 PMID:23710976

  14. Smoldering multiple myeloma.

    PubMed

    Rajkumar, S Vincent; Landgren, Ola; Mateos, Mara-Victoria

    2015-05-14

    Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM). There have been major advances in the diagnosis, prognosis, and management of SMM in the last few years. These include a revised disease definition, identification of several new prognostic factors, a classification based on underlying cytogenetic changes, and new treatment options. Importantly, a subset of patients previously considered SMM is now reclassified as MM on the basis of biomarkers identifying patients with an ?80% risk of progression within 2 years. SMM has assumed greater significance on the basis of recent trials showing that early therapy can be potentially beneficial to patients. As a result, there is a need to accurately diagnose and risk-stratify patients with SMM, including routine incorporation of modern imaging and laboratory techniques. In this review, we outline current concepts in diagnosis and risk stratification of SMM, and provide specific recommendations on the management of SMM. PMID:25838344

  15. [Movement disorders is psychiatric diseases].

    PubMed

    Hidasi, Zoltan; Salacz, Pal; Csibri, Eva

    2014-12-01

    Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases. PMID:25577484

  16. Multimodality imaging features of hereditary multiple exostoses

    PubMed Central

    Fitzgerald, L; Campbell, N; Lyburn, I D; Munk, P L; Buckley, O; Torreggiani, W C

    2013-01-01

    Hereditary multiple exostoses (HME) or diaphyseal aclasis is an inherited disorder characterised by the formation of multiple osteochondromas, which are cartilage-capped osseous outgrowths, and the development of associated osseous deformities. Individuals with HME may be asymptomatic or develop clinical symptoms, which prompt imaging studies. Different modalities ranging from plain radiographs to cross-sectional and nuclear medicine imaging studies can be helpful in the diagnosis and detection of complications in HME, including chondrosarcomatous transformation. We review the role and imaging features of these different modalities in HME. PMID:24004486

  17. Cyclothymic disorder

    MedlinePlus

    ... mental disorder. It is a mild form of bipolar disorder (manic depressive illness), in which a person ... causes of cyclothymic disorder are unknown. Major depression, bipolar disorder, and cyclothymia often occur together in families. ...

  18. Reverse Monte Carlo Modeling of Pair Distribution Function Data as a Tool for Separating the Coordination Environments of Multiple Atoms Disordered Over a Single Site

    NASA Astrophysics Data System (ADS)

    King, Graham; Llobet, Anna; Ricciardo, Rebecca; Soliz, Jennifer; Woodward, Patrick; Ramezanipour, Farshid; Greedan, John

    2012-02-01

    The local structures of 8 perovskite compounds which contain equal concentrations of 2 transition metal cations disordered over the B-sites have been investigated using reverse Monte Carlo (RMC) modeling of neutron pair distribution function (PDF) data. Such compounds are known to display a number of interesting magnetic and electronic properties which, due to the cation disorder, cannot be correlated with the average long range structure and so remain poorly understood. In compounds with B=Mn/Ru there exists a valence degeneracy between Mn^3+/Ru^5+ and Mn^4+/Ru^4+. We demonstrate that the RMC method can be used as an effective tool to separate out the individual coordination environments of these cations and also to monitor the relative concentrations of the different oxidation states. We find that the valency ratio is governed by the size of the A-site cations. In a different series of Sr2FeMnO6-x perovskites we find that locally the structures are quite different from the average cubic structures, with the local coordination environments more closely resembling those of the brownmillerite structure. In all compounds the octahedra containing Mn^3+ are Jahn-Teller distorted, even if this distortion is not evident in the average structure.

  19. Combining Information from Multiple Sources for the Diagnosis of Autism Spectrum Disorders for Toddlers and Young Preschoolers from 12 to 47 Months of Age

    PubMed Central

    Kim, So Hyun; Lord, Catherine

    2011-01-01

    Background Purpose of this study was to systematically examine combined use of the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) for children under age 4 using newly developed and revised diagnostic algorithms. Methods Single and combined use of the ADI-R and ADOS algorithms were compared to clinical best estimate diagnoses for 435 children with Autism Spectrum Disorders (ASD), 113 children with non-spectrum disorders, and 47 children with typical development from 12 to 47 months of age. Sequential strategies to reach a diagnostic decision by prioritizing administrations of instruments were also evaluated. Results Well-balanced sensitivities and specificities above 80% were obtained for ASD diagnoses using both instruments. Specificities significantly improved when both instruments were used compared to one. Scores that can be used to systematically prioritize administrations of instruments were identified. Conclusions The ADI-R and ADOS make independent, additive contributions to more accurate diagnostic decisions for clinicians evaluating toddlers and young preschoolers with ASD. Sequential assessment strategies using the scores identified may be appropriate for some children. PMID:21883205

  20. Autoantibody-associated movement disorders.

    PubMed

    Mohammad, Shekeeb S; Ramanathan, Sudarshini; Brilot, Fabienne; Dale, Russell C

    2013-12-01

    Autoantibodies to the extracellular domain of neuronal proteins cause different neurological conditions with movement disorders as a prominent feature. We reviewed the literature of autoantibody-mediated and autoantibody-associated diseases focusing on anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis, Sydenham chorea, and the rare syndrome of progressive encephalomyelitis with rigidity and myoclonus. NMDAR encephalitis is a diffuse encephalitis with psychiatric and cognitive features associated with autoantibodies against the NR1 subunit of the NMDAR. The movement disorder phenotype is diverse and often generalized in young children. Although orofacial dyskinesia was the initial movement phenotype, chorea, dystonia, catatonia, and stereotypical movements are now described. The stereotypical movements can be bizarre and include cycling movements and compulsive self-injurious behavior. Autoimmune basal ganglia encephalitis is an inflammatory encephalitis localizing to the basal ganglia that is sometimes associated with serum antibodies against dopamine-2 receptor. Although psychiatric features are common, the dominant problem is a movement disorder, with dystonia-parkinsonism being characteristic. Sydenham chorea is the prototypic poststreptococcal autoimmune neuropsychiatric disorder and several autoantibodies may be involved in disease generation. The syndrome is characterized by a pure chorea, although hypotonia, dysarthria, and emotional lability are common. Progressive encephalomyelitis with rigidity and myoclonus is a rare autoimmune disorder causing rigidity, stimulus sensitive spasms, and myoclonus of nonepileptic origin and is associated with autoantibodies of multiple types including those against the glycine receptor. These disorders are important to recognize and diagnose, as immune therapy can shorten disease duration and improve outcome. PMID:24203856

  1. Movement disorders in paraneoplastic and autoimmune disease

    PubMed Central

    Panzer, Jessica; Dalmau, Josep

    2013-01-01

    Purpose of review The most relevant advances in immune-mediated movement disorders are described, with emphasis on the clinical–immunological associations, novel antigens, and treatment. Recent findings Many movement disorders previously considered idiopathic or degenerative are now recognized as immune-mediated. Some disorders are paraneoplastic, such as anti-CRMP5-associated chorea, anti-Ma2 hypokinesis and rigidity, anti-Yo cerebellar ataxia and tremor, and anti-Hu ataxia and pesudoathetosis. Other disorders such as Sydenham's chorea, or chorea related to systemic lupus erythematosus and antiphospholipid syndrome occur in association with multiple antibodies, are not paraneoplastic, and are triggered by molecular mimicry or unknown mechanisms. Recent studies have revealed a new category of disorders that can be paraneoplastic or not, and associate with antibodies against cell-surface or synaptic proteins. They include anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which may cause dyskinesias, chorea, ballismus or dystonia (NMDAR antibodies), the spectrum of Stiff-person syndrome/muscle rigidity (glutamic acid decarboxylase, amphiphysin, GABAA-receptor-associated protein, or glycine receptor antibodies), neuromyotonia (Caspr2 antibodies), and opsoclonus–myoclonus–ataxia (unknown antigens). Summary Neurologists should be aware that many movement disorders are immune-mediated. Recognition of these disorders is important because it may lead to the diagnosis of an occult cancer, and a substantial number of patients, mainly those with antibodies to cell-surface or synaptic proteins, respond to immunotherapy. PMID:21577108

  2. Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study

    PubMed Central

    Lahuerta, Juan José; Mateos, Maria Victoria; Martínez-López, Joaquin; Grande, Carlos; de la Rubia, Javier; Rosiñol, Laura; Sureda, Anna; García-Laraña, José; Díaz-Mediavilla, Joaquín; Hernández-García, Miguel T.; Carrera, Dolores; Besalduch, Joan; de Arriba, Felipe; Oriol, Albert; Escoda, Lourdes; García-Frade, Javier; Rivas-González, Concepción; Alegre, Adrían; Bladé, Joan; San Miguel, Jesús F.

    2010-01-01

    Background The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m2 and melphalan 200 mg/m2 as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study. Design and Methods The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m2; because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m2. Results Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m2 resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m2 group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m2 (58%; P=0.01). Conclusions Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m2 but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients. (Clinicaltrials.gov identifier: NCT00560053). PMID:20663944

  3. Newly discovered quick, non-invasive screening method of bone marrow malignancies including various leukemias, Hodgkin's lymphoma, non-Hodgkin's lymphoma, & multiple myeloma by abnormality of small rectangular area within bone marrow organ representation areas of the face.

    PubMed

    Omura, Yoshiaki; O'Young, Brian; Jones, Marilyn; Nihrane, Abdalla; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

    2012-01-01

    Diagnoses of bone marrow associated malignancies such as Acute & Chronic Lymphocytic Leukemia, Acute & Chronic Myelogenous (Myeloid) Leukemia, Hodgkin's Lymphoma & Non-Hodgkin's Lymphoma, and Multiple Myeloma are often missed without a blood test. However, in 2008, Omura Y reported several newly discovered organ representation areas that exist between the lower end of the eyebrows and upper end of the upper eyelid. This space was divided into 5 organ representation areas. The first space (more than 1/4 of entire space) near the side of the face (temple) is the bone marrow representation area (BMRA). Therefore, we examined the bone marrow representation areas non-invasively using the Bi-Digital O-Ring Test (BDORT). When the small rectangular shaped part of the BMRA is strong negative (-) with more than -2, often there is a malignancy associated with bone marrow. In this area, we found 1) Integrin alpha5beta1 & Oncogen C-fos Ab2 increased very significantly between 125-300 ng BDORT units; 2) very high Chrysotile Asbestos (0.11-0.14 mg); 3) markedly reduced Acetylcholine of less than 1 ng; 4) significantly reduced telomere of less than 1 yg (= 10(-24) g); and 5) Increased 8-OH-dG (often more than 5 ng). Once the abnormal small rectangular area is localized by BDORT, by detecting the specific microscope slide which produces EMF (electromagnetic field) resonance, one can diagnose these malignancies non-invasively in about 10 minutes. When a subject has any one of the above 7 types of bone marrow associated malignancies, the 5 aforementioned abnormal parameters can be detected. When Acetylcholine is markedly reduced to 0.25 ng or less, 8-OH-dG is 10 ng or higher, and Sirtuin 1 (one of the 7 mammalian longevity genes products) in both the Hippocampus and the body is 0.025 pg or less, most of the patients have a very poor prognosis. However, we found that increasing normal cell telomere & longevity gene product Sirtuin 1 can often improve both pathology & prognosis. All measurements are in BDORT units (the weight required to produce maximum EMF resonance). PMID:22852211

  4. Cannabinoid Modulation of Neuroinflammatory Disorders

    PubMed Central

    Saito, Viviane M; Rezende, Rafael M; Teixeira, Antonio L

    2012-01-01

    In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ9-tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses. In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis. PMID:23204985

  5. [Multilingualism and child psychiatry: on differential diagnoses of language disorder, specific learning disorder, and selective mutism].

    PubMed

    Tamiya, Satoshi

    2014-01-01

    Multilingualism poses unique psychiatric problems, especially in the field of child psychiatry. The author discusses several linguistic and transcultural issues in relation to Language Disorder, Specific Learning Disorder and Selective Mutism. Linguistic characteristics of multiple language development, including so-called profile effects and code-switching, need to be understood for differential diagnosis. It is also emphasized that Language Disorder in a bilingual person is not different or worse than that in a monolingual person. Second language proficiency, cultural background and transfer from the first language all need to be considered in an evaluation for Specific Learning Disorder. Selective Mutism has to be differentiated from the silent period observed in the normal successive bilingual development. The author concludes the review by remarking on some caveats around methods of language evaluation in a multilingual person. PMID:25702497

  6. Differences in the Nature of Body Image Disturbances between Female Obese Individuals with versus without a Comorbid Binge Eating Disorder: An Exploratory Study Including Static and Dynamic Aspects of Body Image

    ERIC Educational Resources Information Center

    Legenbauer, Tanja; Vocks, Silja; Betz, Sabrina; Puigcerver, Maria Jose Baguena; Benecke, Andrea; Troje, Nikolaus F.; Ruddel, Heinz

    2011-01-01

    Various components of body image were measured to assess body image disturbances in patients with obesity. To overcome limitations of previous studies, a photo distortion technique and a biological motion distortion device were included to assess static and dynamic aspects of body image. Questionnaires assessed cognitive-affective aspects, bodily

  7. Differences in the Nature of Body Image Disturbances between Female Obese Individuals with versus without a Comorbid Binge Eating Disorder: An Exploratory Study Including Static and Dynamic Aspects of Body Image

    ERIC Educational Resources Information Center

    Legenbauer, Tanja; Vocks, Silja; Betz, Sabrina; Puigcerver, Maria Jose Baguena; Benecke, Andrea; Troje, Nikolaus F.; Ruddel, Heinz

    2011-01-01

    Various components of body image were measured to assess body image disturbances in patients with obesity. To overcome limitations of previous studies, a photo distortion technique and a biological motion distortion device were included to assess static and dynamic aspects of body image. Questionnaires assessed cognitive-affective aspects, bodily…

  8. Psychopharmacology of anxiety disorders

    PubMed Central

    Cassano, Giovanni B.; Rossi, Nicolò Baldini; Pini, Stefano

    2002-01-01

    Exposure of the general population to a 1:4 lifetime risk of disabling anxiety has inspired generations of fundamental and clinical psychopharmacologists, from the era of the earliest benzodiazepines (BZ) to that of the selective serotonin reuptake inhibitors (SSRIs) and related compounds, eg, the serotonin and norepinephrine reuptake inhibitors (SNRIs). This comprehensive practical review summarizes current therapeutic research across the spectrum of individual disorders: generalized anxiety disorder (GAD), panic disorder (PD) and agoraphobia (social anxiety disorder), compulsive disorder (OCD), phobic disorder (including social phobia), and posttraumatic stress disorder (PTSD). Specific diagnosis is a precondition to successful therapy: despite substantial overlap, each disorder responds preferentially to specific pharmacotherapy. Comorbidity with depression is common; hence the success of the SSRIs, which were originally designed to treat depression. Assessment (multidomain measures versus individual end points) remains problematic, as-frequently-do efficacy and tolerability The ideal anxiolytic remains the Holy Grail of worldwide psychopharmacologic research. PMID:22033867

  9. The Cerebellum and Psychiatric Disorders

    PubMed Central

    Phillips, Joseph R.; Hewedi, Doaa H.; Eissa, Abeer M.; Moustafa, Ahmed A.

    2015-01-01

    The cerebellum has been considered for a long time to play a role solely in motor coordination. However, studies over the past two decades have shown that the cerebellum also plays a key role in many motor, cognitive, and emotional processes. In addition, studies have also shown that the cerebellum is implicated in many psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorders, schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorders. In this review, we discuss existing studies reporting cerebellar dysfunction in various psychiatric disorders. We will also discuss future directions for studies linking the cerebellum to psychiatric disorders. PMID:26000269

  10. Free-Energy Barriers and Reaction Mechanisms for the Electrochemical Reduction of CO on the Cu(100) Surface, Including Multiple Layers of Explicit Solvent at pH 0.

    PubMed

    Cheng, Tao; Xiao, Hai; Goddard, William A

    2015-12-01

    The great interest in the photochemical reduction from CO2 to fuels and chemicals has focused attention on Cu because of its unique ability to catalyze formation of carbon-containing fuels and chemicals. A particular goal is to learn how to modify the Cu catalysts to enhance the production selectivity while reducing the energy requirements (overpotential). To enable such developments, we report here the free-energy reaction barriers and mechanistic pathways on the Cu(100) surface, which produces only CH4 (not C2H4 or CH3OH) in acid (pH 0). We predict a threshold potential for CH4 formation of -0.52 V, which compares well to experiments at low pH, -0.45 to -0.50 V. These quantum molecular dynamics simulations included ?5 layers of explicit water at the water/electrode interface using enhanced sampling methodology to obtain the free energies. We find that that chemisorbed hydroxyl-methylene (CH-OH) is the key intermediate determining the selectivity for methane over methanol. PMID:26562750

  11. Autoimmune basal ganglia disorders.

    PubMed

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

    The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

  12. Phosphorylation of Simian Cytomegalovirus Assembly Protein Precursor (pAPNG.5) and Proteinase Precursor (pAPNG1): Multiple Attachment Sites Identified, Including Two Adjacent Serines in a Casein Kinase II Consensus Sequence

    PubMed Central

    Plafker, Scott M.; Woods, Amina S.; Gibson, Wade

    1999-01-01

    The assembly protein precursor (pAP) of cytomegalovirus (CMV), and its homologs in other herpesviruses, functions at several key steps during the process of capsid formation. This protein, and the genetically related maturational proteinase, is distinguished from the other capsid proteins by posttranslational modifications, including phosphorylation. The objective of this study was to identify sites at which pAP is phosphorylated so that the functional significance of this modification and the enzyme(s) responsible for it can be determined. In the work reported here, we used peptide mapping, mass spectrometry, and site-directed mutagenesis to identify two sets of pAP phosphorylation sites. One is a casein kinase II (CKII) consensus sequence that contains two adjacent serines, both of which are phosphorylated. The other site(s) is in a different domain of the protein, is phosphorylated less frequently than the CKII site, does not require preceding CKII-site phosphorylation, and causes an electrophoretic mobility shift when phosphorylated. Transfection/expression assays for proteolytic activity showed no gross effect of CKII-site phosphorylation on the enzymatic activity of the proteinase or on the substrate behavior of pAP. Evidence is presented that both the CKII sites and the secondary sites are phosphorylated in virus-infected cells and plasmid-transfected cells, indicating that these modifications can be made by a cellular enzyme(s). Apparent compartmental differences in phosphorylation of the CKII-site (cytoplasmic) and secondary-site (nuclear) serines suggest the involvement of more that one enzyme in these modifications. PMID:10516011

  13. Immune Disorders and Its Correlation with Gut Microbiome

    PubMed Central

    Hwang, Ji-Sun; Im, Chang-Rok

    2012-01-01

    Allergic disorders such as atopic dermatitis and asthma are common hyper-immune disorders in industrialized countries. Along with genetic association, environmental factors and gut microbiota have been suggested as major triggering factors for the development of atopic dermatitis. Numerous studies support the association of hygiene hypothesis in allergic immune disorders that a lack of early childhood exposure to diverse microorganism increases susceptibility to allergic diseases. Among the symbiotic microorganisms (e.g. gut flora or probiotics), probiotics confer health benefits through multiple action mechanisms including modification of immune response in gut associated lymphoid tissue (GALT). Although many human clinical trials and mouse studies demonstrated the beneficial effects of probiotics in diverse immune disorders, this effect is strain specific and needs to apply specific probiotics for specific allergic diseases. Herein, we briefly review the diverse functions and regulation mechanisms of probiotics in diverse disorders. PMID:23091436

  14. Ion Channels in Neurological Disorders.

    PubMed

    Kumar, Pravir; Kumar, Dhiraj; Jha, Saurabh Kumar; Jha, Niraj Kumar; Ambasta, Rashmi K

    2016-01-01

    The convergent endeavors of the neuroscientist to establish a link between clinical neurology, genetics, loss of function of an important protein, and channelopathies behind neurological disorders are quite intriguing. Growing evidence reveals the impact of ion channels dysfunctioning in neurodegenerative disorders (NDDs). Many neurological/neuromuscular disorders, viz, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and age-related disorders are caused due to altered function or mutation in ion channels. To maintain cell homeostasis, ion channels are playing a crucial role which is a large transmembrane protein. Further, these channels are important as it determines the membrane potential and playing critically in the secretion of neurotransmitter. Behind NDDs, losses of pathological proteins and defective ion channels have been reported and are found to aggravate the disease symptoms. Moreover, ion channel dysfunctions are eliciting a range of symptoms, including memory loss, movement disabilities, neuromuscular sprains, and strokes. Since the possible mechanistic role played by aberrant ion channels, their receptor and associated factors in neurodegeneration remained elusive; therefore, it is a challenging task for the neuroscientist to implement the therapeutics for targeting NDDs. This chapter reviews the potential role of the ion channels in membrane physiology and brain homeostasis, where ion channels and their associated factors have been characterized with their functional consequences in neurological diseases. Moreover, mechanistic role of perturbed ion channels has been identified in various NDDs, and finally, ion channel modulators have been investigated for their therapeutic intervention in treating common NDDs. PMID:26920688

  15. Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6

    PubMed Central

    2014-01-01

    Background Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. Results We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. Conclusions These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a positive feedback mechanism involving GATA factors that maintains lin-39 expression in the vulval lineage. This work indicates that, as in other organisms, the regulation of Hox gene expression in C. elegans is complicated, redundant and robust. PMID:24885717

  16. Symptoms of Major Depressive Disorder Subsequent to Child Maltreatment: Examining Change across Multiple Levels of Analysis to Identify Transdiagnostic Risk Pathways

    PubMed Central

    Shenk, Chad E.; Griffin, Amanda M.; O’Donnell, Kieran J.

    2016-01-01

    Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: 1) neuroendocrine, 2) autonomic, 3) affective, and 4) emotion regulation. Female adolescents (N=110; Age range: 14–19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed eighteen months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed. PMID:26535940

  17. Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways.

    PubMed

    Shenk, Chad E; Griffin, Amanda M; O'Donnell, Kieran J

    2015-11-01

    Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: neuroendocrine, autonomic, affective, and emotion regulation. Female adolescents (N = 110; age range = 14-19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed 18 months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed. PMID:26535940

  18. Panic disorder, phobias, and generalized anxiety disorder.

    PubMed

    Craske, Michelle G; Waters, Allison M

    2005-01-01

    This chapter provides a review of recent empirical developments, current controversies, and areas in need of further research in relation to factors that are common as well as specific to the etiology and maintenance of panic disorder, phobias, and generalized anxiety disorder. The relative contribution of broad risk factors to these disorders is discussed, including temperament, genetics, biological influences, cognition, and familial variables. In addition, the role that specific learning experiences play in relation to each disorder is reviewed. In an overarching hierarchical model, it is proposed that generalized anxiety disorder, and to some extent panic disorder, loads most heavily on broad underlying factors, whereas specific life history contributes most strongly to circumscribed phobias. PMID:17716087

  19. Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways

    PubMed Central

    Kerner, Berit; Rao, Aliz R.; Christensen, Bryce; Dandekar, Sugandha; Yourshaw, Michael; Nelson, Stanley F.

    2013-01-01

    Bipolar disorder is a common, complex, and severe psychiatric disorder with cyclical disturbances of mood and a high suicide rate. Here, we describe a family with four siblings, three affected females and one unaffected male. The disease course was characterized by early-onset bipolar disorder and co-morbid anxiety spectrum disorders that followed the onset of bipolar disorder. Genetic risk factors were suggested by the early onset of the disease, the severe disease course, including multiple suicide attempts, and lack of adverse prenatal or early life events. In particular, drug and alcohol abuse did not contribute to the disease onset. Exome sequencing identified very rare, heterozygous, and likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C, GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among all three affected family members but absent in the unaffected sibling and in more than 200 controls. The genes encode proteins with significant regulatory roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These pathways are central to neuronal and synaptic plasticity, cognition, affect regulation and response to chronic stress. In addition, proteins in these pathways are the target of commonly used mood-stabilizing drugs, such as tricyclic antidepressants, lithium, and valproic acid. The combination of multiple rare, damaging mutations in these central pathways could lead to reduced resilience and increased vulnerability to stressful life events. Our results support a new model for psychiatric disorders, in which multiple rare, damaging mutations in genes functionally related to a common signaling pathway contribute to the manifestation of bipolar disorder. PMID:24348429

  20. Quality of Life in Major Depressive Disorder Before/After Multiple Steps of Treatment and One-year Follow-up

    PubMed Central

    IsHak, Waguih William; Mirocha, James; James, David; Tobia, Gabriel; Vilhauer, Jennice; Fakhry, Hala; Pi, Sarah; Hanson, Eric; Nashawati, Rama; Peselow, Eric D.; Cohen, Robert M.

    2014-01-01

    Objective This study examines the impact of Major Depressive Disorder (MDD) and its treatment on Quality of Life (QOL). Method From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2,280 adult MDD outpatients at entry/exit of each level of antidepressant treatments and after 12-months of entry to follow-up. QOL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring ‘within-normal’ QOL (within 10% of Q-LES-Q community-norms) and those with ‘severely-impaired’ QOL (>2SD below Q-LES-Q community-norms) were analyzed. Results Before treatment, no more than 3% of MDD patients experienced ‘within-normal’ QOL. Following treatment, statistically significant improvements were detected, however the proportion of patients achieving ‘within-normal’ QOL did not exceed 30%, with>50% of patients experiencing ‘severely-impaired’ QOL. Although remitted-patients had greater improvements compared to non-remitters, 32%-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing ‘within-normal’ QOL show a statistically significant decrease in non-remitters. Conclusion Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD. PMID:24954156

  1. Nutritional and Pubertal Disorders.

    PubMed

    Muñoz-Calvo, M Teresa; Argente, Jesús

    2016-01-01

    Caloric-protein malnutrition can slow growth and cause pubertal delay. This chapter focuses on endocrine abnormalities and pubertal alterations in patients with eating disorders, childhood obesity, the female athlete triad and children cancer survivors. Patients with anorexia nervosa (AN) exhibit multiple endocrine abnormalities, including isolated hypogonadotropic hypogonadism. The delay in pubertal development and reduction in growth seen in AN patients may be a direct result of malnutrition. Appropriate psychiatric, nutritional and hormonal therapy is necessary. It is suggested that obesity during childhood can accelerate pubertal onset and these children usually exhibit accelerated linear growth during puberty. In girls the relationship between childhood obesity and early pubertal onset could be related to their insulin resistance and/or hyperinsulinemia. The female athlete triad is often observed in physically active girls and women in whom low energy availability with or without disordered eating, menstrual dysfunction and low bone mineral density can be present. In prepubertal girls excess exercise can cause delayed menarche with no effects on adult height, while in postpubertal females it results in menstrual cycle irregularities. The consequences of childhood cancer depend on the type of cancer, its location, the age at which the disease was diagnosed, the dose of radiotherapy, and the type and dose of chemotherapy. PMID:26680577

  2. Race and Ethnic Group Differences in Comorbid Major Depressive Disorder, Generalized Anxiety Disorder, and Chronic Medical Conditions.

    PubMed

    Watkins, Daphne C; Assari, Shervin; Johnson-Lawrence, Vicki

    2015-09-01

    This study tested whether race and ethnic group differences exist for lifetime major depressive disorder and/or general anxiety disorder with one or more chronic medical conditions. Data from the National Survey of American Life, which included 3570 African American, 1438 Caribbean Black, and 891 non-Hispanic White adults were analyzed. Outcomes included at least one and multiple chronic medical conditions, from a list of 14 medical conditions (e.g., arthritis, cancer, diabetes, kidney disease, stroke, heart disease, etc.). Logistic regressions were fitted to data to determine how the association between major depressive disorder, general anxiety disorder, and one or more chronic medical conditions vary across race and ethnicity. Lifetime major depressive disorder (but not lifetime general anxiety disorder) was associated with at least one chronic medical condition among African Americans and Caribbean Blacks, but not non-Hispanic Whites. Lifetime major depressive disorder was similarly associated with multiple chronic medical conditions among African Americans, Caribbean Blacks, and non-Hispanic Whites. For Caribbean Blacks, stronger associations were found between major depressive disorder and general anxiety disorder with one or more chronic medical conditions compared to African Americans and non-Hispanic Whites. Findings suggest that race and ethnicity may shape the links between comorbid psychiatric disorders and chronic medical conditions. Mental health screening of individuals with chronic medical conditions in primary health-care settings may benefit from tailoring based on race and ethnicity. More research is needed to understand why associations between physical and mental health vary among race and ethnic groups. PMID:26863467

  3. Panic: course, complications and treatment of panic disorder.

    PubMed

    Pollack, M H; Marzol, P C

    2000-01-01

    Panic disorder is a chronic condition typically associated with significant distress and disability. In addition to the acute distress associated with the panic attack itself, the disorder often leads to distressing anticipatory anxiety and phobic avoidance. Affected individuals experience significant impairment in social and vocational functioning, high utilization of medical resources, constriction of function, premature mortality and diminution in overall quality of life. Panic disorder is frequently comorbid with other conditions, particularly depression, as well as alcohol and other substance abuse, and other anxiety disorders including social phobia, generalized anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. A number of pharmacological agents and cognitive-behavioural treatments have been shown to be effective in the treatment of panic disorder, with the selective serotonin reuptake inhibitors (SSRIs) becoming first-line pharmacotherapy for this condition. Among these, the SSRI sertraline appears effective not only in improving symptoms of panic, but also in reducing anticipatory anxiety and improving multiple aspects of quality of life. For patients who remain partly or fully symptomatic despite adequate first-line treatment, a variety of strategies are emerging for the management of refractory conditions. We provide an overview of the prevalence, presentation and associated complications of panic disorder, review the therapeutic options and discuss the management of refractory patients. PMID:10888028

  4. Treatment of comorbidity in conduct disorder with attention-deficit hyperactivity disorder (ADHD).

    PubMed

    Turgay, Atilla

    2005-01-01

    Conduct disorder (CD) is one of the most common psychiatric disorders in childhood and adolescence. It is characterized by a variety of chronic antisocial behaviors, a repetitive and persistent pattern of behavior that violates the basic rights of others, major age-appropriate societal norms, or both. Aggressive behavior, lying, stealing, fire-setting, and running away from home and school are the most frequent manifestations of CD and are often accompanied by hyperactivity, impulsive behavior, explosiveness, cognitive and learning problems, and poor social skills. The rate of comorbidity is high, with attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) being the most common; comorbid anxiety and depressive disorders are also seen, especially in adolescents. The diagnostic process should include the use of structured interviews, and scores from reliable and valid rating scales that cover all psychiatric disorders must be considered in the differential diagnosis, because CD alone is an extreme rarity and multiple disorders are almost always the rule rather than exception. Treatment should include parenting skills training combined with training of the child to improve his or her relationships with peers, academic performance, and compliance with legitimate demands of authority figures. The appropriate use of medications and integration of patient/parent education and support, as well as individual, group, family, residential, and inpatient treatment may be beneficial for patients with CD and ADHD. The article describes a number of psychopharmacological agents that are used in patients with CD with ADHD and other comorbid disorders. Drugs that may be useful include psychostimulants; atomoxetine (Strattera); antidepressants (imipramine [Tofranil], desipramine [Norpramin]); Selective Serotonin Reuptake Inhibitors (SSRIs); atypical antipsychotics such as risperidone (Risperdal); or mood regulators including lithium (Eskalith). PMID:16222912

  5. Mitochondrial Disorders with Significant Ophthalmic Manifestations

    PubMed Central

    Al-Enezi, Mona; Al-Saleh, Hanan; Nasser, Murad

    2008-01-01

    Mitochondrial diseases are a clinically hetyerogenous group of disorders. They can be caused by mutations of nuclear or mitochondrial DNA (mtDNA). Some affect a single organ, but many involve multiple organ systems and often present with prominent neurologic and myopathic features. The eye is frequently affected, along with muscles and brain, but multisystem disease is common. Ophthalmic manifestations include cataract, retinopathy, optic atrophy, cortical visual loss, ptosis and ophthalmoplegia. Kearns-Sayre Syndrome (KSS), Mitochondrial Encephalopathy, Lactic Acidosis Stroke (MELAS), Myoclonic Epilepsy and Ragged Red Fiber myopathy (MERRF) and Lebers Hereditary Optic Neuropathy (LHON) are well known clinical entities that are secondary to mtDNA abnormalities, which has ophthalmic manifestations. Mitochondrial Dysfunction should be considered in the differential diagnosis of progressive multisystem disorder and specifically if there is associated neuro-ophthalmic manifestations, which may be the presenting symptom of these disorders. PMID:21346843

  6. Office management of gait disorders in the elderly

    PubMed Central

    Lam, Robert

    2011-01-01

    Abstract Objective To provide family physicians with an approach to office management of gait disorders in the elderly. Sources of information Ovid MEDLINE was searched from 1950 to July 2010 using subject headings for gait or neurologic gait disorders combined with physical examination. Articles specific to family practice or family physicians were selected. Relevant review articles and original research were used when appropriate and applicable to the elderly. Main message Gait and balance disorders in the elderly are difficult to recognize and diagnose in the family practice setting because they initially present with subtle undifferentiated manifestations, and because causes are usually multifactorial, with multiple diseases developing simultaneously. To further complicate the issue, these manifestations can be camouflaged in elderly patients by the physiologic changes associated with normal aging. A classification of gait disorders based on sensorimotor levels can be useful in the approach to management of this problem. Gait disorders in patients presenting to family physicians in the primary care setting are often related to joint and skeletal problems (lowest-level disturbances), as opposed to patients referred to neurology specialty clinics with sensory ataxia, myelopathy, multiple strokes, and parkinsonism (lowest-, middle-, and highest-level disturbances). The difficulty in diagnosing gait disorders stems from the challenge of addressing early undifferentiated disease caused by multiple disease processes involving all sensorimotor levels. Patients might present with a nonspecific “cautious” gait that is simply an adaptation of the body to disease limitations. This cautious gait has a mildly flexed posture with reduced arm swing and a broadening of the base of support. This article reviews the focused history (including medication review), practical physical examination, investigations, and treatments that are key to office management of gait disorders. Conclusion Family physicians will find it helpful to classify gait disorders based on sensorimotor level as part of their approach to office management of elderly patients. Managing gait disorders at early stages can help prevent further deconditioning and mobility impairment. PMID:21753097

  7. Genetic Disorders

    MedlinePlus

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  8. Mathematics disorder

    MedlinePlus

    Mathematics disorder is a condition in which a child's math ability is far below normal for their ... Children who have mathematics disorder have trouble with simple ... disorder may appear with: Developmental coordination ...

  9. Personality disorders

    MedlinePlus

    Personality disorders are a group of mental conditions in which a person has a long-term pattern of ... Causes of personality disorders are unknown. Genetic and ... a role. Mental health professionals categorize these disorders ...

  10. Bipolar Disorder

    MedlinePlus

    ... a Psychiatrist Patients & Families All Topics Help With Bipolar Disorders Curated and updated for the community by APA Topic Information Bipolar disorders are brain disorders that cause changes in ...

  11. Eating Disorders

    MedlinePlus

    ... and/or maintain an imaginary appearance. Related information Anorexia nervosa fact sheet Binge eating disorder fact sheet ... your area. Eating disorders are serious medical problems. Anorexia nervosa, bulimia nervosa, and binge-eating disorder are ...

  12. Including Multiple Voices in Collaboratively Designing a Teacher Education Program

    ERIC Educational Resources Information Center

    Konecki, Loretta R.; Sturdivant, Robika L.; King, Caryn M.; Melin, Jacquelyn A.; Lancaster, Paula E.

    2012-01-01

    This narrative case study describes the collaborative processes employed by a midwestern university as it designed and implemented a clinically based, postbaccalaureate teacher preparation program for science, technology, engineering, and mathematics (STEM) graduates committed to teaching in high need secondary schools. The program development…

  13. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  14. Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  15. General Information about Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  16. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  17. ELEVATED RISK FOR AUTOIMMUNE DISORDERS IN IRAQ AND AFGHANISTAN VETERANS WITH POSTTRAUMATIC STRESS DISORDER

    PubMed Central

    O’Donovan, Aoife; Cohen, Beth E.; Seal, Karen; Bertenthal, Dan; Margaretten, Mary; Nishimi, Kristen; Neylan, Thomas C.

    2014-01-01

    BACKGROUND Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD. METHODS We conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs (VA) healthcare system between October 7, 2001 and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure (MST) increase risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits. RESULTS PTSD was diagnosed in 203,766 (30.6%) veterans, and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 (19.5%) veterans. Veterans diagnosed with PTSD had significantly higher adjusted relative risk (ARR) for diagnosis with any of the autoimmune disorders alone or in combination compared to veterans with no psychiatric diagnoses (ARR = 2.00, 95% CI, 1.91, 2.09), and compared to veterans diagnosed with psychiatric disorders other than PTSD (ARR = 1.51, 95% CI, 1.43, 1.59, p < .001). The magnitude of the PTSD-related increase in risk for autoimmune disorders was similar in women and men, and MST was independently associated with increased risk in both women and men. CONCLUSIONS Trauma exposure and PTSD may increase risk for autoimmune disorders. Altered immune function, lifestyle factors, or shared etiology may underlie this association. PMID:25104173

  18. Diagnosing developmental coordination disorders.

    PubMed

    Kirby, Amanda; Sugden, David; Purcell, Catherine

    2014-03-01

    Developmental coordination disorder (DCD) affects around 5% of children and commonly overlaps with other developmental disorders including: attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs) and specific language impairment (SLI). There is evidence to demonstrate the wide-ranging impact on all areas of functioning including psychiatric and learning domains. There is increasing evidence of the continuing impact into adulthood and the long-term negative effects on relationships and employment. There is a need for early identification and intervention to limit the likelihood of these secondary consequences from emerging. This paper addresses the diagnosis of DCD. PMID:24255567

  19. [Sleep and movement disorders].

    PubMed

    Poryazova, R; Bassetti, C L

    2007-01-01

    The three different states of being (wakefulness, NREM and REM sleep) are associated with profound neurophysiological and neurochemical changes in the brain. These changes explain the existence of movement disorders appearing only or preferentially during sleep, and the effects of sleep on movement disorders. Sleep-related movement disorders are of clinical relevance for multiple reasons: 1) high frequency (e.g. restless legs syndrome (RLS)); 2) diagnostic relevance (e.g. REM sleep behavior disorder (RBD) as first manifestation of Parkinson disorder); 3) diagnostic uncertainty (e.g. parasomnias vs nocturnal epilepsy); 4) association with injuries (e.g. RBD, sleepwalking), sleep disruption/daytime sleepiness (e.g. RLS), and psycho-social burden (e.g. enuresis); 5) requirement of specific treatments (e.g. nocturnal epilepsy, stridor, RBD). This article gives an overview on clinical manifestations, pathophysiology, work-up and treatment of sleep-related movement disorders (e.g. RLS, bruxism), parasomnias (e.g. sleepwalking, RBD), sleep-related epilepsies, and on sleep-associated manifestations of movement disorders (e.g. Parkinson disease, multiple system atrophy). PMID:17221827

  20. Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments

    PubMed Central

    Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N.

    2015-01-01

    The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions. PMID:26712748