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Sample records for disorders including multiple

  1. A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

    PubMed Central

    2010-01-01

    Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated. PMID:20615259

  2. [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

  3. Bipolar disorder and multiple sclerosis.

    PubMed

    Ybarra, Mariana Ins; Moreira, Marcos Aurlio; Arajo, Carolina Reis; Lana-Peixoto, Marco Aurlio; 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

  4. Stomach Disorders - Multiple Languages: MedlinePlus

    MedlinePLUS

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  5. 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

  6. Blood Disorders - Multiple Languages: MedlinePlus

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  7. Multiple Peroxisomal Enzymatic Deficiency Disorders

    PubMed Central

    Vamecq, Joseph; Draye, Jean-Pierre; Van Hoof, Franois; 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

  8. Psychiatric disorders in multiple sclerosis patients.

    PubMed

    Fazzito, Mirella Martins; Jordy, Srgio 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

  9. Multiple Substance Use Disorders in Juvenile Detainees.

    ERIC Educational Resources Information Center

    McClelland, Gary M.; Elkington, Katherine S.; Teplin, Linda A.; Abram, Karen M.

    2004-01-01

    Objective: To estimate the 6-month prevalence of multiple substance use disorders (SUDs) among juvenile detainees by demographic subgroups (sex, race/ethnicity, age). Method: Participants were a randomly selected sample of 1,829 African American, non-Hispanic white, and Hispanic detainees (1,172 males, 657 females, aged 10 to 18). Patterns and

  10. 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

  11. Esophagus Disorders - Multiple Languages: MedlinePlus

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  12. Throat Disorders - Multiple Languages: MedlinePlus

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  13. Parathyroid Disorders - Multiple Languages: MedlinePlus

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  14. Neuromuscular Disorders - Multiple Languages: MedlinePlus

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  15. 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

  16. 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

  17. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePLUS

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  18. Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

    MedlinePLUS

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  19. Spherical wave analysis of EXAFS data including multiple scattering

    NASA Astrophysics Data System (ADS)

    Furenlid, Lars; Felton, R. H.

    1989-06-01

    A rapid method for spherical-wave calculation of EXAFS spectra including multiple scattering is described. Examples include Co and Cu imidazole complexes, a mixed ligand iron complex, and the native and substrate complexed forms of protocatechuate 3,4-dioxygenase (PCD).

  20. 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

  1. Extending a clinical repository to include multiple sites.

    PubMed

    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

  2. 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...

  3. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    PubMed

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis. PMID:26847090

  4. 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

  5. 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

  6. 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 ([Formula: see text]), and schizophrenia-Crohn's disease with MHC region excluded ([Formula: see text]). 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

  7. Identity diffusion presenting as multiple personality disorder in a female psychopath.

    PubMed

    Bruce-Jones, W; Coid, J

    1992-04-01

    A female psychopath presented multiple forms of psychopathology, including features of 'multiple personality disorder'. It is proposed that a diagnosis of borderline personality disorder, or the psychodynamic features of borderline personality organisation, should be the exclusion criteria for this condition. PMID:1571755

  8. Neck Injuries and Disorders - Multiple Languages: MedlinePlus

    MedlinePLUS

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  9. 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

  10. 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.

  11. 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

  12. Autism Spectrum Disorder - Multiple Languages: MedlinePlus

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  13. Knee Injuries and Disorders - Multiple Languages: MedlinePlus

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  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. 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…

  16. 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

  17. 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…

  18. 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,

  19. 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

  20. Emotional Disorders in People with Multiple Sclerosis

    MedlinePLUS

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  1. 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

  2. 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…

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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) ...

  8. 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) ...

  9. Hip Injuries and Disorders - Multiple Languages: MedlinePlus

    MedlinePLUS

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

  10. 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

  11. 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

  12. 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…

  13. 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

  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. 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

  16. 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.

  17. 42 CFR 137.327 - May multiple projects be included in a single construction project agreement?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... construction project agreement? 137.327 Section 137.327 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF...-GOVERNANCE Construction Project Assumption Process 137.327 May multiple projects be included in a single construction project agreement? Yes, a Self-Governance Tribe may include multiple projects in a...

  18. 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

  19. 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…

  20. Methylphenidate in children with oppositional defiant disorder and both comorbid chronic multiple tic disorder and ADHD.

    PubMed

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

    2008-09-01

    Our primary objective was to determine if immediate-release methylphenidate is an effective treatment for oppositional defiant disorder diagnosed from mother's report in children with both chronic multiple tic disorder and attention-deficit hyperactivity disorder (ADHD). Children (n = 31) aged 6 to 12 years received placebo and 3 doses of methylphenidate twice daily for 2 weeks each under double-blind conditions and were assessed with ratings scales and laboratory measures. Results indicated significant improvement in both oppositional and ADHD behaviors with medication; however, the magnitude of treatment effect varied considerably as a function of disorder (ADHD > Oppositional behaviors), informant (teacher > mother), assessment instrument, and specific oppositional behavior (rebellious > disobeys rules). Drug response was comparable with that in children (n = 26) who did not have diagnosed oppositional defiant disorder, but comorbidity appeared to alter the perceived benefits for ADHD according to mother's report. Methylphenidate is an effective short-term treatment for oppositional behavior in children with comorbid ADHD and chronic multiple tic disorder. PMID:18474932

  1. 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

  2. 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; Wlling, Manuela; Kuijpers, Marijke J E; Khler, 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., Wlling, M., Kuijpers, M. J. E., Khler, 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

  3. Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in BeckwithWiedemann syndrome

    PubMed Central

    Bliek, Jet; Verde, Gaetano; Callaway, Jonathan; Maas, Saskia M; De Crescenzo, Agostina; Sparago, Angela; Cerrato, Flavia; Russo, Silvia; Ferraiuolo, Serena; Rinaldi, Maria Michela; Fischetto, Rita; Lalatta, Faustina; Giordano, Lucio; Ferrari, Paola; Cubellis, Maria Vittoria; Larizza, Lidia; Temple, I Karen; Mannens, Marcel M A M; Mackay, Deborah J G; Riccio, Andrea

    2009-01-01

    Genomic imprinting is an epigenetic phenomenon restricting gene expression in a manner dependent on parent of origin. Imprinted gene products are critical regulators of growth and development, and imprinting disorders are associated with both genetic and epigenetic mutations, including disruption of DNA methylation within the imprinting control regions (ICRs) of these genes. It was recently reported that some patients with imprinting disorders have a more generalised imprinting defect, with hypomethylation at a range of maternally methylated ICRs. We report a cohort of 149 patients with a clinical diagnosis of BeckwithWiedemann syndrome (BWS), including 81 with maternal hypomethylation of the KCNQ1OT1 ICR. Methylation analysis of 11 ICRs in these patients showed that hypomethylation affecting multiple imprinted loci was restricted to 17 patients with hypomethylation of the KCNQ1OT1 ICR, and involved only maternally methylated loci. Both partial and complete hypomethylation was demonstrated in these cases, suggesting a possible postzygotic origin of a mosaic imprinting error. Some ICRs, including the PLAGL1 and GNAS/NESPAS ICRs implicated in the aetiology of transient neonatal diabetes and pseudohypoparathyroidism type 1b, respectively, were more frequently affected than others. Although we did not find any evidence for mutation of the candidate gene DNMT3L, these results support the hypotheses that trans-acting factors affect the somatic maintenance of imprinting at multiple maternally methylated loci and that the clinical presentation of these complex cases may reflect the loci and tissues affected with the epigenetic abnormalities. PMID:19092779

  4. 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…

  5. Including Pupils with Autistic Spectrum Disorders in the Classroom: The Role of Teaching Assistants

    ERIC Educational Resources Information Center

    Symes, Wendy; Humphrey, Neil

    2012-01-01

    The aims of the current study were (i) to explore the extent to which pupils with Autistic Spectrum Disorders (ASD) were effectively included in lessons, compared with pupils with dyslexia (DYS) or no Special Educational Needs (CON) and (ii) to understand how the presence of a teaching assistant (TA) influences the inclusion/exclusion process. One

  6. 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.

  7. Starting Points: Instructional Practices for Young Children Whose Multiple Disabilities Include Visual Impairment.

    ERIC Educational Resources Information Center

    Chen, Deborah; Dote-Kwan, Jamie

    This handbook provides basic information on the needs of young children (ages 3-8) whose multiple disabilities include visual impairments. Chapters address: (1) common disabilities associated with visual impairment, the primary educational needs of these children, and the complexity involved in teaching them; (2) the need for clearly defined

  8. 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.

  9. Nonoperative Management (Including Ultrasound-Guided Injections) of Proximal Biceps Disorders.

    PubMed

    Schickendantz, Mark; King, Dominic

    2016-01-01

    Nonoperative management of conditions of the long head of biceps tendon (LHBT) involves a multifaceted approach, addressing the entire shoulder complex in addition to conditions that involve the LHBT. LHBT pathologic conditions are divided into 3 categories: inflammation, instability and rupture. This article provides an overview of a nonoperative treatment algorithm that addresses these specific categories and includes a review of ultrasound-guided injection techniques used in the diagnosis and management of LHBT disorders. PMID:26614469

  10. 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

  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. 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

  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. 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

  16. 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

  17. Assessing Eating Disorder Symptoms in Adolescence: Is There a Role for Multiple Informants?

    PubMed Central

    Swanson, SA; Aloisio, KM; Horton, NJ; Sonneville, KR; Crosby, RD; Eddy, KT; Field, AE; Micali, N

    2014-01-01

    Objectives Epidemiologic studies of adolescent psychiatric disorders often collect information from adolescents and parents, yet most eating disorder epidemiologic studies rely only on adolescent report. Methods We studied the eating disorder symptom reports provided by 7,968 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), and their parents, who were sent questionnaires at participants ages 14 and 16 years. Both adolescents and parents were asked questions about the adolescent's eating disorder symptoms, including binge eating, vomiting, laxative use, fasting, and thinness. We assessed the concordance of parent and adolescent report cross-sectionally using kappa coefficients, and further looked at how the symptom reports were predictive of adolescent body mass and composition measured at a clinical assessment at 17.5 years. Generalized estimating equations were used to model the symptom reports associations with risk factors and clinical outcomes. Results Parents and adolescents were largely discordant on symptom reports cross-sectionally (kappas<0.3), with the parent generally less likely to report bulimic symptoms than the adolescent but more likely to report thinness. Female adolescents were more likely to report bulimic symptoms than males (e.g., 2-4 times more likely to report binge eating), while prevalence estimates according to parent reports of female vs. male adolescents were similar. Both parent and adolescent symptom reports at ages 14 and 16 years were predictive of age-17.5 body mass and composition measures; parentally-reported binge eating was more strongly predictive of higher body mass and composition. Discussion Parent report of eating disorder symptoms seemed to measure different, but potentially important, aspects of these symptoms during adolescence. Epidemiologic eating disorder studies should consider the potential value added from incorporating parental reports. In particular, studies of male eating disorder presentations may be improved by using multiple sources of information. PMID:24436213

  18. 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.

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

    SciTech Connect

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

    2007-05-15

    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.

  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. 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

  2. Assessment of driving expertise using multiple choice questions including static vs. animated presentation of driving scenarios.

    PubMed

    Malone, Sarah; Brnken, Roland

    2013-03-01

    Novice drivers have a high collision risk compared to more experienced drivers. The optimization of driving assessment's validity should lead to a better identification of those examinees that need further training before solo driving. The aim of the present two studies was to find out whether the integration of animated traffic scenarios can enhance some quality aspects of selected multiple choice items of the official German driving test. For the first study, we developed a static version of a set of multiple choice questions each containing a computerized still picture of a traffic scenario and a dynamic version that included animated instead of still pictures of the same situations. Driving novices (n=57) and experts (n=63) were presented 22 items either in the static or in the dynamic version. Only the novices benefited from the dynamic presentation. Fifty novices and 50 experts participated in a second longitudinal study including three measurements with parallel tests of the dynamic testing materials at intervals of three to four months. The novices, who were currently attending driving school, improved over time whereas the experts' performance remained stable. The results indicate that animation has positive effects on some quality aspects of driving assessment, but the problem of low criterion validity has to be addressed by the means of further approaches. PMID:23207840

  3. 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

  4. 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

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

    PubMed

    Adjizian, Jean-Joseph; Lherbier, Aurlien; M-M Dubois, Simon; Botello-Mndez, Andrs Rafael; Charlier, Jean-Christophe

    2016-01-01

    Two-dimensional (2D) conjugated polymers exhibit electronic structures analogous to that of graphene with the peculiarity of ?-?* 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. PMID:26692370

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Multiple, synchronous ipsilateral soleus muscle flaps, including the Achilles' "wraparound" flap.

    PubMed

    Hallock, G G

    1998-07-01

    Versatility of the soleus muscle beyond its traditional role for the middle third of the leg is often overlooked. Substantial muscle bulk frequently extends even to the calcaneus, although this is quite variable. Its distal reach as a muscle flap then may potentially include encircling the Achilles' tendon itself as a local "wraparound" flap in an area otherwise notorious for requiring the complexity of a free tissue transfer. Since this maneuver only envelops the Achilles' tendon by stretching its own inserting soleus muscle, no muscle dissection per se is required, and nutrition from minor pedicles is sustained. Therefore, concomitant proximally based hemisoleus flaps can be utilized simultaneously and safely for more conventional coverage of midtibial defects. In this fashion, multiple, independent local flaps from a single soleus muscle can achieve coverage of disparate leg wounds, while sacrificing a minimum of donor site function. PMID:9678468

  12. 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

  13. 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

  14. 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)

  15. 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

  16. 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

  17. 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

  18. 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

  19. The Communication Journey of a Fully Included Child with an Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Diehl, Sylvia F.; Ford, Carolyn S.; Federico, Jeanne

    2005-01-01

    This article follows Jose, a child with autism spectrum disorder, through his communication journey from age 3 to age 11. His journey illustrates many of the characteristics and challenges of individuals with autism spectrum disorders, as they become a part of the literate community in the general education classroom. Collaborative, family-based

  20. 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…

  1. 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…

  2. 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

  3. Anxiety symptoms in boys with autism spectrum disorder, attention-deficit hyperactivity disorder, or chronic multiple tic disorder and community controls.

    PubMed

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

    2010-08-01

    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 assessed using parent and teacher versions of a DSM-IV-referenced rating scale. All three groups of boys with co-morbid ADHD evidenced more severe anxiety than Controls. Group differences in anxiety varied as a function of symptom, disorder, informant, and co-morbidity supporting the notion that co-morbid neurobehavioral syndromes differentially impact clinical features of co-occurring anxiety symptoms. Findings also suggest that GAD and SAD are phenomenologically unique, even in children with ASD. Implications for nosology are discussed. PMID:20143146

  4. 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.

  5. Longitudinal Prediction of Disruptive Behavior Disorders in Adolescent Males from Multiple Risk Domains

    PubMed Central

    Trentacosta, Christopher J.; Hyde, Luke W.; Goodlett, Benjamin D.; Shaw, Daniel S.

    2012-01-01

    The disruptive behavior disorders are among the most prevalent youth psychiatric disorders, and they predict numerous problematic outcomes in adulthood. This study examined multiple domains of risk during early childhood and early adolescence as longitudinal predictors of disruptive behavior disorder diagnoses among adolescent males. Early adolescent risks in the domains of sociodemographic factors, the caregiving context, and youth attributes were examined as mediators of associations between early childhood risks and disruptive behavior disorder diagnoses. Participants were 309 males from a longitudinal study of low-income mothers and their sons. Caregiving and youth risk during early adolescence each predicted the likelihood of receiving a disruptive behavior disorder diagnosis. Furthermore, sociodemographic and caregiving risk during early childhood were indirectly associated with disruptive behavior disorder diagnoses via their association with early adolescent risk. The findings suggest that preventive interventions targeting risk across domains may reduce the prevalence of disruptive behavior disorders. PMID:23239427

  6. 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

  7. 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

  8. The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy.

    PubMed

    De Cock, Valrie Cochen; Debs, Rachel; Oudiette, Delphine; Leu, Smaranda; Radji, Fatai; Tiberge, Michel; Yu, Huan; Bayard, Sophie; Roze, Emmanuel; Vidailhet, Marie; Dauvilliers, Yves; Rascol, Olivier; Arnulf, Isabelle

    2011-03-01

    Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system atrophy revealed more expressive faces, and movements that were faster and more ample in comparison with facial expression and movements during wakefulness. These movements were still somewhat jerky but lacked any visible parkinsonism. Cerebellar signs were not assessable. We conclude that parkinsonism also disappears during rapid eye movement sleep behaviour disorder in patients with multiple system atrophy, but this improvement is not due to enhanced dopamine transmission because these patients are not levodopa-sensitive. These data suggest that these movements are not influenced by extrapyramidal regions; however, the influence of abnormal cerebellar control remains unclear. The transient disappearance of parkinsonism here is all the more surprising since no treatment (even dopaminergic) provides a real benefit in this disabling disease. PMID:21310729

  9. 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

  10. Tight-binding coherent-potential approximation including off-diagonal disorder

    NASA Astrophysics Data System (ADS)

    Papaconstantopoulos, D. A.; Gonis, A.; Laufer, P. M.

    1989-12-01

    We present a generalization of the tight-binding coherent-potential approximation (TB-CPA) to substitutionally disordered alloys with both diagonal and off-diagonal disorder (ODD), taking into account all relevant s, p, and d, orbitals. This generalization is based on the work of Blackman, Esterling, and Berk [Phys. Rev. B 4, 2412 (1971)] which treated ODD within a single-band model of a disordered alloy. The method is illustrated with calculations of the density of states of disordered Cu0.75Pd0.25 alloys. We find that inclusion of ODD improves the agreement with specific-heat data, but it does not resolve a discrepancy with the results of first-principles, muffin-tin CPA calculations regarding the Pd component of the density of states.

  11. 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.

  12. 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

  13. 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…

  14. 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

  15. 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…

  16. 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…

  17. 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.…

  18. 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…

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

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

    PubMed

    Braley, Tiffany J; Chervin, Ronald D

    2015-11-01

    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

  5. 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

  6. Challenging Behaviors among Children with Autism Spectrum Disorders and Multiple Disabilities Attending Special Schools in Singapore

    ERIC Educational Resources Information Center

    Poon, Kenneth K.

    2012-01-01

    This study sought to understand the profile of and the factors which impact upon challenging behaviors among children with autism spectrum disorders (ASD) and multiple disabilities (MD). Teachers of 322 and 132 children with ASD and MD, respectively, attending special schools in Singapore, completed the Developmental Behavior Checklist, Teacher

  7. 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

  8. 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

  9. 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.

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

    NASA Astrophysics Data System (ADS)

    Wang, Wenlong; Kevrekidis, P. G.

    2015-03-01

    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. 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.

  11. 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.

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

    PubMed

    Wang, Wenlong; Kevrekidis, P G

    2015-03-01

    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. 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. PMID:25871170

  13. 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

  14. Characterization Methods for the Detection of Multiple Voice Disorders: Neurological, Functional, and Laryngeal Diseases.

    PubMed

    Orozco-Arroyave, Juan Rafael; Belalcazar-Bolanos, Elkyn Alexander; Arias-Londono, Julian David; Vargas-Bonilla, Jesus Francisco; Skodda, Sabine; Rusz, Jan; Daqrouq, Khaled; Honig, Florian; Noth, Elmar

    2015-11-01

    This paper evaluates the accuracy of different characterization methods for the automatic detection of multiple speech disorders. The speech impairments considered include dysphonia in people with Parkinson's disease (PD), dysphonia diagnosed in patients with different laryngeal pathologies (LP), and hypernasality in children with cleft lip and palate (CLP). Four different methods are applied to analyze the voice signals including noise content measures, spectral-cepstral modeling, nonlinear features, and measurements to quantify the stability of the fundamental frequency. These measures are tested in six databases: three with recordings of PD patients, two with patients with LP, and one with children with CLP. The abnormal vibration of the vocal folds observed in PD patients and in people with LP is modeled using the stability measures with accuracies ranging from 81% to 99% depending on the pathology. The spectral-cepstral features are used in this paper to model the voice spectrum with special emphasis around the first two formants. These measures exhibit accuracies ranging from 95% to 99% in the automatic detection of hypernasal voices, which confirms the presence of changes in the speech spectrum due to hypernasality. Noise measures suitably discriminate between dysphonic and healthy voices in both databases with speakers suffering from LP. The results obtained in this study suggest that it is not suitable to use every kind of features to model all of the voice pathologies; conversely, it is necessary to study the physiology of each impairment to choose the most appropriate set of features. PMID:26277012

  15. 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

  16. 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.

  17. Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders.

    PubMed

    Otto, Robert; Penzis, Robert; Gaube, Friedemann; Adolph, Oliver; Fhr, Karl J; Warncke, Paul; Robaa, Dina; Appenroth, Dorothea; Fleck, Christian; Enzensperger, Christoph; Lehmann, Jochen; Winckler, Thomas

    2015-08-27

    Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent ?-carbolinium salts as potent inihitors of both cholinesterases, N-methyl-D-aspartate receptors, and monoamine oxidases. Homobivalent ?-carbolines displayed similar structure-activity relationships on all tested targets and may present promising designed multiple ligands for the treatment of neurodegenerative disorders. PMID:26278660

  18. Investigation of multiple roots of the resistive wall mode dispersion relation, including kinetic effects

    SciTech Connect

    Berkery, J. W.; Sabbagh, S. A.; Betti, R.

    2011-07-15

    The resistive wall mode instability in tokamak plasmas has a complex frequency which can be determined by a dispersion relation that is cubic, in general, leading to three distinct roots. A simplified model of the dispersion relation, including kinetic effects, is presented and used to explore the behavior of these roots. By changing the plasma rotation frequency, it is shown that one root has a slow mode rotation frequency (less than the inverse wall time) while the other two rotate more quickly, one leading and one lagging the plasma rotation frequency. When realistic experimental parameters from the National Spherical Torus Experiment [M. Ono et al., Nucl. Fusion 40, 557 (2000)] are used, however, only one slow rotating, near-marginal stability root is found, consistent with present experiments and more detailed calculations with the MISK code [B. Hu et al., Phys. Plasmas 12, 057301 (2005)]. Electron collisionality acts to stabilize one of the rotating roots, while ion collisionality can stabilize the other. In devices with low rotation and low collisionality, these two rotating roots may manifest themselves, but they are likely to remain stable.

  19. 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

  20. 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

  1. 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 17:62,068,46365,963,102, 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

  2. 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

  3. 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.

  4. [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

  5. 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.

  6. 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

  7. Including thermal disorder of hydrogen bonding to describe the vibrational circular dichroism spectrum of zwitterionic L-alanine in water.

    PubMed

    Orestes, Ednilsom; Bistafa, Carlos; Rivelino, Roberto; Canuto, Sylvio

    2015-05-28

    The vibrational circular dichroism (VCD) spectrum of l-alanine amino acid in aqueous solution in ambient conditions has been studied. The emphasis has been placed on the inclusion of the thermal disorder of the solute-solvent hydrogen bonds that characterize the aqueous solution condition. A combined and sequential use of molecular mechanics and quantum mechanics was adopted. To calculate the average VCD spectrum, the DFT B3LYP/6-311++G(d,p) level of calculation was employed, over one-hundred configurations composed of the solute plus all water molecules making hydrogen bonds with the solute. Simplified considerations including only four explicit solvent molecules and the polarizable continuum model were also made for comparison. Considering the large number of vibration frequencies with only limited experimental results a direct comparison is presented, when possible, and in addition a statistical analysis of the calculated values was performed. The results are found to be in line with the experiment, leading to the conclusion that including thermal disorder may improve the agreement of the vibrational frequencies with experimental results, but the thermal effects may be of greater value in the calculations of the rotational strengths. PMID:25424499

  8. 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

  9. 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

  10. 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

  11. 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

  12. Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder

    PubMed Central

    Szafranski, Przemyslaw; Dharmadhikari, Avinash V.; Brosens, Erwin; Gurha, Priyatansh; Ko?odziejska, Katarzyna E.; Zhishuo, Ou; Dittwald, Piotr; Majewski, Tadeusz; Mohan, K. Naga; Chen, Bo; Person, Richard E.; Tibboel, Dick; de Klein, Annelies; Pinner, Jason; Chopra, Maya; Malcolm, Girvan; Peters, Gregory; Arbuckle, Susan; Guiang, Sixto F.; Hustead, Virginia A.; Jessurun, Jose; Hirsch, Russel; Witte, David P.; Maystadt, Isabelle; Sebire, Neil; Fisher, Richard; Langston, Claire; Sen, Partha; Stankiewicz, Pawe?

    2013-01-01

    An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (lncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including lncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. These deletions define a distant cis-regulatory region that harbors, besides lncRNA genes, also a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. We suggest that lung-transcribed 16q24.1 lncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of lncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development. PMID:23034409

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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

  1. Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1

    PubMed Central

    2014-01-01

    Background Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD). Methods Here we describe a comprehensive genome-wide study of bipolar disorder (BD), cross-referencing analysis from a family-based study of 229 small families with association analysis from over 950 cases and 950 ethnicity-matched controls from the UK and Canada. Further, loci identified in these analyses were supported by pathways identified through pathway analysis on the samples. Results Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as at SYNE1 on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and for schizophrenia. Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling. Conclusions The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 and SYNE1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD, WDR60, SCN7A and SPAG16. PMID:24387768

  2. 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

  3. Review: Effect study of sex hormone in the multiple sclerosis of common neurological disorders.

    PubMed

    Xin, Yanyan; Xu, Dayong; Yang, Xiaoqing; Liu, Aizhen; Zhou, Xinhua; Guo, Baozhi

    2015-07-01

    Multiple sclerosis (MS) is one of most common neurological disorders, mainly affecting women. The central nervous system (CNS) of this autoimmune disease is characterized by intermittent or chronic damage to the myelin sheaths (demyelination), local inflammation and axonal degeneration. During the early relapsing/remitting stages of MS, myelin can regenerate. However, as the disease progresses, both amount and activity of regenerated axons becomes insufficient, leading to impaired axon conduction, neurodegeneration and the worsening symptoms. Epidemiological study found that distinct symptom alleviation of diseases at a certain periods would be shown in women during pregnancy. The following basic researches indicated that sex hormones especially progesterone can significantly reduce the disease severity, moreover, the protective effect of sex hormone on the nervous system has become the research focus. PMID:26431667

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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 ?-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

  9. 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

  10. 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

  11. Posttransplant lymphoproliferative disorder presenting as multiple cystic lesions in a renal transplant recipient.

    PubMed

    Moir, J A G; Simms, R J; Wood, K M; Talbot, D; Kanagasundaram, N S

    2012-01-01

    We report a case of a 67-year-old man who experienced allograft dysfunction following a renal transplantation from a donation after cardiac death. The postoperative course was initially complicated by episodes of E. coli urinary sepsis causing pyrexia and a raised creatinine level. Ultrasound scanning 5 weeks posttransplant revealed mild hydronephrosis with several parenchymal cystic areas measuring up to 2 cm with appearances suggestive of fungal balls. Aspirated fluid again grew Escherichia coli, and this was treated with the appropriate antimicrobial therapy. The patient continued to have episodes of culture-negative sepsis; therefore, a computed tomography scan was performed 6 months posttransplant, which revealed multiple lesions in the renal cortex as well as liver and spleen. Subsequent biopsy revealed an Epstein-Barr virus-driven lymphoproliferation consistent with a polymorphic posttransplantation lymphoproliferative disorder (PTLD). This rare case of PTLD presenting as multiple renal, hepatic and splenic lesions emphasizes the need for a high index of clinical suspicion for this condition. Abnormal para-renal allograft masses should be biopsied to allow swift and effective management of a disease that can disseminate and become significantly more challenging to manage. PMID:22244123

  12. 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

  13. 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

  14. 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

  15. Sleep Disorders Reduce Health-Related Quality of Life in Multiple Sclerosis (Nottingham Health Profile Data in Patients with Multiple Sclerosis)

    PubMed Central

    Veauthier, Christian; Gaede, Gunnar; Radbruch, Helena; Wernecke, Klaus-Dieter; Paul, Friedemann

    2015-01-01

    Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the energy and emotional area of the NHP. In addition, OSA patients also showed increased NHP values in the physical abilities area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS. PMID:26197315

  16. 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

  17. 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

  18. 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

  19. 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…

  20. 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

  1. 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.…

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Extended X-ray absorption fine structure (EXAFS) analysis of disorder and multiple-scattering in complex crystalline solids

    SciTech Connect

    O'Day, P.A.; Brown, G.E. Jr. ); Rehr, J.J.; Zabinsky, S.I. )

    1994-04-06

    Quantitative determination of local atomic structure in complex materials using extended X-ray absorption fine structure (EXAFS) analysis was tested on eight inorganic compounds of known structure, including natural and synthetic crystalline solids, at ambient conditions. Our aim was to test the accuracy of experimental and theoretical EXAFS standard functions in determining the number of backscattering atoms (N) at a distance (R) beyond the ligating shell of the central absorber atom where effects from disorder, multiple-scattering, and overlapping shells of atoms may significantly influence the EXAFS spectra. These compounds have complicated structures compared to metals and contain Fe, Co, or Ni as the central absorbing atom and mixtures of second-row (C,O,F), third-row (Si, Cl), and fourth-row (Ca, Fe, Co, Ni) atoms as backscatters. Comparison of results using both experimental phase shift and amplitude functions (derived from the EXAFS spectra of the compounds) and those calculated from ab initio theory (using the computer code FEFF 5) shows that interatomic distances for single-scattering paths among metal atoms can be determined to within 0.02 A of values determined independently by X-ray diffraction up to a distance of 4 A from the central absorber by either method. 25 refs., 7 figs., 6 tabs.

  8. 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

  9. 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.

  10. P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations.

    PubMed

    Miller, Walter L

    2012-10-23

    Cytochrome P450 enzymes catalyze the biosynthesis of steroid hormones and metabolize drugs. There are seven human type I P450 enzymes in mitochondria and 50 type II enzymes in endoplasmic reticulum. Type II enzymes, including both drug-metabolizing and some steroidogenic enzymes, require electron donation from a two-flavin protein, P450 oxidoreductase (POR). Although knockout of the POR gene causes embryonic lethality in mice, we discovered human POR deficiency as a disorder of steroidogenesis associated with the Antley-Bixler skeletal malformation syndrome and found mild POR mutations in phenotypically normal adults with infertility. Assay results of mutant forms of POR using the traditional but nonphysiologic assay (reduction of cytochrome c) did not correlate with patient phenotypes; assays based on the 17,20 lyase activity of P450c17 (CYP17) correlated with clinical phenotypes. The POR sequence in 842 normal individuals revealed many polymorphisms; amino acid sequence variant A503V is encoded by ~28% of human alleles. POR A503V has about 60% of wild-type activity in assays with CYP17, CYP2D6, and CYP3A4, but nearly wild-type activity with P450c21, CYP1A2, and CYP2C19. Activity of a particular POR variant with one P450 enzyme will not predict its activity with another P450 enzyme: Each POR-P450 combination must be studied individually. Human POR transcription, initiated from an untranslated exon, is regulated by Smad3/4, thyroid receptors, and the transcription factor AP-2. A promoter polymorphism reduces transcription to 60% in liver cells and to 35% in adrenal cells. POR deficiency is a newly described disorder of steroidogenesis, and POR variants may account for some genetic variation in drug metabolism. PMID:23092891

  11. 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=2.0810(-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=2.5010(-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

  12. Using Multiple Approaches, including ?18O Signatures of Phosphate to Investigate Potential Phosphorus Limitation and Cycling under Changing Climate Conditions

    NASA Astrophysics Data System (ADS)

    Roberts, K.; Paytan, A.; Field, C. B.; Honn, E.; Edwards, E.; Gottlieb, R.

    2012-12-01

    Phosphorus (P) is often a limiting or co-limiting nutrient in terrestrial systems. It has been proposed that it will play an even greater role in ecosystems experiencing some of the many predicted effects of climate change, in particular release from nitrogen limitation. Recent work in 2007 by Menge et al. suggests that this is indeed a possibility. To investigate the potential for P limitation, and P cycling under multiple controlled conditions we collected samples from the Jasper Ridge Global Change Experiment (JRGCE) in May 2011. For over a decade the JRGCE has been manipulating four key parameters predicted to change in the future in a native Californian grassland system. Elevated Nitrogen deposition, increased precipitation, increased pCO2, and increased temperature are applied and monitored in a split plot design at the Jasper Ridge Biological Preserve in the eastern foothills of the Santa Cruz Mountains, California. Work done previously at the site using a suite of indicators of the potential P limitation suggest P limitation in some of the manipulated plots in the JRGCE. In this study we replicate a subset of the prior analyses to compare inter-annual signals of P limitation, and further attempt to utilize the oxygen isotopes of phosphate to investigate P cycling in soils at JRGCE. A fractional soil extraction process for phosphate enables separation of several operationally defined P pools, and provides auxiliary information regarding the relative concentrations of bio-available P, and relevant minerals in this grassland system under the varied conditions.

  13. 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

  14. 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

  15. 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;…

  16. 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

  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. 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

  1. Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis

    PubMed Central

    Palma, Jose-Alberto; Fernandez-Cordon, Clara; Coon, Elizabeth A.; Low, Phillip A.; Miglis, Mitchell G.; Jaradeh, Safwan; Bhaumik, Arijit K.; Dayalu, Praveen; Urrestarazu, Elena; Iriarte, Jorge; Biaggioni, Italo; Kaufmann, Horacio

    2015-01-01

    Objectivey Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia frequently affecting patients with synucleinopathies but its exact prevalence in multiple system atrophy (MSA) is unclear. Whether questionnaires alone are sufficient to diagnose RBD is also unknown. Methods Cross-sectional study of patients with probable MSA from six academic centers in the US and Europe. RBD was ascertained clinically and with polysomnography; and meta-analysis according to PRISMA guidelines for studies published before September 2014 that reported the prevalence of RBD in MSA. A random-effects model was constructed using weighted prevalence proportions. Only articles in English were included. Studies were classified into those that ascertained the presence of RBD in MSA clinically and with polysomnography. Case reports or case series (?5 patients) were not included. Results Forty-two patients completed questionnaires and underwent polysomnography. Of those, 32 (76.1%) had clinically-suspected RBD and 34 (81%) had polysomnography-confirmed RBD. Two patients reported no symptoms of RBD but had polysomnography-confirmed RBD. The primary search strategy yielded 374 articles of which 12 met the inclusion criteria The summary prevalence of clinically suspected RBD was 73% (95% CI, 62%-84%) in a combined sample of 324 MSA patients. The summary prevalence of polysomnography-confirmed RBD was 88% (95% CI, 79%-94%) in a combined sample of 217 MSA patients. Interpretation Polysomnography-confirmed RBD is present in up to 88% of patients with MSA. RBD was present in some patients that reported no symptoms. More than half of MSA patients report symptoms of RBD before the onset of motor deficits. PMID:25739474

  2. 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

  3. American Bullfrogs (Lithobates catesbeianus) Resist Infection by Multiple Isolates of Batrachochytrium dendrobatidis, Including One Implicated in Wild Mass Mortality.

    PubMed

    Eskew, Evan A; Worth, S Joy; Foley, Janet E; Todd, Brian D

    2015-09-01

    The emerging amphibian disease chytridiomycosis varies in severity depending on host species. Within species, disease susceptibility can also be influenced by pathogen variation and environmental factors. Here, we report on experimental exposures of American bullfrogs (Lithobates catesbeianus) to three different isolates of Batrachochytrium dendrobatidis (Bd), including one implicated in causing mass mortality of wild American bullfrogs. Exposed frogs showed low infection prevalence, relatively low infection load, and lack of clinical disease. Our results suggest that environmental cofactors are likely important contributors to Bd-associated American bullfrog mortality and that this species both resists and tolerates Bd infection. PMID:26065669

  4. 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-?, TNF-?, TGF-?1, 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-? and TNF-? 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-?/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

  5. 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 ironfolic acid on micronutrient status, maternal nutritional status, birth outcomes, and neonatal...

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  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 case of neuromyelitis optica spectrum disorder developing a fulminant course with multiple white-matter lesions following fingolimod treatment].

    PubMed

    Izaki, Shoko; Narukawa, Shinya; Kubota, Akihiro; Mitsui, Takao; Fukaura, Hikoaki; Nomura, Kyoichi

    2013-01-01

    A 49-year-old female neuromyelitis optica spectrum disorder (NMOSD) patient with positive anti-aquaporin 4 (AQP4) antibody was treated with fingolimod (FTY720). Ten days later, she developed acute disturbance of consciousness, aphasia, right hemi-spatial neglect, and right hemiparesis. Brain MRI showed multiple white-matter lesions with slight Gadolinium enhancement. She was diagnosed of acute exacerbation of NMOSD. Thus, fingolimod may be associated with the development of a fulminant course in NMOSD patients with positive anti-AQP4 antibody. PMID:23892961

  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

    Brown, Linda Morris; Gridley, Gloria; Check, David; Landgren, Ola

    2008-04-01

    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. 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

  17. 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…

  18. 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

  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. 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

  1. 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

  2. Restraint and Cancellation: Multiple Inhibition Deficits in Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Schachar, Russell; Logan, Gordon D.; Robaey, Philippe; Chen, Shirley; Ickowicz, Abel; Barr, Cathy

    2007-01-01

    We used variations of the stop signal task to study two components of motor response inhibition--the ability to withhold a strong response tendency (restraint) and the ability to cancel an ongoing action (cancellation)--in children with a diagnosis of attention deficit hyperactivity disorder (ADHD) and in non-ADHD controls of similar age (ages

  3. 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

  4. P450 oxidoreductase deficiency: a new disorder of steroidogenesis with multiple clinical manifestations.

    PubMed

    Miller, Walter L

    2004-09-01

    Combined partial deficiency of 17alpha-hydroxylase and 21-hydroxylase is well-described, but patients' genes for these enzymes lack mutations. Recent work has identified mutations in the gene for P450 oxidoreductase (POR) in such patients. POR-deficient individuals have a broad range of disorders, from infants with congenital malformations to women with the polycysic ovary syndrome. POR transfers electrons to all microsomal P450 enzymes: its deficiency affects steroidogenesis, drug metabolism and other processes. PMID:15350602

  5. Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas.

    PubMed

    Smith, Miriam J; O'Sullivan, James; Bhaskar, Sanjeev S; Hadfield, Kristen D; Poke, Gemma; Caird, John; Sharif, Saba; Eccles, Diana; Fitzpatrick, David; Rawluk, Daniel; du Plessis, Daniel; Newman, William G; Evans, D Gareth

    2013-03-01

    One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1 in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology. PMID:23377182

  6. Multiple aromatic side chains within a disordered structure are critical for transcription and transforming activity of EWS family oncoproteins.

    PubMed

    Ng, King Pan; Potikyan, Gary; Savene, Rupert O V; Denny, Christopher T; Uversky, Vladimir N; Lee, Kevin A W

    2007-01-01

    Chromosomal translocations involving the N-terminal approximately 250 residues of the Ewings sarcoma (EWS) oncogene produce a group of EWS fusion proteins (EFPs) that cause several distinct human cancers. EFPs are potent transcriptional activators and interact with other proteins required for mRNA biogenesis, indicating that EFPs induce tumorigenesis by perturbing gene expression. Although EFPs were discovered more than a decade ago, molecular analysis has been greatly hindered by the repetitive EWS activation domain (EAD) structure, containing multiple degenerate hexapeptide repeats (consensus SYGQQS) with a conserved tyrosine residue. By exploiting total gene synthesis, we have been able to systematically mutagenize the EAD and determine the effect on transcriptional activation by EWS/ATF1 and cellular transformation by EWS/Fli1. In both assays, we find the following requirements for EAD function. First, multiple tyrosine residues are essential. Second, phenylalanine can effectively substitute for tyrosine, showing that an aromatic ring can confer EAD function in the absence of tyrosine phosphorylation. Third, there is little requirement for specific peptide sequences and, thus, overall sequence composition (and not the degenerate hexapeptide repeat) confers EAD activity. Consistent with the above findings, we also report that the EAD is intrinsically disordered. However, a sensitive computational predictor of natural protein disorder (PONDR VL3) identifies potential molecular recognition features that are tyrosine-dependent and that correlate well with EAD function. In summary we have uncovered several molecular features of the EAD that will impact future studies of the broader EFP family and molecular recognition by complex intrinsically disordered proteins. PMID:17202261

  7. Isolation and characterization of genes in the region of chromosome 8 involved in Langer-Giedion syndrome including a candidate gene for hereditary multiple exostosis

    SciTech Connect

    Wells, D.; Ahn, J.; Cook, A.

    1994-09-01

    Langer-Giedion syndrome (LGS) is a dominantly inherited developmental disorder responsible for a variety of facial and skeletal abnormalities and mental retardation in some cases. LGS is thought to be a contiguous gene syndrome resulting from lesions in the genes for trichorhino-phalangeal syndrome (TRPSI) and hereditary multiple exostoses (EXTI) and is generally accompanied by interstitial deletions in 8q24.1. Since little is known of the nature of these genes, we have begun to isolate and characterize all of the expressed sequences in this region making use of a cosmid contig that we developed for this region. We have successfully used direct screening of cDNA libraries, exon trapping and CAIGES techniques to identify several expressed DNA sequences that map to this region. These cDNAs have been sequenced and analyzed for open reading frames, common sequence motifs and homologies to know genes. In an attempt to focus the search, we have used a variety of probes and hybridization techniques to map various chromosomal breakpoints in this region that have been shown to affect either TRPSI, EXTI or LGS. One of these expressed sequences spans a region that has been shown to contain a chromosomal breakpoint known to be involved in the EXT phenotype. Thus this gene should be considered a candidate gene for EXTI.

  8. 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

  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. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Association of environmental insecticide exposure and fetal growth with a Bayesian model including multiple exposure sources: the PELAGIE mother-child cohort.

    PubMed

    Petit, Claire; Blangiardo, Marta; Richardson, Sylvia; Coquet, Franois; Chevrier, Ccile; Cordier, Sylvaine

    2012-06-01

    It has been suggested that prenatal exposure to insecticides adversely affects fetal growth, but the overall results have been inconsistent, partly because of the different exposure sources and exposure assessments used. In the French PELAGIE (Perturbateurs Endocriniens: tude Longitudinale sur les Anomalies de la Grossesse, l'Infertilit et l'Enfance) mother and child cohort (2002-2006), the authors investigated the association between fetal growth and insecticide exposure (n = 1,213) using an integrated Bayesian latent variable model to include multiple exposure sources: agricultural activities, nonorganic diet, household insecticide use on plants, and household insecticide use against insects. They used a questionnaire to collect information on household use and organic diet, and a national agricultural census provided data on agricultural activities in the women's municipalities of residence. A 0.10-cm decrease in head circumference at birth (95% credibility interval: -0.22, 0.01) was associated with fetal insecticide exposure from agricultural activities in the municipality of residence. Decreases in average birth weight (-27 g; 95% credibility interval: -59, 6) and head circumference (-0.12 cm; 95% credibility interval: -0.26, 0.01) were associated with household insecticide use to treat plants. The present results suggest an inverse association between fetal growth and prenatal insecticide exposure from nearby agricultural activity or household use. Bayesian modeling via latent variables is a natural framework for including multiple sources of exposure to environmental pollutants. PMID:22534205

  16. 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

  17. Metabolic profiling in multiple sclerosis and other disorders by quantitative analysis of cerebrospinal fluid using nuclear magnetic resonance spectroscopy.

    PubMed

    Lutz, N W; Cozzone, P J

    2011-07-01

    Cerebrospinal fluid (CSF) is being analyzed for the diagnosis of a variety of neurological diseases. Among the methods employed, metabolomics and proteomics are increasingly gaining popularity. At present, sensitivity and, in particular, specificity are limited in CSF metabolomics by nuclear magnetic resonance (NMR) spectroscopy. Nonetheless, progress is being made by studying more and more well-defined and homogeneous patient cohorts. This review starts off with a brief overview of classical CSF analysis in multiple sclerosis (MS), followed by a description of NMR spectroscopy in general metabolic CSF analysis. The subsequent sections focus on metabolomic profiling of CSF by NMR spectroscopy in MS and other neurological disorders. Currently existing results are reviewed and compared, and the potential and limits of this approach are discussed. In addition, several methodological questions are addressed, and the prospects for future developments are briefly outlined. PMID:21466459

  18. "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

  19. 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

  20. Personality Disorders

    MedlinePLUS

    ... disorders. Treatment may include individual, group, or family psychotherapy. Medications, prescribed by a patient’s physician, may also ... personality disorders, including problems with anxiety and perceptions. Psychotherapy for patients with personality disorders focuses on helping ...

  1. 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

  2. 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 (6/55versus 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

    PubMed Central

    2014-01-01

    Background Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either reactive or endogenous subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of reactive or endogenous subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of reactive and endogenous depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Methods Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic stress protocols (maternal separation and Unpredictable Chronic Mild Stress) to model reactive depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of endogenous depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. Results In the mouse reactive model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the endogenous rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Conclusions Our results suggest that endogenous and reactive subtypes of depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of reactive depression caused by early stressors differs considerably from that of reactive depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD. PMID:24886127

  8. The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders

    PubMed Central

    Dobryakova, Ekaterina; Genova, Helen M.; DeLuca, John; Wylie, Glenn R.

    2015-01-01

    Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research. PMID:25814977

  9. 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

    ... du chat syndrome (chromosome 5p deletion syndrome) and the infantile onset form of Tay-Sachs disease... include both the juvenile and late-onset forms of Tay-Sachs disease, trisomy X syndrome (XXX syndrome...-Sachs disease, trisomy X syndrome (XXX syndrome), fragile X syndrome, phenylketonuria (PKU),...

  10. 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

    ... include both the juvenile and late-onset forms of Tay-Sachs disease, trisomy X syndrome (XXX syndrome... (chromosome 5p deletion syndrome) and the infantile onset form of Tay-Sachs disease interfere very seriously... the juvenile and late-onset forms of Tay-Sachs disease, trisomy X syndrome (XXX syndrome), fragile...

  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. "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

  13. An Evaluation of a Brief Multiple-Stimulus Preference Assessment with Adolescents with Emotional-Behavioral Disorders in an Educational Setting

    ERIC Educational Resources Information Center

    Paramore, Nancy W.; Higbee, Thomas S.

    2005-01-01

    Brief multiple-stimulus-without-replacement (MSWO) preference assessments were conducted with 3 adolescent boys with emotional-behavioral disorders in the context of their public school educational program. The reinforcing effects of stimuli identified as high, medium, and low preference were then evaluated using an alternating treatments design

  14. 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

  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. Cytogenetic analyses of eight species in the genus Leptodactylus Fitzinger, 1843 (Amphibia, Anura, Leptodactylidae), including a new diploid number and a karyotype with multiple translocations

    PubMed Central

    2012-01-01

    Background The karyotypes of Leptodactylus species usually consist of 22 bi-armed chromosomes, but morphological variations in some chromosomes and even differences in the 2n have been reported. To better understand the mechanisms responsible for these differences, eight species were analysed using classical and molecular cytogenetic techniques, including replication banding with BrdU incorporation. Results Distinct chromosome numbers were found: 2n = 22 in Leptodactylus chaquensis, L. labyrinthicus, L. pentadactylus, L. petersii, L. podicipinus, and L. rhodomystax; 2n = 20 in Leptodactylus sp. (aff. podicipinus); and 2n = 24 in L. marmoratus. Among the species with 2n = 22, only three had the same basic karyotype. Leptodactylus pentadactylus presented multiple translocations, L. petersii displayed chromosome morphological discrepancy, and L. podicipinus had four pairs of telocentric chromosomes. Replication banding was crucial for characterising this variability and for explaining the reduced 2n in Leptodactylus sp. (aff. podicipinus). Leptodactylus marmoratus had few chromosomes with a similar banding patterns to the 2n = 22 karyotypes. The majority of the species presented a single NOR-bearing pair, which was confirmed using Ag-impregnation and FISH with an rDNA probe. In general, the NOR-bearing chromosomes corresponded to chromosome 8, but NORs were found on chromosome 3 or 4 in some species. Leptodactylus marmoratus had NORs on chromosome pairs 6 and 8. The data from C-banding, fluorochrome staining, and FISH using the telomeric probe helped in characterising the repetitive sequences. Even though hybridisation did occur on the chromosome ends, telomere-like repetitive sequences outside of the telomere region were identified. Metaphase I cells from L. pentadactylus confirmed its complex karyotype constitution because 12 chromosomes appeared as ring-shaped chain in addition to five bivalents. Conclusions Species of Leptodactylus exhibited both major and minor karyotypic differences which were identified by classical and molecular cytogenetic techniques. Replication banding, which is a unique procedure that has been used to obtain longitudinal multiple band patterns in amphibian chromosomes, allowed us to outline the general mechanisms responsible for these karyotype differences. The findings also suggested that L. marmoratus, which was formerly included in the genus Adenomera, may have undergone great chromosomal repatterning. PMID:23268622

  17. Equine disorders of sexual development in 17 mares including XX, SRY-negative, XY, SRY-negative and XY, SRY-positive genotypes.

    PubMed

    Villagmez, D A F; Lear, T L; Chenier, T; Lee, S; McGee, R B; Cahill, J; Foster, R A; Reyes, E; St John, E; King, W A

    2011-01-01

    We described the clinical, cytogenetic and molecular findings of 17 clinical equine cases presented for abnormal sexual development and infertility. Six horses with an enlarged clitoris had an XX, SRY-negative genotype, which displayed male-like behavior (adult individuals). Bilateral ovotestes were noted in 2 of those cases, while another case showed increased levels of circulating testosterone. Six horses with a female phenotype, including normal external genitalia, had an XY, SRY-negative genotype. These individuals had small gonads and an underdeveloped internal reproductive tract. Four horses with normal appearing external genitalia had an XY, SRY-positive genotype, 3 of them had hypoplastic testes and male-like behavior. In addition, one young filly with enlarged clitoris and hypoplastic testes had the same genotype but did not show male-like behavior due to her age. Three of these horses were related with 2 being siblings. These findings demonstrate the diversity of disorders of sexual development seen in the horse. Furthermore, they emphasize the need for further research to identify genes involved in abnormal sex determination and differentiation in the horse. PMID:21196712

  18. 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

  19. Irregular Sleep-Wake Rhythm Disorder.

    PubMed

    Abbott, Sabra M; Zee, Phyllis C

    2015-12-01

    Irregular sleep-wake rhythm disorder is a circadian rhythm disorder characterized by multiple bouts of sleep within a 24-hour period. Patients present with symptoms of insomnia, including difficulty either falling or staying asleep, and daytime excessive sleepiness. The disorder is seen in a variety of individuals, ranging from children with neurodevelopmental disorders, to patients with psychiatric disorders, and most commonly in older adults with neurodegenerative disorders. Treatment of irregular sleep-wake rhythm disorder requires a multimodal approach aimed at strengthening circadian synchronizing agents, such as daytime exposure to bright light, and structured social and physical activities. In addition, melatonin may be useful in some patients. PMID:26568126

  20. 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

  1. 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

    Knig, C; Kleber, M; Reinhardt, H; Knop, S; Wsch, 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

  2. Blood Disorders

    MedlinePLUS

    ... a lack of certain nutrients in your diet. Types of blood disorders include Platelet disorders, excessive clotting, and bleeding ... myeloma Eosinophilic disorders, which are problems with one type of white blood cell.

  3. Mental Disorders

    MedlinePLUS

    ... disorders Psychotic disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history ... Biological factors can also be part of the cause. A traumatic brain injury can lead to a ...

  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. 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

  7. 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

  8. 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

  9. 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

  10. Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients

    PubMed Central

    Santos, Lvia O.; Vitrio, Bianca S.; Branquinha, Marta H.; Pedroso e Silva, Conceio M.; Santos, Andr L. S.; d'Avila-Levy, Claudia M.

    2013-01-01

    Objectives There is a general lack of effective and non-toxic chemotherapeutic agents for leishmaniasis and there is as yet no study about the effect of HIV peptidase inhibitors (HIV PIs) on Leishmania/HIV-coinfected patients. In the present work, we performed a comparative analysis of the spectrum of action of HIV PIs on different Leishmania spp., including strains obtained from HIV-positive patients receiving or not receiving antiretroviral treatment. Methods The effects of nelfinavir and saquinavir on Leishmania proliferation were assessed by means of a colorimetric assay (MTT). Subsequently, the effect of nelfinavir on aspartic peptidase activity from Leishmania spp. was assessed by following the degradation of the fluorogenic substrate MCA-G-K-P-I-L-F-F-R-L-K-DNP-Arg-NH2. Results Nelfinavir was capable of significantly reducing the multiplication of many Leishmania reference strains and isolates obtained from HIV-positive patients receiving or not receiving antiretroviral treatment. Leishmania major growth was inhibited by ?50%, while all other flagellates were strongly inhibited (at least 94%), except for a Leishmania chagasi strain obtained from an HIV-positive patient under treatment with highly active antiretroviral therapy (HAART). Culture of this isolate in the presence of nelfinavir induced a considerable reduction in the aspartic peptidase activity. In addition, nelfinavir was also capable of inhibiting the aspartic peptidase activity of all Leishmania strains tested. Conclusions The present data contribute to the study of the effect of HIV PIs on Leishmania infection and add new insights into the possibility of exploiting aspartic peptidases as promising targets in order to generate novel medications to treat leishmaniasis. PMID:23109184

  11. 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

  12. Low selfesteem in women with eating disorders and alcohol abuse as a psychosocial factor to be included in their psychotherapeutic approach

    PubMed Central

    2010-01-01

    Author have analyzed the psychosocial 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 psychosexual. 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 genderrole 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 psychosexual identity versus control group but no correlation with masculinity/feminity index. PMID:21254749

  13. 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

  14. 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

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

    PubMed

    Aldinger, Kimberly A; Lane, Christianne J; Veenstra-VanderWeele, Jeremy; Levitt, Pat

    2015-12-01

    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

  16. 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

  17. 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…

  18. 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;…

  19. 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

  20. 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

  1. Mosaicism for genome-wide paternal uniparental disomy with features of multiple imprinting disorders: diagnostic and management issues.

    PubMed

    Inbar-Feigenberg, Michal; Choufani, Sanaa; Cytrynbaum, Cheryl; Chen, Yi-An; Steele, Leslie; Shuman, Cheryl; Ray, Peter N; Weksberg, Rosanna

    2013-01-01

    Mosaicism for genome-wide paternal uniparental disomy (UPD) has been reported in only seven live born individuals to date. Clinical presentation includes manifestations of multiple paternal UPD syndromes with high variability, likely due to the variable levels of mosaicism in different somatic tissues. We report an eighth case in a female patient with mosaicism for genome-wide paternal UPD which highlights the complex clinical presentation. Our patient had features of Beckwith-Wiedemann syndrome (BWS), Angelman syndrome, and congenital hyperinsulinism. The clinical findings included prematurity, organomegaly, hemihyperplasia, developmental delay, benign tumors, and cystic lesions. The diagnosis in our patient was established utilizing microarray-based genome-wide DNA methylation analysis performed on leukocyte DNA. Targeted multiplex ligation-dependent probe amplification (MLPA) analysis of chromosome regions 11p15 and 15q13 confirmed mosaicism for paternal UPD at these genomic regions. This case represents the first report of microarray-based genome-wide DNA methylation analysis in the diagnosis of genome-wide paternal UPD. The application of microarray-based genome-wide DNA methylation analysis on selected individuals with complex clinical presentations could be a valuable diagnostic tool to improve the detection rate of mosaic genome-wide paternal UPD. This approach, which screens many loci simultaneously, is more cost-effective and less labor-intensive than performing multiple targeted DNA methylation-based assays. Identification of individuals with mosaicism for genome-wide paternal UPD is an important goal as it confers a low recurrence risk for the family and identifies individuals who require surveillance due to increased tumor risk. PMID:23239666

  2. 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

  3. 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 ...

  4. Tailbone Disorders

    MedlinePLUS

    ... the bottom of your backbone, or spine. Tailbone disorders include tailbone injuries, pain, infections, cysts and tumors. ... cause of such injuries. Symptoms of various tailbone disorders include pain in the tailbone area, pain upon ...

  5. 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

  6. 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…

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Communication problems with environment-related health disorders as illustrated by a multiple chemical sensitivity (MCS) chatroom.

    PubMed

    Jaks, Heike; Hornberg, Claudia; Dott, Wolfgang; Wiesmller, Gerhard Andreas

    2004-12-01

    The problem of communication in treating multiple chemical sensitivity (MCS) was analysed and evaluated using the documentation of an MCS chatroom which was set up in April 2001 following the TV programme Gesundheitsmagazin Praxis (Health Magazine: Practice). Approaches were developed for solving communication problems in the chatroom. A total of 490 cases were evaluated, most of which (355) were directly or indirectly affected, 76 came from self-help groups and 10 were from 4 guest experts invited by ZDF (Zweites Deutsches Fernsehen, Second German TV channel). Of these 4 experts, 2 were environmental medicine specialists, 1 psychosomatics expert and 1 psychiatrist. Fourty-nine of the cases included a petition for chatroom participants to join a class-action law. Aside from exchanging basic information on MCS, frequent topics of discussion on the air were the assessment of physicians, clinics, self-help groups and experts. The participants also expressed their views on problems with society, politics, the economy, science and social security. Another common topic was communication in the chatroom itself, which for the most part consisted of sarcasm and insults, which were cause for conflicts in the chatroom. These communication problems led to the conclusion that a chatroom is not the best medium for discussing MCS. If a chatroom is to be used profitably to this end, it is imperative to have a well-defined organisational framework which allows the exchange of current, scientifically accurate information while keeping discussions from escalating and degenerating into arguments. PMID:15729837

  12. [A case of recurrent non-small cell lung cancer successfully treated with multiple modality therapies including S-1 monotherapy as fifth-line chemotherapy hospital)].

    PubMed

    Yokosuka, Tetsuya; Kobayashi, Toshiko; Enomoto, Tatsuji; Takeda, Atsuya

    2013-09-01

    An 80-year-old man with no complaint was referred to our department because of high serum CEA level. He was diagnosed as non-small cell lung cancer(adenocarcinoma)of the left lower lobe(c-T2aN0M0, stage I B), and therefore the left lower lobectomy with lymph node dissection was performed. Pathological staging was p-T2aN1(#10)M0, stage II A, and EGFR mutation was negative. Adjuvant chemotherapy with UFT was started, but multiple hilar and mediastinal lymph nodes metastases soon appeared. Carboplatin(CBDCA)+paclitaxel(PTX), erlotinib, and docetaxel(DOC)were attempted after that, but the lymph nodes increased in size and the CEA level was up to 159.8 ng/mL. At about the same time, brain and pulmonary metastases were recognized. After radiation for the chest lymph nodes and stereotactic radiosurgery(SRS)for the brain metastasis, oral S-1 monotherapy was introduced. Soon after, the lymph nodes shrinked and the CEA level decreased. Also, the pulmonary metastasis disappeared. Although a right supraclavicular lymph node metastasis was resected during the clinical course, the S-1 monotherapy has been continued with no serious adverse event. He is well(PS 0)without recurrent lesion, and his serum CEA level is within the normal limit. PMID:24047779

  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. Smell Disorders

    MedlinePLUS

    ... smell disorder can be an early sign of Parkinson’s disease, Alzheimer’s disease, or multiple sclerosis. It can also be related to other medical conditions, such as obesity, diabetes, hypertension, and malnutrition. If you are experiencing a ...

  15. 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.

  16. 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

  17. 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

  18. Multiple sclerosis: modulation of toll-like receptor (TLR) expression by interferon-? includes upregulation of TLR7 in plasmacytoid dendritic cells.

    PubMed

    Derkow, Katja; Bauer, Jakob M J; Hecker, Michael; Paap, Brigitte K; Thamilarasan, Madhan; Koczan, Dirk; Schott, Eckart; Deuschle, Katrin; Bellmann-Strobl, Judith; Paul, Friedemann; Zettl, Uwe K; Ruprecht, Klemens; Lehnardt, Seija

    2013-01-01

    Interferon-? is an established treatment for patients with multiple sclerosis (MS) but its mechanisms of action are not well understood. Viral infections are a known trigger of MS relapses. Toll-like receptors (TLRs) are key components of the innate immune system, which sense conserved structures of viruses and other pathogens. Effects of interferon-? on mRNA levels of all known human TLRs (TLR1-10) and the TLR adaptor molecule MyD88 were analyzed in peripheral blood mononuclear cells (PBMCs) of healthy donors by quantitative real-time PCR and by transcriptome analysis in PBMCs of 25 interferon-?-treated patients with relapsing-remitting MS. Regulation of TLR protein expression by interferon-? was investigated by flow cytometry of leukocyte subsets of healthy subjects and of untreated, interferon-?-, or glatiramer acetate-treated patients with MS. Interferon-? specifically upregulated mRNA expression of TLR3, TLR7, and MyD88 and downregulated TLR9 mRNA in PBMCs of healthy donors as well as in PBMCs of patients with MS. Plasmacytoid dendritic cells (pDCs) were identified as the major cell type responding to interferon-? with increased expression of TLR7 and MyD88 protein. In line with this, expression of TLR7 protein was increased in pDCs of interferon-?-treated, but not untreated or glatiramer acetate-treated patients with MS. Interferon-?-induced upregulation of TLR7 in pDCs is of functional relevance since pre-treatment of PBMCs with interferon-? resulted in a strongly increased production of interferon-? upon stimulation with the TLR7 agonist loxoribine. Flow cytometry confirmed pDCs as the cellular source of interferon-? production induced by activation of TLR7. Thus, upregulation of TLR7 in pDCs and a consequently increased activation of pDCs by TLR7 ligands represents a novel immunoregulatory mechanism of interferon-?. We hypothesize that this mechanism could contribute to a reduction of virus-triggered relapses in patients with MS. PMID:23950974

  19. 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

  20. Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder

    PubMed Central

    2013-01-01

    Background We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Methods Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. Results The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as development of the cortex and cerebellum, cognition, memory, and spatial learning. Independent ChIP-quantitative PCR analyses confirm binding of RORA1 to promoter regions of selected ASD-associated genes, including A2BP1, CYP19A1, ITPR1, NLGN1, and NTRK2, whose expression levels (in addition to HSD17B10) are also decreased in RORA1-repressed human neuronal cells and in prefrontal cortex tissues from individuals with ASD. Conclusions Findings from this study indicate that RORA transcriptionally regulates A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, and strongly suggest that reduction of this sex hormone-sensitive nuclear receptor in the brain causes dysregulated expression of these ASD-relevant genes as well as their associated pathways and functions which, in turn, may contribute to the underlying pathobiology of ASD. PMID:23697635

  1. Caenorhabditis elegans cyclin B3 is required for multiple mitotic processes including alleviation of a spindle checkpoint-dependent block in anaphase chromosome segregation.

    PubMed

    Deyter, Gary M R; Furuta, Tokiko; Kurasawa, Yasuhiro; Schumacher, Jill M

    2010-11-01

    The master regulators of the cell cycle are cyclin-dependent kinases (Cdks), which influence the function of a myriad of proteins via phosphorylation. Mitotic Cdk1 is activated by A-type, as well as B1- and B2-type, cyclins. However, the role of a third, conserved cyclin B family member, cyclin B3, is less well defined. Here, we show that Caenorhabditis elegans CYB-3 has essential and distinct functions from cyclin B1 and B2 in the early embryo. CYB-3 is required for the timely execution of a number of cell cycle events including completion of the MII meiotic division of the oocyte nucleus, pronuclear migration, centrosome maturation, mitotic chromosome condensation and congression, and, most strikingly, progression through the metaphase-to-anaphase transition. Our experiments reveal that the extended metaphase delay in CYB-3-depleted embryos is dependent on an intact spindle assembly checkpoint (SAC) and results in salient defects in the architecture of holocentric metaphase chromosomes. Furthermore, genetically increasing or decreasing dynein activity results in the respective suppression or enhancement of CYB-3-dependent defects in cell cycle progression. Altogether, these data reveal that CYB-3 plays a unique, essential role in the cell cycle including promoting mitotic dynein functionality and alleviation of a SAC-dependent block in anaphase chromosome segregation. PMID:21124864

  2. 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, 6-8years

  3. 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

  4. 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

  5. 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

  6. Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum beta-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina.

    PubMed

    Melano, Roberto; Corso, Alejandra; Petroni, Alejandro; Centrn, Daniela; Orman, Betina; Pereyra, Adriana; Moreno, Noem; Galas, Marcelo

    2003-07-01

    Klebsiella pneumoniae M1803, isolated from a paediatric patient with chronic urinary infection, presented nine antimicrobial resistance mechanisms harboured on two conjugative megaplasmids, in addition to the chromosomally mediated SHV-1 beta-lactamase. These nine antimicrobial resistance mechanisms comprised two extended-spectrum beta-lactamases (ESBLs) (PER-2 and CTX-M-2), TEM-1-like, OXA-9-like, AAC(3)-IIa, AAC(6')-Ib, ANT(3")-Ia and resistance determinants to tetracycline and chloramphenicol. During fluoroquinolone treatment, a variant derived from M1803 (named M1826) was selected, with an overall increase of MICs, in particular of cefoxitin and carbapenems. No enzymic activity against these latter drugs was found. Mutations in the region analogous to the quinolone resistance-determining region were not found. Strain M1826 was deficient in OmpK35/36 expression, which produced the decrease in the susceptibility to cefoxitin, carbapenems and fluoroquinolones. The blaCTX-M-2 gene was located in an unusual class 1 integron, which includes Orf513, as occurred in the recently described In35. In addition, Tn3 and Tn1331 were detected in both K. pneumoniae isolates. This is the first report of in vivo selection of an OmpK35/36 deficiency in a K. pneumoniae strain that produced a novel combination of two ESBLs (CTX-M-2 and PER-2) during fluoroquinolone treatment in a paediatric patient with chronic urinary infection. PMID:12775675

  7. 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

  8. Childhood Functional GI Disorders

    MedlinePLUS

    ... Buy IFFGD Merchandise Contact Us Donate Childhood Functional GI Disorders A functional disorder refers to a disorder ... regurgitation, heartburn, or food refusal. Examples of functional GI disorders in kids and teens include: Infant regurgitation ...

  9. 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

  10. 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

  11. 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 Central

    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 glandwith 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.

  12. 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

  13. 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

  14. "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

  15. 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 ...

  16. X-ray spectroscopy of electrochemically deposited iridium oxide films: detection of multiple sites through structural disorder.

    PubMed

    Hillman, A Robert; Skopek, Magdalena A; Gurman, Stephen J

    2011-03-28

    We report the results of X-ray absorption spectroscopy studies on electrochemically deposited iridium oxide films. The emphasis of the study is the correlation of X-ray derived structural data with electrochemically controlled charge state. Data were acquired for films subject to redox cycling in neutral and alkaline aqueous media. In both cases, cyclic voltammetric responses show two redox couples, coulometrically of roughly equal magnitude. Assays of the iridium population (based on the iridium L(3) absorption edge amplitude) and the charge injected (based on integration of the voltammetric response) show that overall an average of ca. one electron per iridium atom is transferred. The absorption edge shifts indicate that the formal charge on the iridium changes, on average, from ca. 3.5+ to ca. 4.5+ across the entire process. EXAFS-derived changes in mean Ir-O distance and their mean square variation have been interpreted in terms of a two-site model, in which the two types of site have distinct redox potentials. Variations of local structure and disorder with potential are discussed and a generic model for structural disorder (parameterized via Debye-Waller factor) with diagnostic capability is developed. PMID:21173969

  17. 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.

  18. 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

  19. Project HAPI (Handicapped Achievement Program Improvement): Assessment plus Intervention equal I.E.P. A Handbook on How To Write an Individualized Education Program for Severe Disorders of Language, Including Aphasia and Other Speech-Language Handicapped (Communication Disorders). Book One.

    ERIC Educational Resources Information Center

    Chapman, Jean

    The first of five handbooks developed by Project HAPI (Handicapped Achievement Program Improvement), a multimedia staff development program to help teachers and specialists write effective individualized education programs (IEPs), is in looseleaf workbook format and focuses on children with severe disorders of language, including aphasia and other

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. 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)…

  8. 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 ...

  9. 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

  10. 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

  11. ?F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders.

    PubMed

    Dammacco, Franco; Rubini, Giuseppe; Ferrari, Cristina; Vacca, Angelo; Racanelli, Vito

    2015-02-01

    Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a higher screening and diagnostic sensitivity and specificity over the skeleton X-ray. In patients with monoclonal gammopathy of undetermined significance and in those with smoldering MM, PET/CT is consistently unable to detect focal and/or diffuse marrow abnormalities. Conversely, based on a systematic review of 18 studies comprising almost 800 MM patients, PET/CT was able to detect MM osteolytic lesions with a sensitivity of approximately 80-90% and a specificity of 80-100%. Importantly, a poor degree of concordance has also been emphasized between PET/CT and whole-body magnetic resonance imaging (WB-MRI) in that when both techniques were applied to the same patients, double-positive results were recorded in approximately 30% of the cases, but in the majority of them, a higher number of lesions were revealed with PET/CT than with MRI. Double-negative results, on the other hand, were found in about 22% of the patients. Because PET/CT is able to identify tumor foci throughout the body, it can be usefully applied to the study of solitary bone plasmacytoma and extra-medullary plasmacytoma: In both conditions, the detection of additional, previously overlooked sites of skeletal involvement would falsify the diagnosis of single-district disease, upstage the tumor, and therefore require a different therapeutic approach. In addition, although PET/CT is poorly sensitive to diffuse bone marrow infiltration, it can anticipate a site of impending fracture throughout the body and can discriminate old from new pathologic fractures. MRI should, however, be preferred when vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. PET/CT is a sensitive and reliable procedure to evaluate the response to chemotherapy and/or radiotherapy, which is shown by a remarkable reduction and sometimes total disappearance of FDG accumulation in the involved bony structures, although these structures remain morphologically abnormal. Conversely, an increased focal uptake of FDG in apparent remission patients often precedes clinically overt relapse. PET/CT should be preferred to other imaging techniques to assess the remission status after autologous stem cell transplantation. In patients with primary and remission-induced non-secretory MM, the use of PET/CT may help to early detect single or multiple districts of focal non-secretory relapse. Osteonecrosis of the jaw, its location, and extent in MM patients receiving bis-phosphonates are better defined by both PET/CT and contrast-enhanced MRI compared with dental panoramic views derived from cone beam CT imaging. Little is known as to the possible role of PET/CT in the assessment of disease extension, tumor load, and response to therapy in patients with Waldenstrm's macroglobulinemia (WM). In a study conducted on 35 WM patients, comparative PET/CT before and after therapy was able to detect positive findings in 83% of the patients, in contrast with the previous results achieved with conventional imaging that reported visceral involvement in much lower percentages. Similarly scanty are the data on the use of PET/CT in localized and systemic amyloidosis, given the small number of patients studied so far. A retrospective study has shown that, at variance from (123)Iodine-serum amyloid P component ((123)I-SAP) scintigraphy, which was found to be positive in about one-third of the patients with localized amyloidosis, an increased FDG uptake was detected at the amyloid s

  12. 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 ...

  13. Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

    PubMed Central

    Konishi, Jun; Asami, Takeshi; Hayano, Fumi; Yoshimi, Asuka; Hayasaka, Shunsuke; Fukushima, Hiroshi; Whitford, Thomas J.; Inoue, Tomio; Hirayasu, Yoshio

    2014-01-01

    Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD. PMID:24663245

  14. Compulsive disorders.

    PubMed

    Kuzma, John M; Black, Donald W

    2004-02-01

    Compulsive disorders include a diverse group of conditions characterized by excessive thoughts or preoccupations combined with poorly controlled behaviors. They include trichotillomania, kleptomania, pathologic gambling, compulsive buying disorder, compulsive sexual behavior, and compulsive computer use. Some investigators have suggested that these conditions constitute a spectrum of disorders linked to obsessive-compulsive disorder. Others have questioned the validity of this conceptualization, and have debated the relationship between these disorders. Nevertheless, much has been learned about compulsive disorders, and there have been some successes with psychotherapeutic and psychopharmacologic treatments. Recent therapy-based interventions have moved from psychodynamic treatments toward cognitive-behavioral modalities. Serotonin reuptake inhibitors remain the best-studied pharmacologic treatment, but researchers have also explored other antidepressants, opioid agonists, mood stabilizers, and atypical antipsychotics. PMID:14738707

  15. 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…

  16. 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

  17. 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

  18. 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

  19. 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

  20. Structural characterization and in vitro antioxidant activity of kojic dipalmitate loaded w/o/w multiple emulsions intended for skin disorders.

    PubMed

    Gonalez, Mara Lima; Marcussi, Diana Gleide; Calixto, Giovana Maria Fioramonti; Corra, 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

  1. The intrinsically disordered amino-terminal region of human RecQL4: multiple DNA-binding domains confer annealing, strand exchange and G4 DNA binding.

    PubMed

    Keller, Heidi; Kiosze, Kristin; Sachsenweger, Juliane; Haumann, Sebastian; Ohlenschlger, Oliver; Nuutinen, Tarmo; Syvoja, Juhani E; Grlach, Matthias; Grosse, Frank; Pospiech, Helmut

    2014-11-10

    Human RecQL4 belongs to the ubiquitous RecQ helicase family. Its N-terminal region represents the only homologue of the essential DNA replication initiation factor Sld2 of Saccharomyces cerevisiae, and also participates in the vertebrate initiation of DNA replication. Here, we utilized a random screen to identify N-terminal fragments of human RecQL4 that could be stably expressed in and purified from Escherichia coli. Biophysical characterization of these fragments revealed that the Sld2 homologous RecQL4 N-terminal domain carries large intrinsically disordered regions. The N-terminal fragments were sufficient for the strong annealing activity of RecQL4. Moreover, this activity appeared to be the basis for an ATP-independent strand exchange activity. Both activities relied on multiple DNA-binding sites with affinities to single-stranded, double-stranded and Y-structured DNA. Finally, we found a remarkable affinity of the N-terminus for guanine quadruplex (G4) DNA, exceeding the affinities for other DNA structures by at least 60-fold. Together, these findings suggest that the DNA interactions mediated by the N-terminal region of human RecQL4 represent a central function at the replication fork. The presented data may also provide a mechanistic explanation for the role of elements with a G4-forming propensity identified in the vicinity of vertebrate origins of DNA replication. PMID:25336622

  2. The intrinsically disordered amino-terminal region of human RecQL4: multiple DNA-binding domains confer annealing, strand exchange and G4 DNA binding

    PubMed Central

    Keller, Heidi; Kiosze, Kristin; Sachsenweger, Juliane; Haumann, Sebastian; Ohlenschlger, Oliver; Nuutinen, Tarmo; Syvoja, Juhani E.; Grlach, Matthias; Grosse, Frank; Pospiech, Helmut

    2014-01-01

    Human RecQL4 belongs to the ubiquitous RecQ helicase family. Its N-terminal region represents the only homologue of the essential DNA replication initiation factor Sld2 of Saccharomyces cerevisiae, and also participates in the vertebrate initiation of DNA replication. Here, we utilized a random screen to identify N-terminal fragments of human RecQL4 that could be stably expressed in and purified from Escherichia coli. Biophysical characterization of these fragments revealed that the Sld2 homologous RecQL4 N-terminal domain carries large intrinsically disordered regions. The N-terminal fragments were sufficient for the strong annealing activity of RecQL4. Moreover, this activity appeared to be the basis for an ATP-independent strand exchange activity. Both activities relied on multiple DNA-binding sites with affinities to single-stranded, double-stranded and Y-structured DNA. Finally, we found a remarkable affinity of the N-terminus for guanine quadruplex (G4) DNA, exceeding the affinities for other DNA structures by at least 60-fold. Together, these findings suggest that the DNA interactions mediated by the N-terminal region of human RecQL4 represent a central function at the replication fork. The presented data may also provide a mechanistic explanation for the role of elements with a G4-forming propensity identified in the vicinity of vertebrate origins of DNA replication. PMID:25336622

  3. Gaze disorders: A clinical approach.

    PubMed

    Vinny, Pulikottil Wilson; Lal, Vivek

    2016-01-01

    A single clear binocular vision is made possible by the nature through the oculomotor system along with inputs from the cortical areas as well their descending pathways to the brainstem. Six systems of supranuclear control mechanisms play a crucial role in this regard. These are the saccadic system, the smooth pursuit system, the vestibular system, the optokinetic system, the fixation system, and the vergence system. In gaze disorders, lesions at different levels of the brain spare some of the eye movement systems while affecting others. The resulting pattern of eye movements helps clinicians to localize lesions accurately in the central nervous system. Common lesions causing gaze palsies include cerebral infarcts, demyelinating lesions, multiple sclerosis, tumors, Wernicke's encephalopathy, metabolic disorders, and neurodegenerative disorders such as progressive supranuclear palsy. Evaluation of the different gaze disorders is a bane of most budding neurologists and neurosurgeons. However, a simple and systematic clinical approach to this problem can make their early diagnosis rather easy. PMID:26755003

  4. 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…

  5. 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 ...

  6. Cerebellar Disorders

    MedlinePLUS

    ... hit a tennis ball you are activating the cerebellum. The cerebellum is the area of the brain that controls coordination and balance. Problems with the cerebellum include Cancer Genetic disorders Ataxias - failure of muscle ...

  7. 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)

  8. 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

  9. Circadian clock and stress interactions in the molecular biology of psychiatric disorders.

    PubMed

    Landgraf, Dominic; McCarthy, Michael J; Welsh, David K

    2014-10-01

    Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders. PMID:25135782

  10. Amyloidosis with Multiple Myeloma Presenting with Acromegalic Features.

    PubMed

    Bhatty, Shaheen A; Siddiqui, Abdul Samad; Talib, Abu; Mahmood, Khalid; Naqvi, Iftekhar; Khan, Anam Naveed; Nizam, Mehreen; Saiyed, Ali

    2015-10-01

    Amyloidosis and multiple myeloma are included in the same spectrum of clonal plasma cell disorders. Amyloidosis can present with localized deposits or manifest as systemic disease involving multiple organs. Here we are reporting a case of an elderly female, having amyloidosis leading to facial disfigurement and neuropathy for many years and then presenting with concomitant multiple myeloma as an incidental diagnosis with no typical symptoms related to it at all. PMID:26522192

  11. 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

  12. 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

  13. A de novo 1.58?Mb deletion, including MAP2K6 and mapping 1.28?Mb upstream to SOX9, identified in a patient with Pierre Robin sequence and osteopenia with multiple fractures.

    PubMed

    Smyk, Marta; Roeder, Elizabeth; Cheung, Sau Wai; Szafranski, Przemyslaw; Stankiewicz, Pawe?

    2015-08-01

    Defects of long-range regulatory elements of dosage-sensitive genes represent an under-recognized mechanism underlying genetic diseases. Haploinsufficiency of SOX9, the gene essential for development of testes and differentiation of chondrocytes, results in campomelic dysplasia, a skeletal malformation syndrome often associated with sex reversal. Chromosomal rearrangements with breakpoints mapping up to 1.6?Mb up- and downstream to SOX9, and disrupting its distant cis-regulatory elements, have been described in patients with milder forms of campomelic dysplasia, Pierre Robin sequence, and sex reversal. We present an ?1.58?Mb deletion mapping ?1.28?Mb upstream to SOX9 that encompasses its putative long-range cis-regulatory element(s) and MAP2K6 in a patient with Pierre Robin sequence and osteopenia with multiple fractures. Low bone mass panel testing using massively parallel sequencing of 23 nuclear genes, including COL1A1 and COL1A2 was negative. Based on the previous mouse model of Map2k6, suggesting that Sox9 is likely a downstream target of the p38 MAPK pathway, and our previous chromosome conformation capture-on-chip (4C) data showing potential interactions between SOX9 promoter and MAP2K6, we hypothesize that deletion of MAP2K6 might have affected SOX9 expression and contributed to our patient's phenotype. PMID:26059046

  14. 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 , 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 .

  15. 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

  16. Hereditary multiple exostoses and enchondromatosis.

    PubMed

    Pannier, Stphanie; Legeai-Mallet, Laurence

    2008-03-01

    Hereditary multiple exostoses (HME) is an autosomal-dominant disorder characterized by the development of benign tumours, multiple osteochondromas (exostoses), growing outward from the metaphyses of long bones. Birth prevalence is estimated to be one in 50,000, and the severity of the disease is variable. Osteochondromas may cause complications including pain, deformities and shortening of the long bones, restricted motion of joints, nerve or blood vessel compression, and malignant transformation (5% of cases) in adulthood. HME is a genetically heterogeneous disorder and is associated with mutations in EXT1 or EXT2 genes, which are both tumour suppressor genes. EXT genes encode glycosyltransferases, termed 'exostosins', which are involved in the biosynthesis of heparan sulphate. Enchondromatosis (or Ollier disease) is characterized by the presence of intra-osseous benign cartilaginous tumours. The estimated prevalence of the disease is one in 100,000. An asymmetrical distribution of cartilage lesions is observed in the disease. The number, size and location of the enchondromas can be extremely variable between patients. Clinical problems caused by enchondromas include skeletal deformities, limb length discrepancy, pain and the potential risk for malignant change to chondrosarcoma (20-50% of cases). The condition in which multiple enchondromas is associated with haemangiomas is known as 'Maffucci syndrome'. Ollier disease and Maffucci syndrome are not usually inherited disorders. PMID:18328980

  17. Multiple myeloma

    MedlinePLUS

    Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... National Cancer Institute: PDQ Plasma Cell Neoplasms (Including ... Institute. Date last modified: June 24, 2014. Available at: www. ...

  18. 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

  19. 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

    Glinskii, Anna B; Ma, Shuang; Ma, Jun; Grant, Denise; Lim, Chang-Uk; Guest, Ian; Sell, Stewart; Buttyan, Ralph; Glinsky, Gennadi V

    2011-10-15

    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) invivo 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

  20. 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 ...

  1. Multiple sclerosis (image)

    MedlinePLUS

    Multiple sclerosis is a central nervous system disorder marked by decreased nerve function with initial inflammation of the protective myelin nerve covering and eventual scarring. Symptoms and severity of ...

  2. 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

  3. Development of Computer Aids for Tape-Control of Photocomposing Machines. Final Report, Section B. A System for Computer-Processed Tape Composition to Include the Setting of Multiple Line Equations.

    ERIC Educational Resources Information Center

    American Mathematical Society, Providence, RI.

    This document is the second of three sections of a final report on computer-controlled photocomposition of the periodical Mathematics Reviews. In studying the uses of computer-processed tape for composition, it became evident that economic feasibility is dependent, to a great extent, on multiple use of the input data. Therefore the design of a

  4. 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 ...

  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. 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

  7. 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

  8. 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

  9. 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

  10. 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…

  11. Speech and Communication Disorders

    MedlinePLUS

    ... or understand speech. Causes include Hearing disorders and deafness Voice problems, such as dysphonia or those caused ... language therapy can help. NIH: National Institute on Deafness and Other Communication Disorders

  12. Sleep disorders - overview

    MedlinePLUS

    Sleep disorders are problems with sleeping. These include: Trouble falling or staying asleep Falling asleep at the wrong ... low thyroid function Mononucleosis or other viral illnesses Narcolepsy and other sleep disorders Obesity, especially if it ...

  13. 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

  14. 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

  15. 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

  16. 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…

  17. 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

  18. 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.; DSilva, 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, 68 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

  19. 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

  20. 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

  1. 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 ...

  2. 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...

  3. [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

  4. 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

  5. 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

  6. 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, Alzheimers and Parkinsons 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

  7. 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

  8. 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

  9. 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

  10. What Is a Urea Cycle Disorder?

    MedlinePLUS

    ... like schizophrenia or bipolar disorder. What is the incidence of these disorders? Urea cycle disorders are included ... and death among newborns and infants. The estimated incidence of urea cycle disorders is 1 in 8500 ...

  11. Immunotherapy of multiple sclerosis.

    PubMed

    Meuth, Sven G; Bittner, Stefan; Wiendl, Heinz

    2009-06-01

    Multiple sclerosis (MS) is regarded as a prototypic inflammatory autoimmune central nervous system disorder causing neurological disability in young adults. Recommended basic immunomodulatory therapies of MS are currently interferon beta and glatiramer acetate. Both have proven to be clinically and paraclinically effective and clinical evidence suggests that treatment should be initiated as early as possible. However, despite the fact that therapeutic options for MS have significantly been widened over the past decade there is still tremendous activity in the search for new treatment options for MS. One important development in the field is reflected by the substantial number of promising results for oral therapies. Various phase III clinical trials are currently being initiated or are already underway evaluating the efficacy of a variety of orally administered agents, including cladribine, teriflunomide, laquinimod, fingolimod and fumaric acid. It is hoped that these oral therapies for MS further broaden our armament for MS therapy. PMID:25384864

  12. 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

  13. 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

  14. [Hyperkinetic disorder. A review.].

    PubMed

    Baldursson, G; Gumundsson, O O; Magnsson, P

    2000-06-01

    Attention-deficit/hyperactivity disorder or hyperkinetic disorder is a clinically defined syndrome characterised by age inappropriate deficits in sustained attention, impulsivity and overactivity. Despite extensive investigation, a specific neuroanatomical, physiological, biochemical, or psychological origin has not been identified. Diagnosis is based on detailed medical and developmental history, symptom rating scales, psychological assessment and medical evaluation. Increases in diagnosis and treatment of the disorder have elicited public and professional concern. The main focus in this article is on this disorder in children and adolescents and includes practical information on assessment and treatment. Other disorders, which may be either comorbid with or mistaken for hyperkinetic disorder, are reviewed in less detail. PMID:17018932

  15. 34 CFR 303.18 - Include; including.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Include; including. 303.18 Section 303.18 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  16. 34 CFR 303.18 - Include; including.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Include; including. 303.18 Section 303.18 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  17. 34 CFR 303.15 - Include; including.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Include; including. 303.15 Section 303.15 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  18. 34 CFR 303.15 - Include; including.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Include; including. 303.15 Section 303.15 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  19. 34 CFR 303.18 - Include; including.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Include; including. 303.18 Section 303.18 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  20. [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

  1. 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

  2. Binge Eating Disorder

    MedlinePLUS

    ... Can I Help a Friend Who Cuts? Binge Eating Disorder KidsHealth > For Teens > Binge Eating Disorder Print A A A Text Size What's in ... takes a combination of things to develop an eating disorder including a person's genes, emotions, and behaviors (such ...

  3. 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

  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. 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

  6. 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

  7. [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

  8. 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

  9. 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. ...

  10. Balance Disorders

    MedlinePLUS

    ... Involved You are here Home » Health Info » Balance Balance Disorders On this page: What is a balance ... additional information about balance disorders? What is a balance disorder? A balance disorder is a condition that ...

  11. Bipolar Disorder

    MedlinePLUS

    ... disorder can sometimes be mistaken for illnesses like schizophrenia and posttraumatic stress disorder, attention deficit hyperactivity disorder (ADHD), and other depressive disorders. That's why a complete, detailed history is so important. previous continue How Do Doctors ...

  12. 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 clinicalimmunological 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 opsoclonusmyoclonusataxia (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

  13. Flecked retina disorders.

    PubMed

    De Laey, J J

    1993-01-01

    This survey describes a number of fundus conditions characterized by flecks in the retina. The term "flecked retina" was introduced by Krill and Klien to describe fundus conditions characterized by multiple yellowish-white lesions of various size and configuration, without vascular or optic nerve abnormalities. Originally this group consisted of four diseases: fundus albipunctatus, fundus flavimaculatus, familial drusen and fleck retina of Kandori. However, far more diseases correspond to the rather vague definition, including primary hereditary ocular diseases such as retinitis punctata albescens or Bietti's crystalline dystrophy, neuro-ophthalmologic syndromes such as Kjellin's syndrome, secundary retinal flecks due to metabolic disorders such as Alport's syndrome, cystinosis, oxalosis or membrano-proliferative glomerulonephritis, iatrogenic retinopathy due to Tamoxifen or Canthaxanthin and carential diseases such as vitamin A deficiency. The precise diagnosis is not only based on the close observation of the fundus, but demands often extensive psychophysical examination of the patient and sometimes of his family. PMID:7952338

  14. Disordered graphene Josephson junctions

    NASA Astrophysics Data System (ADS)

    Muoz, W. A.; Covaci, L.; Peeters, F. M.

    2015-02-01

    A tight-binding approach based on the Chebyshev-Bogoliubov-de Gennes method is used to describe disordered single-layer graphene Josephson junctions. Scattering by vacancies, ripples, or charged impurities is included. We compute the Josephson current and investigate the nature of multiple Andreev reflections, which induce bound states appearing as peaks in the density of states for energies below the superconducting gap. In the presence of single-atom vacancies, we observe a strong suppression of the supercurrent, which is a consequence of strong intervalley scattering. Although lattice deformations should not induce intervalley scattering, we find that the supercurrent is still suppressed, which is due to the presence of pseudomagnetic barriers. For charged impurities, we consider two cases depending on whether the average doping is zero, i.e., existence of electron-hole puddles, or finite. In both cases, short-range impurities strongly affect the supercurrent, similar to the vacancies scenario.

  15. Parathyroid disorders.

    PubMed

    Michels, Thomas C; Kelly, Kevin M

    2013-08-15

    Disorders of the parathyroid glands most commonly present with abnormalities of serum calcium. Patients with primary hyperparathyroidism, the most common cause of hypercalcemia in outpatients, are often asymptomatic or may have bone disease, nephrolithiasis, or neuromuscular symptoms. Patients with chronic kidney disease may develop secondary hyperparathyroidism with resultant chronic kidney disease-mineral and bone disorder. Hypoparathyroidism most often occurs after neck surgery; it can also be caused by autoimmune destruction of the glands and other less common problems. Evaluation of patients with abnormal serum calcium levels includes a history and physical examination; repeat measurement of serum calcium level; and measurement of creatinine, magnesium, vitamin D, and parathyroid hormone levels. The treatment for symptomatic primary hyperparathyroidism is parathyroidectomy. Management of asymptomatic primary hyperparathyroidism includes monitoring symptoms; serum calcium and creatinine levels; and bone mineral density. Patients with hypoparathyroidism require close monitoring and vitamin D (e.g., calcitriol) replacement. PMID:23944728

  16. 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

  17. Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder

    PubMed Central

    Hornig, Mady; Briese, Thomas; Licinio, Julio; Khabbaz, Rima F.; Altshuler, Lori L.; Potkin, Steven G.; Schwemmle, Martin; Siemetzki, Ulrike; Mintz, Jim; Honkavuori, Kirsi; Kraemer, Helena C.; Egan, Michael F.; Whybrow, Peter C.; Bunney, William E.; Lipkin, W. Ian

    2013-01-01

    In 1983, reports of antibodies in subjects with major depressive disorder to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to the molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV).1,2 This advance enabled the development of new diagnostic assays including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990 more than 80 studies have reported an association between BDV and a wide range of human illnesses that include major depressive disorder, bipolar disorder, schizophrenia, anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme.3,4 However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serologic and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially-collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 schizophrenia/control pairs, 66 bipolar disorder/control pairs, and 80 major depressive disorder/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders. PMID:22290118

  18. [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

  19. 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

  20. 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 Jos; Mateos, Maria Victoria; Martnez-Lpez, Joaquin; Grande, Carlos; de la Rubia, Javier; Rosiol, Laura; Sureda, Anna; Garca-Laraa, Jos; Daz-Mediavilla, Joaqun; Hernndez-Garca, Miguel T.; Carrera, Dolores; Besalduch, Joan; de Arriba, Felipe; Oriol, Albert; Escoda, Lourdes; Garca-Frade, Javier; Rivas-Gonzlez, Concepcin; Alegre, Adran; Blad, Joan; San Miguel, Jess 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

  1. 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

  2. [Skin-picking disorder].

    PubMed

    Niemeier, V; Peters, E; Gieler, U

    2015-10-01

    The disorder is characterized by compulsive repetitive skin-picking (SP), resulting in skin lesions. The patients must have undertaken several attempts to reduce or stop SP. The disorder must have led to clinically significant limitations in social, professional, or other important areas of life. The symptoms cannot be better explained by another emotional disorder or any other dermatological disease. In the new DSM-V, skin-picking disorder has been included in the diagnostic system as an independent disorder and describes the self-injury of the skin by picking or scratching with an underlying emotional disorder. SP is classified among the impulse-control disorders and is, thus, differentiated from compulsive disorders as such. There are often emotional comorbidities. In cases of pronounced psychosocial limitation, interdisciplinary cooperation with a psychotherapist and/or psychiatrist is indicated. PMID:26391325

  3. 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

  4. Response inhibition in motor conversion disorder.

    PubMed

    Voon, Valerie; Ekanayake, Vindhya; Wiggs, Edythe; Kranick, Sarah; Ameli, Rezvan; Harrison, Neil A; Hallett, Mark

    2013-05-01

    Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P?multiple comparisons and after controlling for attention, sustained attention, depression, and anxiety. There were no significant differences in other cognitive measures. We highlight a specific deficit in motor response inhibition that may play a role in impaired inhibition of unwanted movement such as the excessive and aberrant movements seen in motor conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups. 2013 Movement Disorder Society. PMID:23554084

  5. Testing multiple levels of influence in the intergenerational transmission of alcohol disorders from a developmental perspective: The example of alcohol use promoting peers and ?-opioid receptor M1 variation

    PubMed Central

    CHASSIN, LAURIE; LEE, MATTHEW R.; CHO, YOUNG IL; WANG, FRANCES L.; AGRAWAL, ARPANA; SHER, KENNETH J.; LYNSKEY, MICHAEL T.

    2013-01-01

    This study examined the interplay between the influence of peers who promote alcohol use and ?-opioid receptor M1 (OPRM1) genetic variation in the intergenerational transmission of alcohol use disorder (AUD) symptoms while separating the traitlike components of AUD symptoms from their age-specific manifestations at three ages from emerging adulthood (1723 years) to adulthood (2940 years). The results for males were consistent with genetically influenced peer selection mechanisms as mediators of parent alcoholism effects. Male children of alcoholics were less likely to be carriers of the G allele in single nucleotide polymorphism A118G (rs1799971), and those who were homozygous for the A allele were more likely to affiliate with alcohol use promoting peers who increased the risk for AUD symptoms at all ages. There was evidence for women of an interaction between OPRM1 variation and peer affiliations but only at the earliest age band. Peer influences had stronger effects among women who were G-carriers. These results illustrate the complex ways in which the interplay between influences at multiple levels of analysis can underlie the intergenerational transmission of alcohol disorders as well as the importance of considering age and gender differences in these pathways. PMID:22781865

  6. Relationship of mood disorders to violence.

    PubMed

    Collins, J J; Bailey, S L

    1990-01-01

    Past research on the relationship between mood disorders and violent behavior has been inconsistent, sometimes finding a relationship between the two and sometimes finding no relationship. Any relationship is arguably complex, and this area of research would benefit from attempts to clarify the relationship. This paper addresses the issue of complexity by examining the relationship between specific mood disorder categories and symptoms and six conceptually different indicators of violent behavior. Relationships are analyzed in logistic regression models where demographic and problem drinking variables are included to control variation that may be accounted for by these factors. The study uses a sample of 1140 recently incarcerated male felons. Psychiatric disorder diagnoses are based on the Diagnostic Interview Schedule. There is evidence of a direct relationship between a lifetime diagnosis of dysthymia and an arrest or incarceration history for robbery as well as with multiple incidents of fighting since age 18. Recurrent depression was significantly associated with a robbery incarceration history. Depression symptoms (regardless of whether a disorder diagnosis was made) were associated with multiple incidents of fighting since age 18. Manic symptoms were inconsistently associated with "expressive" violence and a number of mood disorder/violence models showed no significant relationship between the two. PMID:2295889

  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. 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…

  9. 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

  10. 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

  11. Protein intrinsic disorder in plants.

    PubMed

    Pazos, Florencio; Pietrosemoli, Natalia; Garca-Martn, Juan A; Solano, Roberto

    2013-01-01

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks. PMID:24062761

  12. 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

  13. IBS and Non-GI Functional Disorders

    MedlinePLUS

    ... fibromyalgia, IBS, TMJ, interstitial cystitis, chronic pelvic pain, tension headache, multiple chemical sensitivities and other functional disorders ... Fibromyalgia (FMS) Chronic fatigue syndrome (CFS) Migraine and tension headaches Temperomandibular joint disorder (TMJ) Post-traumatic stress ...

  14. 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

  15. Growth inhibition of pancreatic cancer cells by histone deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NFkB, and mTOR signaling in vitro and in vivo.

    PubMed

    Chien, Wenwen; Lee, Dhong Hyun; Zheng, Yun; Wuensche, Peer; Alvarez, Rosie; Wen, Ding Ling; Aribi, Ahmed M; Thean, Su Ming; Doan, Ngan B; Said, Jonathan W; Koeffler, H Phillip

    2014-09-01

    Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403, Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1? at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P?=?0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. PMID:23475695

  16. Functional neurological disorders: imaging.

    PubMed

    Voon, V

    2014-10-01

    Functional neurological disorders, also known as conversion disorder, are unexplained neurological symptoms. These symptoms are common and can be associated with significant consequences. This review covers the neuroimaging literature focusing on functional motor symptoms including motor functioning and upstream influences including self-monitoring and internal representations, voluntariness and arousal and trauma. PMID:25306074

  17. 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

  18. Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways.

    PubMed

    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

  19. 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

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. Anxiety Disorders

    MedlinePLUS

    ... of Anxiety Disorders Risk Factors and Diagnosis Medications Psychotherapy Research Frequently Asked Questions Learn More Anxiety Disorders ... disorders are treated with medication, specific types of psychotherapy, or both. Treatment choices depend on the type ...

  6. Diagnosis and treatment of cutaneous paraneoplastic disorders.

    PubMed

    Abreu Velez, Ana Maria; Howard, Michael S

    2010-01-01

    The skin plays a critical role in the detection of internal malignances. Cutaneous signs of these disorders afford clinicians opportunities for early diagnosis and treatment. We aim to succinctly review the recognition, diagnosis, and treatment of selected cutaneous paraneoplastic diseases. Skin disorders that may be associated with paraneoplastic syndromes include: cutaneous metastases, tripe palms, Sweet's syndrome, glucagonoma, Paget's disease and extramammary Paget's disease, acanthosis nigricans, Birt-Hogg-Dube syndrome, basal cell nevus syndrome, Bazex syndrome (acrokeratosis paraneoplastica), carcinoid syndrome, Cowden's disease(multiple hamartoma syndrome), dermatomyositis, erythema gyratum repens, ichthyosis aquisita, von Recklinghausen's disease, pityriasis rotunda, pyoderma gangrenosum, Quincke's edema (angioedema and paraneoplastic uricaria), paraneoplastic pemphigus, Degos' disease, superior vena cava syndrome, Werner's syndrome, diffuse normolipemic plane xanthomas, and yellow nail syndrome. Treatment for these disorders depends on the nature and anatomic distribution of the primary neoplastic process. PMID:21054710

  7. 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

  8. [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

  9. 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

  10. Multiple Myeloma and Diabetes

    PubMed Central

    Issa, Zeinab A.; Zantout, Mira S.; Azar, Sami T.

    2011-01-01

    Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers. It is characterized by accumulation of clonal plasma cells, predominantly in the bone marrow. The prevalence of type 2 diabetes is increasing; therefore, it is expected that there will be an increase in the diagnosis of multiple myeloma with concomitant diabetes mellitus. The treatment of multiple myeloma and diabetes mellitus is multifaceted. The coexistence of the two conditions in a patient forms a major challenge for physicians. PMID:22363889

  11. Multiple myeloma and diabetes.

    PubMed

    Issa, Zeinab A; Zantout, Mira S; Azar, Sami T

    2011-01-01

    Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers. It is characterized by accumulation of clonal plasma cells, predominantly in the bone marrow. The prevalence of type 2 diabetes is increasing; therefore, it is expected that there will be an increase in the diagnosis of multiple myeloma with concomitant diabetes mellitus. The treatment of multiple myeloma and diabetes mellitus is multifaceted. The coexistence of the two conditions in a patient forms a major challenge for physicians. PMID:22363889

  12. Differences in compassion fatigue, symptoms of posttraumatic stress disorder and relationship satisfaction, including sexual desire and functioning, between male and female detectives who investigate sexual offenses against children: a pilot study.

    PubMed

    Lane, Eric J; Lating, Jeffrey M; Lowry, Jenny L; Martino, Traci P

    2010-01-01

    Law enforcement detectives who work with traumatized individuals, especially children who were victims of sexual abuse or assault, are likely to experience job-related emotional distress. The purpose of this study was to examine the relations among compassion fatigue, probable PTSD symptoms, and personal relationship satisfaction, including communication and sexual satisfaction, in a sample of 47 male and female detectives. Responses to the administered questionnaires indicated a relation between compassion fatigue symptoms and probable PTSD symptoms. There also were compelling gender differences. For example, for male detectives, open communication with their spouse or significant other was negatively correlated with burnout, indicating the more open the communication, the lower the reported burnout. However for female detectives there was a negative correlation between open communication with spouse or significant other and compassion satisfaction, suggesting that more open communication was related to lower levels of satisfaction with their ability to be a professional caregiver Furthermore, although stepwise regression analysis indicated that years of service as a detective is independently associated with sexual desire, female detectives evidenced less sexual desire and more difficulty with sexual functioning than did male detectives. Implications of these preliminary findings are discussed and limitations addressed. PMID:21870384

  13. Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments.

    PubMed

    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

  14. 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

  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. 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 ...

  17. Recent developments in multiple sclerosis therapeutics.

    PubMed

    Spain, Rebecca I; Cameron, Michelle H; Bourdette, Dennis

    2009-01-01

    Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-beta, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought. PMID:19968863

  18. Borderline Personality Disorder

    MedlinePLUS

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  19. Panic Disorder among Adults

    MedlinePLUS

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  20. Bipolar Disorder Among Adults

    MedlinePLUS

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  1. Any Personality Disorder

    MedlinePLUS

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  2. Antisocial Personality Disorder

    MedlinePLUS

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  3. Oppositional defiant and conduct disorder behaviors in boys with autism spectrum disorder with and without attention-deficit hyperactivity disorder versus several comparison samples.

    PubMed

    Guttmann-Steinmetz, Sarit; Gadow, Kenneth D; Devincent, Carla J

    2009-07-01

    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) community controls. Parents rated children in the three ADHD groups comparably for each symptom of oppositional defiant disorder (ODD) and conduct disorder. Teacher ratings indicated that the ASD + ADHD group evidenced a unique pattern of ODD symptom severity, differentiating them from the other ADHD groups, and from the ASD Only group. The clinical features of ASD appear to influence co-morbid, DSM-IV-defined ODD, with implications for nosology. PMID:19288296

  4. Sleep disorders in the elderly

    MedlinePLUS

    Sleep disorders in the elderly involve any disrupted sleep pattern. This can include problems falling or staying asleep, ... for medical causes and determine which type of sleep disorder is causing the problem.

  5. Pleurisy and Other Pleural Disorders

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Are Pleurisy and Other Pleural Disorders? Pleurisy (PLUR-ih-se) is a condition in ... conditions can cause pleurisy, including viral infections. Other Pleural Disorders Pneumothorax Air or gas can build up in ...

  6. Is multiple sclerosis a mitochondrial disease?

    PubMed Central

    Mao, Peizhong; Reddy, P. Hemachandra

    2009-01-01

    Multiple sclerosis (MS) is a relatively common and etiologically unknown disease with no cure treatment. It is the leading cause of neurological disability in young adults, affecting over two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder of the central white matter in which ensuing demyelination results in physical disability. Recently, MS has become increasingly viewed as a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system lead to permanent neurological and clinical disability. In this article, we discuss the latest developments on MS research, including etiology, pathology, genetic association, EAE animal models, mechanisms of neuronal injury and axonal transport and therapeutics. In this article, we also focus on the mechanisms of mitochondrial dysfunction that are involved in MS, including mitochondrial DNA defects, and mitochondrial structural/functional changes. PMID:19607913

  7. Pump apparatus including deconsolidator

    SciTech Connect

    Sonwane, Chandrashekhar; Saunders, Timothy; Fitzsimmons, Mark Andrew

    2014-10-07

    A pump apparatus includes a particulate pump that defines a passage that extends from an inlet to an outlet. A duct is in flow communication with the outlet. The duct includes a deconsolidator configured to fragment particle agglomerates received from the passage.

  8. Multiple sclerosis.

    PubMed

    Files, Daniel Kane; Jausurawong, Tani; Katrajian, Ruba; Danoff, Robert

    2015-06-01

    Multiple sclerosis (MS) is a chronic, debilitating disease that can have devastating effects. Presentation varies widely in symptoms, pace, and progression. In addition to a thorough history and physical examination, diagnostic tools required to diagnose MS and exclude other diagnoses include MRI, evoked potential testing, and cerebrospinal fluid analysis. Although the disease is not curable presently, quality of life can be improved by minimizing the frequency and severity of disease burden. Disease modification, symptom management, preservation of function, and treatment of psychosocial issues are paramount to enhance the quality of life for the patient affected with MS. PMID:25979578

  9. Nuclear gene causing multiple mtDNA deletions in autosomal dominant ophthalmoplegia maps to a distinct chromosomal region - involvement of both nuclear and mitochondrial DNA in a single disorder

    SciTech Connect

    Suomalainen, A.; Kaukonen, J.; Timonen, R.

    1994-09-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by muscle weakness, most prominent in ocular muscles. The symptoms are caused by accumulation of multiple large deletions of mitochondrial DNA (mtDNA) in the tissues of the patient, especially in those tissues that are most dependent on oxidative metabolism: brain, skeletal muscle and heart. However, the disorder shows autosomal dominant way of transmission, suggesting a primary defect in a nuclear encoded protein, which only secondarily results in mtDNA deletions. The candidate genes could be those actively participating in the mtDNA replication, or those associated with oxidative metabolism and e.g. via overproduction or inefficient elimination of fire oxygen radicals fragmenting mtDNA. We applied random mapping approach to localize the autosomal adPEO gene locus in a large Finnish family. The affected subjects were identified by detection of multiple mtDNA deletions in the Southern blot analysis of DNA extracted from the muscle biopsy specimens. All the family members underwent muscle biopsy. After analysis of 248 highly polymorphic dinucleotide repeat markets dispersed throughout the genome we were able to assign the adPEO gene locus to a distinct chromosomal region with the maximum pairwise lod score of 4.52, recombination fraction 0.0. This is the first evidence that a mutation in a nuclear gene may interfere mtDNA. The pathogenesis of adPEO involves both the genomes: the primary nuclear gene defect leads to secondary mtDNA mutations that cause the symptoms of the patients.

  10. Myeloma (multiple)

    PubMed Central

    2006-01-01

    Introduction Multiple myeloma is the most common primary cancer of the bones in adults, representing about 1% of all cancers diagnosed in the US in 2004, and 14% of all haematological malignancies. In the UK, multiple myeloma accounts for 1% of all new cases of cancer diagnosed each year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment in people with asymptomatic early stage multiple myeloma (stage I)? What are the effects of first-line treatments in people with advanced stage multiple myeloma (stages II and III)? What are the effect of salvage treatments, or supportive therapy, in people with advanced stage multiple myeloma (stages II and III)? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2004 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogenic transplant (non-myeloablative), autologous stem cell transplant (early or late transplantation, double or single, purging of), bisphosphonates, bone marrow stem cells, bortezomib, chemotherapy (combination, conventional dose, intermediate dose plus stem cell rescue, high-dose plus stem cell rescue), combination chemotherapy plus corticosteroids, deferred treatment (in stage I disease), early chemotherapy plus corticosteroids (in stage I disease), epoetin alpha, first-line treatments, infection prophylaxis, interferon, maintenance therapy (in advanced multiple myeloma), melphalan (normal dose, high dose before autologous stem cell transplantation, plus total body irradiation), optimum priming regimen, peripheral blood stem cells, plasmapheresis, salvage therapy regimens, single-agent chemotherapy (adding prednisolone), single-agent chemotherapy (bendamustine, melphalan, cyclophosphamide, lomustine, carmustine) with or without corticosteroid (prednisolone, dexamethasone), syngeneic transplantation, and thalidomide (and derivatives).

  11. BORDERLINE PERSONALITY DISORDER IN THE MEDICAL SETTING: Suggestive Behaviors, Syndromes, and Diagnoses

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as difficult patients rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder. PMID:26351624

  12. BORDERLINE PERSONALITY DISORDER IN THE MEDICAL SETTING: Suggestive Behaviors, Syndromes, and Diagnoses.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2015-01-01

    Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as "difficult patients" rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder. PMID:26351624

  13. A Review of Co-Morbid Disorders of Asperger's Disorder and the Transition to Adulthood

    ERIC Educational Resources Information Center

    Robinson, Stephanie; Curwen, Tracey; Ryan, Thomas G.

    2012-01-01

    This review includes empirical peer-reviewed articles which support the examination of Asperger's Disorder and co-morbid disorders, as well as an analysis of how adolescents with Asperger's Disorder transition to adulthood. Although the focus was on Asperger's Disorder, some studies include Autism Spectrum Disorder samples. It was found that

  14. Parenting Multiples

    MedlinePLUS

    ... Allergy Emergency Cerebral Palsy: Caring for Your Child Parenting Multiples KidsHealth > For Parents > Parenting Multiples Print A ... to take care of your babies. previous continue Parenting Issues With Multiples It can be impossible to ...

  15. Do Comorbid Anxiety Disorders Moderate the Effects of Psychotherapy for Bipolar Disorder? Results From STEP-BD

    PubMed Central

    Deckersbach, Thilo; Peters, Amy T.; Sylvia, Louisa; Urdahl, Anna; Magalhes, Pedro V.S.; Otto, Michael W.; Frank, Ellen; Miklowitz, David J.; Berk, Michael; Kinrys, Gustavo; Nierenberg, Andrew

    2013-01-01

    Objective At least 50% of individuals with bipolar disorder have a lifetime anxiety disorder. Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration, greater illness severity, and poorer treatment response. The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome. Method In the Systematic Treatment Enhancement Program randomized controlled trial of psychotherapy for bipolar depression, participants received up to 30 sessions of intensive psychotherapy (family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy) or collaborative care, a three-session comparison treatment, plus pharmacotherapy. Using the number needed to treat, we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year. Results A total of 269 patients (113 women) with a comorbid lifetime anxiety disorder (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in the analysis. Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care (66% compared with 49% recovered over 1 year; number needed to treat=5.88, small to medium effect). For patients without a lifetime anxiety disorder, there was no difference between rates of recovery in psychotherapy compared with collaborative care (64% compared with 62% recovered; number needed to treat=50, small effect). Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care (84% compared with 53% recovered; number needed to treat=3.22, medium to large effect), whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments (54% compared with 46% recovered; number needed to treat=12.5, small effect). Conclusions Depressed patients with bipolar disorder and comorbid anxiety may be in particular need of additional psychotherapy for treating acute depression. These results need to be replicated in studies that stratify bipolar patients to treatments based on their anxiety comorbidity status. PMID:24077657

  16. Preventing Eating Disorder Pathology: Common and Unique Features of Successful Eating Disorders Prevention Programs

    PubMed Central

    Ciao, Anna C.; Loth, Katie; Neumark-Sztainer, Dianne

    2014-01-01

    Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors’ descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research. PMID:24821099

  17. Preventing eating disorder pathology: common and unique features of successful eating disorders prevention programs.

    PubMed

    Ciao, Anna C; Loth, Katie; Neumark-Sztainer, Dianne

    2014-07-01

    Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors' descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research. PMID:24821099

  18. [The role of vitamin D in multiple sclerosis].

    PubMed

    Kfoczy?ska, Medea; Kucharska, Alicja; Si?ska, Beata

    2015-01-01

    Multiple sclerosis is a chronic, inflammatory, demyelinating disease which affects the central nervous system and is linked to autoimmune disorders. Although the precise causes of multiple sclerosis remain unknown, some evidence points towards hypovitaminosis D. Apart from the maintenance of calcium and phosphorus homeostasis, vitamin D also plays a major role in other aspects of human health. It is caused by the vitamin D receptor, which is present in many human organs and tissues. Vitamin D is an immunomodulating factor and accordingly has a potential to be effective in both preventing and treating autoimmune diseases, including multiple sclerosis. The aim of this review was to present up-to-date knowledge about vitamin D, especially its impact on risk of multiple sclerosis onset, relapses, and potential to modify the immune response. A further objective was to describe the role of vitamin D supplementation and its provision in the everyday diet for both prevention and treatment of multiple sclerosis. PMID:25897104

  19. Defining Oppositional Defiant Disorder

    ERIC Educational Resources Information Center

    Rowe, Richard; Maughan, Barbara; Costello, E. Jane; Angold, Adrian

    2005-01-01

    Background: ICD-10 and DSM-IV include similar criterial symptom lists for conduct disorder (CD) and oppositional defiant disorder (ODD), but while DSM-IV treats each list separately, ICD-10 considers them jointly. One consequence is that ICD-10 identifies a group of children with ODD subtype who do not receive a diagnosis under DSM-IV. Methods: We

  20. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement

    PubMed Central

    Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

    2014-01-01

    Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990

  1. Developmental Vulnerability of Synapses and Circuits Associated with Neuropsychiatric Disorders

    PubMed Central

    Penzes, Peter; Buonanno, Andres; Passafarro, Maria; Sala, Carlo; Sweet, Robert A.

    2013-01-01

    Psychiatric and neurodegenerative disorders, including intellectual disability (ID), autism spectrum disorders (ASD), schizophrenia (SZ), and Alzheimer's disease (AD), pose an immense burden to society. Symptoms of these disorders become manifest at different stages of life: early childhood, adolescence, and late adulthood, respectively. Progress has been made in recent years toward understanding the genetic substrates, cellular mechanisms, brain circuits, and endophenotypes of these disorders. Multiple lines of evidence implicate excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis in these disorders. Excitatory/inhibitory balance modulated largely by dopamine critically regulates cortical network function, neural network activity (i.e. gamma oscillations) and behaviors associated with psychiatric disorders. Understanding the molecular underpinnings of synaptic pathology and neuronal network activity may thus provide essential insight into the pathogenesis of these disorders and can reveal novel drug targets to treat them. Here we discuss recent genetic, neuropathological, and molecular studies that implicate alterations in excitatory and inhibitory synaptic circuits in the pathogenesis of psychiatric disorders across the lifespan. PMID:23574039

  2. Neural and psychological underpinnings of gambling disorder: A review.

    PubMed

    Grant, Jon E; Odlaug, Brian L; Chamberlain, Samuel R

    2016-02-01

    Gambling disorder affects 0.4 to 1.6% of adults worldwide, and is highly comorbid with other mental health disorders. This article provides a concise primer on the neural and psychological underpinnings of gambling disorder based on a selective review of the literature. Gambling disorder is associated with dysfunction across multiple cognitive domains which can be considered in terms of impulsivity and compulsivity. Neuroimaging data suggest structural and functional abnormalities of networks involved in reward processing and top-down control. Gambling disorder shows 50-60% heritability and it is likely that various neurochemical systems are implicated in the pathophysiology (including dopaminergic, glutamatergic, serotonergic, noradrenergic, and opioidergic). Elevated rates of certain personality traits (e.g. negative urgency, disinhibition), and personality disorders, are found. More research is required to evaluate whether cognitive dysfunction and personality aspects influence the longitudinal course and treatment outcome for gambling disorder. It is hoped that improved understanding of the biological and psychological components of gambling disorder, and their interactions, may lead to improved treatment approaches and raise the profile of this neglected condition. PMID:26497079

  3. The Cerebellum and Neurodevelopmental Disorders.

    PubMed

    Stoodley, Catherine J

    2016-02-01

    Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior. PMID:26298473

  4. Plasma cell disorders in HIV-infected patients: epidemiology and molecular mechanisms

    PubMed Central

    2013-01-01

    Highly active antiretroviral therapy (HAART) has significantly improved the outcome and survival of human immunodeficiency virus (HIV)-infected patients. Subsequently, long-term morbidities including cancer have become of major public health and clinical interest for this patient population. Plasma cell disorders occur at higher incidence in HIV-infected patients; however, the molecular mechanisms driving the plasma cell disease process and the optimal management for these patients remain to be defined. This article provides an up-to-date review of the characteristics and management of HIV-infected patients with plasma cell disorders. We first present 3 cases of plasma cell disorders in HIV-infected patients, ranging from polyclonal hypergammaglobulinemia to symptomatic multiple myeloma. We then discuss the epidemiology, clinical presentation, and management of each of these plasma cell disorders, with an emphasis on the molecular events underlying the progression of plasma cell diseases from monoclonal gammopathy to symptomatic multiple myeloma. We propose a three-step hypothesis for the development of multiple myeloma. Finally, we discuss the use of high dose chemotherapy and autologous hematopoietic stem cell transplantation in the treatment of HIV-infected patients with multiple myeloma. Our review includes the care of HIV-infected patients with plasma cell disorders in the current era of HAART and novel agents available for the treatment of multiple myeloma. PMID:24252328

  5. Mood and affect disorders.

    PubMed

    Tang, Michael H; Pinsky, Elizabeth G

    2015-02-01

    Depressive disorders are common in children and adolescents, with estimates for depressive episodes as high as 18.2% for girls and 7.7% for boys by age 17 years, and are a major cause of morbidity and even mortality. The primary care pediatrician should be able to (1) diagnose depressive disorders and use standardized instruments; (2) ask about suicide, self-harm, homicide, substance use, mania, and psychosis; (3) triage the severity of illness; (4) be aware of the differential diagnosis, including normal development, other depressive disorders, bipolar disorders, and comorbid disorders, such as anxiety and substance use; (5) refer to evidenced-based psychotherapies; (6) prescribe first-line medications; and (7) provide ongoing coordination in a medical home. Pediatric bipolar disorders and the new disruptive mood dysregulation disorder (DMDD) diagnoses are controversial but not uncommon, with prevalence estimates ranging from 0.8% to 4.3% in children at various ages. Although the pediatrician is not likely to be prescribing medications for children with bipolar disorder and DMDD diagnoses, all clinicians should be familiar with common neuroleptics and other mood stabilizers, including important potential adverse effects. Basic management of depressive and bipolar disorders is an important skill for primary care pediatricians. PMID:25646309

  6. Latest advances in connective tissue disorders

    PubMed Central

    Rao, Vijay

    2013-01-01

    The connective tissue disorders comprise a number of related conditions that include systemic lupus erythematosus (SLE) and the antiphospholipid (Hughes) syndrome, scleroderma, myositis and Sjgrens syndrome. They are characterized by autoantibody production and other immune-mediated dysfunction. There are common clinical and serological features with some patients having multiple overlapping connective tissue disorders. The latest advances include new approaches to therapy, including more focused utilization of existing therapies and the introduction of biological therapies in SLE, more precise protocols for assessment of severe disease manifestations such as in interstitial lung disease and pulmonary artery hypertension in scleroderma, new antibodies for disease characterization in myositis and new approaches to patient assessment in Sjgrens syndrome. B cells have a critical role in most, if not all of these disorders such that B-cell depletion or suppression of B-cell activating cytokines improves disease in many patients. In particular, the introduction of rituximab, a monoclonal antibody targeting the CD20 molecule on B cells, into clinical practice for rheumatoid arthritis and B-cell lymphoma has been a key driver of experimental approaches to therapy in connective tissue disorders. Genetic studies also suggest a role for the innate immune system in disease pathogenesis, suggesting further future targets for biological therapies over the next few years. PMID:23904866

  7. Genetics of bipolar disorder.

    PubMed

    Kerner, Berit

    2014-01-01

    Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a "risk" allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are currently not fulfilled for common genomic variants in psychiatric disorders. Further work is clearly needed before genetic testing for common variants in psychiatric disorders should be established. PMID:24683306

  8. Genetics of bipolar disorder

    PubMed Central

    Kerner, Berit

    2014-01-01

    Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are currently not fulfilled for common genomic variants in psychiatric disorders. Further work is clearly needed before genetic testing for common variants in psychiatric disorders should be established. PMID:24683306

  9. Testing the role of circadian genes in conferring risk for psychiatric disorders.

    PubMed

    Byrne, Enda M; Heath, Andrew C; Madden, Pamela A F; Pergadia, Michele L; Hickie, Ian B; Montgomery, Grant W; Martin, Nicholas G; Wray, Naomi R

    2014-04-01

    Disturbed sleep and disrupted circadian rhythms are a common feature of psychiatric disorders, and many groups have postulated an association between genetic variants in circadian clock genes and psychiatric disorders. Using summary data from the association analyses of the Psychiatric Genomics Consortia (PGC) for schizophrenia, bipolar disorder and major depressive disorder, we evaluated the evidence that common SNPs in genes encoding components of the molecular clock influence risk to psychiatric disorders. Initially, gene-based and SNP P-values were analyzed for 21 core circadian genes. Subsequently, an expanded list of genes linked to control of circadian rhythms was analyzed. After correcting for multiple comparisons, none of the circadian genes were significantly associated with any of the three disorders. Several genes previously implicated in the etiology of psychiatric disorders harbored no SNPs significant at the nominal level of P?included in the PGC datasets were significant after correction for multiple testing. There was no evidence of an enrichment of associations in genes linked to control of circadian rhythms in human cells. Our results suggest that genes encoding components of the molecular clock are not good candidates for harboring common variants that increase risk to bipolar disorder, schizophrenia, or major depressive disorder. PMID:24687905

  10. Protective effects of ginseng on neurological disorders

    PubMed Central

    Ong, Wei-Yi; Farooqui, Tahira; Koh, Hwee-Ling; Farooqui, Akhlaq A.; Ling, Eng-Ang

    2015-01-01

    Ginseng (Order: Apiales, Family: Araliaceae, Genus: Panax) has been used as a traditional herbal medicine for over 2000 years, and is recorded to have antianxiety, antidepressant and cognition enhancing properties. The protective effects of ginseng on neurological disorders are discussed in this review. Ginseng species and ginsenosides, and their intestinal metabolism and bioavailability are briefly introduced. This is followed by molecular mechanisms of effects of ginseng on the brain, including glutamatergic transmission, monoamine transmission, estrogen signaling, nitric oxide (NO) production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels. The molecular mechanisms of the neuroprotective effects of ginseng in Alzheimer’s disease (AD) including β-amyloid (Aβ) formation, tau hyperphosphorylation and oxidative stress, major depression, stroke, Parkinson’s disease and multiple sclerosis are presented. It is hoped that this discussion will stimulate more studies on the use of ginseng in neurological disorders. PMID:26236231

  11. Protective effects of ginseng on neurological disorders.

    PubMed

    Ong, Wei-Yi; Farooqui, Tahira; Koh, Hwee-Ling; Farooqui, Akhlaq A; Ling, Eng-Ang

    2015-01-01

    Ginseng (Order: Apiales, Family: Araliaceae, Genus: Panax) has been used as a traditional herbal medicine for over 2000 years, and is recorded to have antianxiety, antidepressant and cognition enhancing properties. The protective effects of ginseng on neurological disorders are discussed in this review. Ginseng species and ginsenosides, and their intestinal metabolism and bioavailability are briefly introduced. This is followed by molecular mechanisms of effects of ginseng on the brain, including glutamatergic transmission, monoamine transmission, estrogen signaling, nitric oxide (NO) production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels. The molecular mechanisms of the neuroprotective effects of ginseng in Alzheimer's disease (AD) including ?-amyloid (A?) formation, tau hyperphosphorylation and oxidative stress, major depression, stroke, Parkinson's disease and multiple sclerosis are presented. It is hoped that this discussion will stimulate more studies on the use of ginseng in neurological disorders. PMID:26236231

  12. [Therapy of multiple sclerosis].

    PubMed

    Sim, Magdolna

    2009-03-01

    Multiple sclerosis (MS) is one of the most frequent neuroimmunological disorders of the central nervous system. It is a multifactorial disease with possible causes including genetic and environmental factors. MS is characterized in essence by an autoimmune inflammation in the central nervous system, resulting in the damage of the myelin sheath and the axons. There are four pathological subtypes of the disease. Its clinical course can either be of the relapsing-remitting or primary and secondary progressive type. All structures of the central nervous system may be involved, but the longest tracts are affected the most often. According to the revised McDonald criteria, the diagnosis of MS is based on the clinical course and the MRI findings. Its therapy can be divided into the acute treatment of relapses, symptomatic relief and long-term immunomodulatory treatment. With respect to differential diagnosis, it is of special concern to distinguish between MS and neuromyelitis optica, as early diagnosis and appropriate treatment of the latter may prevent the development of severe residual symptoms associated with this disease. PMID:19731815

  13. Multiple system atrophy.

    PubMed

    Peeraully, Tasneem

    2014-04-01

    Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies. PMID:24963676

  14. Multiple epiphyseal dysplasia.

    PubMed

    Anthony, Steven; Munk, Richard; Skakun, William; Masini, Michael

    2015-03-01

    Multiple epiphyseal dysplasia is a genotypically and phenotypically heterogeneous disorder affecting the epiphysis of long bones. Inheritance may be autosomal dominant or autosomal recessive. Autosomal dominant variants include mutations of the collagen oligomeric matrix protein, collagen type IX α-1, collagen type IX α-2, collagen type IX α-3, and matrilin-3 genes. The autosomal recessive variant is caused by a mutation of the sulfate transporter gene SLC26A2. These mutations cause disorganized endochondral ossification of the epiphysis, ultimately leading to destruction of the articular cartilage. Patients typically present in childhood, but some may not present until early adulthood. A presumptive diagnosis can be made with clinical history, physical examination, detailed family history, and radiographic findings. Definitive diagnosis requires genetic testing. Treatment is based on the age of the patient, the amount of limb deformity, the level of joint destruction, and the needs of the patient. Children can greatly benefit from limb realignment procedures, and adults can have excellent outcomes with joint arthroplasty. PMID:25667404

  15. Asthma and Mood Disorders

    PubMed Central

    Kewalramani, Anupama; Bollinger, Mary E.; Postolache, Teodor T.

    2009-01-01

    The high rate of comorbidity of asthma and mood disorders would imply the possibility of potential shared pathophysiologic factors. Proposed links between asthma and mood disorders include a vulnerability (trait) and state connection. Vulnerability for both asthma and mood disorders may involve genetic and early developmental factors. State-related connections may include obstructive factors, inflammatory factors, sleep impairment, psychological reactions to chronic medical illness, as well as exacerbation of asthma in individuals with chronic stress. Treatment for asthma may also exacerbate mood disorders. New research suggests involvement of the central nervous system in asthma and allergy. Further characterization of clinical, psychological, cellular and molecular interconnections between asthma and mood disorders is needed to better evaluate and treat these patients. A close collaboration between mental health professionals and allergists could result in improved symptom control, quality of life, overall functioning and ultimately, decreased mortality. PMID:19180246

  16. Genetics of autism spectrum disorders.

    PubMed

    Kumar, Ravinesh A; Christian, Susan L

    2009-05-01

    Autism spectrum disorders (ASDs) are a clinically complex group of childhood disorders that have firm evidence of an underlying genetic etiology. Many techniques have been used to characterize the genetic bases of ASDs. Linkage studies have identified several replicated susceptibility loci, including 2q24-2q31, 7q, and 17q11-17q21. Association studies and mutation analysis of candidate genes have implicated the synaptic genes NRXN1, NLGN3, NLGN4, SHANK3, and CNTNAP2 in ASDs. Traditional cytogenetic approaches highlight the high frequency of large chromosomal abnormalities (3%-7% of patients), including the most frequently observed maternal 15q11-13 duplications (1%-3% of patients). Newly developed techniques include high-resolution DNA microarray technologies, which have discovered formerly undetectable submicroscopic copy number variants, and genomewide association studies, which allow simultaneous detection of multiple genes associated with ASDs. Although great progress has been made in autism genetics, the molecular bases of most ASDs remains enigmatic. PMID:19348707

  17. Gene therapy for multiple myeloma.

    PubMed

    Adachi, Yasuo; Yoshio-Hoshino, Naoko; Nishimoto, Norihiro

    2008-08-01

    Prognosis of multiple myeloma (MM) remains insufficient despite the intervention of high dose chemotherapy with auto- or allo- hematopoietic stem cell transplantation and the advent of molecular target drugs such as thalidomide, lenalidomide, and bortezomib. Further development or new concepts of therapeutic approaches are still required for MM treatment. Current standard protocol for MM treatment does not include gene delivery method or oncolytic virus approaches. Since MM is a disorder originated from B cell lineage, it involves immunological aspects in both pathogenesis and clinical manifestations. Therefore, the comprehension of immunology as well as oncology is essential to exploit new therapeutic approaches. Recently, novel therapeutic concepts for MM have been emerging. In this review, we present current progress of gene therapy related to MM treatments as well as the overview of MM treatment history. PMID:18691020

  18. Child Behavior Disorders

    MedlinePLUS

    ... a death in the family may cause a child to act out. Behavior disorders are more serious. ... The behavior is also not appropriate for the child's age. Warning signs can include Harming or threatening ...

  19. Obsessive-compulsive disorder

    MedlinePLUS

    Obsessive-compulsive neurosis; OCD ... Doctors do not know the exact cause of OCD. Factors that may play a role include head ... out other mental disorders. Questionnaires can help diagnose OCD and track the progress of treatment.

  20. Types of Vestibular Disorders

    MedlinePLUS

    ... include complications from aging, autoimmune disorders, and allergies. Acoustic Neuroma Acoustic neuroma (also called a vestibular schwannoma) is a ... This nerve is also referred to as the acoustic nerve, hence the name.) As an acoustic neuroma ...